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Synthesis of Electroactive Molecules
Based on Benzodioxins and Tetrathiafulvalenes
Emma Dahlstedt
Department of Chemistry, Organic Chemistry Royal Institute of Technology
Stockholm 2003
Akademisk avhandling som med tillstånd av Kungl Tekniska Högskolan i Stockholm framlägges till offentlig granskning för avläggande av filosofie doktorsexamen i organisk kemi, fredagen den 26:e september 2003 kl 10.00 i Kollegiesalen, KTH, Valhallavägen 79, Stockholm. Avhandlingen försvaras på engelska. Opponent är Professor Martin R. Bryce, University of Durham, Durham, England.
ISBN 91-7283-567-2 ISRN KTH/IOK/FR--03/81--SE ISSN 1100-7974 TRITA-IOK Forskningsrapport 2003:81 Emma Dahlstedt 2003 Tryck: Universitetsservice AB, Stockholm 2003
To My Family with Love
Dahlstedt, Emma; Synthesis of Electroactive Molecules Based on Benzodioxins and Tetrathiafulvalenes Department of Chemistry, Organic Chemistry KTH, SE 100 44 Stockholm, Sweden. ISBN 91-7283-567-2
Abstract This thesis deals with the synthesis of electroactive organic compounds. The synthesis of ethylenedioxy-benzodioxins tri-dioxin and tetra-dioxin are described. These molecules were prepared with the aim of creating donor molecules for cationic radical salts. The symmetric analogs of tri-dioxin, methylenedioxy-derivative and ethylenedioxy-naphthalene were also synthesized. Three different cation radical salts with 2:1 stoichiometries were obtained from tri-dioxin, while tetra-dioxin merely provided polycrystalline materials. Tri-dioxin and tetra-dioxin were also successful as operational matrixes in PALDI-TOF. Tetrathiafulvalenes with the 2-dialkyl-amino-1,3-dithiolium-4-thiolate mesoion as building-block was also synthesized. A series of doubly alkylthiol-substituted TTFs were prepared with the aim of forming self-assembly monolayers on gold surfaces in the application of organic thin film field-effect transistors. Film-formation for two TTFs were studied and they provided relatively dense packed monolayers with a discrete distance of the TTF moiety from the gold surface. The mesoionic compound was also for the first time used in an umpolung reaction. The electrophile obtained in situ by treatment of mesoion with sulfuryl chloride was reacted with a variety of electron-rich aromatic compounds. From the received products three new arylthio-substituted TTFs were synthesized. Keywords: Synthesis, Benzodioxin, Tetrathiafulvalene, Mesoion, Organic Conductor, Cation Radical Salt, Cyclic Voltammetry, Electrocrystallization, Self-Assembly Monolayer, SAM, Organic Field-Effect Transistor, OFET
Table of Contents Abstract Preface 1 Organic Conductors 1 1.1 Introduction 1 1.2 Electrical Conduction in a Material 4 1.3 Donor Molecules 5 1.3.1 Charge Transfer Salts 6 1.3.2 Cation Radical Salts 6 1.3.3 Stoichiometry 7 1.3.4 Suitable Donors 7 1.4 Electrochemistry 8 1.4.1 Cyclic Voltammetry 8 1.4.2 Electrocrystallization 10 1.5 Applications 11 1.5.1 Field-Effect Transistors 11 1.5.2 Self-Assembly Monolayers 12 1.6 Aim of This Thesis 14 2 Benzodioxins 15 2.1 Introduction 15 2.2 Synthesis of Benzodioxins 16 2.3 Donors Based on BenzodioxinsI 17 2.3.1 Introduction 17 2.3.1.1 Pentacyclic Dioxins 17 2.3.2 Symmetric Benzodioxins 18 2.3.2.1 Tri-dioxin 19 2.3.2.2 Tetra-dioxin 20 2.3.2.3 The bis(ethylenedioxy)-structures 21 2.3.3 Extended Benzodioxins 22 2.3.3.1 Outlook of the Synthesis 22 2.3.3.2 6,7-Dihydroxybenzo-1,4-dioxane; Route 1 23 2.3.3.3 6,7-Dihydroxybenzo-1,4-dioxane; Route 2 25 2.3.3.4 Nucleophilic Aromatic Substitution 26 2.3.4 Electrochemistry 29 2.4 Other Benzodioxin Projects 32 2.4.1 Soluble Benzodioxins 32 2.4.2 Chiral Benzodioxins 34 2.4.3 Thiophene-Fused Benzodioxins 35
3 Tetrathiafulvalenes 37 3.1 Introduction 37 3.2 TTF Derivatives 38 3.3 Synthesis of TTFs 40 3.4 The Mesoion – A Useful Building Block 45 3.5 TTFs for Self-Assembly StructuresII, III 49 3.5.1 Introduction 49 3.5.2 Results and Discussion 52 3.5.2.1 Synthesis 52 3.5.2.2 Electrochemistry 55 3.5.2.3 Film-Formation 57 3.6 Arylthio-Substituted TTFsIV 63 3.6.1 Introduction 63 3.6.2 Results and Discussion 65 3.6.2.1 Synthesis 65 3.6.2.2 Electrochemistry 75
4 Concluding Remarks 78 Acknowledgements 79 Appendix A 80 Appendix B 81 Papers I-IV List of Papers Discussed in This Thesis: I Synthesis of Annulated Dioxins as Electron-Rich Donors for Cation
Radical Salts J. Hellberg, E. Dahlstedt, M. E. Pelcman Manuscript for Tetrahedron II Synthesis of TTF-Containing Molecules for Self-Assembly Structures E. Dahlstedt, J. Hellberg Synth. Met. 2001, 119, 181. III Synthesis of Tetrathiafulvalenes Suitable for Self-Assembly Applications
E. Dahlstedt, J. Hellberg, R. M. Petoral Jr., K. Uvdal Submitted to J. Mater. Chem. IV Umpolung of the 2-Dimethylamino-5-alkyl-1,3-dithiolium-4-thiolate
Mesoion and its Application in the Synthesis of Some New Tetrathiafulvalenes E. Dahlstedt, J. Hellberg, A. Woldegiorgis
Submitted to Synthesis
“You step into the Road, and if you don’t keep your feet, there is no knowing where you might be swept off to.” Frodo in The Fellowship of the Ring by J. R. R. Tolkien.
Preface The work presented in this thesis was carried out during the years 1998 to 2003 at the Organic Chemistry Department at the Royal Institute of Technology, Stockholm. My work has mainly been focusing on the synthesis of oxygen- and sulfur-containing heterocyclic compounds with the aim of creating new materials for electronic applications. Under the guidance of Docent Jonas Hellberg, I started on a project to synthesize alkoxylated benzodioxins that were potential donors for cation radical salts. Other projects in the group concerned the synthesis of new tetrathiafulvalenes and thiophene structures. After some time I also became involved in the synthesis and characterization of tetrathiafulvalene-containing molecules. During my time as PhD student I had the opportunity to take part in a number of congresses concerning the organic synthesis and properties of organic materials; Poster presentations: European Conference on Molecular Electronics – Linköping 1999 Organikerdagarna – Stockholm 2000 International Conference on Science and Technology of Synthetic Metals – Bad Gastein, Austria 2000 18th International Congress of Heterocyclic Chemistry – Yokohama, Japan 2001 5th International Symposium on Functional π-Electron Systems – Ulm, Germany 2002 20th European Colloquium on Heterocyclic Chemistry – Stockholm 2002 Oral presentations: Center for Organic Informatics Meeting – Linköping 2001 Center for Organic Informatics Meeting – Norrköping 2002
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Organic Conductors
1
1.1 Introduction Organic compounds were historically believed to originate from plants and animals. This belief started to change in 1828 when Wöhler converted ammonium cyanate into urea.1 For the first time a compound from a living organism was created from inorganic materials. The carbon atom (C) together with hydrogen (H) and the heteroatoms nitrogen (N), oxygen (O) and sulfur (S), are the main elements from the Periodic Table of Elements (Figure 1), of which common organic compounds and materials are formed.
IA VIIIA1 6 Atomic number 2
H C Symbol Semimetal He1 12 4
3 4 5 6 7 8 9 10
Li Be B C N O F Ne7 9 11 12 14 16 19 2011 12 13 14 15 16 17 18
Na Mg Al Si P S Cl Ar23 24 27 28 31 32 35 4019 20 21 22 23 24 25 26 28 29 30 31 32 33 34 35 36K Ca Sc Ti V Cr Mn Fe Ni Cu Zn Ga Ge As Se Br Kr39 40 45 48 51 52 55 56 59 64 65 70 72 75 79 80 8437 38 39 40 41 42 43 44 46 47 48 49 50 51 52 53 54
Rb Sr Y Zr Nb Mo Tc Ru Pd Ag Cd In Sn Sb Te I Xe85 88 89 91 93 96 98 101 106 108 112 115 119 122 128 127 13155 56 71 72 73 74 75 76 78 79 80 81 82 83 84 85 86
Cs Ba Lu Hf Ta W Re Os Pt Au Hg Tl Pb Bi Po At Rn133 137 175 179 181 184 186 190 195 197 201 204 207 209 209 210 22287 88 103 104 105 106 107 108 110 111 112 113 114 115 116 117 118Fr Ra Lr Rf Db Sg Bh Hs Uun Uuu Uub Uut Uuq Uup Uuh Uus Uuo223 226 262 261 262 266 264 269 271 272 277 289 289 293
57 58 59 60 61 62 64 65 66 67 68 69 70La Ce Pr Nd Pm Sm Gd Tb Dy Ho Er Tm Yb139 140 141 144 145 150 157 159 163 165 167 169 17389 90 91 92 93 94 96 97 98 99 100 101 102Ac Th Pa U Np Pu Cm Bk Cf Es Fm Md No227 232 231 238 237 244 247 247 251 252 257 258 259
Mt268
63
77Ir192109
Eu152
Metal
Nonmetal
Co5945
Rh103
95Am243
IIIB IVB VB VIB VIIB VIIIB27
IB IIB
IIA IIIAAtomic weight IVA VA VIA VIIA
Figure 1 The Periodic Table of Elements. With the development of organic synthesis came the possibility to create a lot of new materials with properties that cannot be associated with living organisms. These different properties are interesting when creating materials that may be used in a variety of new applications.
1 F. Wöhler, Poggendorff’s Ann. Phys. Chem. 1828, 12, 253; A. Williams, W. P Jencks, J. Chem. Soc., Perkin Trans. 2 1974, 1753; J. Shorter, Chem. Soc. Rev. 1978, 7, 1.
2
Materials can be divided into three different groups based on their ability to conduct electricity: conductors, semiconductors and insulators (Figure 2). An electrical conductor is a material with conductivity (σ) larger than 10-6 S/cm.2 Organic compounds such as plastics and cellulose are electrical insulators and have room temperature conductivities in the order of 10-14 to 10-10 S/cm. Inorganic compounds, such as the transition metals and metalloids3, have on the other hand commonly been used as materials for electronic applications. Metallic conductors such as copper and silver have room temperature conductivities in the vicinity of 106 S/cm, while common semiconductors such as silicon and germanium lie in the 10-3 to 100 S/cm range.
insulators semiconductors conductors
glass coppersilver
(σ) S/cm10-18
10-16
10-1410-12
10-1010-8
10-610-4
10-2100
102104
106
quartzpolyethylene
diamondnylon
germaniumsilicon
1
n
6 dopedwith AsF5
S
S
S
S
3
NC
NC
CN
CN
2
δ-δ+
dopedwith Br2
Conductivity
Figure 2 Conductivities for some materials. The idea of employing organic substances as conductors was raised in the early 1950s. Akamoto et al. discovered that an ordinary organic compound, perylene (1), could be made electrically semi-conducting by doping4, in this case with bromine vapor.5 Kepler et al. then published the synthesis of the organic electron acceptor tetracyanoquinodimethane (TCNQ) (2), in the beginning of the 1960s.6 A real breakthrough came with the synthesis of the organic electron donor
2 Definition: σ = n µ e. Conductivity (σ) depends on the number (n) of charge carriers (e, charge of an electron) and how easy they can move (µ, mobility) in the material (unit: Siemens/cm, S/cm). The conductivity also relies on temperature, in metallic materials it increases with decreasing temperature, while it decreases with lowered temperature for semiconductors and insulators. 3 The elements in the groups IIIA-IVA in the Periodic Table of Elements. 4 Doping means varying the electrical properties of a material by the action of additives, compounds that are either electron donating (n-type dopant) or electron attracting (p-type dopant), traditionally in minor amounts. 5 H. Akamoto, A. Inokutchi, Y. Matsunaga, Nature 1954, 173, 168. 6 R. G. Kepler, P. E. Bierstedt, R. E. Merrifield, Phys. Rev. Lett. 1960, 5, 503; D. S. Acker, W. R. Hertler, J. Am. Chem. Soc. 1962, 84, 3370; L. R. Melby, R. J. Harder, W. R. Hertler, W. Mahler, R. E. Benson, W. E. Mochel, J. Am. Chem. Soc. 1962, 84, 3374.
3
tetrathiafulvalene (TTF) (3) in the beginning of the 1970s.7 Shortly after that, the charge transfer complex between TTF (3) and TCNQ (2) was prepared.8 This was the first proper organic metal with metallic properties even at low temperatures. A lot of effort was at that time devoted to synthesizing a range of TTF derivatives. With the ability to electrochemically oxidize tetramethyltetraselenafulvalene (TMTSF) (4), in the presence of non-nucleophilic inorganic anions, Bechgaard et al. realized the first organic superconductor9 in 1980.10 After this achievement, much focus shifted to the bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) (5), reported by Cava et al.11 This donor has been the most successful one in creating superconducting materials.12 Alongside the molecular conductors, conjugated polymers have also been given a lot of attention due to their ability to conduct electricity. In 1977 Alan J. Heeger, Alan G. MacDiarmid and Hideki Shirakawa reported on their first results regarding a highly conductive polymer, polyacetylene (6) doped with halogens.13 They were awarded the Nobel Prize in chemistry in 2000, “for the discovery and development of electrically conductive polymers”.14 This was motivated by “the important scientific position that the field has achieved and the consequences in terms of practical applications and of interdisciplinary development between chemistry and physics”. Today, numerous organic materials are being investigated for many different applications for electronic and optical properties.15
Se
Se
Se
Se
4
S
S
S
S
5
H3C
H3C
CH3
CH3
S
S S
S
2 2
ClO4I3
7 F. Wudl, G. M. Smith, E. J. Hufnagel, J. Chem. Soc., Chem. Commun. 1970, 1453; D. L. Coffen, Tetrahedron Lett. 1970, 2633. 8 J. Ferraris, D. O. Cowan, V. J. Walatka, J. H. Perlstein, J. Am. Chem. Soc. 1973, 95, 948; L. B. Coleman, M. J. Cohen, D. J. Sandman, F. G. Yamagishi, A. F. Garito, A. J. Heeger, Solid State Commun. 1973, 12, 1125. 9 Superconductivity can only arise in a material at very low temperatures, near absolute zero. Above the critical temperature, the material may have conventional metallic conductivity or may even be an insulator. When the temperature is lowered below the critical point, the resistivity rapidly drops to zero and the current will flow freely without any resistance whatsoever. 10 K. Bechgaard, C. S. Jacobssen, K. Mortensen, M. J. Thorup, Solid State Commun. 1980, 33, 1119; D. Jerome, A. Mazaud, M. Ribault, K. Bechgaard, J. Phys. Lett. 1980, 41, L95; M. Ribault, G. Benedek, D. Jerome, K. Bechgaard, J. Phys. Lett. 1980, 41, L397. The superconducting state of the (TMTSF)2PF6 salt was obtained under pressure at 1K. Later the (TMTSF)2ClO4 salt was found to be superconducting at ambient pressure and 1.2K; K. Bechgaard, K. Carneiro, F. B. Rasmussen, M. Olsen, G. Rindorf, C. S. Jacobsen, H. J. Pedersen, J. E. Scott, J. Am. Chem. Soc. 1981, 103, 2440; K. Bechgaard, K. Carneiro, M. Olsen, F. B. Rasmussen, C. S. Jacobsen, Phys. Rev. Lett. 1981, 46, 852. 11 M. Mizuno, A. F. Garito, M. P. Cava, J. Chem. Soc., Chem. Commun. 1978, 18. 12 J. M. Williams, A. M. Kini, H. H. Wang, K. D. Carlson, U. Geiser, L. K. Montgomery, G. J. Pyrka, D. M. Watkins, J. M. Kommers, S. J. Boryschuk, A. V. Strieby Crouch, W. K. Kwok, J. E. Schirber, D. L. Overmeyer, D. Jung, M-H Whangbo, Inorg. Chem. 1990, 29, 3272. The complex (BEDT-TTF)2CuN(CN)2Cl was obtained with a Tc as high as 12.8K. 13 H. Shirakawa, E. J. Louis, A. G. MacDiarmid, C. K. Chiang, A. J. Heeger, Chem. Commun. 1977, 578. 14 http://www.nobel.se/chemistry/laureates/2000/press.html. 15 P. Bernier, S. Lefrant, G. Bidan, Advances in Synthetic Metals; Twenty Years of Progress in the Science and Technology, Elsevier 1999.
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1.2 Electrical Conduction in a Material The ability of a material to conduct electricity is related to its electronic structure. Electrons can only move within the material if there are one or several vacancies in the valence orbitals of the atom or molecule. In a metal, atomic orbitals overlap with equivalent orbitals of neighboring atoms, forming molecular orbitals that can be compared with those of normal molecules. Since metals have so many molecular orbitals spaced together in a given range of energies, they are said to form continuous energy bands (Figure 3).
Atomic Orbitals Molecular Orbitals
Energy Band
1 atom 2 atoms 4 atoms
many atoms
Figure 3 Molecular orbitals form continuous energy bands. The molecular orbitals formed from the combination of atomic orbitals are bonding or antibonding. Electrons prefer the region between two nuclei i.e. in the bonding molecular orbital, rather than the region away from the nuclei i.e. the antibonding molecular orbital. Thus, the bonding orbitals are lower in energy and a certain energy is required to move an electron to an antibonding orbital. These bonding and antibonding orbitals correspond to filled and empty bands of different energy levels. The highest occupied band is called the valence band and the lowest unoccupied band is called the conduction band. The energy spacing between the highest occupied and the lowest unoccupied bands are called the band gap (Eg). Electrical conductivity in a material is achieved when an electron can move freely between the valence band and the conduction band. Consequently, the ability of a material to conduct electricity arises from how large the band gap is (Figure 4).
5
Energy
Conduction band
Valence band
Band gap (Eg)
metal semiconductor insulator
no Eg narrow Eg
wide Eg
Figure 4 Band models for a metal, a semiconductor and an insulator. The valence orbitals of metals are not completely filled, with the result that the valence band and the conduction band overlap and for this reason electrons are able to move freely in the material. In organic materials the valence orbitals are completely filled, hence an electrically conducting material can only be realized if the electrons can be excited to the higher-energy conducting band. Thus, for band gaps of approximately 0<Eg<3 eV,16 the electrons must be thermally excited to the conduction band, which is the case for semiconductors. Room temperature is often enough to make the material conductive. Once the band gap is over 3 eV it is too wide for any excitation of electrons to take place and this gives an insulating material.
1.3 Donor Molecules Consequently, to achieve an electrically conducting organic material, the band gap must be sufficiently small for the excitation of electrons to occur. A smaller band gap can be realized by creating electron-rich molecules. This will render the molecules more susceptible to lose their outer-shell electrons and they are therefore called donor molecules. Acceptor molecules also exist, such as TCNQ (2). They are on the contrary electron-poor, i.e. willing to accept electrons. This criterion alone is not enough to get a conducting substance. The molecules must be able to stack on top of each other closely enough so that the electrons can move between the molecular units. Excluding conductive oligomers and polymers, organic electroactive materials can be divided into two groups: charge transfer salts and ionic radical salts.
16 1 eV (electron volt) = 1.6 · 10-19 J.
6
1.3.1 Charge Transfer Salts Charge transfer (CT) salts consist of a donor (D) and an acceptor (A) molecule and are formed by mixing a solution of the donor and the acceptor (Equation 1).
Equation 1: D + A CT Dδ+ Aδ-
Under favorable conditions partial charge transfer can occur, which leads to stacking of molecules into crystals, e.g. TTF-TCNQ (Figure 2) and the resulting salt precipitates from the solution. Both separate and mixed stacks are likely to form (Figure 5) but the highly conductive materials typically restrain to separate stacked molecules,17 in which one or both stacks are contributing to the overall conductivity.
D δ+
D δ+
D δ+
D δ+
A δ-
A δ-
A δ-
A δ-
D δ+
A δ-
D δ+
A δ-
A δ-
D δ+
A δ-
D δ+
D + A
separate stack
mixed stack
Figure 5 Main crystal formations of charge transfer salts.
1.3.2 Cation Radical Salts Both cation and anion radical salt exist but we are mainly interested in cationic ones, since they are most frequently prepared by the electrocrystallization method (see section 1.4.2). Upon oxidation, the donor may form a salt together with an inorganic anion. The anion is preferably non-nucleophilic to prevent it from reacting with the donor. Different anions, for instance ClO4-, PF6- and NO3- are used. This is because different coordination geometries18 of the inorganic anions give rise to different stoichiometries of the produced radical salts. Cation radical salts are referred to as being quasione-dimensional or low-dimensional, since the crystal packing in the material often gives a higher conductivity in the stacking direction than perpendicular to it.
17 J. B. Torrance, Acc. Chem. Res. 1979, 12, 79. 18 Coordination geometries of some anions: ClO4
- (tetrahedral), PF6- (octahedral) and NO3
- (planar).
7
1.3.3 Stoichiometry The most common stoichiometries for cation radical salts are the 1:1 and 2:1 mixtures of the donor (D) and the anion (X-). 2:1 stoichiometry is the best combination when metallic conductivity is desired. In 2:1 salts only fractional charge transfer (CT) is obtained upon oxidation and consequently the salt is not completely ionized, which allows electrons to move between the stacks. 1:1 salts are on the other hand completely ionized. Moving an electron within the stack creates charge separation, leading to an insulating material (Figure 6).
DX-
D0
DX-
D0
D0
X-
D0
X-2:1 stoichiometry
1:1 stoichiometryDX- D2+X-
DX- X-
DX- X-
DX- D0X-
e-
e-
e-
D
D
D
D
Figure 6 Cation radical salts with separate stacks of 2:1 stoichiometry and 1:1 stoichiometry of donors (D) and anions (X-).
1.3.4 Suitable Donors In the field of organic electroactive materials, there are many different interesting applications that can be envisaged and realized with slight alterations of the molecular structure. As seen from the discussion above, some specific properties of the molecular structures are required for the donor molecules to be suitable. The cation must of course be stable and to some extent soluble in common aprotic organic solvents. For the molecules to be able to stack closely, planar systems such as aromatic structures are preferable. With π-orbitals perpendicular to the molecular plane, the orbitals may overlap in the stacking direction. As stated before, the stability of the system is increased with more electron-rich compounds. By incorporating electron-donating substituents into the donor, these will help to maintain the delocalized electron deficiency in the cation radical. At the same time, these substituents may lead to steric hindrance that disrupts the close-stacking of the molecules. Heteroatoms such as chalcogens may be introduced into the aromatic system. This will lead to a more localized charge distribution on the heteroatoms, which will enhance the overlap due to their larger d-orbitals in the stacking direction.
8
It is known that strong inter- and intrastacking in charge transfer complexes lead to an increased dimensionality and inhibits Peierls transitions19 at low temperatures.20
1.4 Electrochemistry The properties of a cation radical salt are hard to predict just by looking at the structure. Some assumptions can be made, but the best method to test the ability of a donor to form a cation radical salt, is by performing the actual electrocrystallization experiment.21 Even so, the fastest and the most widely used method to investigate the possibility for donor molecules to form stable cation radicals is by cyclic voltammetry.22
1.4.1 Cyclic Voltammetry In cyclic voltammetry the donor is dissolved in an electrolyte (the same as in electrocrystallization, section 1.4.2) and subsequently placed in a three-electrode cell (Figure 7). A time-dependent potential is applied between the working and the counter electrode.
+-
glassy carbonworking electrodeplatinum wire
counter electrode SCE reference electrode
cell with electrolyte
Figure 7 Three-electrode cell for cyclic voltammetry. SCE means saturated calomel electrode.
19 Peierls transition or distortion can in a simple way be explained as a way for a crystal to lower its energy by redistribution of charge. The distortion in a uniformly spaced stack causes the molecules to dimerize and open up a band gap with the result that the material goes from being an electrical conductor to an insulator. 20 J. M. Williams, M. A. Beno, H. H. Wang, P. C. W. Leung, T. J. Emge, U. Geiser, K. D. Carlson, Acc. Chem. Res. 1985, 18, 261; È. B. Yagubskii, R. P. Shibaeva, J. Mol. Electronics 1989, 5, 25; A. Graja, Condenced Matter News 1994, 3, 14. 21 P. Batail, K. Boubekeur, M.Fourmigué, J.-C. P. Gabriel, Chem. Mater. 1998, 10, 3005. 22 J. Heinze, Angew. Chem. Int. Ed. Eng. 1984, 23, 831.
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The current is measured towards a reference electrode as a function of the cycled potential, giving a cyclic voltammogram. Ferrocene (7) and TTF (3) are reversible and stable one- and two-electron donors, respectively (Figure 8). When the voltage (E) is increased from zero, a slow increase in current (I) is observed, which corresponds to the oxidation of the donor (D) to a cation radical (D+.). Since no stirring of the solution is used, the mass transport of the oxidizable (or reducible) electroactive species occurs only by diffusion. This leads to saturation at the electrode after a while and the current decreases. For TTF, the process is repeated when the voltage is increased further, and the cation radical (D+.) is oxidized to the corresponding dication (D2+). After the potential has reached its top value it starts to decrease, and if the donors are stable (as in Figure 8) they are reversibly reduced. The experiment is usually carried out with a scan rate between 0.1 and 1 V/s and with a maximum voltage of 2 V, which makes this a fast method for evaluating the stability of the cation radical of the donor candidate. The difference in potential between the oxidation and the reduction is called the half-wave potential (E1/2). This potential can be compared among different donors and gives information of how easily oxidized the donors are, on a relative scale.
Ferrocene (7)TTF (3)
0
D+.
D2+
D+.
D+.
DD
-e- -e-
-e-
D
D D+.
D2+D+.
+e- +e-
+e-
Fe
7
Figure 8 The reversible cyclic voltammograms of the one-electron donor ferrocene and the two-electron donor TTF.
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1.4.2 Electrocrystallization In electrocrystallization, cation radical salts are grown in a two-compartment electrochemical cell (Figure 9). Both U- and H-shaped cells are utilized, and the anode and cathode compartments are separated by a porous glass frit to avoid cross-contamination. The donor is transferred to the anode compartment where the cation radical salt is grown. The crystals are usually formed on the anode, consisting of a platinum wire, or in the anode compartment together with a suitable inorganic anion (X-), such as ClO4-, PF6-, NO3- or AsF6-. The anion is employed in the form of a tetrabutylammonium salt (Q+-salt), which serves as an electrolyte to enhance the poor conductivity of most organic solvents and the tetrabutylammonium ion also makes the inorganic counter ion soluble. Common solvents used for electrocrystallizations are dichloromethane, 1,2-dichloroethane, benzonitrile and tetrahydrofuran (THF), which are transferred to both compartments while purging with nitrogen or argon to exclude oxygen. The platinum electrodes are then immersed and the cell is sealed. The electrolysis is carried out at constant current with a current density set at 0.1-10 µA/cm2. The experiment time ranges from one week up to three months. To generate well-shaped large single crystals, the current density is low in the beginning and increased towards the end of the crystallization. Not all donor-anion combinations form salts and furthermore, many different crystal structures can be shaped from the same donor-anion combination. As mentioned earlier, the crystals form separate stacks of donor molecules and anions with different stoichiometries. The factors controlling the crystal growth are not general; different donors require different conditions.
platinumanode
platinumcathode
D
cation radical saltgrowing on theanode
porous glass frits
Q+X- Q+X-
+ -
D
Figure 9 Electrochemical cell (U-shaped) used for growing cation radical salts.
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1.5 Applications The interest in creating organic electroactive molecular materials and polymers for electronic applications is expanding. This is due to the fact that these compounds show interesting qualities for semiconducting and optical applications that can be used in commercial products. The material properties are widely tunable by small alterations in the molecular structure. Compared to the manufacturing of rigid inorganic devices made of silicon that requires clean rooms and high temperatures, the organic electronic devices hold apparent advantages. Due to the amorphous or polycrystalline nature of these materials, flexible and light weighting devices may be obtained. Organic electronics are potentially inexpensive since relatively low process temperatures and fast techniques can be used. Processing on large-area by printing on flexible substrates, such as plastics is one example. Much research has focused on organic light-emitting diodes (OLEDs),23 and organic thin-film transistors (OTFTs).24 At present, organic electronics has reached its early stages of commercial viability. Personal electronic devices incorporating small displays based on OLEDs are for instance now available.25 Many key challenges still remain, which currently hinder wide-ranging implementation of organic electronic devices. Some of the shortcomings of the current devices involve poor charge carrier mobilities, high contact resistance at the organic/metal interfaces and poor device stabilities.
1.5.1 Field-Effect Transistors Today, the field-effect transistor (FET) is one of the most important components in microelectronics, both as a separate device and integrated into circuits. Field-effect transistors based on organic semiconductors (OFETs) were first described in 198726 and are now receiving a lot of interest.27 The schematic picture of a FET is illustrated in Figure 10.
source drainsemiconductor
insulatorgate
conductivity
Figure 10 Schematic picture of a FET.
23 U. Mitschke, P. Bäuerle, J. Mater. Chem. 2000, 10, 1471. 24 C. D. Dimitrakopoulos, P. R. L: Malenfant, Adv. Mater. 2002, 14, 99. 25 B. Wessling, Chemical Innovation, Am. Chem. Soc. 2001, 35. 26 This was the first OFET identified as a potential component of an electronic device. H. Koezuka, A. Tsumura, T. Ando, Synth. Met. 1987, 18, 699. 27 See, G. Horrowitz, Adv. Mater. 1998, 10, 365; and references cited therein.
12
The FET consists of a semi-conducting material placed between two electrodes, the source and the drain. A third electrode, the gate, is separated from the semi-conducting layer by an insulating material. If a negative bias voltage is applied to the gate, then at some threshold voltage electrons are repelled from the insulator-semiconductor interface. In this depletion-layer formed, holes are created and the material becomes conducting. Hence, the transistor is “ON” and a current can flow between the source and the drain. At zero gate bias voltages, the depletion-layer is reduced and the material becomes insulating. No currant can flow between the source and the drain. The transistor is “OFF” (Figure 11).
I (µA)
E (V)
"ON"
"OFF"
thresholdvoltage
Figure 11 When a bias voltage (E) is applied to the gate, at some threshold voltage a current (I) starts to flow between the source and the drain.
For organic FETs, two parameters in particular are of importance: � The mobility (µ) of charge carriers should be high in the semi-conducting layer;
this allows fast switching of the device. � The “ON”/”OFF” ratio should be high (in the order of 106-109 Hz). Thus, the
current flowing between the source and the drain should be substantially lower when the FET is turned “OFF”.
1.5.2 Self-Assembly Monolayers To overcome the contact resistance at organic/metal interfaces some improvements have been put forward and realized. The spontaneous adsorption of long-chain alkylthiols, e.g. CH3(CH2)nSH on metal surfaces, leads to the formation of self-assembled monolayers, and was first described in 1983.28 The stability of these monomolecular layers is due to intermolecular van der Waals interactions between the hydrocarbon chains and the ability of sulfur to covalently bind to metal (mainly gold) surfaces. The prospect of SAMs has rendered a lot of interest due to the possibility of chemically tailor-make substrate surfaces by organic synthesis.29
28 R. G. Nuzzo, D. L. Allara, J. Am. Chem. Soc. 1983, 105, 4481. 29 A. Ulman, An Introduction to Ultrathin Organic Films, Academic Press, Inc. 1991.
13
Organic molecules that are able to form self-assembly monolayers on solid substrates generally consist of three components, a head (anchoring) group, an alkyl chain and a functional group (Figure 12).
alkyl chain
functionalgroup
head group
metal surface
Figure 12 A self-assembled monolayer on a metal surface. The head group connects the molecule to the substrate. It has been found that sulfur compounds such as thiols coordinate very strongly to gold surfaces, but also to other metals such as copper and silver. Most work has been focused on gold surfaces since gold does not have a stable oxide, for that reason it can be handled at ambient conditions. Other head groups than thiols may also be used to modify other types of surfaces, e.g. alkyltrichlorosilanes, which form monolayers on hydroxylated surfaces.30 The alkyl chains are able to form stable ordered monolayers by electrostatic interactions between the carbon chains. By introducing functional groups, different properties of the thin films may be obtained.31 SAMs of alkylthiols are easy to prepare. A clean hydrophilic gold substrate is immersed into a dilute solution of the organic thiol in an organic solvent. The immersion time varies but after evaporation of solvent close-packed and ordered monolayers are obtained.
30 J. Sagiv, J. Am. Chem. Soc. 1980, 102, 92; N. Tillman, A. Ulman, J. S. Schildkraut, T. L. Penner, J. Am. Chem. Soc. 1988, 111, 6136. 31 E. Delamarche, B. Michel, Thin Solid Films, 1996, 273, 54; W. Knoll, M. Liley, D. Piscevic, J. Spinke, M. J. Tarlov, Adv. Biophys. 1997, 34, 231; N. K. Chaki, K. Vijayamohanan, Biosensors & Bioelectronics 2002, 17, 1.
14
1.6 Aim of This Thesis This thesis is divided into two parts since it involves two different types of molecular systems; benzodioxins and tetrathiafulvalenes. Still, both structures are potential candidates as donor molecules in cation radical salts. The aim of this study was mainly to synthesize heterocyclic structures based on benzodioxins and tetrathiafulvalenes, and subsequently evaluate these compounds in the sense of their electroactive properties, for the application of field-effect transistors.
15
Benzodioxins
2
2.1 Introduction Our group has previously synthesized donor molecules consisting of alkoxylated dibenzofurans32 and naphthalenes33 for cation radical salts.34 These compounds generally resulted in modest conductivities and high intermolecular electron repulsions in the solid state. However, they did show good charge-carrier mobilities35 as a result of regular π-stacking and strong, narrow ESR-signals that indicated highly stable cation radicals. In order to reduce the intermolecular electron repulsions, the communicative π-system should be enlarged to spread out charges on a larger area. It is also important to maintain a planar structure, not to disrupt the stacking ability of the molecules. The disadvantage of this is often a lowered solubility of the compounds, which render them less useful for practical purposes. A possible solution to this problem is to use annulated benzodioxins as the core π-system. Dibenzodioxin (8) is a heterocyclic compound with benzene rings connected via oxygen bridges, which can contribute to a more flexible system but at the same time maintain planarity. The halogenated derivatives of compound 8, such as 2,3,7,8-tetrachlorodibenzodioxin (TCDD) (9), form a disreputable class of compounds due to their ecotoxicity.36 Although the stability of the corresponding cation radicals had been noted earlier,37 not much was known about more electron-rich derivatives.
O
O
O
OCl
Cl Cl
Cl
8 9
32 S. Söderholm, H. P. Werner, J. Krzystek, J. U. von Schütz, J. Hellberg, G. Ahlgren, Synth. Met. 1987, 20, 15. 33 J. Krzystek, J. U. von Schütz, G. Ahlgren, J. Hellberg, S. Söderholm, G. J. Olovsson, Physique 1986, 47, 1021; S. Söderholm, J. U. von Schütz, J. Hellberg, Synth. Met. 1986, 19, 403. 34 J. Hellberg, Dissertation: Alkoxylated Aromtics as Donors for Cation Radical Salts-Synthesis and Properties, Royal Institute of Technology, Stockholm 1987, ISBN 99-0726813-5. 35 J. Hellberg, S. Söderholm and J. U. von Schütz, Synth. Met. 1991, 41-43, 2557. 36 A. P. Gray, S. P. Cepa, I. J. Solomon, O. Aniline, J. Org, Chem. 1976, 41, 2435; R. d’Argy, J. Bergman, L. Dencker, Pharmacol. Toxicol. 1989, 64,33. 37 M. Tomita, S. Ueda, Y. Nakai, Y. Deguchi, H. Takaki, Tetrahedron Lett. 1963, 1189.
16
The stability and planarity of the dibenzodioxin-system38 was a motivation to synthesize a new series of substituted dibenzodioxins for evaluation as candidates for the active component in field-effect transistors. The synthesis of these compounds should also render interest from other research areas since pharmacological applications of dihydrodioxins39 and dibenzodioxins40 have recently been reported.
2.2 Synthesis of Benzodioxins Dibenzodioxins 10 had previously been prepared by condensation of catechols 11 with chlorobenzenes 12, activated for nucleophilic aromatic substitution (Scheme 1).41 These syntheses suffer from low yields when the substrate is non-activated,42 and from the use of hexamethylphosphoramide (HMPA), which is a carcinogenic solvent.43 Segura et al. have recently reported a procedure for preparing π-extended dioxins via condensation of catechols and 2,3-dichloro-1,4-naphthoquinones by using pyridine as solvent.44
OH
OH
Cl
Cl+
R1
R2
R1
R2O
O
11 12 10
Scheme 1 Dibenzodioxins via condensation.
38 In contrast to e. g. thianthrenes, dibenzodioxines are essentially planar; E. A. Meyers, R. A. Zingaro, D. Rainville, K. J. Irgolic, N. L. M. Dereu, R. Chakraworthy, G. C. Pappalardo, Proceedings of the Fourth International Conference of the Organic Chemistry of Selenium and Tellurium, Editors F. J. Barry, W. R. McWhinnie, The University of Aston in Birmingham 1983, 391-405. 39 A. Czompa, Z. Dinya, S. Antus, Z. Varga, Arch. Pharm. Pharm. Med. Chem. 2000, 333, 175; W. Gu, X. Jing, X. Pan, A. S. C. Chan, T.-K. Yang, Tetrahedron Lett. 2000, 41, 6079; R. S. Ward, Nat. Prod. Rep. 1999, 16, 75; M. L. Bolognesi, R. Budriesi, A. Cavalli, A. Chiarini, R. Gotti, A. Leonardi, A. Minarini, E. Poggesi, M. Recanatini, M. Rosini, V. Tumiatti, C. Melchiorre, J. Med. Chem. 1999, 42, 4214; K. J. Hodgetts, A. Kieltyka, R. Brodbeck, J. N. Tran, J. W. F. Wasley, A. Thurkauf, Bioorganic & Medicinal Chem. 2001, 9, 3207. 40 J. A. Spicer, W. A. Denny, Anti-Cancer Drug Design 2000, 15, 453; A. Mastrolorenzo, A. Scossafava, C. T. Supuran, J. of Enzyme Inhibition, 2000, 15, 557; R. J. Booth, V. P. V. N. Josyula, A. L. Meyer, B. A. Steinbaugh, WO Patent 2001-051479, Chem. Abstr. 2001, 135, 107243; G. Coudert, S. Khatib, P. Moreau, D.-H. Caiganrd, P. Renard, G. Atassi, A. Pierre, Eu. Patent EP 841337, Chem. Abstr. 1998, 129, 4652. 41 S. K. Singh, S. Kumar, J. Agric. Chem. 1993, 41, 1511. 42 S. Ueda, Yakugaku Zasshi 1963, 83, 805 (Chem. Abstr. 1964, 59, 15279g); R. C. Cambie, S. J. Janssen, P. S. Rutledge, P. D. Woodgate, J. Organomet. Chem. 1991, 420, 387; A. A. Dembek, P. J. Fagan, Organomet. 1996, 15, 1319. 43 H. H. Lee, W. L. Denny, J. Chem. Soc. Perkin Trans. 1 1990, 1071. 44 J. L. Segura, N. Martín, C. Seoane, M. Hanack, Synth. Met. 1995, 75, 249.
17
2.3 Donors based on BenzodioxinsI
2.3.1 Introduction The following section is a short background to the project of symmetric and extended benzodioxins.
2.3.1.1 Pentacyclic Dioxins
Our group has previously used 2,3-dihydroxynaphtalene (13) as a nucleophile in a modified Ullmann aryl ether synthesis,45 for the preparation of annulated dioxins. The nucleophile reacted with several diiodinated and dibrominated aromatic electrophiles (Scheme 2).46
X
X
R
OH
OH+
(i)
O
O
R
13 14 15
Scheme 2 Reagents and conditions: X = I or Br; (i) Cu(I)I, DMPU.46 1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone (DMPU) was chosen as solvent, as a non-carcinogenic alternative to HMPA. The products were obtained in low to modest yields, but despite the relative inefficiency of this methodology, a fast route to highly substituted pentacyclic dioxins was provided (Figure 13). Both sterically demanding and electron-rich electrophiles were suitable for this protocol. Some of the products 16-24 are representatives of entirely new heterocyclic systems.
45 G. M. Whitesides, J. S. Sadowski, J. Lilburn, J. Am. Chem. Soc. 1974, 96, 2829; T. Cohen, I. Cristea, J. Am. Chem. Soc. 1976, 98, 748; W. Chin-Hsien, L. Xiang-Te, C. Xiao-Hun, Synthesis 1982, 858; J. Lindley, Tetrahedron 1984, 40, 1433; A. J. Paine, J. Am. Chem. Soc. 1987, 109, 1496; M. A. Keegstra, T. H. A. Peters, L. Brandsma, Tetrahedron 1992, 48, 3633. 46 J. Hellberg, M. E. Pelcman, Tetrahedron Lett. 1994, 35, 1769.
18
O
O O
O O
O
CH3
CH3
CH3
CH3
O
O S
SCH3
CH3
O
O O
OO
O
OCH3
OCH3
16
21
22
18
24
20
O
O17
O
O S
S
23
O
O
OCH3
OCH3
OCH3
OCH3
19
O
OS
CH3
CH3
Figure 13 Pentacyclic dioxins from the Ullmann aryl ether reaction.
Worth noting is that the fourfold etherification of 13 with 1,2,4,5-tetraiodobenzene (25) or 2,3,4,5-tetrabromothiophene (26) were unsuccessful. No clear difference between diiodinated and dibrominated electrophiles could be observed. Although 2,3-naphthalenediol (13) was useful as the nucleophilic part, the target structure was limited to a napthodioxin, rendering donors with limited solubility and an “unemployed” side for substitution. Other nucleophiles were unsuccessfully used in the reaction protocol.
I
I
I
I
25 26
S
Br Br
BrBr
2.3.2 Symmetric Benzodioxins Inspired and triggered by the accomplished results so far, a new series of target molecules had been set up when I joined the group. Initially tri-dioxin 27 and its higher homolog tetra-dioxin 28, were chosen as compounds to be prepared.
O
O
27
O
O O
O
O
O
28
O
O O
O
O
O
These molecules are interesting since they are both electron-rich and highly symmetric, which reduces the possibility of structural disorder in the solid state. At the peripheral sites of the benzodioxin-system, the ethylenedioxy-group was chosen.
19
This end-cap group renders a nice symmetric system and this substitution also often serves as an excellent compromise between donating ability and steric demand. As a comparison, the methoxy-group lowers the oxidation potential more effectively. Unfortunately the relatively unhindered rotation of the methyl group prevents efficient stacking of the π-donors in the cation radical salt. Another potential assembly is the methylenedioxy-group, which is even less sterically demanding. This end-cap group also takes part in hydrogen bonding in the solid state.47 Compounds 29 and 30 were for that reason also included as target molecules, as valuable homologs that possibly also could be synthesized by the same methodology. The hypothesis was that these structures should be both soluble and have a comparably low oxidation potential as well as lower separation between the first and the second half-wave in their cyclic voltammogram. In order to effectively evaluate the effects of the dioxin moiety inserted into linear aromatic compounds, the bis(ethylenedioxy)-substituted naphthalene 31 and anthracene 32 were chosen as target compounds as well.
O
O
29
O
O
30
O
OO
O O
O
O
O O
O O
O O
O
31 32
O
O O
O
2.3.2.1 Tri-dioxin
As mentioned above, the synthesis protocol for 2,3-dihydroxynaphthalene (13) was unsuccessful with other nucleophiles than this molecule. Thus, 6,7-dihydroxybenzo-1,4-dioxane (33) failed to react with both 6,7-dibromo-1,4-dioxane (34a) or 6,7-diiodobenzo-1,4-dioxane (34b) (Scheme 3).
O
O
OH
OH
O
O
X
X
(i) XO
O O
O
O
O+
33 34a: X = Br34b: X = I
27
Scheme 3 Reagents and reaction conditions: (i) Cu(I)I, DMPU, 150 °C.
47 J. Hellberg, G. Ahlgren, S. Söderholm, G. Olovsson, J. U. von Schütz, Mol. Cryst. Liq. Cryst. 1985, 120, 273; G. Olovsson, Acta Cryst. C 1987, 43, 465.
20
Another route for the synthesis of tri-dioxin 27 was therefore chosen (Scheme 4). The commercially available diaryl ether of benzodioxane 35 could conveniently be dibrominated to give compound 36 in 94 % yield. Monolithiation with n-butyllithium (n-BuLi) in THF and quenching with N,N-dimethylformamide (DMF) gave the monoaldehyde 37 in 49 % yield after chromatography. Bayer-Villiger oxidation with m-chloroperbenzoic acid (MCPBA) gave a formate in 84% yield, which was hydrolyzed without purification in quantitative yield to corresponding phenol 38. Target tri-dioxin 27 could be isolated in 42% yield via the Ullmann ether reaction under conditions developed in our laboratory.
O
35
O
O O
OO
36
O
O
O
O
Br
Br
O
37
O
O
O
O
Br
CHO
O
O
27
O
O O
O
(i) (ii)
(v)(iii), (iv)O
38
O
O
O
O
Br
OH
Scheme 4 Reagents and reaction conditions: (i) Br2, CH2Cl2, rt, (ii) n-BuLi, THF, -70 °C, DMF, (iii) MCPBA, CH2Cl2, reflux, (iv) KOH, MeOH, rt, (v) NaH, CuI, DMPU, 140 °C. Analogously, methylenedioxy-derivative 29 could be synthesized from corres-ponding diaryl ether 39 in four steps and in 14% yield (Scheme 5).
O
O
29
O
O O
OO
39
O
O O
O 4 steps
Scheme 5 Synthesis of 29 in four steps from 39, with an overall yield of 14%.
2.3.2.2 Tetra-dioxin
Even though the stepwise procedure had been successful for the synthesis of the pentacyclic structures 27 and 29, it was thought to be impractical when constructing the higher homologs 28 and 30. Another procedure, employing aromatic nucleophilic substitution, which will be described further in the next section, was applied for these systems.
21
A fourfold aromatic nucleophilic substitution reaction (Scheme 6) was carried out with two equivalents of 6,7-dihydroxybenzo-1,4-dioxane (33) and one equivalent of 1,2,4,5-tetrafluorobenzene (40) in N-methylpyrrolidone (NMP) at 205 °C. Tetra-dioxin 28 was obtained in 81 % yield.
O
O O
OO
O O
O
28
OH
OHO
O
33
F
F F
F
40
+(i)
2
Scheme 6 Reagents and reaction conditions: (i) NaH, NMP, 205 °C.
Surprisingly, extension of this protocol to the analogous methylenedioxy-derivative 30 was unsuccessful (Scheme 7).
O
O O
O
30
O
O O
OOH
OH
41
F
F F
F
40
O
O+
(i) X2
Scheme 7 Reagents and reaction conditions: (i) NaH, NMP, 205 °C.
2.3.2.3 The bis(ethylenedioxy) structures
2,7-dibromo-3,6-dimethoxynaphthalene 42 was synthesized in line with a literature procedure from commercially available 2,7-dihydroxynaphthalene.48 Bis(ethylene-dioxy)naphthalene 31 could then be obtained from compound 42 in three steps (Scheme 8).
H3CO
Br Br
OCH3
HO
HO OH
OH O
O O
O
H3CO
H3CO OCH3
OCH3
31
42 43
44
(i) (ii)
(iii)
Scheme 8 Reagents and reaction conditions: (i) NaOMe, CuI, DMF; (ii) conc. HBr, n-BuNH4Br, reflux; (iii) 1-chloro-2-bromoethane, K2CO3, DMSO, 100 °C.
48 B. Laundon, G. A. Morrison, J. Chem. Soc. C, 1971, 1694.
22
Methoxylation of 2,7-dibromo-3,6-dimethoxynaphthalene49 (42) with sodium methoxide in the presence of copper(I) iodide in DMF gave 2,3,6,7-tetramethoxy-naphthalene (43) in up to 80% yield. By refluxing 2,3,6,7-tetramethoxynaphthalene in concentrated hydrobromic acid in the presence of a catalytic amount of tetrabutylammonium bromide,50 a fourfold demethylation occurred to give 2,3,6,7-tetrahydroxynaphthalene (44) in quantitative yield. 2,3,6,7-tetrahydroxynaphthalene was used immediately in the next step without further purification. 2,3,6,7-Tetrahydroxynaphthalene (44) seemed to be quite unstable, since the primary off-white material turned green and then darkened further within minutes when exposed to ambient laboratory atmosphere. Treatment of 2,3,6,7-tetrahydroxy-naphthalene (44) with 1-chloro-2-bromoethane in dimethylsulfoxide (DMSO) in the presence of potassium carbonate gave the desired bis(ethylenedioxy)naphthalene 31 in 15-27% yield. The synthesis of the corresponding bis(ethylenedioxy)anthracene 32 has not yet been performed.
2.3.3 Extended Benzodioxins Encouraged by the successful preparation of the tri-dioxin and the tetra-dioxin, we wanted to investigate if we could extend the benzodioxin-system further to the corresponding penta-dioxin 45 and even hexa-dioxin 46.
2.3.3.1 Outlook of the Synthesis
As mentioned earlier, the preferred route for synthesis of these electron-rich benzodioxins was via nucleophilic aromatic substitution. Since 2,3,7,8-tetra-halogenated dibenzodioxins had to be avoided for environmental reasons, we thought compounds 45 and 46 could be obtained from building block 47 (Scheme 9).
O
OO
O O
OO
O
O
O
O
O
45
O
OO
O
O
O
O
O
O
O
46
OH
OH
O
O
O
O
47
Scheme 9 Compound 47, hypothetical building block for structures 45 and 46. 49 R. G. Cooke, B. L. Johnson, W. R. Owen, Austral. J. Chem. 1960, 13, 256. 50 D. Landini, F. Montanari, F. Rolla, Synthesis 1978, 771.
23
Compound 41 would then be available from the 6,7-dihydroxybenzo-1,4-dioxane (33) and electron-poor benzene derivatives 48 via a nucleophilic aromatic substitution. Two different routes from commercial 1,4-benzodioxane-6-carboxaldehyde (50) and 1,4-benzodioxane (52) to the building block 33 were selected (Scheme 10).
OH
OH
O
O X
X
Y
Y33 48
OH
OH
O
O
O
O
OH
O
O CHO
O
O
OH
OH
O
O
33
OCH3
OCH3
O
O
X
X
O
O
O
O
47
34 5251
49 50
Route 1
Route 2
Scheme 10 Two different routes for the synthesis of building block 33.
2.3.3.2 6,7-Dihydroxybenzo-1,4-dioxane; Route 1
The synthesis of the desired 6,7-dihydroxybenzo-1,4-dioxane 33 by means of oxidation was straightforward (Scheme 11). Under Bayer-Villiger conditions, 1,4-benzodioxane-6-carboxaldehyde (50) was in the first step treated with MCPBA to form the corresponding formate in 88% yield and without purification the formate was hydrolyzed with potassium hydroxide, giving phenol 49 in 85% yield.
CHO
O
O OH
O
O
O
O O
O OH
OH
O
O
33544950
(i), (ii) (iii) (iv)
Scheme 11 Reagents and reaction conditions: (i) MCPBA, CH2Cl2, reflux; (ii) KOH, MeOH, rt; (iii) (KSO3)2NO (53), KH2PO4, H2O, 0 °C; (iv) Na2S2O4, H2O/Et2O, rt.
24
In the next step, which also involves an oxidation, potassium nitrosodisulfonate (Fremy’s radical or Fremy’s salt) (53) was used. This has previously been shown to oxidize phenols under very mild conditions and usually in good yields to either orto- or para-benzoquinones.51 Since the starting material was substituted only in the para-position, orto-benzoquinone 54 formed as a red solid, in 71% yield. Finally, a reduction52 with sodium dithionite was carried out, yielding 75% of 33 as beige crystals.
N OO3S
O3S2K
53 Oxidation with Fremy’s salt (53) gave product 33 in usable yields, but this reagent is quite expensive. Since we wanted to develop a fast and cheap route for large amounts of compound 33, we considered performing the oxidation of 49 with another oxidizing reagent. The quite stable reagent orto-iodoxybenzoic acid (IBX) (55), which can be prepared and isolated from orto-iodobenzoic acid (56) and oxone (Scheme 12),53 was therefore chosen.
CO2H
I
56 55
OI
HO
O
(i)O
Scheme 12 Reagents and reaction conditions: (i) Oxone, H2O, 70 °C. The reaction of 49 with IBX (55) was carried out in THF, in line with a published procedure,54 affording 33 in modest 13% yield after subsequent reduction with sodium dithionite. The low yield was probably due to the fact that the compound 54 was not isolated prior to the reduction. Oxidation was also performed on sesamol (57), with both Fremy’s salt and IBX, giving the corresponding orto-benzoquinone 58 in 71% and 60% yields, respectively (Scheme 13). The following reduction with sodium dithionite yielded 68% of the catechol derivative 41. Both compounds are known from the literature.55
51 For a review see H. Zimmer, D. C. Lankin, S. W. Horgan, Chemical Reviews 1971, 71, 229. 52 L. F. Fieser, J. Am. Chem. Soc. 1931, 53, 2329; O. Louis-André, G. Gelbard, Bull. Soc. Chim. Fr. 1986, 565. 53 D. B. Dess, J. C. Martin, J. Org. Chem 1983, 48, 4155. 54 D. Magdziak, A. A. Rodriguez, R. W. Van De Water, T. R. R. Pettus, Org. Lett. 2002, 4, 285. 55 K. C. Fylaktakidou, D. R. Gautam, D. J. Hadjipavlou-Litina, C. A. Kontogiorgis, K. E. Litinas, D. N. Nicolaides, J. Chem. Soc., Perkin Trans. 1 2001, 3073; F. Dallacker, W. Edelmann, A. Weiner, Justus Liebigs Annalen der Chemie 1969, 719, 112.
25
OH O
O OH
OH
415857
(i) (ii)O
O
O
O
O
Oa or b
Scheme 13 Reagents and reaction conditions: (i) a. (KSO3)2NO (53), KH2PO4, H2O, 0 °C; b. IBX (55), THF; (iv) Na2S2O4, H2O/Et2O, rt.
2.3.3.3 6,7-Dihydroxybenzo-1,4-dioxane; Route 2
To avoid the oxidation with the rather expensive Fremy’s salt we chose a second route for the synthesis of building block 33. From commercially available 1,4-benzodioxane (52) the diiodinated structure 34b was obtained in 82% yield by Suzuki iodination56 (Scheme 14). The corresponding dibrominated derivative 34a was produced in 90% yield from bromination with bromine in dichloromethane (Scheme 15).
I
I
O
O
34b
O
O
52
(i)
Scheme 14 Reagents and reaction conditions: (i) I2, HIO5, HOAc/ H2O/H2SO4, 50 °C.
Br
Br
O
O
34a
O
O
52
(i)
Scheme 15 Reagents and reaction conditions: (i) Br2, CH2Cl2, rt.
Both compounds 34a and 34b were evaluated in dimethoxylation reactions, according to the Ullmann arylether protocol.57 The electrophiles were reacted with freshly prepared sodium methoxide, copper(I) iodide as catalyst and DMF as solvent (Scheme 16). Unfortunately, the yields of product 51 were after purification very low, 26% and 8% from 34a and 34b, respectively. This was probably due to reduction of starting material to a monohalogenated species, among several byproducts formed.
56 Suzuki, H.; Nakamura, K,; Goto, R. Bull. Chem. Soc. Jap. 1966, 39, 128. 57 A. McKillop, B. D. Howarth, J. Kobylecki, Synth. Commun. 1974, 4, 35; P. S. Manchand, J. M. Townsend, P. S. Belica, H. S. Wong, Synthesis 1980, 409; H. L. Aalten, G. van Koten, D. M. Grove, T. Kuilman, O. G. Piekstra, L. A. Hulshof, R. A. Sheldon, Tetrahedron 1989, 45, 5565; M. A. Keegstra, T. H. A. Peters, L. Brandsma, Synth. Commun. 1990, 20, 213.
26
Optimization of the reactions, using different solvents and catalysts according to some recently published procedures,58 were fruitless.
OCH3
OCH3
O
O
51
O
O
34a: X = Br34b: X = I
(i)X
X OH
OH
O
O
33
(ii)
Scheme 16 Reagents and reaction conditions: (i) NaOMe, CuI, DMF, 70-80 °C; (ii) BBr3S(CH3)2, 1,2-dichloroethane, reflux.
Despite the fairly small amount obtained of 51, this compound was demethylated in line with a literature procedure59 to give the desired 6,7-dihydroxybenzo-1,4-dioxane (33). The reaction was carried out overnight, with a dimethylsulfide complex of boron tribromide in refluxing 1,2-dichloroethane, to give a yield of 94%.
2.3.3.4 Nucleophilic Aromatic Substitution
As shown in the synthesis of tetra-dioxin 28, the nucleophilic aromatic substitution proved useful for the construction of benzodioxin-systems.60 6,7-Dihydroxybenzo-1,4-dioxane (33) was reacted with some 1,2-dihalo-substituted benzenes with both electron-withdrawing and electron-donating groups in orto/para-positions in order to extend the compound further. The results are shown in Table 1. Reaction of 6,7-dihydroxybenzo-1,4-dioxane (30) with 1,2-dibromo-4,5-difluoro-benzene (59) proceeded smoothly to give the dibrominated dibenzodioxin 60 in quantitative yield. This reaction nicely demonstrates the difference in the reactivity of the halogen substituents. Analogously, difluorodibenzodioxin 61 could be synthesized in useful yields from 33 and 1,2,4,5-tetrafluorobenzene (40). However, when 3,4-difluorobromobenzene (62) was used as electrophile, adopting the same procedure, monobromodibenzodioxin 63 was isolated in only 43% yield. Simultaneously, reaction of 3,4-difluorobenzaldehyde 64 with catechol 33 to the corresponding dibenzodioxinaldehyde 65 was even less rewarding, yielding the product in only 26%. At the same time 4,5-difluoroveratrol (66) was unwilling to react, showing the importance of the para-substitutents and their influence on the reactivity.
58 M. Wolter, G. Nordman, G. E. Job, S. L. Buchwald, Org. Lett. 2002, 4, 973; P. J. Fagan, E. Hauptman, R. Shapiro, A. Casalnuovo, J. Am. Chem. Soc. 2000, 122, 5043. 59 P. G. Williard, C. B. Fryhle, Tetrahedron Lett. 1980, 21, 3731. 60 M. Jones Jr., Organic Chemistry, 2nd Ed. W. W. Norton & Company, ISBN 0-393-97405-7.
27
Table 1 Reaction of 6,7-dihydroxybenzo-1,4-dioxane (33) with some electrophiles.a
Electrophile Product Yield (%) Br
BrF
F
59
O
O Br
BrO
O60
Quant.
F
F F
F
40
O
O F
FO
O61
72
F
F
Br
62
O
O
BrO
O63
43
F
F
CHO
64
O
O
CHOO
O65
26
F
F
OCH3
66OCH3
No reaction -
a Reagents and conditions: NaH, DMPU, 140 °C. Selective methoxylation of difluoroderivative 61 to either the fluoromethoxy-dibenzodioxin 67 or the dimethoxy-analogue 68 proceeded in useful 81% and 63% yields, respectively (Scheme 17). Every attempt to substitute the dibromodibenzo-dioxin 60 was unsuccessful or, as in the case of methoxylation, less rewarding than the corresponding reactions for the fluoroderivative 61.
O
O F
FO
O
O
O F
FO
O
O
O OCH3
OCH3O
O
O
O F
OCH3O
O
61
61
67
68
(i) a
(i) b
Scheme 17 Reagents and reaction conditions: (i) a. NaOMe (1.1 equiv.), NMP, 90 °C; b. NaOMe (4 equiv.), NMP, 140 °C.
Compounds 67 and 68 could then conveniently be demethylated using the boron tribromide dimethylsulfide complex, yielding the corresponding phenols 69 and 47 in 93% and 86% yields, respectively (Scheme 18).
28
O
O F
OCH3O
O
O
O OCH3
OCH3O
O
O
O OH
OHO
O
O
O
OHO
O67
68
69
47
(i)
(i)
F
Scheme 18 Reagents and reaction conditions: (i) BBr3S(CH3)2, 1,2-dichloroethane, reflux.
Unfortunately, dihydroxy-derivative 47 seemed to be more or less useless as nucleophile; all attempts to react this compound with 1,2,4,5-tetrafluorobenzene (40), 1,2-dibromo-4,5-difluorobenzene (59), difluoro-derivative 61 or even iodomethane (70) failed. The self-condensation of 69 to the desired penta-dioxin 45, also failed (Scheme 19).
Br
BrF
F
59
F
F F
F
40
O
OF
F O
O
O
O OH
OHO
O
O
O
OHO
O
61
69
47
F
O
O OH
OHO
O47
O
O OH
OHO
O47
+
+
+
X
X
X
X
O
O OH
OHO
O47
CH3I+ X70
Scheme 19 Unsuccessful syntheses of penta-dioxin 45 and hexa-dioxin 46.
29
To this section can be added that some attempts to receive target penta-dioxin 45 from compounds 68 and 47 were carried out in refluxing solvent, and in the presence of various acids (Scheme 20). However, these experiments were all fruitless.
O
O OCH3
OCH3O
O
O
O OH
OHO
O
68
47
O
O OCH3
OCH3O
O
O
O OH
OHO
O68 47
X(c) or (d)
X(b)
X(a)+
Scheme 20 Reagents and reaction conditions: (a) NaHSO4, toluene, reflux; (b) 48% HBr, TBABr, ∆; (c) CH3SO3H, 1,2-dichloroethane, reflux; (d) (CF3CO)2O, CF3CO2H, ∆.
2.3.4 Electrochemistry Cyclic voltammetry was performed on pentacyclic benzodioxins 16-24 and symmetric benzodioxins 27-29 and 31. All compounds except 16 and 31 showed one quasi-reversible oxidation-reduction couple (Table 2). As expected the bis-alkoxy-substituted dibenzodioxins 27 and 29 have the lowest oxidation potentials. However, some of the mono-annulated derivatives i.e. 20, 21 and 24 were only roughly 100 mV higher. Furthermore, the addition of more than two methoxy-substituents to the dioxin is inefficient in lowering the oxidation potential, for instance donor 19 has 200 mV higher oxidation potential than 20. Also, the addition of one more benzodioxin unit is not lowering the oxidation potential, as seen by the comparison between 27 and 28. Unfortunately this is not an accurate comparison due to the rather low solubility of 28, which makes cyclic voltammetry difficult to perform.
30
Table 2 Cyclic voltammetric results from synthesized benzodioxins.a
Compound E1/2 Compound E1/2 O
O O
O
16
1,12
O
O S
S
23
1,14
O
O
17
>1,6 O
O S
SCH3
CH324
1,05
O
O
CH3
CH3
CH3
CH3
18
1,24
O
O
OCH3
OCH3
OCH3
OCH3
19
1,24
O
O O
O
O
O
27
0,93
O
O
OCH3
OCH3
20
1,02
O
O O
OO
O O
O
28
1,03
O
O O
O
21
1,04 O
O
29
O
O O
O
0,93
22
O
OS
CH3
CH3
1,46
O
O O
O
31
1,35
a 1 mM in TBAPF6 (0.15 M) in CH2Cl2, scan rate 100 mVs-1, E vs. SCE. Electrocrystallization experiments were performed for some of the target dioxins, to examine them as donors for cation radical salts. The experiments were conducted at constant current electrolysis, in a divided U-shaped cell. Donors 17, 18, 19, 20, and 23 did not yield any cation radical salts under these conditions. This is perhaps not surprising in the case of 17, since its donor is either very insoluble nor very hard to oxidize.
31
In the case of donors 18, 19 and 20, their sterically demanding substituents should make precipitation less favorable. In these cases we observed a strongly colored solution under electrolysis, which support the hypothesis that the cation radicals of these donors are too soluble under these conditions. Electrolysis was therefore conducted in a freezer. However, this did not improve the situation for donor 18. More rewarding were the electrolyses of donors 16, 20, 21 and 27. Well-formed crystals with the composition (16)2AsF6 (2:1-salt), (22)AsF6 (1:1-salt), and (27)2AsF6, (27)2PF6, (27)ClO4, (2:1-salts), could be collected after approximately one week of electrolysis. The dimethoxy-substituted donor 20 formed a non-stoichiometric salt with AsF6, with a donor equivalent of 1.1-1.2. The salt (16)2AsF6 is a semiconductor with a room temperature conductivity of σ ˜ 6 · 10 -3 S/cm and a very high number of spins according to ESR measurements (0.25 spins/molecular unit). Unfortunately, donors 28 and 31 provided only polycrystalline materials that were difficult to analyze. Apart from the electron-donating properties of tri-dioxin 27 and tetra-dioxin 28 another successful application was obtained in PALDI-TOF (polymer assisted laser desorption ionization-time of flight) spectrometry. These compounds are working as matrixes in the analysis of low to high molecular weight compounds. This is possible for the reason that these benzodioxins give distinct molecular ion peaks without fragmentation, which make them easy to distinguish from the analyte. This property also provide means for calibrating the instrument.61
61 A. Woldegiorgis, F. von Kieseritzky, J. Hellberg, E. Dahlstedt, T. Brinck, J. Roeraade, Manuscript.
32
2.4 Other Benzodioxin Projects In the next sections, the preparation of other benzodioxin-derivatives are presented. These include alkoxy-substituted benzodioxins, which were synthesized in order to enhance solubility of the benzodioxin-system. Benzodioxins containing a chiral center for optical properties and finally, thiophene-fused benzodioxins for the possibility of creating new monomers for oligo- and polythiophenes.
2.4.1 Soluble Benzodioxins Despite our ambition to create more soluble compounds with extended π-systems, these benzodioxins had a tendency to form precipitates that were hard to dissolve. We therefore thought of how to make the compound more soluble without losing its ability of stacking. One way of enhancing solubility is to insert alkyl-chains into the aromatic moiety. As a test system we thought of exchanging the ethylenedioxy-bridges of tetra-dioxin 28 for longer alkyloxy-chains. Thus, we decided to prepare a structure like 71, and hopefully, the peripheral alkyl-chains would not interfere with the stacking-ability of the aromatic systems.62
RO
RO
71
O
O
O
O OR
OR
With confidence, we started the reaction sequence (Scheme 21) with alkylation of 3,4-dihydroxybenzaldehyde (72) with excess of 1-octylbromide in acetone and 73 was obtained in usable yields after purification by column chromatography. Phenol 74 was obtained via a Bayer-Villiger oxidation followed by acid hydrolysis of the corresponding formate. However, the next oxidation of 74 was more difficult to perform due to oily nature of the compound. Tetrabutylammonium chloride (TBACl) was added to the reaction mixture to obtain a more efficient mixing of the reagents. Orto-quinone 75 was received as red crystalline compound after recrystallization from acetone. The succeeding reduction yielded product 76 as an oily residue, but the waxy crystals of 76 could be precipitated from hexane by cooling in freezer. The overall yield for the conversion of 72 to 76 was 34%. Nucleophilic aromatic substitution of two equivalents of 76 with 1,2,4,5-tetrafluorobenzene (40) in NMP at 140 °C was performed, unfortunately this reaction yielded only the halfway-product 77 and not the target molecule 78.
62 C. F. van Nostrum, S. J. Picken, A.-J. Schouten, R. J. M. Nolte, J. Am. Chem. Soc. 1995, 117, 9957.
33
CHO
C8H17O
C8H17O OH
C8H17O
C8H17O
7473
(ii), (iii) (iv)
C8H17O
C8H17O O
O OH
OH
C8H17O
C8H17O
7675
(v)
CHO
HO
HO
72
(i)
(vi)
C8H17O
C8H17O
77
O
O F
F
C8H17O
C8H17O
78O
O
O
O OC8H17
OC8H17
X
Scheme 21 Reagents and reaction conditions: (i) 1-octylbromide, K2CO3, acetone, reflux; (ii) MCPBA, CH2Cl2, reflux; (iii) p-TsOH, MeOH, N2, 65 °C; (iv) (KSO3)2NO (53), KH2PO4, TBACl, H2O/THF, 0 °C; (v) Na2S2O4, H2O/Et2O, rt; (vi) 1,2,4,5-tetrafluorobenzene (40), NaH, NMP, 140 °C.
Subsequently, derivative 79 was synthesized from aldehyde 80 via the corresponding phenol 81 and orto-quinone 82, by the same route as that for the preparation of compound 76, in 23% overall yield (Scheme 22). Compound 80 was obtained by alkylation of 3,4-dihydroxybenzaldehyde (72) with tetrahydropyrane (THP) terminated alkoxy-chains. The THP-group serves as a protecting group for alcohols.63
CHO
THPOC11H22O
THPOC11H22O OH
THPOC11H22O
THPOC11H22O
8180
(ii), (iii)
(iv)
THPOC11H22O
THPOC11H22O O
O OH
OH
THPOC11H22O
THPOC11H22O
7982
(v)
CHO
HO
HO
72
(i)
Scheme 22 Reagents and reaction conditions: (i) 11-bromododecyl-OTHP, K2CO3, acetone, reflux; (ii) MCPBA, CH2Cl2, reflux; (iii) KOH, EtOH, rt; (iv) (KSO3)2NO (53), KH2PO4, TBABr, H2O/THF, rt; (v) Na2S2O4, H2O/Et2O, rt.
Unfortunately, the nucleophilic aromatic substitution of 79 with 1,2,4,5-tetrafluoro-benzene (40) in DMPU at 160 °C (Scheme 23) was not successful. The crystallization of product is assumed to be the driving force of the reaction. Hence the lack of crystallization in these two cases may explain why no products 78 or 83 formed. 63 B. S. Babu, K. K. Balasubramanian, Tetrahedron Lett. 1998, 39, 9287. N. Miyashita, A. Yoshikoshi, P. A. Grieco, J. Org. Chem. 1977, 42, 3772.
34
OH
OH
THPOC11H22O
THPOC11H22O
79
THPOC11H22O
THPOC11H22O
83
O
O
O
O OC11H22OTHP
OC11H22OTHPX(i)
Scheme 23 Reagents and reaction conditions: 1,2,4,5-tetrafluorobenzene (40), NaH, DMPU, 160 °C.
2.4.2 Chiral Benzodioxins Some of the interest in our group has also been motivated by the potential in combining electrical conductivity with optical properties. Any material that rotates the plane of polarized light is said to be optically active. For the material to be optically active the molecule must be non-superimposable on its mirror image; this feature is called chirality. A lot of research in the area of polymeric substances has been devoted to chiral polymers for optical applications.64 Smaller molecules with main-chain chirality for instance structure 84,65 are also studied. The chirality in this structure is caused by the helical shape of the molecule. We decided to synthesize a chiral building block i.e. structure 85, which would offer the possibility to produce benzodioxins with a built-in chirality. It was not the stereogenic center it self that was interesting but the possibility of the structure to form stacks with a specific orientation in the crystalline state.
O
O
O
O
85
O
O O
O
SSS
S
S
SS
BrBr
TMS
TMS
84 Methylenedioxy-catechol 41 was chosen as starting material since we thought it would be possible to remove the methylene group by demethylation, in order to have the possibility of extending the π-system further. The (2S,3S)-1,4-dichloro-2,3-butanediol (86) was obtained via a literature procedure.66 This chiral substrate was subjected to a nucleophilic substitution reaction with methylenedioxy-catechol 41 in DMF (Scheme 24).
64 L. Ma, Q.-S. Hu, K. Y. Musick, D. Vitharana, C. Wu, C. M. S. Kwan, L. Pu, Macromolecules 1996, 29, 5083. 65 A. Rajca, H. Wang, M. Pink, S. Rajca, Angew. Chem. Int. Ed. 2000, 39, 4481. 66 K. P. M. Vanhessche, Z.-M. Wang, K. B. Sharpless, Tetrahedron Lett. 1994, 35, 3469.
35
OH
OH
86
Cl Cl
OHHO+
41
O
O
87O
O
O
O
HO OH
O O
OH HO(i)X
Scheme 24 Reagents and reaction conditions: (i) NaH, CuI, DMF, 90 °C. To our disappointment no product 87 formed. The explanation for this may be the minor differences in pKa values for phenols versus alcohols. Hydroquinone has pKa 10.35 and ethylene glycol pKa 14.22.67 The relatively low acidity of compound 41 may be the reason to its unwillingness to react. Instead we tried sesamol (57) as nucleophile, and this reaction yielded disubstituted product 88 in modest 25% after purification (Scheme 25). The subsequent bromination of 88 produced crude product 89 in 67 % yield. However, after recrystallization only 19% of pure product 89 was obtained. The reaction sequence ended sadly since no product 85 formed when 89 was exposed to Ullmann aryl ether conditions.
89O
O
O
O
HO OH
O O
88
HO OH
O O
Br Br
(i) (ii)
(iii)XO
O
O
O
85
O
O O
O
OH
86
Cl Cl
OHHO+
57
O
O
O
O O
O
Scheme 25 Reagents and reaction conditions: (i) NaH, CuI, DMF, 90 °C; (ii) Br2, 1,2-dichloroethane, rt; (iii) NaH, CuI, DMF, 110 °C.
2.4.3 Thiophene-Fused Benzodioxins 3,4-diethylenedioxythiophene (EDOT) (90) and its corresponding polymer PEDOT (91) (Scheme 26), have received a lot of attention due to the combination of high electrical conductivity, optical transparency and stability in the doped conducting state.68 The polymer has for instance been useful for antistatic coatings69 and several modifications of the polymer are being explored.70
67 Handbook of Chemistry and Physics 78th Ed. CRC Press 1997. 68 P. Blanchard, A. Cappon, E. Levillain, Y. Nicolas, P. Frère, J. Roncali, Org. Lett. 2002, 4, 607. 69 G. Heywang, F. Jonas, Adv. Mater. 1992, 4, 116. 70 P. J. Steel, Chem. Mater. 1996, 8, 882.
36
S
OO
90
S
OO
91
n
Scheme 26 EDOT (90) and the corresponding polymer PEDOT (91). Our group has recently investigated the synthesis of 3,4-dimethoxythiophene (92).71 We wanted to study the condensation reaction of 3,4-dimethoxythiophene (92) with various catechol-derivatives i.e. 11, in order to learn how an extension of the aromatic system would affect the properties of the EDOT (90) molecule. As first test system, 3,4-dimethoxythiophene (92) was reacted with catechol (93) to establish suitable reaction conditions.72 Compounds 92 and 93 were reacted in refluxing 1,2-dichloroethane in the presence of methanesulfonic acid (MeSO3H) (Scheme 27). Hitherto only 11% yield of pure product 94 has been obtained. This is probably due to competing polymerization of 3,4-dimethoxythiophene (92).
S
OCH3H3CO
92
OH
OH+
93
(i)
94
O
OS
Scheme 27 Reagents and reaction conditions: (i) MeSO3H, 1,2-dichloroethane, reflux.
The reaction of 92 and 6,7-dihydroxy-1,4-benzodioxane (33) was also studied (Scheme 28). This reaction was carried out in refluxing toluene with p-toluenesulfonic acid (p-TsOH). As for compound 94 only small amounts of product 95 was obtained after purification. The corresponding methylenedioxy-derivative 41 was not suitable for this reaction.
S
OCH3H3CO
92
OH
OH+
33
O
O
(i)
95
O
O O
OS
Scheme 28 Reagents and reaction conditions: (i) p-TsOH, toluene, reflux.
71 Previous methods; A. Merz, C. Rehm, J. Prakt. Chem. 1996, 338, 672; B. M. W. Langeveld-Voss, R. A. J. Janssen, E. W. Meijer, J. Mol. Structure 2000, 521, 285. 72 A recent patent describes this reaction; G. Rauchschwalbe, A. Klausener, S. Kirchmeyer, K. Reuter, Benzodioxinothiophenes; their preparation and use, U. S. Patent Appl. 0028024, Feb. 6, 2003.
37
Tetrathiafulvalenes
3
3.1 Introduction Tetrathiafulvalene (3) is a planar non-aromatic 14π-electron system. Upon oxidation, TTF-molecules may form highly ordered stacks. The sulfur atoms in the TTF-core are primarily responsible for the close packing and overlap between the TTF-molecules. Tetrathiafulvalene is a reversible and stable two-electron donor (Figure 14). The contribution from a 6π-electron heteroaromaticity of both the 1,3-dithiolium cation 96 and the dication 97, leads to a thermodynamically very stable donor system.
S
S
S
S
3S
S
S
S
S
S
S
S-e-
+e-
-e-
+e-
96 97
Figure 14 Reversible oxidations of TTF. The oxidation potentials are established from cyclic voltammetry experiments and they are relatively low. For the unsubstituted TTF (3) the reported half-wave potentials are E11/2 = 0.33 and E21/2 = 0.71.73 These redox properties can be adjusted by replacing the hydrogens on TTF (3) by different substituents (R) forming various TTF derivatives, i.e. structure 98 (Figure 15).
S
S
S
S
98
R
R R
R
S
S
S
S
3
Figure 15 TTF derivative 98 from substitution of TTF (3).
Tetrathiafulvalene (TTF) (3) and its derivatives have been thoroughly studied during the last two decades due to their ability to act as π-donors in charge-transfer salts and cation radical salts.
73 G. Schukat, A. M. Richter, E. Fanghänel, Sulfur Reports 1987, 7, 155; G. Schukat, E. Fanghänel, Sulfur Reports 1993, 14, 245.
38
3.2 TTF Derivatives The reason to study TTFs in the first place, was for the development of molecular conductors and superconductors. The replacement of sulfur with selenium in TMTSF (4) has already been mentioned; this compound gives highly conductive cation radical salts upon oxidation. This is a result of the enhanced overlap between the heavier chalcogens, which facilitates the formation of highly ordered stacks. Even though the implementation of TTFs in molecular electronics has not yet been realized, developments of TTF syntheses have made it possible to utilize TTF derivatives as building blocks in macromolecular structures and for new applications. The unique combinations of properties, which the TTF molecular system displays, explain why it has been studied so extensively. The field of functionalized TTFs has been summarized in several review articles.74, 75, 76 In the following section some of these new compounds and their applications are presented. One of the first applications besides molecular metals was TTF derivatives working as cation sensors. By substituting TTFs with crown-ethers77 the metal-binding properties78 could be investigated by changes in the cyclovoltammetric behavior of the TTF-system. The crown-ether substituted TTFs 99 and crown-annelated π-extended TTFs 100 (Figure 16) are examples of structures that have been described by Becher et al.79 and Bryce et al.80 respectively, with the aim of creating molecular detectors for metal cations.
H3CS
S
S
SCH3
S
S
S
S
OO
S
SOO
S
S OO
S
S OO
S
S
99 100
S
S
S
Figure 16 Crown-ether substituted TTFs for sensor applications.
74 J. Becher, J. Lau, P. Mørk, Electronic Materials: The Oligomer Approach by K. Müllen, G. Wegner, Weinheim VCH 1998, ISBN: 3-527-29438-4. 75 M. R. Bryce, J. Mater. Chem. 2000, 10, 589. 76 J. L. Segura, N. Martín, Angew. Chem. Int. Ed. 2001, 40, 1372. 77 First presented by: T. Otsubo, F. Ogura, Bull. Chem. Soc. Jpn. 1985, 58, 1343. 78 T. K. Hansen, T. Jørgensen, P. C. Stein, J. Becher, J. Org. Chem. 1992, 57, 6403; R. Gasiorowski, T. Jørgensen, J. Møller, T. K. Hansen, M. Pietraszkiewicz, J. Becher, Adv. Mat. 1992, 4, 568. 79 F. Le Derf, M. Mazari, N. Mercier, E. Levillain, P. Richomme, J. Becher, J. Garín, J. Orduna, A. Gorgues, M. Sallé, Chem. Commun. 1999, 1417. 80 M. R. Bryce, A. S. Batsanov, T. Finn, T. K. Hansen, A. J. Moore, J. A. K. Howard, M. Kamenjicki, I. K. Lednev, S. A. Asher, Eur. J. Org. Chem. 2001, 933.
39
Rotaxanes and catenanes with TTF as building block have been reported by Stoddart et al., and proposed to function as molecular shuttles (Figure 17).81 It has been suggested that these systems can be used as nanomachines that rely on external energy transfer processes, since these compounds may be able to store and process information at a molecular level.82
SS
SS
O O
OO
O
O O
O
OO
NN
NN
N N
N N
SS
SS
O O
OO
O
O OO
OO
-e-
+e-
/2+
Figure 17 Electrochemically triggered redox-switching of a catenane. The syntheses and properties of TTF analogs containing rigid π-spacers like structure 101, have been explored by Roncali et al., for the possibility of tuning the conduction mechanism between the “vertical” conduction of TTF charge transfer salts and the “horizontal” conduction of linear systems.83 TTFs have also been used in order to create multi-redox systems, potentially to act as unimolecular rectifiers,84 single-component conductors85 and as artificial photosynthetic centers.86, 87 One example of this is the D-σ-A system, structure 102, which contains a strong electron donor, in this case a TTF derivative linked to a strong electron acceptor. This system was reported by Bryce et al. and the intended function was an intramolecular photoinduced electron transfer.88 The synthesis of π-conjugated TTF-polymers bearing electronic and optical functional groups has recently been reported by Yamamoto.89 The TTF-containing polymer PTTF(Ar) 103 was for instance prepared
81 M. Asakawa, P. R. Ashton, V. Balzani, A. Credi, C. Hammers, G. Mattersteig, M. Montalti, A. N. Shipway, N. Spencer, J. F. Stoddart, M. s. Tolley, D. J. Williams, Angew. Chem., Int. Ed. Engl. 1998, 37, 333. 82 J.-M. Lehn, Angew. Chem., Int. Ed. Engl. 1988, 27, 89; M. B. Nielsen, C, Lomholt, J. Becher, Chem. Soc. Rev. 2000, 29, 153; D. B. Amabilino, J. F. Stoddart, Chem. Rev. 1995, 95, 2725; D. Philp, J. F. Stoddart, Angew. Chem. Int. Ed. Engl. 1996, 35, 1154; F. M. Raymo, J. F. Stoddart, Chem. Rev. 1999, 99, 1643. 83 J. Roncali, J. Mater. Chem. 1997, 7, 2307. 84 R. M. Metzger, J. Mater. Chem. 1999, 9, 2027. 85 T. Suzuki, M. Yamada, M. Ohkita, T. Tsuji, Heterocycles 2001, 54, 387. 86 G. Kodis, P. A. Liddell, L. de la Garza, A. L. Moore, T. A. Moore, D. J. Gust, Mater. Chem. 2002, 12, 2100. 87 See; D. F. Perepichka, M. R. Bryce, I. F. Perepichka, S. B. Lyubchik, C. A. Christensen, N. Godbert, A. S. Batsanov, E. Levillain, E. J. L. McInnes, J. P. Zhao, J. Am. Chem. Soc. 2002, 124, 14227; and references cited therein. 88 D. F. Perepichka, M. R. Bryce, E. J. L. McInnes, J. P. Zhao, Org. Lett. 2001, 3, 1431. 89 T. Yamamoto, Synlett 2003, 425.
40
by the Yamamoto group, by organometallic polycondensations.90 Fabre et al. have also incorporated TTFs into polymers by attaching them to a styrene polymer backbone 104.91 Other applications of TTFs that are reported in literature are in C60 complexes for photoinduced electron transfer,92 for non-linear optical (NLO) applications93 and in organic ferromagnets.94
S
S
S
S
S
S
SCH3
SCH3
H3CS
H3CS
101
Cl O
SS
SS
n n n
104
S
S
S
S
102
C5H11
C5H11 CH3
O
O
SO
O
NO2 NO2
NO2
NCCN
S
S
S
S
103
Ph
Ph
Ar
n
As demonstrated above, the use of the TTF derivatives in electronic applications seems potentially rewarding. Due to difficulties involving the synthesis and characterization of TTFs, use in commercial applications may or may not be applicable. However, in academic research it serves as a valuable test system.
3.3 Synthesis of TTFs Many routes for the syntheses of TTF and its derivatives have been developed and reviewed.73, 95 The synthetic approach to make TTFs has mainly used either one of two building blocks, 2H-1,3-dithiolium salts 105 or 2-chalcogenone-1,3-dithioles 106.
90 T. Yamamoto, T. Shimizu, J. Mater. Chem. 1997, 7, 1967. 91 F. Bonfils, J. M. Fabre, L. Giral, C. Montginoul, A. Mungroo, R. Sagnes, F. Schue, Macromol. Chem. 1989, 190, 2579. 92 N. Martín, L. Sánchez, B. Illescas, I. Pérez, Chem. Rev. 1998, 98, 2527. 93 B. J. Coe, Chem. Eur. J. 1999, 5, 2464. 94 P. Day, M. Kurmoo, J. Mater. Chem. 1997, 8, 1291. 95 M. Narita, C. U. Pittman, Synthesis 1976, 489; Khodorkovsky, Lat. 1982, 2, 131; A. Krief, Tetrahedron 1986, 42, 1209.
41
S
S
R1
R1
H
105X S
S
R1
R1
Z
106
X = PF6 or BF4Z = O, S or Se
The 2-thiono-1,3-dithioles 106 and their derivatives are also precursors to the 2H-1,3-dithiolium salts 105. These can be obtained by direct treatment with peracetic acid in acetone,96 or by alkylation of compound 107 with dimethylsulfate to yield cation 108 after anion exchange. After reduction with sodium borohydride followed by treatment with tetrafluoroboric acid, the 2H-1,3-dithiolium salt 109 is obtained (Scheme 29).97
S
SS
107
S
SSHCH3
108
(iv) (v)
S
SH
109
BF4
S
SSCH3
HS
S
S
S
S
S
S
SBF4
(i), (ii), (iii)
Scheme 29 Preparation of 2H-1,3-dithiolium salt 109.97 Reagents and reaction conditions: (i) Dimethylsulfate, 95-100 °C, 30 min; (ii) AcOH, 0 °C, 10 min; (iii) HBF4, 0 °C, 10 min; (iv) NaBH4, EtOH, 0 °C - 20 °C, 2h; (v) Ac2O, HBF4, 0 °C, 15 min.
TTFs are obtained by deprotonation of 2H-1,3-dithiolium salts with tertiary aliphatic amines. Coupling of unsymmetrically substituted dithiolium salts 110 normally leads to a mixture of Z- and E-isomers of TTF 111 and the chemical and physical properties of these are most often very similar. The isomers are thus hard to identify and separate (Scheme 30).98
S
SR1
H
110X S
S
S
SR1 R1(i)
Z - 111
S
S
S
S
R1
R1
E - 111
+R2 R2 R2 R2
R2
Scheme 30 Reagents and reaction conditions: Et3N, CH3CN, rt.108 The proposed intermediate in this reaction is a carbene 112, which is stabilized by 6π-electrons (Scheme 31).99 Formation of TTF 111 is believed to proceed via either a polar nucleophilic attack at C-2 of the 1,3-dithiolium cation 110 followed by loss of a proton (Route 1) or by a non-polar dimerization of the carbene (Route 2). 96 E. Klingsberg, J. Am. Chem. Soc. 1964, 86, 5290. 97 A. J. Moore, M. R. Bryce, Synthesis 1991, 26. 98 A. Souizi, A. Robert, P. Batail, L. Ouahab, J. Org. Chem. 1987, 52, 1610. 99 H. Prinzbach, H. Berger, A. Lüttringhaus, Angew. Chem. Int. Ed. Engl. 1965, 4, 435.
42
S
SR1
112
S
SR1
R2 R2
S
S R1
R2S
SR1
H
XR2
S
S
S
SR1 R1
R2 R2
H
X
S
S
S
SR1 R1
111R2 R2
-HX
Route 2Route 1110
Scheme 31 Resonance stabilization of the proposed1,3-dithiolium carbene 112 and possible mechanisms for the formation of TTF 111.
A more general route for the synthesis of TTFs is the dechalcogenization of the 2-chalcogenone-1,3-dithioles 106 with trivalent phosphorus compounds. Cross-coupling of the appropriate 1,3-dithiole derivatives e.g. 106 and 113 with triethyl phosphite usually leads to a mixture of the three possible TTF-isomers 114a-c that have to be separated by column chromatography (Scheme 32). The use of bulky substituents alters the properties so much that the isomers can be separated by chromatography.
S
S
S
SR1 R1
114a
S
S
S
S
R2
R1
114b
+S
S
S
S
R2
R2
114c
+R1 R1 R1
R2
R2
R2
S
S
R1
R1
Z
106
(i)
S
S
R2
R2
Z
113
+
Scheme 32 Cross-coupling of 1,3-dithioles 106 and 113 yields a mixture of TTF-isomers 114a-c. Z = O, S, Se. Reagents: (RO)3P or R3P.
Another precursor for both compounds 105 and 106 is the 2-dialkylamino-1,3-dithiolium salts 115. The preparation of 105 is described below (Section 3.4) while 106 can be obtained by treatment of 115 with hydrogensulfide (H2S) or hydrogenselenide (H2Se).100
100 E. Campaigne, N. W. Jacobsen, J. Org. Chem. 1964, 29, 1703.
43
S
S
R1
R1
NR2
115X
One example of the preparation of 115 is the synthesis of the 2-dimethylamino-1,3-dithiolium bromide 116, which was reported by Wudl et al. (Scheme 33).101
O
O
O
O
O
O
S N(CH3)2
S
S
SN(CH3)2
Br
(i)
(iv)
116
Cl
Cl O
O S
S
SN(CH3)2
SN(CH3)2
(ii)
(iii)
O
O
S
SN(CH3)2
Br
Br
Scheme 33 Reagents and reaction conditions: (i) (CH3)2NCS2-, CH3CN; (ii), DMSO, 110 °C; (iii) Br2, CH2Cl2; (iv) 110 °C, 25 torr.101
The 2-dialkylamino-1,3-dithiolium salts 115 have been used in the synthesis of unsymmetrical TTFs. By this procedure symmetrical products can be avoided. The coupling of 115 with phosphonate esters of various substituted 1,3-dithioles 117 was carried out under Wittig-like conditions (Scheme 34).102
S
S
R2
R2
H
117
(R3O)2PO
+(i), (ii)
S
S
S
S
R2R1
R2R1
S
S
R1
R1
NR2
115X
Scheme 34 Preparation of unsymmetrical TTFs.102 Reagents: (i) t-BuOK; (ii) AcOH.
TTFs such as derivative 118 can also be obtained by thermal decomposition of 2-alkoxy-1,3-dithioles 119 at 200 °C (Scheme 35).103
101 T. Suzuki, H. Yamochi, G. Srdanov, K. Hinkelmann, F Wudl, J. Am. Chem. Soc. 1989, 111, 3108; J. Hellberg, M. Moge, Synthesis 1996, 198. 102 J. Hellberg, M. Moge, H. Schmitt, J.-U. von Schütz, J. Mater. Chem. 1995, 5, 1549; H. J. Cristau, F. Darviche, E. Torreilles, J.-M- Fabre, Tetrahedron Lett. 1998, 39, 2103; H. J. Cristau, F. Darviche, M.-T. Babonneau, J.-M- Fabre, E. Torreilles, Tetrahedron 1999, 55, 13029. 103 J. Nayama, Synthesis, 1975, 168.
44
S
SOR
H
S
S
S
S
119
(i)
118
Scheme 35 Thermal decomposition of 2-alkoxy-1,3-dithioles 118 to the corresponding TTF derivative 119. R = CH3, n-C4H9, i-C5H11, n-C6H13. Conditions: (i) 200 °C.103
TTFs are rather stable under basic and weakly acidic conditions. This makes it possible to modify the TTF-core without destroying the basic skeleton. TTF is mono-lithiated by butyllitium (BuLi) or lithium diisopropylamide (LDA) in ether at –78 °C and can then be reacted with various electrophiles. Tetralithiated TTF 120 can also be obtained by raising the temperature to –20 °C or with excess of lithium base. Treatment of the tetraanionic intermediate 120 with dimethyl-disulfide afforded tetrakis(methylthio)TTF (121)(Scheme 36).104
S
S
S
S
3
S
S
S
S
120
Li(i)
S
S
S
S
121Li
Li
Li
H3CS
H3CS SCH3
SCH3(ii)
Scheme 36 Preparation of tetrakis(methylthio)TTF (121). Reagents and reaction conditions: (i) LDA, THF, –78 °C; (ii) CH3-S-S-CH3.104
Polytetrathiafulvalenes have also been prepared via the deprotonation route from bis-1,3-dithiolium salt 122 to give the planar poly-TTF 123 (Scheme 37).105
S
S
S
SH
H
122
S
S
S
S
(i)
123
Scheme 37 Preparation of poly-TTF 123. Reagents: Et3N.
104 S.-Y. Hsu, L. Y. Chiang, J. Org. Chem. 1987, 52, 3444. 105 Q. Vu Trinh, L. Van Hinh, G. Schukat, E. Fanghänel, J. Prakt. Chem. 1989, 331, 826.
45
3.4 The Mesoion – A Useful Building Block As presented in section 3.3, the 2-dialkylamino-1,3-dithiolium salts 115 can be used for preparing both 2H-1,3-dithiolium salts and 2-thiono- and 2-oxo-1,3-dithioles in order to obtain TTFs. Another analogous compound is the 2-dialkylamino-1,3-dithiolium-4-thiolate mesoion 124, which is readily alkylated to give the corresponding 2-dialkylamino-4-alkylthio-1,3-dithiolium salt 125. The mesoion 124 was first described by Robert and Souizi,106 and could be prepared via a multi-step reaction from 2,2-dicyanooxirane by the reaction with carbon disulfide. The synthesis of mesoion 124 was improved by Jørgensen et al.107 Their route involved a substitution reaction of an α-bromocarboxylic acid 126 with excess of N,N-dialkyldithio carbamate 127 in ethanol. The intermediate 128 provided mesoion 124 upon treatment with acetic anhydride, triethylamine and subsequently carbon disulfide (Scheme 38).
SHO
R1
ONR2
S
BrHO
R1
O
NaS NR2
S(i)
+(ii), (iii), (iv)
S
S
S
R1
NR2
126 127 128 124
Scheme 38 Preparation of mesoion 124.107 Reagents and reaction conditions: (i) EtOH, 0°C; (ii) Ac2O, (iii) Et3N, (iv) CS2, acetone, rt.
The reaction takes place via the transesterified carbamate 129 to a 4-oxylmesoion 130, which is the presumed intermediate. The 4-oxylmesoion 130 subsequently undergoes a [1,3]-dipolar cycloaddition with simultaneous release of carbonyl sulfide when carbon disulfide is added to the solution (Scheme 39).
106 A. Souizi, A. Robert, C. R. Acad. Sc. Paris 2 1982, 295(5), 571; A. Souizi, A. Robert, Synthesis 1982, 1059; A. Souizi, A. Robert, Tetrahedron 1984, 40, 1817. 107 M. Jørgensen, K. A. Lerstrup, K. Bechgaard, J. Org. Chem. 1991, 56, 5684; M. Jørgensen, K. Lerstrup, K. Bechgaard, Synthetic Metals 1991, 41-43, 2561.
46
SHO
R1
ONR2
SAc2O
S
SNR2
O
R1
-HOAc
C SS
SO
R1
ONR2
SH3C
O
S
SR1
O
NR2
S
S
-COS
S
SNR2
O OH3C
OR1 H
S
SNR2
S
R1
128 129
130
124
S
SNR2
O
R1H
Et3N
Scheme 39 Proposed mechanism for the formation of mesoion 124. After alkylation of mesoion 124 to the corresponding 4-alkylthio-1,3-dithiolium salt 125, the 2H-1,3-dithiolium salts 132 can be obtained by reduction with sodium borohydride and subsequent deamination of the resultant amino compound 131 with strong acids (Scheme 40).
S
SNR2
S
R1
124
S
SNR2
R2S
R1
125X
S
SNR2
R2S
R1
131
S
S
R2S
R1
H
132
X
(i) (ii) (iii)
Scheme 40 Preparation of 2H-1,3-dithiolium salt 132. Reagents: (i) R2X; (ii) NaBH4; (iii) HX.
TTF-syntheses from the mesoion 124 have been used for various applications such as creating amphiphiles such as structure 133 for use in Langmuir-Blodgett film deposition,108 for the synthesis of tetrathiafulvalenophanes structure 134,109 research towards self-assembling molecular wires110 and for other purposes.111
108 R. P. Parg, J. D. Kilburn, M. C. Petty, C. Pearson, T. G. Ryan, Synthesis 1994, 613. 109 F. Bertho-Thoraval, A. Robert, A. Souizi, K. Boubekeur, P. Batail, J. Chem. Soc., Chem. Commun. 1991, 843; K. Boubekeur, C. Lenoir, P. Batail, R. Carlier, A. Tallec, M-P Le Paillard, D. Lorcy, A. Robert, Angew. Chem. Int. Ed. Engl. 1994, 33, 1379. 110 M. Jørgensen, K. Bechgaard, J. Org. Chem. 1994, 59, 5877. 111 F. Bertho, A. Robert, P. Batail, P. Robin, Tetrahedron 1990, 46, 433; D. Lorcy, M-P Le Paillard, A. Robert, Tetrahedron Lett. 1993, 34, 5289; M-P Le Paillard, A. Robert, Bull. Soc. Chim. Fr. 1992, 129, 205; M. Fourmigué, I. Johannsen, K. Boubekeur, C. Nelson, P. Batail, J. Am. Chem. Soc. 1993, 115, 3752; K. Bechgaard, K. Lerstrup, M. Jørgensen, I. Johannsen, J. Christensen, J. Larsen, Mol. Cryst. Liq. Cryst. 1990, 181, 161.
47
2-Dialkylamino-5-alkyl-1,3-dithiolium-4-thiolate mesoion 124 have apart from the preparation of TTFs also been used as starting material for the formation of dithiadiazafulvalenes such as compound 135,112 as well as 1,4-dithiafulvenes i.e. compound 136113 and other extended π-systems.114 Biological studies using mesoion 124 have recently been reported by de Almeida et al.115
S
SS
H3C
O
H3C
136
N
S
H3CS S
N SCH3
Cl
135
Cl
SCH2CO2H
S
S
S
S
SCH2CO2H
133
C10H21S
C10H21S S
S
S
S
S
134
S
H3C CH3
(CH2)6
Mesoion 124 has been used by us, as a building-block in the two different projects presented in the next sections of this thesis.
112 M. Bssaibis, A. Robert, P. Lemaguerès, L. Ouahab, R. Carlier, A. Tallec, J. Chem. Soc., Chem. Commun. 1993, 601; N. Bellec, D. Lorcy, A. Robert, Synthesis 1998, 1442; M. Bssaibis, A. Robert, A. A. Souizi, J. Chem. Soc., Perkin Trans. 1 1994, 1469. 113 H. Gotthardt, M. Oppermann, Tetrahedron Lett. 1985, 26, 1627. 114 P. Hascoat, D. Lorcy, A. Robert, K. Boubekeur, P. Batail, R. Carlier, A. Tallec, J. Chem. Soc., Chem. Commun. 1995, 1229; D. Lorcy, A. Robert, R. Carlier, A. Tallec, Bull. Soc. Chim. Fr. 1994, 131, 774; G. Morel, E. Marchand, S. Sinbandhit, R. Carlier, Eur. J. Org. Chem. 2001, 655. 115 P. Alfonso de Almeida, T. M. Sarmento da Silva, A. Echevarria, Heterocyclic Comm. 2002, 8, 593.
48
49
3.5 Tetrathiafulvalenes for Self-Assembly StructuresII, III
3.5.1 Introduction The outline of this project was to combine the self-assembling properties of alkylthiols and the charge-transporting abilities of π-stacks of tetrathiafulvalenes, in an organic thin film field-effect transistor (OTF-FET) (Figure 18). The conducting TTF-layer would be separated from the surface by the insulating layer of sufficiently long alkylthiol chains that would form a well-ordered monomolecular coating on the surface. Hopefully this would lead to an appreciably high mobility of charge-carriers parallel to the surface when applying a gate-bias over the device.
S SS S
S S
S SS S
S S
S SS S
S S
e-
SOURCE
DRAIN
GATE
Gate surface
Conductivity
σ high
σ low
σ low= TTF
Figure 18 Principle of a TTF-SAM field-effect transistor. The redox properties of TTFs in combination with SAMs attached to gold electrodes were first reported by Yip and Ward.116 The previously reported TTF-SAMs with only a single alkyl-chain terminated in a thiol group i.e. structure 137, have proved to
116 C. M. Yip, M. D. Ward, Langmuir 1994, 10, 549.
50
be electrochemically rather unstable upon repeated voltammetric cycling.117 Further developments have been made by Echegoyen et al., by incorporating thioctic acid into the TTF, structure 138, more stable SAMs were formed due to the disulfide-anchoring group.118 In addition Fujihara et al. have recently reported on a TTF compound, i.e. structure 139, containing four short alkylthiol chains that formed very stable SAMs even after repeated voltammetric cycling.119
OO
S
SOO
S
S
S
S SR
SSH
R = CH3 or n-C6H13137
S
S
S
S
138
S
S
O
n
O
O
O
OSS
SS
n = 0, 3, 4 or 5
S(CH2)3SH
S
S
S
S
S(CH2)3SH139
HS(H2C)3S
HS(H2C)3S
We therefore considered that a TTF like structure 140, with doubly substituted alkylthiols would render a more robust SAM. If we employed the mesoion 124 for creating the TTF-system we could attach alkylthiols by substitution of the thiolate functionality. Then we would have the possibility of varying the functionality in the 5-position of the mesoion as well (Figure 19).
S
S
S
S
S S(CH2)n(CH2)n
R1 R1
SHSH
S
S
S
R1
NR2
124
140
Figure 19 TTF 140 from mesoion 124; Potential structure for SAM.
117 A. J. Moore, L. M. Goldenberg, M. R. Bryce, M. C. Petty, A. P. Monkman, C. Marenco, J. Yarwood, M. J. Joyce, S. N. Port, Adv. Mat. 1998, 10, 395; A. J. Moore, L. M. Goldenberg, M. R. Bryce, M. C. Petty, J. Moloney, J. A. K. Howard, M. J. Joyce, S. N. Port, J. Org. Chem. 2000, 65, 8269. 118 H. Liu, S. Liu, L. Echegoyen, Chem. Commun. 1999, 1493; S. Liu, H. Liu, K. Bandyopadhyay, Z. Gao, L. Echegoyen, J. Org. Chem. 2000, 65, 3292. 119 H. Fujihara, H. Nakai, M. Yoshihara, T. Maeshima, Chem. Comm. 1999, 733.
51
From mesoion 124 we would then hopefully obtain highly symmetrical TTF-SAM-candidates of structure 140. From the chosen route of synthesis TTF 140, both Z- and E-isomers are formed. There is an equilibrium between the Z- and E-diastereomers in the presence of acids.120 This could make the kinetics of monolayer formation more difficult to study, but we thought it might be possible to overcome this by performing the self-assembly under equilibrium conditions, i.e. low pH and elevated temperatures. In designing TTF structure 140 we chose a rather long alkyl chain (-C12H24-) in order to get a sufficient distance between the π-system and the surface, for the possibility of the alkyl-(sp3) chains to self-assembly but also to isolate the conducting layer. The substituents (R1) "above" the electroactive region were then varied in order to find out if the monolayer could be stabilized further when exchanging shorter alkyl chains (CH3, C2H5, C3H7, C4H9) for longer ones (C6H13, C10H21, C12H25). We also wanted to determine if a SAM structure could be obtained by extending the π-system by aromatic R1-substituents, e.g. 1- and 2-naphthyl. We anticipated TTF-system 140 to hold several advantages, but also a few drawbacks: � The reliable route for synthesis of 140, should allow relatively straightforward
strategies for easy variation of the two different alkyl chains. � The double alkyl thiols should provide SAMs with stability, probably enhanced
by a long upper alkyl chain, which also may self-assemble and form a stabilizing layer “above” the TTF π-stacking layer.
� The two lower sulfur substituents should facilitate a more extended overlap between adjacent tetrathiafulvalenes, leading to higher charge carrier mobility.
� The alkyl thiol chains are rather separated by the TTF-units, which can create empty spaces in the SAM. This “void” perhaps has to be filled with additional free alkyl thiols to develop a more uniform layer, but this will in turn lead to more complicated SAM-studies.
120 A. Souizi , A. Robert, P. Batail, L. Ouahab, J. Org. Chem. 1987, 52, 1611.
52
3.5.2 Results and Discussion
3.5.2.1 Synthesis
The route based on mesoion 124 is slightly modified from the one earlier described by Jørgensen et al.107 (Scheme 41).
S
SH
R
S(CH2)12Br
R
Br CO2H
S
SN(CH3)2
S
R
(CH2)12
Br
CO2HS(H3C)2N
RS S
SN(CH3)2
S
R
S
SR
S S
S R
S(CH2)12 (CH2)12
BrBr
S
SN(CH3)2
S
R
(CH2)12
Br
S
SR
S S
S R
S(CH2)12 (CH2)12
SHSH
(i) (ii) (iii)
(iv) (v)
(vi) (vii)
148a-d147a-i
146a-i145a-i144a-i
143a-i142a-i141a-i
Br PF6
Scheme 41 a: R=CH3, b: R=C2H5, c: R=C3H7, d: R=C4H9, e: R=C6H13, f: R=C10H21, g: R=C12H25, h: R=1-naphthyl, i: R=2-naphthyl. Reagents and reaction conditions: (i) Me2NCS2Na, EtOH, 0°C; (ii) Ac2O, Et3N, CS2, acetone, rt; (iii) Br(CH2)12Br, acetone, reflux; (iv) NaBH4, EtOH, rt; (v) HPF6, H2SO4, 0°C; (vi) Et3N, CH3CN, rt, N2; (vii) (Me3Si)2S, TBAF, THF,-10°C.
α-Brominated carboxylic acids 141a-i underwent substitution when treated with the sodium salt of N,N-dimethyldithiocarbamic acid, to give 142a-i in 60-93% yield. The crystallinity varies with the chain length of the R-substituent. Starting materials 141a-g are commercially available whereas 141h and 141i were obtained by bromination of 1- and 2-naphthylacetic acid with N-bromosuccinic imide (NBS). Compounds 142a-i were, without further purification, dissolved in acetone and treated with acetic anhydride, triethylamine and carbon disulfide, respectively. Mesoionic products 143a-i were obtained as yellow precipitates in 40-96% yield. The mesoions are stable at room temperature and can be stored at ambient temperature and atmosphere for several years without significant decomposition.
53
The subsequent alkylation of mesoions 143a-i at the thiolate functionality was carried out in acetone with 1,12-dibromododecane in excess. The reaction proceeded smoothly at reflux in less than six hours, to yield 4-dodecylthio-1,3-dithiolium salts, 144a-i in 72-99% yield. Bromine salts 144a-i precipitated from solution when hexane was added to form white crystals that were used as received in the next step. Compounds 144a-i were then reduced with sodium borohydride in ethanol to give the corresponding amines 145a-i. The products were obtained as yellow oils in 61-91% yield and of high purity according to NMR. Deaminations of compounds 145a-i were carried out by treatment with concentrated sulfuric acid. The formed 2H-1,3-dithiolium sulfate salts were precipitated by anion exchange with the addition of hexafluorophosphoric acid, which gave crude 1,3-dithiolium hexafluorophosphates 146a-i in 62-91% yield.121 These compounds are rather hygroscopic and decompose fast in air or if dissolved in an organic solvent such as dichloromethane. Because of their oily appearance no purification by crystallization could be performed. The 1,3-dithiolium salts 146a-i were reacted without purification with triethylamine in dry acetonitrile affording TTFs 147a-i in almost quantitative yield of crude product in some cases. Some of the TTFs crystallized from solution and could be collected by filtration. Others formed as dark red oils and the residual solvent had to be evaporated after decanting, giving crude TTFs. Purification of TTFs 147a-i raised some problems. After some unsuccessful trials with different eluents for chromatography, carbon disulfide was chosen for TTFs 147a-g.122 This was the only solvent in which the compounds could be separated from accompanying byproducts. The target substances could also visibly be detected by thin layer chromatography (TLC) because of their green color in carbon disulfide. TTFs 147h and 147i could be purified by chromatography on a deactivated silica gel column with a mixture of hexane and dichloromethane as eluent. Pure 147h was obtained as orange crystals while 147i was received as red oil. A well-established method to generate the thiol groups for the anchoring of the TTFs to the surface is to convert R–Br to R–SH by refluxing the alkyl bromide with thiourea in ethanol, followed by hydrolysis with potassium hydroxide.116, 117 Besides that the reported yields from this reaction were rather low, thiourea is a highly carcinogenic substance.123 Thus, TTFs 147a-i were treated with hexamethyldisila-thiane and tetrabutylammonium fluoride (TBAF) in THF in accordance to a recent 121 PF6
- and BF4- are the most common counter ions for 1,3-ditiolium cations because of better stability compared
to HSO4- (highly hygroscopic) and ClO4
- (explosive). The properties of 1,3-dithiolium salts have been reviewed by: H. Prinzbach, E. Futterer, Advances in Heterocyclic Chemistry 1966, 7, 103, A. R. Katritzky, A. J. Boulton, Eds., Academic Press, New York 122 Carbon disulfide is a highly toxic substance, thus care must be taken when handle it. 123 Prohibited to use in Sweden.
54
published article.124 Thiol-substituted TTFs 148a-e were obtained from 147a-e as orange to red, almost insoluble substances. However, 147f-i failed to react according to MALDI-TOF (matrix assisted laser desorption ionization- time of flight) spectrometry, which showed only starting material. Compounds 147e-i were instead converted to the corresponding cyclic disulfide-substituted TTFs 149e-i by reaction with a nucleophilic sulfur transfer agent 150125 in N,N-dimethylformamide (DMF) (Scheme 42). The products precipitated from the solution and were filtered and washed with diethyl ether to give red and sticky compounds.
S
SR
S S
S R
S(CH2)12 (CH2)12
BrBr
S
SR
S S
S R
S(CH2)12 (CH2)12
SS
(i)
149e-i147e-i
NH2
2
WS42-150 =
Scheme 42 Synthesis of disulfide-substituted TTFs 149e-i. Reagents and reaction conditions: (i) 150, DMF, 70°C.
The synthesis was in principle straightforward until the very last step. Analyses of TTF structures 148 and 149 are not trivial. These compounds were not suitable for NMR-characterization, due to low solubility in most organic solvents. The issue was further complicated by FAB (fast atom bombardment) MS and MALDI-TOF spectrometry, since mass spectra of products 148b-e showed the M+-2 ion predominantly (Figure 20 shows the FAB-spectrum of 148d). This indicates the presence of a disulfide (intra- or intermolecular) or other unsaturations. However, treatment of 148d with dithiothreitol (DTT) would have reduced all disulfide groups,126 but no difference in the mass spectrum could be observed after such treatment. IR spectra of 148b and 148d also showed a weak absorption at 2522 (cm)-1, indicating the presence of an S-H bond. Our speculation is that the compounds interacts, self-assembles with a metal surface in the mass spectrometer, which causes an oxidation to the dehydrogenated form. Finally, elemental analysis confirmed that bromine had been substituted with sulfur.
124 J. Hu and M. A. Fox, J. Org. Chem. 1999, 64, 4959. 125 P. Dhar, N. Chidambaram and S. Chandrasekaran, J. Org. Chem., 1992, 57, 1699. 126 W. W. Cleland, Biochemistry, 1964, 3, 480.
55
M+-2
Figure 20 FAB-Mass -Spectrum of 148d.
3.5.2.2 Electrochemistry
The electrochemical behavior of TTFs 147a-i was investigated by cyclic voltammetry (CV) in dichloromethane (Figure 21) and the data are collected in Table 3.
-20
-10
0
10
20
30
0 0,5 1
147a147b147c147d147e147f147g147h147i
E (V)
I (µA)
Figure 21 Cyclic voltammograms for TTFs 147a-i.
56
Table 3 Electrochemical data for TTFs 147a-ia
TTF Substituent (R) E1 (V) E2 (V) ∆E = E2 – E1 (V)
147a CH3 0.43 0.78 0.36
147b C2H5 0.42 0.78 0.36
147c C3H7 0.41 0.77 0.36
147d C4H9 0.42 0.78 0.36
147e C6H13 0.42 0.77 0.36
147f C10H21 0.42 0.78 0.36
147g C12H25 0.42 0.77 0.36
147h 1-naphthyl 0.49 0.78 0.29
147i 2-naphthyl 0.50 0.81 0.30 a 1 mM TBAClO4 (0.1 M) in CH2Cl2, scan rate 500 mVs-1, E vs. SCE.
Due to the low solubility of TTFs 148a-d and 149e-i in dichloromethane at room temperature, no cyclic voltammograms could be obtained from solution. All cyclic voltammograms exhibit two reversible one electron transfer processes corresponding to the successive formation of the cation radical (E1) and dication (E2) as expected for TTFs. The 1-naphthyl-substituted TTF 147h even showed a third oxidation illustrated in Figure 22. This may be due to oxidation of the naphthalene ring system. No corresponding reduction was however observed, indicating a more reactive, unstable oxidized species. As was expected, the values of the oxidation potentials and the difference ∆E = E2 – E1 were comparable with the previously reported results for TTF (3).73 What could be observed was that the naphthyl-substituted TTFs showed a slight positive shift of E1, compared to the alkyl-substituted TTFs, but similar potential of E2 that gave a 60-70 mV decrease of ∆E.
57
-30
-15
0
15
30
45
0 0,5 1 1,5
E (V)
I (µA)�
147a147h147i
Figure 22 Cyclic voltammograms for TTFs 147a, h and i. 1 mM TBAClO4 (0.1 M) in CH2Cl2, scan rate 500 mVs-1, E vs. SCE.
3.5.2.3 Film-Formation
TTFs 148d and 149g were studied in the film-formation on gold surfaces. The compounds were dissolved in toluene, with or without the addition of methanesulfonic acid (MeSO3H), and the gold surfaces were incubated in the solutions. Different immersion times and temperatures were used to establish suitable conditions for film formation. The results from characterization of the TTF-incubated gold surfaces by ellipsometry and contact angle goniometry are presented in Table 4.
Table 4 Ellipsometric Thickness (d), Advancing (θa) and Receding (θr) Contact angles of Water of TTFs 148d and 149g on Gold.
TTF Sample d (Å) θa (deg) θr (deg) 148db 19.6 ± 0.3 75 63
148da, b 19.2 ± 0.2 69 55 149gb 15.0 ± 0.3 76 67 148dc 16.0 ± 0.4 77 65 148dd 15.9 ± 0.4 74 49
148da, e 18.0 ± 0.3 63 53 a in presence of 0.5 µmol of (10 mol%) MeSO3H b incubated for 4 weeks ( 3 weeks at 70 °C + 1 week at rt) c incubated for 1 week at rt d incubated for 48 hours at 70 °C e incubated for 24 hours at 70 °C
58
The theoretical thickness of an ordered monolayer of TTF molecules 148d and 149g with both sulfur groups bound to the substrate is approximately 25 Å and 33 Å, respectively. The measured thickness of 148d and 148d from acidic solution was about 19 Å, when adsorbed for a month. This result suggested a more densely packed film than compared to a sample that had been incubated for a shorter period, with a thickness of about 16 Å. For TTF 149g, the measured thickness indicated a less densely packed film. The advancing contact angle of water on the 148d and 149g monolayer should support a more hydrophobic than hydrophilic surface, when the alkyl chains are present on the topmost part of the organic film. However, these result do not suggest a high surface hydrophobocity implying that the ring structure may somehow be on top of the film, partially influencing the hydrophilicity of the surface. The advancing contact angle value is comparable to that of the HS(CH2)11OCH3 monolayer (θa = 74°) when adsorbed on gold.127 For comparison the HS(CH2)16CH3 exhibit a contact angle of 115°.127 The high hysteresis value128 also indicates a more heterogeneous outermost layer. The thickness and contact angle measurement results suggest a film formation of 148d and 149g incubated for a month having a densely packed thiol chain and with ring structure and alkyl tails exposed on the topmost part of the surface. The upper alkyl tail is not enough organized to give a highly hydrophobic surface. IR spectra were also recorded for TTFs 148d and 149g, both in the transmission (T-A) and the reflection (R-A) absorption mode (Figure 23). The CH2 and CH3 stretch regions suggests an amorphous or (gauche) spaghetti-like orientation of the long methylene chains, both for 148d and 149g when adsorbed for a month.
127 C. D. Bain, E. B. Troughton, Y.-T. Tao, J. Evall, G. M. Whitesides and R. G. Nuzzo, J. Am. Chem. Soc., 1989, 111, 321. 128 The hystersis value is the difference between advancing and receding contact angle.
59
Abs
orba
nce
Wavenumber (cm-1)
-0.0005
0
0.0005
0.001
0.0015
0.002
0.0025
27002750280028502900295030003050
148d (MeSO3H, 1 month, 70 C)148d (MeSO3H, 24 hours, 70 C)148d (1 month, 70 C)148d (1 week, room temp)149g (1 month, 70 C)
Figure 23 IRAS spectra of TTFs 148d and 149g adsorbed on gold surface.
For gold substrates incubated with 148d in presence of MeSO3H, it is interesting to note that after 24 hours of incubation and heating at 70 °C, the peak position corresponding to CH2 stretches is lower in wave-number positions (2921 and 2851 cm-1) suggesting an all trans structure with terminal gauche formation of the films.129 Absence of the CH3 stretches (expected at 2960 and 2879 cm-1) indicates that the alkyl tail, specifically the C-CH3 region, is lying parallel to the gold surface. After a month of incubation, the peak values of the CH2 stretch peaks shift to a higher wave-number indicating an amorphous structure of the films. Presence of CH3 stretches is also visible, which may indicate that the average orientation of the alkyl tail tend to lie perpendicularly relative to the Au surface. From this initial study, it is shown that incubation of gold from an 148d/MeSO3H solution (incubated for 24 hours, at 70 °C) gives a relatively densely-packed structure (thickness of 18 Å) with the outermost layer or the tail group unordered. The inner part of the film is interpreted to be relatively well-organized. Prolongation of the incubation period at high temperature disturbed the organization of the films, resulting in a film thickness of 19 Å but with an amorphous structure. In the IR fingerprint region where we hoped to find out how the central and ring C=C bonds are oriented when adsorbed on the surface, is at this moment still difficult to interpret. Careful assignment of peaks still has to be done and future calculations will help to further analyze the orientation and structure of the TTF-system.
129 An all trans configuration has CH2 stretches at 2917 and 2850 cm-1.
60
Table 5 IR mode assignments (cm-1) for TTFs 148d and 149g on gold incubated for 1 month period (including 3 weeks heating at 70 °C and 1 week at rt)
TTF 148d TTF 148d/ MeSO3H
TTF 149g Assignment
T-A, KBr R-A, multi
R-A, mono (1 week)
R-A, mono (48 hours)
T-A, KBr
R-A, mono
2958 2956 2964
(2960) 2964 2960
CH3 asym str
2925 2927 2930 2929
(2921) 2923 2928
CH2 asym str
2871 2871 2879 2879
2870 2879 CH3 sym str
2853 2853 2857 2858
(2851) 2852 2857 CH2 sym str
1721 1725
(1690) 1692
(1685) 1722 *
1672 1685 1630, broad (1610)
(1548)
1648 1672 *
1464 1464 1462
1462
(1462) 1459 1461 *
1412 1419
1434 *
1379 1379 1379
(1405) 1384 *
1231 1271 1274 * 1160 1163 * 1058 1124 *
1069 * 927 * 881 * 847 * 722 *
* assignment of vibration peaks are still uncertain! T-A, transmission-absorption; R-A, reflection-absorption.
TTF 148d was also analyzed with X-ray Photoelectron Spectroscopy (XPS). The S (2p) XPS spectra for TTF 148d multilayer130 and adsorbates on gold surfaces are shown in Figure 24.
130 Multilayer was obtained simply by evaporation of solvent.
61
Binding Energy (eV)
Inte
nsity
(a.u
.)
(a)
(b)
(c)
160162164166168
Figure 24 S (2p) XPS core level spectra for TTF 148d: (a) Multilayer prepared on gold, (b) Adsorbate on gold surface in bulk-sensitive mode, (c) Adsorbate on gold surface in surface-sensitive mode.
The sulfur peak for TTF 148d multilayer consists of spin-orbit split doublet with the S (2p3/2) and S (2p1/2) binding energies of 163.9 eV and 165.1 eV, respectively with a full-width at height maximum (FWHM) of 1.7 eV. The peak corresponds to the unbound sulfur and sulfur present on the TTF moiety. For TTF 148d adsorbate, the S (2p) peak is found at about 162 eV with FWHM of 1.6 eV. A chemical shift of about 2.1 eV to lower energy compared to multilayer was observed. The chemical shift is a result of a strong molecule-surface interaction. The TTF 148d molecule binds through the sulfur atoms present on the thiol chain. The sulfur binding energy of 162 eV is consistent with sulfur atoms bound to gold surface as thiolate species. The S (2p) peak at about 164 eV was assigned to the sulfur present on the TTF moiety as compared to publish reports; 163.5 eV for TTF, 163.9 eV for BEDT-TTF, 164.0 eV for TTM-TTF).131 The S (2p) peak at about 163 eV was assigned to the sulfur present in between the alkyl chain and the TTF moiety.
131 S.-G. Liu, Y.-Q. Liu, S.-H. Liu, D.-B. Zhu, Synth. Met. 1995, 74, 137.
62
Results from the relative intensity ratios between the different elemental peaks for the TTF 148d monolayer is shown in Table 6. The adsorbate C/S values are comparable to the stoichiometric C/S value. Slight increase of value in the adsorbate is due to orientational effect of the monolayer.
Table 6 XPS Relative Intensities for TTF 148d (adsorbates have been incubated for 1 week at rt).
C / S
CTTF / Sbound
STTF / Sbound
Stoichiometric value 4.8 3 2
4.7
4.2
1.0
Adsorbate
Bulk modea Surface modeb 5.4 11.0 2.2
aTOA = 80° bTOA = 30°
Orientational effect is seen when the intensity of the carbon peak associated with the TTF is compared with the intensity of sulfur that is bound to the Au surface. The notable increase in the CTTF / Sbound in the surface sensitive mode as compared to the bulk mode further supports that the S-Au bond is formed during adsorption. Also, the increase in the relative intensity of the peak associated with the sulfur present in the TTF (STTF) as compared to the peak assigned to sulfur bound to gold (Sbound), from the bulk mode to surface mode, supports that the TTF moiety is oriented away from the bound sulfur and consequently far from the gold surface.
63
3.6 Arylthio-Substituted TetrathiafulvalenesIV
3.6.1 Introduction The umpolung of thiols 151 with sulfuryl chloride (SO2Cl2) to the corresponding sulfenyl chlorides 152 is a well known reaction (Scheme 43).132
R SH
SO
OClCl
-HClR S S Cl
O
O
Cl
-SO2R S Cl
151 152
δ+ δ-
Scheme 43 Umpolung of thiols 151 to sulfenyl chlorides 152. There is however no previous example of attempts to transform mesoions of type 124 to dicationic electrophiles with the generic structure 153 by umpolung of the thiolate anion (Scheme 44).
(i)
153124
S
SNR2
S
R1S
SNR2
S
R1
ClCl
δ+δ-
Scheme 44 Umpolung of mesoion 124 with sulfuryl chloride. Reagents: SO2Cl2.
We speculated that compounds of type 153 could be used as electrophiles with electron rich nucleophiles, thereby giving a new synthesis of TTFs substituted with a variety of electron-rich moieties. Furthermore, since the alkyl group in the 5-position could easily be varied and also be replaced by other aromatic systems like for example naphthalene, it should be possible to construct donor structures containing several different assembled π-systems. Of special interest and temptation was the possibility of synthesizing tetrathiafulvalenes with phenolic substituents, since these structures would be good candidates for single-component conductors, forming an "inner" salt with the TTF radical cation and the corresponding phenolic anion (Figure 25).
132 R. Schubart, Houben-Weyl, Georg Thieme Verlag 1985, E11/1, 72; D. N. Harpp, B. T. Friedlander, R. A. Smith, Synthesis 1979, 181.
64
S
S
S
S S
S
C2H5
C2H5
OH
HO
-e-
OO
OO -H+ S
S
S
S S
S
C2H5
C2H5
O
HO
S
S S
S SS
C2H5 C2H5
O OH
OO O
O
OO
OO
Figure 25 Hypothetical TTF with phenolic substituent, possible candidate for single-component conductors.
Umpolung of thiols has previously been studied in our group.133 An ethylenedithio end-capped thiophene was obtained from 3-methoxithiophene (154). Intermediate 156 was obtained by condensation of 154 with ethandithiol (155). Treatment of structure 156 with sulfuryl chloride afforded ring-closure to the new thiophene structure EDTT (157) (Scheme 45).
S
S
HSS S
S(ii)
S
OCH3 HS
HS
(i)+
154 155 156 157
Scheme 45 Preparation of EDTT (157). Reagents and reaction conditions: (i)NaHSO4, reflux; (ii) SO2Cl2, Et2O.
Sulfenyl chlorides are not very reactive in themselves. An activation of the electrophile may therefore be necessary. In the initial experiments of the umpolung of mesoion 124 we used aluminum chloride.134 However, the compound obtained did not show any increased tendency to add to electrophiles; the reaction was more dependent on the nucleophilicity of the substrate. Thus we decided to study the reaction with a variety of different electron-rich aromatic and heteroaromatic compounds as nucleophiles.
133 T. Remonen, J. Hellberg, J. Slätt, Synth. Met. 1999, 101, 107; J. Hellberg, T. Remonen, F. Allared, J. Slätt, M. Svensson, Accepted in Synthesis. 134 Aluminum chloride (AlCl3) is a Lewis Acid e.g. it likes electrons.
65
3.6.2 Results and Discussion
3.6.2.1 Synthesis
N,N-Methylmesoion 143 could conveniently be umpoled with sulfuryl chloride in dichloromethane at room temperature (Scheme 47). The obtained intermediate 161 was treated with the nucleophilic substrate (R1) in situ, and the reaction progress could be monitored by TLC and was usually complete overnight, affording chloride salt 162.
(ii)(i)
161
S
SN(CH3)2
S
R
R1Cl
143 162
S
SN(CH3)2
S
R S
SN(CH3)2
S
R
ClCl
δ+δ-
Scheme 47 Reagents and reaction conditions: (i) SO2Cl2, CH2Cl2, rt; (ii) Nucleophilic substrate: R1.
According to the above described procedure, three mesoions, 143a, 143b and 143f with different alkyl-chain lengths, were reacted with a variety of electron-rich aromatic substrates 49, 57, 154 and 163-168 (Table 7). The chloride salts obtained were dissolved in water and precipitated with KPF6 (Scheme 48) to provide the corresponding hexafluorophosphonium salts 169-181 (Table 7).
S
SN(CH3)2
S
R
R1
(i)S
SN(CH3)2
S
R
R1Cl PF6
162 172 - 184
Scheme 48 Anion exchange. Reagents and reaction conditions: (i) KPF6, H2O, rt.
66
Table 7 Electrophile aromatic substitution with in situ umpoled mesoion 143.a
Mesoion R R1 Product Yieldb
(%)
143b C2H5
O
O
OH
49
S
SN(CH3)2
S
C2H5
OH
O
O
PF6 169
78
143b C2H5 O
O
OH
57
S
SN(CH3)2
S
C2H5O
O
OHPF6
170
88
143a CH3 O
O
OH
57
S
SN(CH3)2
S
H3CO
O
OHPF6
171
75
143a CH3
OH
H3CO 163
S
SN(CH3)2
S
H3C
OH
H3CO
PF6 172
64
143a CH3
OH
H3CO 163
S
SN(CH3)2
S
H3C
OH
OCH3
S
S
S
CH3
(H3C)2N
PF6PF6 173
26c
143a CH3
OH
HO 164
S
SH3C
S
OH
HO
N(CH3)2SS
S(H3C)2N
CH3
PF6
PF6
174
74
143f C10H21
OH
HO 164
S
SC10H21
S
OH
HO
N(CH3)2SS
S(H3C)2N
C10H21
PF6
PF6
175
63
67
Table 7 Continued.
Mesoion R R1 Product Yieldb
(%)
143a CH3
OCH3
H3CO 165
S
SH3C
S
OCH3
H3CO
N(CH3)2
PF6
176
75
143a CH3
NH
166
S
HN
S
SH3C
N(CH3)2
PF6
177
74
143a CH3 NCH3
167
S
NH3C
S
SH3C
N(CH3)2
PF6
178
76
143a CH3 S
OCH3
154
S
SH3C
S
S
H3CO
N(CH3)2
PF6
179
77
143f C10H21 S
OCH3
154
S
SC10H21
S
S
H3CO
N(CH3)2
PF6
180
70
143a CH3 S
OCH3H3CO
168
S
OCH3H3CO
SS SSS
S
N(CH3)2(H3C)2N
CH3 CH3
PF6 PF6
181
68
a Reagents and reaction conditions: (i) SO2Cl2, CH2Cl2, rt; (ii) Substrate: R1. b Yield of isolated pure product based on substrate R1. c Product not analytically pure.
68
The reprecipitation to hexafluorophosphonium salts led to pure and crystalline materials that were stable at ambient temperature and atmosphere. Thus, the electrophilic intermediate 162 adds to electron-rich phenols such as 1,4-benzodioxane-6-ol (49), sesamol (57) and p-methoxyphenol (163) yielding products 169-173. From p-methoxyphenol (163) both mono- and disubstituted products, e.g. 172 and 173, could be obtained depending on the amount of electrophile used. However, total conversion to compound 173 was not accomplished, since the reaction partially stopped at the halfway product 172. Even at prolonged reaction times, elevated temperature and with increased amount of electrophile, the reaction could not be driven to completion. Unfortunately, we were not able to separate the products in order to obtain analytically pure 173. Electrophile 162 was reacted with 2,6-dihydroxynaphthalene (164) and 2,6-dimethoxynaphthalene (165). In the first case, the 1,5-disubstitued products 174 and 175 formed, whereas in the second case, only monosubstituted product 176 was obtained. We also tried to substitute 1,5-dihydroxynaphthalene but received only oxidation products. Electrophilic substitution on heteroaromatic systems such as indole and electron-rich thiophenes were also rewarding. Indole (166) and N-methylindole (167) were substituted in the 3-position to give 177 and 178. While 3-methoxythiophene (154) also yielded the 2-substituted products, 179 and 180, 3,4-dimethoxythiophene (168) yielded disubstituted product 181. In some cases where additional amount of electrophiles were used to increase the conversion of starting material, the electrophile 162 seemed to form a rather stable dimer 182 with sulfuryl chloride, instead of reacting with the substrate. 1H NMR analysis and mass spectrometry confirmed the structure of 182. This problem could not be overcome by either inert atmosphere, prolonged reaction times or elevated temperatures. Reverse addition of substrates resulted, in some cases, in chlorination of the substrate prior to umpolung of mesoion 143.
S
SN(CH3)2
S
R
S Cl
182
S
S(H3C)2N
S
R
ClO
O
The 2-(N,N-dimethylimino)-4-arylthio-1,3-dithiolium salts could then be used in the synthesis of TTFs according to the procedure outlined in Scheme 49.
69
S
SN(CH3)2
S
R
R1
S
SN(CH3)2
S
R
R1
195 - 198
200, 201 and 202
(ii)(i)
(iii)
PF6 PF6169 - 172174 - 181
183 - 194
S
SH
S
R
R1
S
SS
R
R1
S
S S
R
R1
S
SS
R
R1 S
S S
R
R1
+
Scheme 49 Reagents and reaction conditions: (i) NaBH4, EtOH, rt; (ii) HPF6, H2SO4, 0 °C; (iii) Et3N, CH3CN, N2, rt.
Salts 169-172 and 174-181 were reduced with sodium borohydride to the corresponding amino compounds 183-194 (Table 8). Products 183-194 were obtained in almost quantitative yields, as either oils or crystalline compounds. The oily products were not stable at ambient temperature and had to be used as soon as possible. The crystalline compounds were somewhat more stable. Deamination of the amino compounds 183-194 proved more complicated. To exclude water from the desired products, we wanted to avoid the use of hexafluoro-phosphoric acid. For that reason the amino-compounds, which were suspended in diethyl ether, were treated with tetrafluoroboric acid (HBF4). After a few minutes a precipitate formed and the solvent was decanted. The products were dried in vacuum and without purification dissolved in dry acetonitrile and treated with triethylamine under inert atmosphere. Substances precipitated from solution and were isolated as red to purple crystals. However, these compounds could not be identified by 1H NMR analysis or mass spectrometry.
70
Table 8 Compounds 183-194 from reductiona of the arylthio-1,3-dithiolium salts 169-172 and 174-181.
Product Yield (%)
Product Yield (%)
S
SN(CH3)2
S
H5C2
OH
O
O
183
93
S
SN(CH3)2
S
H5C2
OO
OH 184
98
S
SN(CH3)2
S
H3CO
O
OH 185
95
S
SN(CH3)2
S
H3C
OH
H3CO
186
quant.
S
SH3C
S
OH
HO
N(CH3)2SS
S(H3C)2N
CH3 187
79 S
SH21C10
S
OH
HO
N(CH3)2SS
S(H3C)2N
C10H21 188
99
S
SH3C
S
OCH3
H3CO
N(CH3)2
189
94 S
HN
S
SH3C
N(CH3)2
190
88
S
NH3C
S
SH3C
N(CH3)2
191
98 S
SH3C
S
S
H3CO
N(CH3)2
192
95
S
SH21C10
S
S
H3CO
N(CH3)2
193
93 S
OCH3H3CO
SS SSS
S
N(CH3)2(H3C)2N
CH3 CH3 194
89
a Reagents and reaction conditions: NaBH4, EtOH, rt. We then decided to use the hexafluorophosphoric acid approach instead. Four 1,3-dithiolium salts 195-198 (according to Scheme 49) were obtained in moderate 60-70% yields. Compounds 195 and 196 were characterized with 1H NMR analysis while structures 197 and 198 afforded complex spectra, which is quite common for 1,3-dithiolium salts.
71
TTF 199 could not be obtained from 1,3-dithiolium salt 195, although salts 196, 197 and 198 yielded the desired TTFs 200, 201 and 202 upon treatment with triethylamine in acetonitrile (Scheme 50). TTFs 200 and 201 were fully characterized and TTF 202 was identified by mass spectrometry. Unfortunately TTF 202 could not be obtained of analytical purity, due to decomposition during purification by column chromatography. TTF 200 was obtained in 35% yield after purification, while TTF 201 only gave 16% yield.
S
SH3C
S
S
H3CO
S
S CH3
S
S
OCH3
S
S CH3
S
H3CO
OCH3S
SH3C
S
OCH3
H3CO
S
NH3C
S
SH3C S
NCH3
S
S CH3
200
201
202
S
SH3C
S
S
H3CO
H
PF6
S
NCH3
S
SCH3
H
S
SH3C
S
OCH3
H3CO
H
PF6
PF6
197
196
198
(i)
(i)
(i)
S
SH
C2H5
S
OH
OO
PF6195
(i) S
SC2H5
S
OH
OO
199
S
S C2H5
S
HO
OO
X
Scheme 50 Synthesis of arylthio-substituted TTFs. Reagents and reaction conditions: (i) Et3N, CH3CN, N2, rt.
Of special interest was the attempt to synthesize TTF 199 from the 1,3-dithiolium precursor 195. Yet the synthetic procedure held some fundamental drawbacks: � Triethylamine perhaps abstracted the phenolic proton and the resulting phenolate
ion could then react, probably intermolecularly, with the 1,3-dithiolium ion, forming oligomeric substances (Figure 26).
72
� Triethylamine reacted with the 1,3-dithiolium proton, creating the desired carbenoid specie, which either dimerized to the desired TTF, or reacted with a phenol to give products similar to the ones mentioned above.
S
SC2H5
S
OO
O
H
n
Figure 26 Proposed structure obtained from deamination of compound 195. The reaction of 195 with triethylamine yielded a mixture of products according to 1H NMR analysis. However, mass spectrometry showed predominant peaks at m/z 298, 181, 434, and 254 of both the crude material and products from column chromatography. There was a small signal (1%) at m/z 596 that matches to the molecular ion (M+) of TTF 199. If one assumes a mixture of oligomeric products and a dimer 203, the m/z 596 is the M+ of the dimer, m/z 434 would correspond to a “sesamol-1,3-dithiol-sesamol” fragment and the mother ion (m/z 298) would be a sesamol-1,3-dithiol fragment (Figure 27).
S
SC2H5
S
OO
O
S
S C2H5
S
O O
O
H
H
203
m/z = 298
m/z = 434
Total: m/z = 596
Figure 27 MS fragments from compound 203.
This would then explain the behavior in chromatography, NMR and mass spectrometry. It is therefore fair to conclude that the present synthetic strategy was not a method of choice for synthesizing hydroxy-functionalized TTFs, e.g. TTF 199. Thionation or protection of the hydroxy groups in 170 , could be other strategies to examine in order to obtain hydroxy-functionalized TTFs.
73
Attempts to polymerize 187 and 194 were also carried out (Scheme 51). Although deamination of these compounds with hexafluorophosphoric acid, followed by treatment with triethylamine yielded nice crystalline products, analytical results are yet uncertain.
S
SH3C
S
OH
HO
N(CH3)2SS
S(H3C)2N
CH3
S
OCH3H3CO
SS
S
SS
SN(CH3)2(H3C)2N
CH3 H3C
187
194
(i), (ii) X
(i), (ii)X
Scheme 51 Attempts to polymerize 187 and 194. Reagents and reaction conditions: (i) HPF6, H2SO4, 0 °C; (ii) Et3N, CH3CN, N2, rt.
MALDI-TOF mass spectrometry failed to reveal any high molecular weight products. On the other hand, size exclusion chromatography (SEC) of “poly-187” and “poly-194” could detect higher molecular fractions in DMF, but due to poor solubility of the compounds in the eluent, these results should be viewed only as preliminary. “Poly-194” was just partially soluble in DMF and only a low molecular weight fraction (Mn) could be calculated from the chromatogram, with a Mn value of 850 g mol-1 that corresponded to starting material. A higher molecular weight fraction was detected in the SEC, but the weak signal rendered calculations of this molecular weight impossible. From the elution time, the estimated molecular weight of this peak is around 700 000 g mol-1 with a rather broad polydispersity. “Poly-187” dissolved better in DMF and two distinct peaks could be seen in the chromatogram. The higher molecular weight fraction had a Mn value of 360 500 g mol-1, with a higher molecular weight shoulder. The lower molecular weight fraction could not be calculated since it was out of the range for the standards, but the elution time indicated a molecular weight of about 500 g mol-1, i.e. starting material.
74
This project was extended further since we wanted to find an alternative and more consistent way to obtain arylthio-substituted TTFs. We thought that we could create the bis-sulfenyl chloride-TTF 204 in situ via the debenzylation of the bis-benzylthio-substituted TTF 205135 with sulfuryl chloride according to Scheme 52. Compound 204 would then be treated with different electron-rich aromatic compounds.
C2H5
S S
S
S
S
S
C2H5(i) C2H5
S S
S
S
S
S
C2H5
Cl Cl
205 204
Scheme 52 Reagents and reaction conditions: (i) SO2Cl2, CH2Cl2, rt. Reaction of 205 with sulfuryl chloride followed by treatment with sesamol (57) in situ provided a number of products. From NMR analysis and mass spectrometry we could identify compound 206, as well as the chlorinated byproduct 207. Comparable results were obtained with two or four equivalents of sulfuryl chloride. We could not detect any non-benzylated 206 in the reaction mixtures, which leads us to the hypothesis that the benzylation of the hydroxy function is occurring at the same time as the electrophilic attack of the sulfur.
C2H5
S
C2H5
S S
S
S
S
O
O
O
206
O
O
OH
Cl
207
135 TTF 205 was obtained from mesoion 143b, which was alkylated with benzylbromide and then the resulting product was treated according to the reaction sequence outlined in Scheme 49.
75
3.6.2.2 Electrochemistry
Electrochemical behaviors of TTFs 200 and 201 were investigated by cyclic voltammetry in dichloromethane and the results are shown in Figures 28 and 29.
-30
-15
0
15
30
45
0 0,5 1
E (V)
I (µA)
200201205
Figure 28 Cyclic voltammograms of TTFs 200, 201 and 203. 1 mM in TBAClO4 (0.1 M) in CH2Cl2, scan rate 500 mV s-1, E vs. SCE.
The cyclic voltammograms displays two reversible one electron transfer processes corresponding to successive formation of the cation radical (E1) and dication (E2) as expected for TTFs. We anticipated that the sulfur-bridge between the TTFs and the aromatic substituents would not completely disrupt the conjugation within the molecule, but instead allow electronic "cross-talk" between the π-systems within the molecules and thereby reduce the oxidation potential. Such an inductive behavior was not detected in the quite normal potentials measured, but compared to the corresponding bis-benzylthio-substituted TTF 205, also shown in Figure 28, the potentials were a little lower (data in Table 9).
Table 9 Electrochemicala data for TTFs 200, 201 and 203. TTF E1 (V) E2 (V) ∆E = E2 – E1 (V) 200 0,38 0,76 0,39 201 0,37 0,75 0,38 205 0,43 0,81 0,38
a 1 mM in TBAClO4 (0.1 M) in CH2Cl2, scan rate 500 mV s-1, E vs. SCE.
The compounds also show a third irreversible oxidation potential (illustrated in Figure 29), possibly due to an additional oxidation of the aromatic substituents. The
76
first and second reduction waves of indole-TTF 201 were severely perturbed by the third oxidation, whereas the reductions of naphthalene-TTF 200 were less affected, as seen in Figure 29.
-60
-20
20
60
100
140
0 0,5 1 1,5 2
E (V)
I (µA)
200201
0
Figure 29 Cyclic voltammograms of TTFs 200 and 201. 1 mM in TBAClO4 (0.1 M) in CH2Cl2, scan rate 500 mV s-1.
Cyclic voltammetry of indole-TTF 201 was examined by scanning to different maximum potentials (Figure 30). The electrochemical behavior of indole-TTF 201 could be a result of a more reactive tricationic species formed upon the oxidation of the indole structure, which affects the TTF moiety, or the absence of first and second reduction might be the consequence of precipitation on the anode.
-60
-40
-20
0
20
40
60
80
100
0 0,5 1 1,5 2
E (V)
I (µA)
0-1 V0-1.5 V0-2 V
TTF 201
Figure 30 Cyclic voltammograms of TTF 201. 1 mM in TBAClO4 (0.1 M) in CH2Cl2, scan rate 500 mV s-1.
77
The first attempts to electrocrystallize TTF 200 were performed in the presence of four different counterions (TBAClO4, TBABF4, TBAPF6, and TBAAsF6). Electrocrystallization was carried out in a U-shaped electrocrystallization cell. These experiments were carried out with a platinum wire anode, at ambient temperature and the currents were 1.0 µA cm-2 at the start of the experiments and increased to 4 µA cm-2 over a period of 15 days. So far only polycrystalline materials have been obtained.
78
Concluding Remarks
4
This thesis dealt mainly with the synthesis of electroactive molecules for electronic applications. Nucleophilic aromatic substitution was studied in the sense of creating extended ethylenedioxy end-capped benzodioxins. When comparing the synthesized tri-dioxin 27 and tetra-dioxin 28, the later did not exhibit the expected decrease in oxidation potential. Furthermore, from the tri-dioxin 27 three different cation radical salts with 2:1 stoichiometry were obtained by electrocrystallization, while the tetra-dioxin 28 only yielded polycrystalline material. The longer analogs penta-dioxin 45 and hexa-dioxin 46 could not be obtained due to incompetence of the chosen building block dihydroxydibenzodioxin 47. In summary, the results from CV and electrolysis experiments clearly shows the superiority of the ethylenedioxy-substituent as good compromise between donor strength and good crystallinity through low steric demands. It also seems as annulated benzodioxins are not as effective donor molecules as we had expected compared to their naphthalene and anthracene analogs. Evaluation of the electrochemical properties for the thiophene-fused benzodioxins have not been performed but these structures seems to be the most promising substrates for future studies. We have also synthesized a TTF structure with doubly substituted alkylthiol chains in order to form self-assembly monolayers on gold surfaces. Two of the molecules with different lengths of the upper alkyl chains were adsorbed on gold and formed relatively ordered films. The TTF moieties appeared to be separated from the surfaces but displaying a hydrophilic surface on the top, indicating that the upper alkyl chains are pointing downwards. The results are encouraging and further studies on film-forming and electronic properties of these compounds would be interesting to perform. Apart from the nice results from the alkyltio-substituted TTFs, the umpolung of the mesoion and subsequent reaction with a range of different electron-rich aromatic compounds was the most rewarding project from my point of view. The synthesis of three new arylthio-substituted TTFs demonstrated an alternative method for the preparation of electron-rich TTFs with the aim of creating monomolecular/single-component devices, which in the end will have to be an object for future studies.
79
Acknowledgements
There are a number of people who I would like to thank for contributing to this achievement; First of all my sincere appreciation and thanks to Jonas Hellberg who trusted in me and gave me the chance to learn more about organic synthesis. It has been an inspiring and pleasant time to work with you. The members in the Hellberg group; Fredrik von Kieseritzky for being a good friend and for invaluable help. Fredrik Allared for helpful assistance and comments on the manuscripts. Thanks to all colleagues at the organic chemistry department at KTH, in particularly; Prof Christina Moberg for discussions regarding this thesis. Johan Andersson and Ellen Santangelo for being good friends and showing me Brazil, the wonderful homeland of “cheese buns” and “Guarana”. Ingvor Larsson and Lena Skovron, Jan Sidén and Henry Challis for always helping out. Special thanks to Rodrigo Petoral Jr. and Kajsa Uvdal for the valuable cooperation on the TTF-SAM project. Anna Carlmark, Mats Jonsson and Andreas Woldegeorgis for assistance with analyses. Appreciations to all my friends in IFK Lidingö athletics and orienteering, in particularly; Martin Johnsson for first-class barbecues all summer. Casper Giding and Charlotta Lundgren for being good friends. To all other friends that are cheering me up. To Göran Jonsson and Markanläggningar AB for support. Most of all, thankfulness to my family; Linus for making me smile. Måns and Elin for being the best brother and sister. Maria and Greger. My parents, Monika and Olle for never-ending love and support.
80
Appendix A
The following is a description of my contribution to Papers I-IV, as requested by KTH; I I performed part of the lab work and part of the writing. II I performed all lab work and part of the writing. III I synthesized all compounds and performed all cyclic voltammetry experiments.
I also performed part of the writing. IV I performed all lab work (except for MALDI-TOF spectrometry and SEC
analysis) and part of the writing.
81
Appendix B
Supplementary Material
Experimental Section Synthesis of 73. 3,4-dihydroxibenzaldehyde (72) (7 g, 51 mmol) and 1-octylbromide (21 g, 106 mmol) was dissolved in DMF (65 mL) under N2. K2CO3 (16 g, 113 mmol) was added and the mixture was stirred for 16 h in an oil bath at 100 °C. After subsequent cooling to rt, H2O (200 mL) was added and the phase was extracted with CHCl3 (4x50 mL). The combined organic layers were dried over MgSO4 and the evaporation of solvent yielded brown oily crude product. The oil crystallized upon standing in freezer overnight and was recrystallized from cold acetone yielding beige crystals of pure 67. Yield: 5.15 g (28%). Rf (CH2Cl2) = 0.51.
1H NMR (400 MHz, CDCl3) δ = 0.88 (t, 6H, J = 6.9 Hz), 1.28-1.38 (m, 16H), 1.45-1.50 (m, 4H), 1.80-1.89 (m, 4H), 4.05 (t, 2H, J = 6.7 Hz), 4.08 (t, 2H, J = 6.7 Hz), 6.94 (d, 1H, J = 8.2 Hz), 7.39 (d, 1H, J = 1.8 Hz), 7.41 (dd, 1H, J = 8.2, 1.8 Hz), 9.83 (s, 1H). MS (EI) m/e (%) 362.4 (M+, 100). Synthesis of 74. 73 (4.81 g, 13 mmol) was dissolved in CH2Cl2 (120 mL). MCPBA (6.96 g, 20 mmol, 50% in H2O) was dissolved in CH2Cl2 (30 mL) and added by addition funnel (to exclude H2O) to the solution. The mixture was gently refluxed at 45 °C. After 17 h the solution had turned yellow and CH2Cl2 was evaporated. The residue was dissolved in EtOAc, washed with a saturated aqueous solution of sodium hydrogen carbonate, followed by brine and then dried over MgSO4. The solvent was evaporated yielding the formate as brown oil. Yield: 3.94 g (78%). Rf (CH2Cl2) = 0.59. 1H NMR (400 MHz, CDCl3) δ = 0.86-0.90 (m, 6H), 1.27-1.33 (m, 16H), 1.42-1.49 (m, 4H), 1.76-1.85 (m, 4H), 3.96 (q, 4H, J = 6.3 Hz), 6.63 (dd, 1H, J = 8.5, 2.7 Hz), 6.66 (d, 1H, J = 2.7 Hz), 6.85 (d, 1H, J = 8.5 Hz), 8.28 (s, 1H).
82
The obtained formate (3.94 g, 10 mmol) was dissolved in MeOH (20 mL) and a small amount of p-TsOH was added. The mixture was refluxed under N2 for 2 h. Subsequently H2O (20 mL) and CH2Cl2 (20 mL) was added and the layers were separated. The aqueous phase was extracted with additional CH2Cl2 (3x10 mL). The combined organic layers were dried over MgSO4 and evaporated to dryness yielding crude 74 as a dark grey solid. Yield: 3.55 g (98%). Rf (CH2Cl2) = 0.28. 1H NMR (400 MHz, CDCl3) δ = 0.86-0.90 (m, 6H), 1.28-1.34 (m, 16H), 1.40-1.47 (m, 4H), 1.72-1.83 (m, 4H), 3.98-3.95 (m, 4H), 6.29 (dd, 1H, J = 8.5, 2.8 Hz), 6.44 (d, 1H, J = 3.0 Hz), 6.75 (d, 1H, J = 8.5 Hz). Synthesis of 75. KH2PO4 (0.83 g, 6 mmol) and TBACl (1.12 g, 5 mmol) was dissolved in H2O (200 mL) and cooled in an ice-bath. NO(KSO3)2 (5.6 g, 20 mmol) was added in portions under vigorous stirring. Phenol 74 (3.55 g, 10 mmol) was dissolved in THF (500 mL) and was added dropwisely to the mixture over a period of 25 min. The mixture was left on vigorous stirring in ice-bath for further 2 h. The solution was then saturated with the addition of NaCl. The two phases were stirred for additional 1 h. The layers were separated and the organic phase was evaporated. The obtained residue was dissolved in CH2Cl2 and washed with H2O. After subsequent drying over MgSO4, the solvent was evaporated. The obtained crude product was recrystallized from acetone, yielding red crystals of pure 75. Yield: 2.05 g (56%). Rf (CH2Cl2:EtOH; 95:5) = 0.70. 1H NMR (400 MHz, CDCl3) δ = 0.89 (t, 6H, J = 6.9 Hz), 1.29-1.36 (m, 16H), 1.41-1.47 (m, 4H), 1.80-1.86 (m, 4H), 3.97 (t, 4H, J = 6.7 Hz), 5.71 (s, 2H). MS (EI) m/e (%) 365.4 (M++1, 30), 336.4 (20), 139.1 (35), 71.3 (45), 57.2 (60), 43.2 (100). Synthesis of 76. 75 (2.05 g, 5.6 mmol) was suspended in H2O and reduced by addition of Na2S2O4. Et2O was added and the solution was vigorously stirred for 2 h. The suspension was transferred to a separatory funnel and extracted with Et2O. The organic phase was washed with brine, dried over MgSO4 and the solvent was evaporated yielding crude 76 as brown oil. The oily product could be recrystallized from hexane upon cooling in freezer. Pure catechol 76 was obtained as light-red waxy crystals. Yield: 1.67 g (81%). Rf (CH2Cl2:EtOH; 95:5) = 0.46. 1H NMR (400 MHz, CDCl3) δ = 0.88 (t, 6H, J = 6.9 Hz), 1.28-1.30 (m, 16H), 1.39-1.43 (m, 4H), 1.71-1.76 (m, 4H), 3.87 (t, 4H, J = 6.7 Hz), 4.97 (bs, 2H), 6.52 (s, 2H). MS (EI) m/e (%) 366.4 (M+, 100), 142.1 (90).
83
Synthesis of 77. Catechol 76 (0.85 g, 2.3 mmol) was dissolved in NMP (35 mL) and purged with N2. NaH (0,24 g 60% oil dispersion, 6 mmol) was added, followed by 1,2,4,5-tetrafluorobenzene (40). The temperature was kept at 50 °C for 1 h, then it was raised to 180 °C and subsequently stirred for 6 days. The dark brown mixture was allowed to cool to rt and was poured on ice. The solution was acidified with the addition of HCl. The precipitate that formed was filtered and dissolved in CH2Cl2. The organic phase was dried over MgSO4 and evaporated, yielding a brown oil that crystallized after a couple of days at rt. Yield: 0.57 g (total conversion of 40). Rf (CH2Cl2:EtOH; 95:5) = 0.89. 1H NMR (400 MHz, CDCl3) δ = 0.86-0.91 (m, 6H), 1.23-1.59 (m, 20H), 1.76-1.81 (m, 4H), 3.89-3.98 (m, 4H), 6.45 (s, 2H), 6.67 (dd, 2H, J = 9.2, 8.9 Hz). MS (EI) m/e (%) 476.5 (M+, 100), 462.4 (15), 252.5 (60). Synthesis of 80. 3,4-dihydroxibenzaldehyde (72) (3 g, 22 mmol) and n-dodecylbromide-THP-ether (21 g, 106 mmol) was dissolved in DMF (65 mL) under N2. K2CO3 (16 g, 113 mmol) was added and the mixture was stirred for 16 h in an oil bath at 100 °C. After subsequent cooling to rt, H2O (200 mL) was added and extraction with CHCl3 (4x50 mL) was performed. The combined organic layers were dried over MgSO4 and evaporation of the solvent yielded brown oily crude product. The oil crystallized upon standing in freezer overnight and was recrystallized from cold acetone yielding beige crystals of pure 67. Yield: Quant. of crude product. Rf (CH2Cl2:EtOAc;9:1) = 0.65.
1H NMR (400 MHz, CDCl3) δ = 1,21-1.38 (m, 26H), 1.41-1.61 (m, 14H), 1.68-1.88 (m, 8H), 3.34-3.40 (m, 2H), 3.47-3.50 (m, 2H), 3.69-3.75 (m, 2H), 3.83-3.88 (m, 2H), 4.02-4.12 (m, 4H), 4.55-4.57 (m, 2H), 6.94 (d, 1H, J = 7.9 Hz), 7.38 (d, 1H, J = 1.5 Hz), 7.41 (dd, 1H, J = 8.2, 1.8 Hz), 9.81 (s, 1H). Synthesis of 81. The bis-alkoxyaldehyde was treated according to the procedure for compound 74, forming a formate in 71% yield. The intermediate formate (3.45 g, 5.2 mmol)was dissolved in EtOH (10 mL). KOH (0.65 g, 5.7 mmol) dissolved in H2O (30 mL) was added and the reaction mixture was then stirred at rt for 1 h. Next, the solution was neutralized by the addition of 2M HCl (25 mL). The red precipitate formed, was dissolved in CH2Cl2. The layers were separated and the organic phase was washed with water and then dried over MgSO4. After evaporation the obtained red oil was dissolved in EtOAc and extracted with NaHCO3 (10% H2O solution) to remove remaining m-chlorobenzoic acid (leftovers from oxidation with MCPBA). After drying and evaporation 81 was obtained as a red-brown semi-solid.
84
Yield: 2.3 g (70%). 1H NMR (400 MHz, CDCl3) δ = 1.21-1.38 (m, 26H), 1.41-1.61 (m, 14H), 1.68-1.88 (m, 8H), 3.34-3.40 (m, 2H), 3.47-3.50 (m, 2H), 3.69-3.75 (m, 2H), 3.83-3.88 (m, 2H), 4.02-4.12 (m, 4H), 4.55-4.57 (m, 2H), 6.29 (dd, 1H, J = 8.5, 3.0 Hz), 6.43 (d, 1H, J = 2.8 Hz), 6.73 (d, 1H, J = 8.5 Hz). Synthesis of 82. The reaction was carried out by the same procedure used for compound 75, except for the reaction was performed at rt with TBABr as catalyst. Product 82 was obtained as red-brown waxy crystals. Yield: 1.35 g (57%). Rf (CH2Cl2:EtOAc; 9:1) = 0.56. 1H NMR (400 MHz, CDCl3) δ = 1.2-1.9 (m, 46H), 3.34-3.40 (m, 2H), 3.44-3.52 (m, 2H), 3.61-3.67 (m, 4H), 3.71-3.75 (m, 2H), 3.84-3.89 (m, 2H), 3.95-3.98 (m, 2H), 4.04-4.07 (m, 2H), 4.56-4.58 (m, 2H), 5.70 (s, 2H). Synthesis of 79. The catechol derivative 79 was received as a red oil, via reduction in line with the procedure for compound 76. Yield: 1.1 g (80%). Rf (CH2Cl2:EtOAc; 9:1) = 0.24.
1H NMR (400 MHz, CDCl3) δ = 1.2-1.9 (m, 46H), 3.36-3.40 (m, 2H), 3.46-3.51 (m, 2H), 3.61-3.66 (m, 4H), 3.69-3.75 (m, 2H), 3.83-4.05 (m, 6H), 4.56-4.57 (m, 2H), 6.52 (s, 2H). Synthesis of 88. Sesamol (57) (4.3 g, 31.4 mmol) and (2S,3S)-1,4-dichloro-2,3-butanediol (86) (2.5 g, 15.7 mmol) was dissolved in DMF (50 mL) under argon. NaH (1.26 g, 60% oil dispersion, 31.4 mmol) was added cautiously and the reaction was stirred at rt for 1 h. Then CuI (0.6 g, 3.1 mmol) was added and the mixture was put in an oil bath and stirred at 90 °C for a week (the reaction was monitored by TLC). After distillation of the solvent (30 mL), H2O (200 mL) was added to the resulting slurry. The layer was extracted with CH2Cl2 (4x40 mL). Then the combined organic layer was washed with H2O (2·50 mL) and brine (2·50 mL), before it was dried over MgSO4 and evaporated, yielding 88 as brown oil (4.87 g). A precipitate was received in the organic phase (CH2Cl2) and could be filtered yielding beige crystals of pure 88. Yield: 0.88 g (25%). Rf (CH2Cl2:EtOAc; 9:1) = 0.18.
1H NMR (400 MHz, DMSO-d6) δ = 3.83-3.86 (m, 4H), 3.97-4.00 (m, 2H), 5.01 (bs, 2H), 5.95 (s, 4H), 6.37 (dd, 2H, J = 8.5, 2.6 Hz), 6.62 (d, 2H, J = 2.6 Hz), 6.80 (d, 2H, J = 8.5 Hz). 13C NMR (100 MHz, DMSO-d6) δ = 69.3, 69.7, 97.8, 100.9, 105.7, 107.9, 141.0, 147.2, 154.1. MS (EI) m/e (%) 361.7 (M+, 40), 225.3 (90), 137.2 (100).
85
Synthesis of 89. 88 (0.3 g, 1.4 mmol) was dissolved in 1,2-dichloroethane (20 mL). Bromine (0.48 g, 3.0 mmol) was dissolved in 1,2-dichloroethane (20 mL) and added under 5 minutes to the mixture, and then stirred at rt overnight. H2O was then added and the layers were separated. The organic phase was washed with Na2S2O4 and brine. Subsequent drying over MgSO4 and evaporation of solvent afforded crude 89 as a light yellow powder (0.35 g, 67%). The product was recrystallized from EtOH, and pure 89 was obtained as white crystals. Yield: 0.1 g (19%). Rf (CH2Cl2:EtOAc; 9:1) = 0.37.
1H NMR (400 MHz, CDCl3) δ = 2.98 (bs, 2H), 4.10-4.14 (m, 2H), 4.16-4.20 (m, 2H), 4.24-4.26 (m, 2H), 5.96 (s, 4H), 6.61 (s, 2H), 6.98 (s, 2H). Synthesis of 94. 92 (0.72 g, 5 mmol) and catechol (93) (0.66 g, 6 mmol) was dissolved in chlorobenzene (5 mL), the flask was sealed with a septum and purged with N2. When all starting material was dissolved an chlorobenzene solution (5 mL) of MeSO3H was added dropwisley to the reaction mixture, which was monitored my TLC. The mixture was refluxed overnight, then the reaction was terminated by evaporation of solvent. There was still some unreacted starting material 92 but according to TLC by-products had started to form. The obtained black tar, was dissolved (most of it) in CH2Cl2 and filtrated through a silica gel, which was flushed with CH2Cl2. Crude 94 was obtained as brown oil after evaporation of solvent. Column chromatography afforded pure 94 as white glimmering crystals. The Yield: 105 mg (11%). Rf (CH2Cl2:EtOAc; 9:1) = 0.37.
1H NMR (400 MHz, CDCl3) δ = 6.39 (s, 2H), 6.88 (s, 4H). Synthesis of 95. 92 (0.36 g, 2.5 mmol) and 33 (0.42 g, 2.5 mmol) was dissolved in toluene (10 mL). The system was kept under N2 and p-TsOH was added to the mixture. The temperature was raised to 80 °C and the reaction was monitored by TLC. After evaporation of solvent, the yielded brown crystals (115 mg) was submitted to chromatography on silica gel column with hexane:CH2Cl2 (3:1) as eluent. Since the crystals were poorly soluble on a small amount of pure 95 was obtained. The Yield: 15 mg (2%). 1H NMR (500 MHz, CDCl3) δ = 4.21 (s, 4H), 6.40 (s, 2H), 6.48 (s, 2H). 13C NMR (125 MHz, CDCl3) δ = 64.4, 100.6, 105.0, 134.7, 138.9, 139.9. GC-MS (EI) m/e (%) 248 (M+, 100). Anal. Calcd. for C12H8O4S: C, 58.06; H, 3.25. Found: C, 57.86; H, 3.41.
86
Characterization Methods � Ellipsometry:
Single-wavelength ellipsometry was performed using an automatic Rudolph Research AutoEL ellipsometer with He-Ne laser light source, λ = 632.8 nm, at an angle of incidence of 70°. The freshly cleaned gold sample substrates were measured prior to their incubation, and the collected average value s of the refractive index were later used in a model “ambient/organic film/gold”, assuming an isotropic, transparent organic layer with the refractive index of n = 1.5. The film thickness was calculated as an average of measurements at five different spots on the sample of each compound.
� Contact Angle Goniometry: Contact angles were measured with Ramé-Hart NRL 100 goniometer, in air, i.e. in ambient atmosphere without control of the humidity, using fresh MilliQ water. At least five measurements of advancing and receding contact angle were done per sample.
� Infrared Spectroscopy: Transmission IR measurement were made on a Bruker IFS48 Fourier transform infrared spectrometer continuously purged with dry air. The samples were prepared by smearing an ample amount of the molecule on a CaF2 pellet. Each spectrum was obtained by averaging 500 interferograms at 2 cm-1 resolution using deuterated triglycine sulphate (DTGS) detector. IRAS measurement were performed on a Bruker IFS66 Fourier transform spectrometer equipped with a grazing angle of incidence reflection accessory aligned at 85°. The infrared radiation was polarized parallel to the plane of incidence. Interferograms were apodized with a three term Black-Harris function before Fourier transformation. The spectra were recorded by averaging 2000 interferograms at 4 cm-
1 resolution using liquid nitrogen cooled mercury cadmium telluride (MCT) detector. The measurement chamber was continuously purged with nitrogen gas during the measurement.
� X-ray Photoelectron Spectroscopy: The XPS spectra were collected on a commercial VG spectrometer with a CLAM2 analyzer and a twin Mg/Al anode. The measurements were carried out with unmonochromatized Mg Kα photons (1253.6 eV). The analyzer resolution was determined from the full width half-maximum (FWHM) of the Au (4f7/2) line which was 1.3 eV with a pass energy of 50 eV. The pressure in the analysis chamber was approximately 5 x 10-10 mbar while the sample’s temperature is approximately 300 K. The binding energy scales of the spectra were aligned through the hydrocarbon C1s peak (285 eV). Angle dependent measurements were made using photoelectron take-off angles of 30° and 80° with respect to the surface normal of the sample. The software used to analyze peak positions and calculate elemental composition were the VGX900 data analysis software and the XPSPEAK peak fitting software.