Indian Journal of Chemistry Vol. 38B. October 1999. pp.1154 - 1158

Ladderane-like motifs: Solid state architecture of trans-l ,2-diphenyl-l­cyclobutene-3,4-diol dinittate

Goverdhan Mehta* & R Urna

School of Chemistry. University of Hyderabad. Hyderabad 500 046. India

Received 19 August 1999; accepted 31 August 1999

CrSymmetric trans-l.2-diphenyl-l-cyclobutene-3,4-diol dinitrate defines a novel ladderane-Iike motif in the solid state tl\rough a network of C-H. .. O interactions between aromatic C-H donor and a weak acceptor like the nitrate ester group.

[n]-Ladderanes are a class of novel molecular arrays composed entirely of linearly fused cyclobutane rings, and we have recently shown that appropriately substituted cyclobutadienes, I, serve as an effective molecular building-block. (synthon) for the rapid assembly of polyquadranoid frameworks through cascade cycloadditions. 1a

Employing this strategy, it has been possible to stitch tog~ther cyclobutane rings through 'cr' bonds to unfold [n]-ladderanes e.g. 2 (n = 13), of record length and nano01etric dimension in a completely re~io- and stereoselective manner, (cf Scheme 1).1 .2 The successful.construction and characterization of such molecular ladders through conventional covalent synthesis provided an impetus to explore the generation of such ensembles in the solid state employing non-covalent protocols. In analogy with the term [n]-ladderanes l for the covalently fused assemblies of cyclobutane rings 3, several motifs like 4 or 5 (Scheme II), generated through weak interactions between four-membered rings can be conceptualized and regarded as non-covalent ladderane motifs. In such an endeavour towards non­covalent ladderanes, hydrogen bonds (both classical and non-conventionae) and aromatic 1t-1t and related weak interactions must play an important role in promoting the molecules to self-assemble into well­defined aggregates.

R R ~ lj R lj R lj R IJ R !}

~ lj R

~~JI I I I I 1 I 1 1 I I( .lon H a H R g 11 11 R 11 R 11 R

IR=COOCH3 lR=COOCH3

Scheme I

Thus, a tecton having a four-membered nng, preferably a square-like planar cyclobutene ring, which is appropriately embellished with functional groups at all the four comers and having positional and stereochemical complementarity, might have a prospect to self-assemble in the solid state into a ladderane-like motif. In this context, we have observed that a highly crystalline tetrasubstituted cyclobutene derivative 6, endowed with C2-symrnetry and readily available from the trans-dibromide 7,4 as shown in Scheme III, exhibits ladderane-like architecture in the solid state.

The trans-dibromide 7 was obtained ,tarting from tolan and dichloroketene in four steps.5,6 Facile addition of dichloroketene to tolan was mediated by zinc and ultrasound, to furnish adduct 8 in 87% yield, Hydrolysis of the geminal dichloride 8 in 90% sulphuric acid at 80-90 DC provided the corresponding

4

X H X H X H

~ I.e? ff' H x- -H x·· H x H x' X

~ ~ ~ H " ~ H,

X H 'x H 'x H

~ ~ ~ H X H X H X

S

Scheme II

MEHTA et al.: LADDERANE - LIKE MOTIFS 1155

dione 9 in high yield.5 Reduction of the dione 9 under H .. . O hydrogen bonded to all the four nearest Luche7 conditions, using a mixture of cerium(III) neighbors, two above and two below through its two chloride and sodium borohydride in ethanol at 0 °c, donor sites (H2 and H2a) and two acceptor sites (01 afforded the diol 10 in near quantitative yield. The and 0Ia). These interactions, with the H. .. O distance diol 10 could be readily converted to the dibromide 7 4.72 A (C. .. O 3.48 A and C-H ... O angle of 140.6°) by treatment with PBr3 in 75% yield.6 Stirring a are in the generally accepted range of attractive C-solution of the dibromide 7 with AgN03 in H ... O contacts reported in the literature8

, (see Figure acetoni trile , furnished a mixture of trans- and cis- 2). The functional group complementarity present in dinitrates 6 and 11 respectively in 85: 15 ratio, (see 6, coupled with suitable spatial disposition enables Scheme III). each unit to enter into quadruple C-H ... O interactions

The Crsymmetric 6 crystallized from ethyl acetate- to weave a layered, columnar molecular array as hexane in a centrosymmetric space group C2/c, and shown in Figure 2. It is to be noted that nitrate the ORTEP diagram of the molecular structure is groups, which hav(f been generally regarded as poor shown in Figure 1. Analysis of the crystal packing in acceptors, do effectively participate in C-H ... O

~ ,. ~

6 has rev~aled many new and n'ovel features that · we hydrogen bonding in the present example with each were interested in . The crystal lattice of 6 has a- -~' ~ monomeric unit engaged in four such interactions. layered structure . and the cyclobutene rings are Although weak, these numerous C-H ... O interactions stacked one over the other resulting in a columnar seem to be the main directors of the self-assembly of 6 arrangement. Within the ab plane, each molecule is C- into a columnar arrangement and a ladderane-like

Ph Ph Cl Ph 0 PhnOR

III a U'a b )I1 c 87%" I 70% I 98%

Ph Ph 0 Ph 0 Ph .OR 8 9 10

81% 1 d

PhnONOj PhnON~ Ph ,Br · e

PhUBr

+ ~-

80% Ph ~ONOj Ph ONC),)

6 (85%) 11(15%) 7

Reagents and conditions: a) Zn. CCI3COCl, DME, ether, sonication, 10-15 DC, 2 hr; b) 90 % H2S04, 80 - 90°C, Ihr, c) NaBH4, CeCl}.7H20, ethanol, room temperature, 90 min ; d) PBr3, CHCl}, - 60°C to room temperature, to reflux, 12 hr; e) AgN03, CH3CN, room temperature, 14 hr.

Scheme III

Figure 1 - ORTEP plot of 6

architecture (cj Figure 2). ,. The phenyl rings in the two adjacent ab planes are

offset from each other and the interplanar separation is - 3.8 A. As the molecule has a Crsymmetry and is chiral, the inversion related molecules form an enantiomeric pair when viewed down the c axis (cf Figure 3). An interes~ing aspect of the crystal packing in 6 is that all the pitI-ate groups and the phenyl rings are ~ligned, and when viewed down the c axis appears as alternate hydrophilic and hydrophobic columns. This arrangement a1s,? !eads to supramolecu-Iar host cavities with aromatic· walls and nitrate group occupying penphery of the cavity, which form infinite channels, (cf Figure 3).

The crystal packing in 6 is quite unique and notably different. A search of the Cambridge Structural Database for substituted cyclobutenes, like 1,2 diphe­nylc~c1obutene9a. cis-cyclobut-l-ene-3,4-dicarboxylic acid band cyclobut-l-ene-l,2-dicarboxylic acid9c

failed to reveal a ladderane-Uke motif in any of them. The marked difference in the packing pattern of 1,2 diphenylcyclobutene and its dinitrate derivative 6 is clearly indicative of the ability of the trans-disposed nitrate groups to engineer the self-assembly in 6 in a subtle manner to generate the ladderane motif. A CSD search 10 of structures possessing organic nitrate groups, e.g. cis-benzocyclobutene-l ,2-diol dinitrate lOb, indicated that in none of them the nitrate. oxygen was involved in any significant C-H ... O interaction, thus rendering 6 as the first example.

In short, the crystal structure of a functionalized cyclobutene 6 has revealed a ladderane-like pattern in the solid state, II which appears to be largely sustained by extensive C-H ... O hydrogen bonds. Our observa-

1156 INDIAN 1. CHEM. SEC. B, OCTOBER 1999

•

. ~ FlIgure 2 -. Packing diagram showing supramolecular ladderane-like motifs; dashed lines ( .... ) represent C-H ... O hydrogen bonds.

a

o c b

Figure 3 - Crystal packing of 6 viewed along the crystallographic c axis showing supramolecular cavities and nitrate group stacking.

tions should stimulate interest in the synthesis and crystal structure determination of a range of donor­acceptor, square-shaped cyclobutenes, which are likdy to exhibit interesting motifs in the solid state.

Experimental Section

General. . All melting points are uncorrected and were deternrined on a Buchi SMP 20 apparatus. The spectra and analytical data were recorded on the following instruments: JASCO Ff-IR 5300 spectrometer (IR), Bruker AC 200 spectrometer eH and l3C NMR) and Perkin-Elmer 240C (CHN analysis). Column chromatography was performed with Acme's silica gel (100-200 mesh). All nonhalogenated solvents were dried over sodium wire. Dichloromethane and chloroform were distilled over P20 S•

4,4-Dichloro-2,3-diphenyl-3-cyclobutenones 8. An oven-dried 1 L round bottom flask was centred in an ultrasound cleaning bath and charged with diphenylacetylene (23.2 g, 0.13 mole) and zinc dust (18.3 g, 0.26 mole) in 300 mL of dry diethyl ether under an argon atmosphere. The flask was fitted with a dropping funnel, which contained ether (50 mL), DME (60 mL) and trichloroacetyl choride (21.8 mL, 0.195 mole). This solution was added dropwise over 45 min, while the flask was sonicated; the temperature was maintained at 10-15 °C by adding ice to the bath. The reaction mixture was sonicated for 2 hr including addition period. The mixture was quenched with ether, filtered through Celite, then washed with water (3 x 70 mL) and saturated NaHC03 (2 x 50 mL) solution. The organic layer was dried, and removal of solvent furnished a residue, which was directly

MEIIT A et aI.: LADDERANE - LIKE MOTIFS 1157

crystallized frOin ether-hexane to give clear needles of 8 (30.2 g, 87%), mp 121°C (tit.s I20-I2I OC); IR (KBr): Vmax 1772 cm-'.

3,4-Diphenyl-3-cyclobutene-1,2-dione 9. The compound 8 (860 mg, 2.99 mmoles) was placed in a RB flask and immersed in an oil-bath maintained at 80-90 dc. 90% (v/v) H2S04 (10 mL) was then added and the mixture stirred for 1 hr. The reaction mixture was poured over ice and extracted with ether (3 x 20 mL). The ethereal layer was washed with water (2 x 20 mL) and saturated with NaHC03 solution (3 x 20 mL). The organic layer was dried and removal of solvent afforded a residue, which was charged on a silica gel column. Elution with 25% ethyl acetate­hexane furnished the dione 9 (489 mg, 70%), which was recrystallized from DCM-hexane to give yellow crystals, mp 97°C (lit.5 97-97.2 0C); IR (KBr): Vrnax

1777,1599,1566,1352,1080cm-'. cis-3,4-Diphenyl-3-cyclobuten-1,2-diol 10. To a

solution of 1,2-dione 9 (1.21 g, 5.15 mmoles) in absolute ethanol (25 mL), cooled to 0 °C was added a solution of CeCh.7H20 (3.83 g, 10.31 mmoles) in ethanol (30 mL). While stirring, NaBlLt (418 mg, 10.99 mmoles) was added in small portions. After the addition was over, the reaction mixture was further stirred for 1.5 hr and quenched with saturated NILtCI solution and extracted with ethyl acetate (3 x 70 mL). The combined organic extracts were washed and dried to give the crude diol 10 (1.21 g, 98%) which was directly crystallized from DCM-hexane, mp 135°C (lit.4 135.5-136.5°C); IR (KBr): Vrnax 3312 (br), 1427, 1127 cm-'; 'H NMR (200 MHz, CDCh): 87.67-7.62 (4H, m), 7.35-7.32 (6H, m), 5.00 (2H, bs), 3.45 (2H, bs, D20 exchangeable); l3C NMR (50 MHz, CDCh): 8144.2, 133.2, 128.8, 128.6, 127.2, 71.0.

trans-1,2-Dibromo-3,4-diphenyl-3-cyclobutene 7. To a 50 mL RB flask containing 1,2-dioI10 (238 mg, 1.0 mmoles) in dry chloroform (15 mL) at -60 °C was slowly added phosphorous tribromide (0.05 mL, 0.5 mmoles). The solution was stirred for 1 hr, warmed to room temperature, then refluxed for 12 hr. After cooling, the solution was quenched with saturated NaHC03 solution (30 mL), and then extracted with DCM (3 x 75 mL). The combined organic extracts were washed and dried. Removal of solvent under reduced pressure afforded the crude dibromide 7 (295 mg, 81%) which was crystallized from DCM-hexane, mp 115°C (lit.4 115-116.5 DC); IR (KBr): Vrnax 1445, 1348, 1173, 1154 cm-'; 'H NMR (200 MHz, CDCh): 87.63-7.58 (4H, m), 7.44-7.41 (6H, m), 5.42 (2H, s); l3C NMR (50 MHz, CDCh): 8 39.0, 130.7, 129.9, 128.7, 127.8,50.7.

Conversion of dibromide 7 to dinitrates 6 and 11. A mixture of trans-dibromide 7 (200 mg, 0.549 mmole) and AgN03 (195mg, l.154 mmoles) in"dry acetonitrile (10 mL) was stirred in dark at room temperature for 14 hr. The precipitated silver bromide was filtered off and washed with acetonitrile. The filtrate was concentrated under reduced pressure and the residue taken up in CH2Ch (30 mL) and washed with water. Removal of solvent furnished a mixture of the dinitrates 6 and 11 in 85: 15 ratio respectively, in 80% yield. A combination of fractional crystallisation and column chromatography (neutral alumina) enabled separation of trans-6 and cis-11 dinitrates, which were fully characterized as given below:

trans-1,2-Diphenyl-1-cyclobutene-3,4-diol dini­trate 6: mp 137°C; IR (KBr): Vrnax 1634, 1277, 862 cm-'; 'H NMR (200 MHz, CDCI3): 8 7.59-7.51 (4H, m), 7.46-7.39 (6H, m), 6.17 (2H, s); I3C NMR (50 MHz, CDCh): 8 136.3, 130.3, 129.8, 129.0, 127.4, 79.8. Anal. Calcd for CIJ112N206: C, 58.54; H, 3.68; N, 8.53 %. Found: C, 58.57; H, 3.66; N, 8.55 %.

cis-1,2-Diphenyl-1-cyclobutene-3,4-diol dinitrate 11: mp 68°C; IR (KBr): Vrnax 1643, 1287 cm-I; 'H NMR (200 MHz, CDCh): 8 7.62-7.53 (4H, m), 7.45-7.40 (6H, m), 6.47 (2H, s); l3C NMR (50 MHz, CDCI3): 8140.2, 130.7, 130.4, 129.0, 127.3, 79.8. Anal. Calcd for C'6H12N206: C, 58.54; H, 3.68; N, 8.53 %. Found: C, 58.54; H, 3.68; N, 8.56 %.

Crystallography

Single-crystal X-ray analysis of 6

Crystal data: CI6H120~2, M = 328.28, colorless crystals from ethyl acetate-hexane, monoclinic, space group Cl./c, a = 8.016(1), b = 17.177(2) and c = 11.334(2) A, f3= 102.19(1t, V= 1525.5(4) A3, Z= 4, Dc = 1.429 Mg m-3; T = 293 OK, F(OOO) = 680, J.-l( Mo-Ka) = O.l1mm-', crystal dimensions 0.16xO.13 xO.22mm.

Data collection and structure solution: Data were collected on an Enraf-Nonius MACH-3 diffracto­meter, graphite monochromated Mo-Ka radiation (A = 0.71073 A), by the roscan method in the range 2::; 8::; 25°; 1347 unique reflections [Rint = 0.0], 979 having Fo > 4 o(Fo) , were used in all calculations. At final convergence RI[I > 20(1)]=0.036, wR2 = 0.0909 for 109 parameters, GOF = 1.04, !:J.Prnax = 0.15 eA-3, !:J.pmin

= -0.17 eA-3. The data were reduced using XTAL (ver 3.4), solved by direct methods, refined by full-matrix least-squares on r with the non-H atoms anisotropic, and H atoms placed in calculated positions and allowed to ride on their parent atoms. 12

1158 INDIAN 1. CHEM. SEC. B, OCTOBER 1999

Acknowledgement

We thank Dr K Ravikumar for his interest and help and CSIR, New Delhi for the award of a fellowship to R U. The support from the Department of Science and Technology, Government of India, New Delhi in establishing the X-ray facility at the University is greatly appreciated. We would like to thank Dr K Sekar of Bio-informatics Center of Indian Institute of Scimlce, Bangalore for help.

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