W. Schmidt, F. Vogtle, E. Poetsch 1319

Spiro Units as Building Blocks in Thermotropic Liquid Crystals: Synthesis and Physical Properties of Terminally Substituted Spiro[5.5]undecanes Wolfgang Schmidt", Fritz Vogtle*a, and Eke Poetschb

Institut fur Organische Chemie und Biochemie der Universitat Bonna, Gerhard-Domagk-Strale 1, D-53121 Bonn, Germany E. Merck, Liquid Crystal Researchb, Frankfurter StraDe 250, D-64271 Darmstadt, Germany

Received January 26, 1995

Key Words: Spiranes / Liquid crystals / Structure-property relations of LC substances / TosMIC

A number of terminally substituted spiranes were prepared from 9-pentyl-3-spiro[5.5]undecanone (jl), which was obtai- ned in a five-step synthesis starting from 4-pentylcyclohex- anone (l), using an intramolecular cyclisation with 4-toluene- sulfonylmethyl isocyanide (TosMIC) as a key step. By a com-

parison of the physical data of the new spiro[5S]undecane derivatives I with those of several well-known, analogous substituted compounds - solely differing in their central building unit - conclusions regarding the effects of the spiro ring system on its mesogenic potential are drawn.

Thermotropic liquid crystalline properties can be ex- pected, if certain basic principles of chemical structure are considered in the design of the corresponding molecules[']. The required linear shape and rigidity of molecules leading to calamitic liquid crystals are e.g. excellently realized by the bicyclohexyl derivatives TI published by Eidenschink et a1.I21. Because of their broad nematic phases, low viscosity and low birefringence they are successfully applied in mod- ern LC display technology as basic materials for highly ad- vanced actively addressed TN- (twisted nematic) LCDs.

A similar rigid building block is found in nematic all- trans-perhydrophenanthrenes IIII31, which illustrates the re- lation between the bicyclohexyls I1 and the steroid skeleton of the well-known cholesteryl esters - the first liquid crys- tals observed by Reinitzer in 1888I41.

I I1 III

Hitherto, we described an alternative approach to stiffen the ring connection between the two cyclohexane units via a spiro-anellation, illustrated by several oblong carbocyclic dispiro compounds with mesogenic propertiest5I.

In this contribution we report on the effect of connecting the terminal ring units directly by one common carbon atom, which simplifies the stereochemistry of the resulting monospirane unit I as a side effect (unsymmetrical terminal substitution of I causes axial chirality whereas in the case of I1 cisltrans diastereomers can be formed). On the other hand, this decreases not only the length-to-diameter ratio in comparison with the bicyclohexyls 11, but also causes a twist in the long axis of the molecule, due to the sp3-hybrid- ised spiro carbon atom.

In order to investigate, whether substitution in the ter- minal positions (C-3 and C-9) can still lead to the rod-like geometry necessary for mesogenic behaviour, we syn- thesised and examined several spiro[S. Slundecane deriva- tives I containing typical end groups, which have proven successful in various liquid crystalline compounds.

Syntheses

9-Pentyl-3-spiro[S.S]undecanone (7) was prepared by a five-step sequence starting from 4-pentylcyclohexanone (l)[3bl in 23% overall yield (Scheme 1).

The dicarboxylic acid 4 was prepared by hydrolysis and decarboxylation of the dicyano imide 2, which was obtained from 4-pentylcyclohexanone (1) and two equivalents of ethyl cyanoacetate according to Vogel[61 and Grogan et al.r7I. Reduction of 4 with lithium aluminium hydride fol- lowed by reaction of the obtained mesogenic diol 5 with a mixture of 48% aqueous hydrobromic acid and concd. sul- furic acid led to the dibromide 6r8l.

In the reaction of 6 with 4-toluenesulfonylmethyl isocy- anide (TosMIC) involving intramolecular cyclisation, the optimum conditions (dry DMF and sodium hydride) used in the first reaction step afforded the desired spiro[5S]unde- canone 7 in 78% yield. However, the conditions employed by van Leusen et al.U9] in the reaction of aliphatic dibro- mides with TosMIC only led to small amounts of 7 (deter- mined by GC/MS).

Proceeding from 7 as a key intermediate, we synthesised the spiro[SS]undecane derivatives 8-17 (Scheme 2) . Due to the axial chirality of the 3,9-disubstituted spiro[S.S]unde- cane unit, racemic mixtures of the two enantiomers were obtained (except in the case of 13).

The 3-phenyl-substituted spiro[SS]undecanes 8- 12 were prepared by an efficient sequence of reactions involving Grignard addition of the appropriate bromobenzene, dehy-

Liebigs Ann. 1995,1319- 1326 0 VCH Verlagsgesellschaft mbH, D-69451 Weinheim, 1995 0947-3440/95/0707- 1319 $10.00+.25/0

W. Schmidt, F. Vogtle, E. Poetsch 1320

Scheme 1. Svnthesis of 9-~entv~-3-suiro~~.5~undecanone (7). Re- agents and conhitick: i:' 1) ithi1 cyanoacetatk,'NH3, ethanol, O"C, 2) HCI, H20. - ii: 1) H2S04, HzO, 150"C, 2) NaOH, H20, 90°C. - iii: 1) LiAlH4, THF, 2) HCl, H20. - iv: HBr, H2S04, 100°C. - v: 1) TosMIC, NaH, DMF, 2 ) HCl, H20

0

1 2

r 0 1

----+

5 6

(4 - Scheme 2.

Hl lC5 go 7

Preparation of several spiro[5S]undecane derivatives starting from 9-pentyl-3-spiro[5.5]undecanone (7)

8 : X = F; Y,Z = H Y x 9 : X , Y = F ; Z = H

10 : X.Y,Z = F 11 : x = O C F ~ ; Y,Z = H

H11C5 12 : X = OC5H11 ; Y,Z = H

o / 13

Hl lC5

14

15 i

17

dration and catalytic hydrogenation in the presence of 10% palladium charcoal. The transformation of the carbonyl function into the difluoromethylidene unit was performed by reaction of 7 with dibromodifluoromethane and tris(di- methy1amino)phosphane in anhydrous triethyleneglycol di- methyl ether[l0I. The carbonitrile 14 was obtained from 7 by using again TosMIC as reagent according to the method of van Leusen et al.["]. Subsequent alkylation with 1- bromopentane (lithium diisopropylamide, THF, - 78 "C) led to 15. Reduction of the spiro ketone 7 with lithium alu- minium hydride and esterification of the obtained alcohol 16 with (all-trans)-4'-pentyIbicyclohexyl-4-carboxylic ac- id[2a] via the carboxylic acid chloride supplied 17.

Results and Discussion In Table 1 the physical properties of the spiranes 8-15

and 17 are compiled. Since none of the compounds 8-15 exhibits a nematic or smectic phase, it was necessary to carry out the measurements of clearing points on mixtures of the test compounds in the nematic host ZLI-4792, ex- trapolated to 100% concentration from measurements made of solutions of 10% concentration[121. In the same way the data of dielectric anisotropy (AE), optical an- isotropy (An) and viscosity ( v ~ ~ ) were determined. Table 1. Physical properties of the spiro[5.5]undecane derivatives 8-15 and 17. - Phase transition temperatures in "C; C = crystal- line, I = isotropic, S = smectic. - TNI: extrapolated temperature of the phase transition from the nematic to the isotropic state ["C]. - A&: Dielectric anisotropy (20°C, 1 kHz). - An: Optical aniso-

tropy (20°C, 589 nm). - vZ0: Viscosity at 20°C [mm2 s-I]

Transitions TNI A€ An y 2 0

8 9 10 11 12 13 14 15 17

-

C 42 I - 75 C 9 1 - 77 C 7 1 - 93 C I I - 68 c 22 I - 17

- 104 C20I -177 C40I -148

c 5 3 s loo 88 Sa 189 I

-0.92 1.39 2.98 1.32

- 1.98 -0.20 -0.80 -6.30 -2.61

0.01 1 48 0.014 64 0.012 64 0.028 45 0.032

-0.013 14 -0.036 219 -0.044 337

0.031

To estimate the influence of the geometry of the spiro- [5. Slundecane unit on the mesogenic behaviour, the physical data of analogous 4,4'-disubstituted all-trans-bicyclohexyl derivative^"^] (see Table 2) and analogous truns-l,4-disub- stituted cyclohexane (see Table 3) were examined.

Table 2. Physical properties of 4-substituted all-trans-4'-pentylbi- cyclohexyl derivatives['3a]

TNI Substituents in position 4

4-fluorophenyl[al 161 3,4-difluorophenyl 116 3,4,5trifluorophenyl 84 4-trifluoromethoxyphenl 149 4-butyloxyphenyl[a] 215 =CF* - 92 CN 34 CN. CGH, 1 26

~

3.76 0.094 19 6.30 0.079 25 1.23 0.085 20 6.34 0.097 16 0.79 0.110 51 0.1 0.010 14

7.46 0.053 66 -8.38 0.014 104

Listed data refer to the analogous 4'-propyl derivative.

Liebigs Ann. 1995, 1319-1326

Terminally Substituted Spiro[5S]undecanes 1321

The comparison of the compounds listed in Tables 1 and 2 allows some conclusions: First, replacement of the bi- cyclohexyl unit I1 by the spiro[5.5]undecane unit I in most cases causes a disruption of the mesogenic tendency, re- sulting in a substantial decrease of the transition tempera- ture TNI.

This becomes particularly evident in the case of the car- bonitriles 14 and 15. Although the comparatively low phase transition temperatures TNI and high viscosities v20 of 14 and 15 may be also due to the poor compatibility of the spiro[5.5]undecane compounds with the host ZLI-4792[l2J, the differences still seem striking.

Apart from the decrease in length of the building block (bicyclohexyl unit: approximately 7.,3 A, spiro[5.5]undecane unit: 5.8 A, cyclohexane unit: 2.9 this can be essen- tially explained by the three-dimensional orientation of the terminal substituents. Whereas in the bicyclohexyl unit (as well as in the cyclohexane unit) the end groups are found to be exactly in plane, the twist of the longitudinal axis of the spiro skeleton causes a torsion angle of approximately 68”[14] between the equatorially aligned terminal substitu- ents[15] (compare Figure 1). The negative dielectric an- isotropy of the carbonitrile 14 (the analogous bicyclohexyl derivative shows Ae = +4) is in accord with this presump- tion. The deviation from the required rod-like geometry ap- parently prevents a parallel arrangement of the molecules in the liquid crystalline state.

In contrast to this, both difluoromethylidene-substituted compounds (13 and the analogous bicyclohexyl derivative) show a relatively low extrapolated phase transition tem- perature TNl of about - 100 “C and a similar viscosity. Here, elongation of the basic building block by a further 1,4- cyclohexane or 1,3-cyclobutane unit results in stable me- sophases with clearing points above 90°C after

The fluoro-, trifluoromethoxy- and pentyloxy-substituted 3-phenylspiro[5.S]undecanes 8- 12 show lower melting points and lower optical anistropies (An = 0.01-0.03) in comparison with the homologous bicyclohexyl derivatives (An = 0.08-0.11). But even though the rigid basic unit is de facto elongated by the addition of a benzene unit, the fluorinated spiro[S.S]undecane derivatives 8 - 11 show phase transition temperatures TNI of 70°C up to 120°C below their melting point. Nevertheless, replacement of the fluo- rine atoms by a flexible end group as in the case of the pentyloxy-substituted compound 12 leads to markedly higher TNI values.

How strongly the twisted molecular shape (see Figure l), which is reflected in negative respectively relatively low di- electric anisotropies AE too, influences the mesogenic ten- dency, is elucidated by comparison of the spiro compounds with analogously substituted trans-l,4-disubstituted cyclo- hexane derivatives“ 3a1 (Table 3). Their phase transition tem- peratures are in the same order of magnitude as in the case of the spiro[5.5]undecane derivatives 8- 12, although the aliphatic part of the rigid building block is shortened to half of its length.

However, further elongation of the basic unit by at- taching a bicyclohexyl unit to the spiro[S.S]undecane unit

Figure 1. Energy-minimised structure (AM 1) of

via an esterification as in compound 17 appears to cause the formation of a smectic phase stable over a 55°C tem- perature range (Table 1). But the mesogenic behaviour of 17 is probably dominated by the bicyclohexyl unit, since the analogous cyclohexane derivative exhibits a significantly broader smectic phase (Table 3)[161.

Table 3. Physical properties of 1 -substituted trans-4-pentylcyclo- hexane

~

Substituents in position 1 TNI LW An ’20

4-fluorophenyl -51 1.87 0.031 5

4trifluoromethoxyphenyl -44 3.59 0.054 5

all-trans-4’-pent Ibicyclo- 188 -1.7 0.06 34

3,4,5-trifluorophenyl -118 4.28 0.019 8

4-pentyloxyphenyl 20 -0.6 14

hexyl-4-carboxy&de

It has to be further investigated, whether an additional “crooked” centre within the building block containing the spiro[5.5]undecane unit I results in higher TNI valued’’1.

We thank Merck, Darmstadt, for their kind supply of several chemicals. The physical measurements of extrapolated phase tran- sition data, birefringence, viscosity, and dielectric constants were made by Dr. J Kruuse (Merck) who also contributed the data of the reference compounds; the authors gratefully acknowledge this support.

Experimental Melting points: Kofler Mikroskop-Heiztisch (Reichert), uncor-

rected; melting points below room temp. were obtained by slowly warming a sealed glass tube containing a crystalline specimen in a Dewar vessel. - Phase transition temperatures were determined by means of polarizing microscopy as well as by differential scanning calorimetry (DSC) measurements. - IR: Perkin-Elmer FTIR 1600. - NMR: Bruker AM-250 (lH: 250 MHz, I3C: 62.9 MHz, 19F: 235.4 MHz), Bruker AM-400 (‘H: 400 MHz, 13C NMR: 100.6 MHz). Assigned ‘H and 13C signals are proved by DEPT 135, ‘H/ ‘H and ‘H/13C COSY experiments. - EI MS: A.E.I. MS-50; Hew- lett Packard HP 5989 A. - FAB MS: Kratos Concept 1 H; +-FAB, matrix: m-nitrobenzyl alcohol. - Elemental analyses: Microana- lytic department of “Institut fur Organische Chemie und Bio- chemie”, University of Bonn. - Purities of the fluorine-substituted compounds were checked by HPLC (column: LiChrosorb RP 18- 5 pm, mobile phase: methanol/dichloromethane, 4: 1). - TLC: Merck silica gel plates 60 F254; detection of the aliphatic com-

Liebigs Ann. 1995, 1319-1326

1322 W. Schmidt, F. Vogtle, E. Poetsch

pounds by treatment with a solution of rhodamine 6G in etha- nol["]. - CC: Merck silica gel 60 (mesh size 63-100 pm). - 1- Bromo-4-fluorobenzene, 4-bromo- 1,2-difluorobenzene, 5-bromo- 1,2,3-trifluorobenzene and 1-bromo-4-trifluoromethoxybenzene were obtained from Merck, Darmstadt, Germany.

(1 RS,5 R S ) -2,4-Dioxo-9-pentyl-3-azaspiro [S. Slundecane-I ,5- dicarbonitrile (2): To ethanol (200 ml), previously saturated with anhydrous ammonia at - 5 "C (the solution expands to approxi- mately 300 ml), a mixture of 4-pentylcyclohexanone (1) (42.1 g, 0.25 mol) and ethyl cyanoacetate (84.8 g, 0.75 mol, 50% excess) is added. After mixing, the flask is closed and stored at 0-5°C for 2-4 d. The precipitated ammonium salt of the dicyano imide 2 is filtered off, washed with cold diethyl ether, dissolved in boiling water (300 ml) and the solution is acidified with concd. hydro- chloric acid (100 ml). After 12 h, the dicyano imide 2 is filtered off, washed with water until neutral and dried at 100°C. On recrystal- lisation from ethanollwater 3:l (vlv) 28.4 g (38% yield) colourless crystals is obtained, m.p. 157-157.5"C. - 'H NMR (250 MHz,

1.49-1.93 (m, 6H), 4.87 (s, lH, CHCO), 4.89 (s, lH, CHCO), [D,]DMSO): S = 0.86 (t, 3 J = 6.7 Hz, 3H, CH3), 1.23 (s, 11 H),

12.19 (s, 1 H, NH)[19'. - I3C NMR (62.9 MHz, [D6]DMSO): S = 13.93 (CH,), 22.13 (CH,), 25.91 (2 CH,), 26.26 (CH,), 29.28 (CH,), 31.52 (CHZ), 33.16 (CH,), 35.31 (CHZ), 35.77 (CH), 38.03 (Cq), 39.45 (CH), 45.96 (CH), 114.39 (CN), 114.47 (CN), 163.47 (CO), 164.68 (CO)["l. - IR (KBr): P = 822 cm-' (m), 1252 (s), 1364 (m), 1462 (m), 1717 (s), 2249 (w), 2863 (s), 2934 (s), 3129 (m), 3222 (s). - MS (EI, 35 eV, 180°C): m/z (%) = 301 (0.6) [M+], 300 (2.5) [M+

(301.39): calcd. C 67.75, H 7.69, N 13.94; found C 67.72, H 7.73, N 13.70.

- HI, 286 (3), 272 (loo), 258 (71), 244 (56). - C17Hz3N30,

4-Pentylcyclohexane-1,l-diacetic Acid (4): The dicyano imide 2 (55.0 g, 182 mmol) is dissolved in 100 ml of concd. sulfuric acid in a spacious flask and the solution is stirred overnight. Then water (90 ml) is slowly added with frequent stirring. When the intensity of the exothermic reaction decreases, the suspension is heated at 150°C for 24 h (initial frothing subsides after 2-3 h). The cooled mixture is diluted with water, cooled again and filtered. If the crude product contains larger amounts of the cyclic imide 3 (determined by 'H-NMR analysis), it is additionally heated with a 15% aqueous NaOH solution at 90°C for 4 h. After cooling and acidification with concd. hydrochloric acid, the crude acid is filtered off, washed with water until neutral and dried at 60"C, to yield 48.7 g (99%). Recrystallisation from ethyl acetate/petroleum ether (40/60) 1 : 1 (v/v) furnishes colourless crystals, m.p. 126-126.5"C. - 'H NMR

(m, 13H), 1.59 (d, br., ' J = 10.4 Hz, 2H, He& 1.84 (d, br., =

10.36 (s, br., 2H, COOH). - 13C NMR (62.9 MHz, [D6]DMSO):

(250 MHz, CDC13): 6 = 0.87 (t, 3 J = 6.8 Hz, 3H, CH3), 1.00-1.35

12.9 Hz, 2H, Heq), 2.52 (s, 2H, CH,CO), 2.66 (s, 2H, CHZCO),

F = 13.97 (CH3), 22.21 (CHI), 26.14 (CH,), 27.74 (2 CHZ), 31.72 (CH,), 34.24 (Cq), 34.73 (2 CHJ, 36.46 (CH,), 36.65 (CH), 36.75 (CHzCOOH), 44.37 (CH,COOH), 172.91 (COOH), 173.30 (COOH). - IR (KBr): P = 1209 cm-I (m), 1428 (m), 1708 (s), 2851 (s), 2921 (s), 3000-3250 (m, br.). - MS (EI, 35 eV, 180°C): m/z ('34) = 271 (0.5) [M+ + HI, 253 (7) [M' - OH], 252 (7) [M+ - HlO], 224 (17) [M+ - (CO, H,O)], 211 (81) [M+ - CH,COOH], 193 (77) [211 - HZO], 165 (40) [211 - (CO, H,O)], 151 (100) [ClIH&J. - CI5HZ6O4 (270.37): calcd. C 66.64, H 9.69; found C 66.53, H 9.61.

9-Pentyl-3-azaspiro[5.S]undecane-2,4-dione (3): m.p. 140°C. -

0.93-1.40 (m, 13H), 1.54-1.65 (m, 4H), 2.38 (s, 2H, CH2CO), 2.55 (s, 2H, CH2CO), 8.21 (s, br., lH , NH). - I3C NMR (62.9

'H NMR (250 MHz, CDC13): S = 0.86 (t, ,J= 6.8 Hz, 3H, CH3),

MHz, CDC13): S = 14.13 (CH,), 22.70 (CHZ), 26.56 (CH,), 28.01 (2 CHZ), 32.12 (CH,), 33.28 (Cq), 35.88 (2 CHZ), 36.65 (CHZ), 37.02 (CH), 39.58 (CH,CO), 46.62 (CHZCO), 172.26 (2 CONH). - IR (KBr): P = 1269 cm-' (s), 1683 (s), 1720 (s), 2848 (s), 2921 (s), 3086 (m), 3180 (m). - MS (EI, 35 eV, 180°C): mlz (YO) = 251

C15H25N02 (270.37): calcd. C 71.67, H 10.02, N 5.57; found C 71.68, H 10.16, N 5.59.

I, I -Bis(2-hydroxyethyl) -4-pentylcyclohexane (5): A solution pre- pared from the dicarboxylic acid 4 (27.0 g, 100 mmol) in dry THF (150 ml) is added dropwise to a stirred suspension of lithium alu- minium hydride (8.5 g, 225 mmol) in dry THF (450 ml). The result- ant mixture is stirred for 1 h at room temp. and for a further 3 h at reflux. When cooled, unreacted lithium aluminium hydride is hydrolysed carefully by dropwise addition of water. The precipi- tated hydroxide is dissolved by addition of the necessary amount of hydrochloric acid. After removal of the organic solvent under reduced pressure, water is added to the residue and the product is extracted several times with trichloromethane. The combined or- ganic phases are washed successively with dild. hydrochloric acid and water and dried with Na2S04. After removal of the solvent 24.2 g (quantitative yield) of a colourless, viscous residue is ob- tained. This product is of suficient purity to be used in further reactions. Recrystallisation from trichloromethane at -40 "C pro- vides 5 as colourless crystals, m.p. 25.5"C, which shows a meso- phase between 25.5 and 35.5"C. - 'H NMR (250 MHz, CDC13): S = 0.86 (t, , J= 6.8 Hz, 3H, CH,), 0.95-1.35 (m, 13H), 1.48-1.61 (m, 4H) partly covering 1.54 (t, 3 J = 6.9 Hz, 2H, CH&H,OH), 1.68 (t, 3J = 7.1 Hz, 2H, CH2CH20H), 1.94 (s, br., 2H, OH), 3.69 (t, 3J = 7.1 Hz, 2H, CHzOH), 3.73 (t, 3J = 6.9 Hz,

(51) [M+], 223 (75) [M+ - CO], 209 (98) [M' - CON]. -

2H, CHZOH). - 13C NMR (62.9 MHz, CDC13): F = 14.10 (CH3), 22.69 (CH,), 26.65 (CH,), 28.16 (2 CHZ), 32.19 (CHZ), 33.82 (Cq), 34.67 (CHzCHZOH), 36.24 (2 CHz), 37.08 (CH,), 37.55 (CH), 44.22 (CH2CH,OH), 58.31 (CH,OH), 58.56 (CHZOH). - IR (KBr): 0 = 1016 cm-' (m), 1052 (m), 1456 (m), 2852 (s), 2920 (s), 3312 (s, br.). - MS (EI, 35 eV, 180°C): m/z (Yo) = 243 (0.1) [M+ + HI, 224 (12) [M+ - HZO], 206 (7) [Mt - 2 HZO], 197 (52) [M+ - CHZCH~OH], 179 (58) [197 - HzO], 166 (10) [197 - CH20H], 151 (19) [Cl1H:,]. - C15H3002 (242.40): calcd. C 74.33, H 12.47; found C 74.39, H 12.59.

I,I-Bis(2-bromoethyl)-I-pentylcyclohexane (6): A mixture of the dialcoho15 (26.7 g, 110 mmol) and 47% aqueous hydrobromic acid (75 ml) is cooled and concd. sulfuric acid (37 ml) is slowly added with stirring; the temperature must be kept below 5 "C during ad- dition. Subsequently, the reaction mixture is heated at 95- 100°C for 24 h and, after cooling, it is poored on ice and extracted several times with diethyl ether. The combined extracts are washed twice with water, once each with a 5% NaHC03 and a satd. NaCl solu- tion and dried with Na2S04. The ether is evaporated and the resi- due subjected to column chromatography (column 17 X 9 cm) on silica gel using petroleum ether (40/60) as eluent. 31.9 g (79% yield) of a colourless liquid is obtained, which crystallises on standing, m.p. 31-31.5"C, b.p. 164"C/0.05 Torr (decomp.), Rf = 0.45-0.5 [petroleum ether (40160)l. - 'H NMR (250 MHz, CDC1,): S = 0.87 (t, 3J = 6.8 Hz, 3H, CH3), 0.96-1.36 (m, 13H), 1.45-1.61 (m, 4H), 1.81 (AA'XX' system, 2H, CH2CH2Br), 1.94 (AA'XX' sys- tem, 2H, CH2CH2Br), 3.30 (AA'XX' system, 2H, CH2Br), 3.36 (AA'XX' system, 2H, CHzBr). - I3C NMR (62.9 MHz, CDCl,):

(CHIBr), 28.29 (CH2Br), 32.16 (CH,), 35.03 (2 CH,), 36.61 (CH2CH2Br), 36.87 (CH,), 37.33 (CH), 38.36 (Cq), 44.73 (CH2CHzBr). - IR (KBr): i, = 1459 cm-' (w), 2853 (s), 2922 (s). - MS (EI, 35 eV, 180°C): mlz (YO) = 370/368/366 (<I) [M+], 342/

S = 14.16 (CH,), 22.71 (CHz), 26.62 (CH2), 27.95 (2 CHz), 28.19

Liebigs Ann. 1995, 1319-1326

Terminally Substituted Spir0[5S]undecanes 1323

340/338 (1/2/1) [Mf - CzH41, 2611259 (100/99) [M+ - CH2CH2Br]. - C15H2s79Br2: calcd. 366.0558, found 366.0560 (MS). - C15H28Br2 (368.19): calcd. C 48.93, H 7.66; found C 48.86, H 7.70.

9-Pentyl-3-spiro[5.5]undecanone (7): A suspension of sodium hy- dride (80% in mineral oil; 4.5 g, 150 mmol) in dry DMF (250 ml) is stirred at room temp. under argon and a solution of the dibro- mide 6 (8.4 g, 50 mmol) and TosMIC (9.8 g, 50 mmol) in dry DMF (200 ml) is added within 4 h. Afterwards the mixture is stirred for further 16 h. Excess base is hydrolysed by dropwise addition of the necessary amount of water, then the solvent is distilled under re- duced pressure and the residue is treated with trichloromethane and water. After the mixture has been neutralised with hydrochloric acid, the turbid organic layer is separated and the aqueous phase is extracted several times with trichloromethane. The combined or- ganic extracts are concentrated to a volume of 50 ml under reduced pressure and concd. hydrochloric acid (50 ml) is added at room temp. with vigorous stirring. After the mixture has been stirred for 30 min, it is diluted with water, the organic layer is separated and the aqueous layer extracted three times with trichloromethane. The combined organic phases are washed successively with water and a satd. NaHC03 solution, dried with Na2S04 and the solvent is evaporated. The residue is subjected to column chromatography (silica gel) using dichloromethane as eluent to afford the desired product 7 as a colourless, viscous liquid, which crystallises on standing. For further purification it can be recrystallised from pe- troleum ether (40/60) or methanol to afford 9.2 g (78% yield) of colourless, crystalline 7, m.p. 31 "C, Rf = 0.53 (dichloromethane). - 'H NMR (400 MHz, CDCl3): 6 = 0.87 (t, 3 J = 7.0 Hz, 3H, CH3), 1.04 (ddd, 2J= 13.2 Hz, 3 J = 11.8 and 2.9 Hz, 2H, H,,), 1.15-1.33 (m, 11H), 1.56-1.63 (m, 2H) partly covering 1.60 (t, 3 J = 6.9 Hz, 2H, CH2CH2CO), 1.71 (d, br., ,J= 13-14 Hz, 2H, He& 1.74(t, 3 J = 7.1 Hz,2H,CH,CHZCO),2.26(t, 3 J = 7.1 Hz, 2H, CHZCO), 2.33 (t, 3 J = 6.9 Hz, 2H, CH2CO). - I3C NMR (62.9 MHz, CDC13): 6 = 14.18 (CH3), 22.77 (CH,), 26.70 (CH,), 28.61 (2 CH,), 31.54 (CH2CH2CO), 32.10 (Cq), 32.25 (CH,), 35.54 (2 CH,), 37.07 (CH,), 37.22 (CHzCO), 37.59 (CHZCO), 37.98 (CH), 40.72 (CH2CH2CO), 213.20 (CO). - IR (KBr): 0 = 1454 cm-' (w), 1717 (s), 2852 (m), 2920 (s). - MS (EI, 70 eV, 200°C): rnlz (%) = 236 (58) [M+], 218 (12), 207 (45). - C16H280: calcd. 236.2140, found 236.2137 (MS). - (236.40): calcd. C 81.29, H 11.94; found C 81.55, H 11.89.

General Procedure for the Preparation of Phenyl-Substituted Spi- ro[5.5]undecanes from 7 by Grignard Addition of the Corresponding Bromobenzenes: To magnesium splinters (270 mg, 11 mmol) and dry diethyl ether (10 ml) 5 ml of a solution of the appropriate bromide (11 mmol) in dry diethyl ether (15 ml) is added under argon. When the Grignard reaction starts, the rest of the solution is added dropwise and the mixture is heated at reflux for 1 h. There- upon a solution of the spiro ketone 7 (2.4 g, 10 mmol) in dry diethyl ether (20 ml) is added and heating is continued for a further 2 h. After cooling the white suspension is poored in ice/water and acidi- fied with dild. hydrochloric acid. The organic layer is separated and the aqueous phase extracted twice with diethyl ether. The combined organic phases are washed with a satd. NaCl solution and the sol- vent is evaporated. In a flask fitted with a water separator, the crude hydroxyspirane and 4-toluenesulfonic acid (300 mg) in tolu- ene (100 ml) are heated at reflux for 40 min. The reaction mixture is washed with a 5% NaHC03- and a satd. NaCl solution and dried with Na2S04. After addition of 10% palladium charcoal (1 g) the solution is stirred at room temp. under hydrogen (pressure: 3 bar). Subsequently, the catalyst is filtered off and the solvent re-

moved under reduced pressure to afford the crude product (8- 11). According to this general procedure are obtained:

(RS) -3- (4-Fluorophenyl) -9-pentylspiro[5. S]undecane (8): The crude product is recrystallised from petroleum ether (40/60) and diethyl ether to yield 2.8 g (87%) of 8, m.p. 41.5-42SoC, Rf = 0.71 [petroleum ether (40/60)]. - 'H NMR (250 MHz, CDC13): 6 = 0.88 (t, 3J(HH) = 6.8 Hz, 3H, CH3), 0.90-1.69 (m, 23H), 2.06 (q, 2H), 2.42 (mc, 1H), 6.95 (dd, AA'BB'X system, 3J(HH) and 3J(HF) = 8.8 Hz, 2H, Ha,), 7.16 (dd, AA'BB'X system, 3J(HH) = 8.8 Hz, 4 J ( H ~ ) = 5.5 Hz, 2H, Ha,). - I3C NMR (62.9 MHz, CDCI,): 6 = 14.23 (CH3), 22.83 (CH,), 26.81 (CH2), 28.36 (CH,), 28.47 (CH,), 29.65 (CH,), 29.69 (CH,), 31.62 (CH,), 31.95 (Cq), 32.35 (2 CH3, 37.29 (CH,), 38.24(CH), 41.71 (CH,), 41.79 (CH,), 44.42 (CH), 114.97 (d, 2 J ( ~ ~ ) = 20.9 Hz, 2 CH,,), 128.15 (d, 3J(c~) = 7.6 HZ, 2 CH,,), 143.56 (d, 4J(c~) = 3.3 Hz, Cqar), 161.22 (d, 'J(cF) = 243 Hz, Cqar). - "F NMR (235.4 MHz, CDC13/ CFC13): 6 = -118.45 (tt, 3 J ( ~ ~ ) = 8.7 HZ, 4 J ( ~ ~ ) = 5.5 HZ). - IR (KBr): S = 830 cm-' (s), 1228 (s), 1447 (m), 1509 (s), 2851 (s), 2920 (s). - MS (EI, 70 eV, 200°C): mlz (YO) = 316 (41) [M+], 190

calcd. 316.2566, found 316.2568 (MS). (26), 161 (16), 150 (28), 135 (37), 122 (68), 109 (100). - C22H33F:

(RS)-3-(3,4-DiJluorophenyl)-9-pentylspiro[S.5]undecane (9): The crude product is purified by column chromatography [silica gel, petroleum ether (40/60)] to afford 2.9 g (86% yield) of 9 as a colourless liquid. A distilled specimen (kugelrohr, 0.03 Torr, 220-240°C) crystallises at -40°C and shows m.p. 8-9"C, Rf = 0.74 [petroleum ether (40/60)]. - 'H NMR (400 MHz, CDC13): 6 = 0.88 (t, 3 J = 7.0 Hz, 3H, CH3), 0.91-1.68 (m, 23H), 2.04 (q, 2H), 2.40 (q, IH), 6.90 (mc, 1 H, H,,), 6.97-7.07 (m, 2H, 2 Ha& - I3C NMR (62.9 MHz, CDCl3): 6 = 14.21 (CH,), 22.85 (CHZ), 26.83 (CH,), 28.34 (CH,), 28.45 (CH,), 29.48 (2 CH,), 31.60 (CH,), 31.91 (Cq), 32.21 (CH,), 32.38 (CHZ), 37.30 (CH2), 38.24 (CH), 41.62 (CH,), 41.64 (CH,), 44.38 (CH), 115.50 (d, 'J{cF) = 16.7 Hz, CHar), 116.82 (d, 2 J ( ~ ~ ) = 16.7 Hz, CHar), 122.58 (dd, 3 J ( ~ ~ ) = 5.7 Hz, 4J(cq = 3.4 HZ, CH,,), 144.94 (dd, 3J(c~) = 4.6 HZ, 4J(c~) =

3.9 Hz, Cq,,), 148.63 (dd, 'J(CF) = 245 Hz, ,J(CF) = 12.6 Hz, CqarF), 150.27 (dd, 'J(cF) = 247 Hz, 2J(cF) = 12.8 Hz, Cq,,F). -

6 = -142.99 (d, 3 J ( ~ ~ ) = 21.2 HZ), -139.11 (d, 3 J ( ~ ~ ) = 21.2 HZ). "F NMR (235.4 MHz, 'H broad-band decoupled, CDC13/CFC13):

- IR (KBr): S = 815 cm-' (m), 1283 (m), 1447 (m), 1519 (s), 1607 (m), 2852 (s), 2920 (s). - MS (EI, 70 eV, 200°C): rnlz (YO) = 334

C22H32F2: calcd. 334.2472, found 334.2474 (MS). (91) [M+], 208 (55), 179 (62), 168 (61), 140 (75), 127 (100). -

(RS)J-Pentyl-9-(3,4,5-trijluorophenyI)spiro[5.5 lundecane (10): The crude product is purified by column chromatography [silica gel, petroleum ether (40/60)] to afford 3.3 g (94% yield) of 10 as a colourless liquid. A distilled specimen (kugelrohr, 0.03 Torr, 220-240OC) crystallises at -40°C and shows m.p. 6.5-7"C, Rf = 0.79 [petroleum ether (40160)l. - 'H NMR (250 MHz, CDC13): 6 = 0.88 (t, 3J(HH) = 6.8 Hz, 3H, CH3), 0.91-1.68 (m, 23H), 2.03 (mc, 2H), 2.38 (tt, 3J(HH) = 11.5 and4.6 Hz, lH , CH,,), 6.80 (dd, 3J(HF) = 9.1 Hz, 4J(HF) = 6.6 Hz, 2H, €Iar). - I3C NMR (62.9 MHz, CDC13): 6 = 14.19 (CH3), 22.81 (CH,), 26.79 (CH,), 28.29 (CH,), 28.40 (CHZ), 29.22 (2 CHZ), 31.55 (CHZ), 31.88 (Cq), 32.06 (CH,), 32.33 (CH,), 37.24 (CHZ), 38.19 (CH), 41.40 (CH,), 41.55 (CH,), 44.45 (CH), 110.62 (dd, 2J(~F) = 13.6 Hz, 'J(CF) = 6.5 Hz, 2 CH,,), 137.89 (dt, 'J(cF) = 249 Hz, 2J(c~) = 15.5 Hz, CqarF), 144.15 (td, 3 J ( c ~ ) = 6.3 Hz, 4J(c~) = 4.9 Hz, Cq,,), 151.11 (ddd, 'J(cF) = 249 Hz, 2J(c~) = 9.7 Hz, 3J(c~) = 4.1 Hz, 2 Cq,F). - I9F NMR (235.4 MHz, CDC13/CFC13): 6 = -148.38 (tt, 3 J ( ~ ~ ) = 20.1 HZ, 4 J ( ~ ~ ) = 6.5 HZ, 1 F), -135.89 (dd, 3 5 ( ~ ~ ) = 20.1 HZ, 3 J ( ~ ~ , = 9.1 Hz, 2 F). - IR (KBr): S = 850 cm-' (m), 1041 (s), 1445 (m),

Liebigs Ann. 1995, 1319-1326

1324 W. Schmidt, F. Vogtle, E. Poetsch

1530 (s), 1615 (m), 2851 (s), 2921 (s). - MS (EI, 70 eV, 200°C): rnlz (%) = 352 (40) [M+], 179 (38), 145 (56), 123 (59), 109 (75). - C2,H3,F3: calcd. 352.2378, found 352.2376 (MS).

(RS) -3-Pentyl-9- (4-trijl'uoromethoxyphenyl) spiro[S. Slundecane (11): The crude product is purified by column chromatography [sil- ica gel, petroleum ether (40160)l to afford 2.8 g (73% yield) of 11 as a colourless liquid. A distilled specimen (kugelrohr, 0.03 Torr, 220-240°C) crystalises at -40°C and shows m.p. 0- 1 "C, Rf = 0.80 [petroleum ether (40/60)]. - 'H NMR (400 MHz, CDC1,): 6 = 0.88 (t, 3 J = 7.0 Hz, 3H, CH3), 0.91-1.68 (m, 23H), 2.06 (mc, 2H), 2.45 (mc, IH), 7.11 (d, 3 J = 7.9 Hz, 2H, H,,), 7.21 (d, 3 J = 7.9 Hz, 2H, H,,). - I3C NMR (62.9 MHz, CDC13): 6 = 14.21 (CH3), 22.85 (CH,), 26.84 (CHI), 28.37 (CH,), 28.48 (CH,), 29.49 (CH,), 29.53 (CH,), 31.63 (CH,), 31.97 (Cq), 32.32 (CH,), 32.38 (CH,), 37.31 (CH,), 38.27 (CH), 41.72 (2 CHz), 44.57 (CH), 120.69 (q, lJ(cp, = 256 Hz, OCF3), 120.88 (2 CH,,), 128.09 (2 CH,,), 146.62 (Cqar), 147.39 (q, 3J(cF) = 1.6 Hz, Cq,,OCF,). - "F NMR (235.4 MHz, CDCI3/CFCl3): 6 = -58.46. - IR (KBr): C = 846 cm-' (w), I165 (s), 1222 (s), 1261 (s), I447 (w), 1509 (m), 2852 (m), 2920 (s). - MS (EI, 70 eV, 200°C): mlz (%) = 382 (100) [M']. -

C23H33F30: calcd. 382.2484, found 382.2484 (MS).

( R S ) -3- Pentyl-9- (4-pentyloxyphenyl)spiro[S. Slundecune (12):

a) (RS) -9-Pentyl-3- (4-pentyloxyphenyl)spiro[5.5]undecan-3-ol: To magnesium splinters (150 mg, 6 mmol) 2 ml of a solution of 1- brom0-4-pentyloxybenzene[~~] (1.5 g, 6 mmol) in dry THF (10 ml) is added under argon and the mixture is heated to 70°C in an ultrasonic water bath. When the Grignard reaction starts, the rest of the solution is added dropwise and the mixture is heated at re- flux until all of the magnesium has dissolved. Thereupon the ultra- sonic bath is removed, a solution of the spiro ketone 7 (1.2 g, 5 mmol) in dry THF (10 ml) is added and heating of the mixture is continued for a further 4 h. After cooling, the reaction mixture is diluted with water and acidified with dild. hydrochloric acid. The solvent is removed under reduced pressure and the residue is treated with diethyl ether and water. The organic layer is separated and the aqueous phase extracted twice with diethyl ether. The com- bined organic phases are washed with satd. NaCl solution and dried with Na2S04. After evaporation of the solvent the product is separated by column chromatography (silica gel, dichloromethane) and purified by recrystallisation from methanol or petroleum ether (40/60) to afford 1.2 g (60% yield), m.p. 57 "C, Rf = 0.45 (dichloro- methane). - IH NMR (250 MHz, CDC13): 6 = 0.83-2.10 (m, 38H), 3.94 (t, ' J = 6.5 Hz, 2H, OCH,), 6.86 (d, 3 J = 8.7 Hz, 2H, H,,), 7.40 (d, ,J= 8.7 Hz, 2H, Har). - I3C NMR (62.9 MHz, CDC13): 6 = 14.12 (CH,), 14.21 (CH,), 22.54 (CH,), 22.79 (CH,), 26.75 (CH,), 27.53 (CH,), 28.27 (CH,), 28.37 (CH,), 28.46 (CH,), 29.06 (CH,), 31.63 (CH2 and Cq), 32.29 (CH,), 34.38 (2 CH2),

73.03 (CqOH), 114.02 (2 CH,,), 125.78 (2 CH,,), 141.28 (Cq,,), 157.90 (Cq,,O). - IR (KBr): B = 830 cm-' (m), 1246 (m), 1510 (w), 2852 (s), 2920 (s), 3505 (w), 3560 (m). - MS (EI, 70 eV, 200°C): mlz (%) = 400 (2) [M+], 382 (37) [M+ - H,O], 216 (97), 146 (100). - C&&: calcd. 400.3341, found 400.3338 (MS). - (400.64): calcd. C 80.94, H 11.07; found C 81.24, H 10.76.

b) (RS) -3- Pen ty l-9- (4-pen ty loxypheny 1) spiro f 5. Slundecane (12) : The transformation of 9-pentyl-3-(4-pentyloxyphenyl)spiro[5.5]un- decan-3-01 (1.2 g, 3 mmol) into the corresponding spirane 12 via dehydration and hydrogenation is accomplished in the same way as described in the general procedure. The crude product is chromato- graphed (silica gel, dichloromethane) to yield 930 mg (81%) of a colourless oil, which crystallises at 0°C. - m.p. 22-22.5"C, Rf = 0.89 (dichloromethane), 0.42 [petroleum ether (40/60)]. - 'H NMR

36.95 (CH,), 37.22 (CHI), 38.15 (CH), 40.54 (CH,), 67.96 (OCH,),

(250 MHz, CDC1,): 6 = 0.87-1.89 (m, 35H), 2.10 (mc, 2H), 2.43 (mc, 1 H), 3.96 (t, 3J = 6.6 Hz, 2H, OCHz), 6.86 (d, ' J = 8.6 Hz, 2H, H,,), 7.16 (d, 3J = 8.6 Hz, 2H, Har). - I3C NMR (62.9 MHz, CDCl3): 6 = 14.12 (CH3), 14.21 (CH,), 22.57 (CH,), 22.81 (CH,), 26.80(CH,), 28.35(2 CH,),28.48 (CH,), 29.17(CH2), 29.69(CHZ), 29.75 (CHZ), 31.63 (CHI), 31.96 (Cq), 32.35 (CH,), 32.43 (CH,), 37.29 (CH,), 38.25 (CH), 41.75 (CH,), 41.90 (CHZ), 44.27 (CH), 68.00 (OCHz), 114.31 (2 CH,,), 127.64 (2 CH,), 139.94 (Cq,,), 157.33 (Cq,,O). - IR (KBr): 0 = 825 cm-' (m), 1245 (s), 1511 (s), 2851 (s), 2920 (s). - MS (EI, 70 eV, 200°C): rnlz (%) = 384 (100) [M+], 314 (18) [M+ - C5HI0]. - C27H440 (384.64): calcd. 384.3392, found 384.3393 (MS). - C27H440 X 0.1 CH,CI,: C 82.80, H 11.33; found C 82.76, H 11.19.

3-Dijl'uorornethylidene-9-pentylspir0[5~5]undecane (13): To dibro- modifluoromethane (1 ml, 10 mmol) Tn dry triethyleneglycol di- methyl ether (triglyme) (I5 ml) a solution of tris(dimethy1amino)- phosphane (3.4 g, 21 mmol) in dry triglyme (10 ml) is added under argon at 0°C via a syringe. The white suspension is allowed to warm up to room temp. and after stirring for 30 min a solution of the spiro ketone 7 (1.2 g, 5 mmol) in dry triglyme (5 ml) is added in the same way. Stirring is continued for 30 min at room temp., then for 4 h at 80°C. After cooling, hexamethylphosphoric acid amide (HMPA) formed during the reaction and the main amount of the solvent are separated by column chromatography [silica gel, petroleum ether (40160)l. The crude product, containing minor amounts of the starting material and triglyme, is then chromato- graphed again to yield 970 mg (72%) of pure 13 as a colourless liquid, Rf = 0.83 [petroleum ether (40/60)]. - 'H NMR (250 MHz, CDCI,): F = 0.87 (t, ,J= 6.8 Hz, 3H, CH3), 0.97-1.35 (m, 13H), 1.39-1.64 (m, 8H), 2.05 [m,, 4H, (CH2)IC=CF2]. - 13C NMR (62.9 MHz, CDC1,): 6 = 14.20 (CH,), 19.55 (CHZ), 19.69 (CH,), 22.79 (CH,), 26.74(CHz), 28.27 (2 CHI), 31.57 (CH,), 32.30 (CH,), 32.40 (Cq), 35.92 (2 CH,), 37.19 (CH,), 38.10 (CH), 40.73 (CHZ), 88.13 (t, ' J ( C F ) = 18.4 Hz, C=CF2), 150.74 (t, lJ(CF) = 280 Hz, = CFZ). - "F NMR (235.4 MHz, CDCI,/CFC13): 6 = -99.70. - IR (KBr): 0 = 1048 cm-' (m), 1222 (m), 1272 (m), 1448 (w), 1758 (s), 2853 (s), 2920 (s). - MS (EI, 70 eV, 200°C): rnlz (%) = 270 (30) [M+], 199 (99). - C17H28F2: calcd. 270.2159, found 270.2160 (MS).

(RS)-9-Pentylspiro[S.S]undecane-3-carbonitrile (14): Solid po- tassium tert-butoxide (2.7 g, 24 mmol) is added in portions to a stirred solution of the spiro ketone 7 (2.4 g, 10 mmol) and TosMIC (2.3 g, 12 mmol) in a mixture of dry THF (120 ml) and dry ethanol ( I ml) while keeping the temperature below 5 "C. Stirring is con- tinued for 30 min at room temp. and for 1 h at 40°C. Thereupon the suspension is diluted with water and the solvent is removed under reduced pressure. The residue is treated with water and ex- tracted several times with petroleum ether (40l60). The combined organic layers are washed with water and a satd. NaCl solution and dried with Na2S04. After removal of the solvent the residue is chromatographed (silica gel, dichloromethane) to afford 1.8 g (73%) 14 as a colourless liquid. A distilled specimen (kugelrohr, 0.03 Torr, 120-140°C) crystallises at 0°C and shows, m.p. 19.5-2OoC, Rf = 0.80 (dichloromethane). - 'H NMR (250 MHz, CDCI,): 6 = 0.86 (t, 3 J = 6.8 Hz, 3H, CH3), 0.93-1.35 (m, 15H), 1.37-1.56 (m, 4H), 1.57-1.88 (m, 6H), 2.54 (tt, 3J = 8.3 and 4.6 Hz, 1 H, CH,,CN). - I3C NMR (62.9 MHz, CDC13): 6 = 14.07 (CH3),22.66 (CH,),24.65 (2 CHZ), 26.61 (CH,),27.94 (CH,), 28.03 (CH,), 28.17 (CH), 29.60 (CHZ), 31.68 (Cq), 32.16 (CH,), 34.97 (br., CH,), 37.00 (CH,), 37.11 (br., CH,), 37.89 (CH), 38.59 (CH,), 122.60 (CN). - IR (KBr): 3 = 1449 cm-' (m), 2237 (w), 2849 (s), 2918 (s). - MS (EI, 70 eV, 200°C): mlz (YO) = 247 (47) [M+], 219 (100) [M+ - CZH~]. - Cl7H29N: calcd. 247.2300, found 247.2305

Liebigs Ann. 1995, 13 19- 1326

Terminally Substituted Spiro[5.5]undecanes 1325

(MS). - (247.42): calcd. C 82.53, H 11.81, N 5.66; found C 82.38, H 11.48, N 5.90.

(RS)-3,9-Dipentylspiro[5.5]undecane-3-carbonitrile (15): n-Bu- tyllithium (l5”/0 in hexane; 3 ml, 4.8 mmol) is added to a solution of diisopropylamine (0.6 ml, 4.2 mmol) in 30 ml of anhydrous THF at -78°C under argon, and the mixture is stirred for 15 min. Then a solution of the carbonitrile 14 (920 mg, 3.7 mmol) in 10 ml of anhydrous THF is added via a syringe. After stirring for 20 min, 1-bromopentane (0.5 ml, 4 mmol) is added in the same way and stirring is continued for 1 h. Thereupon the reaction mixture is allowed to warm up to room temp., the reaction is quenched with ice/water and the mixture acidified with dild. hydrochloric acid. After the solvent has been removed under reduced pressure, the residue is treated with water and the product is extracted several times with petroleum etb.(40/60). The combined organic layers are washed successively with a 5% NaHC03 and a satd. NaCl solu- tion and dried with Na2S04. After evaporation of the solvent, the product 15 is separated by column chromatography (silica gel, dichloromethane) and purified by distillation under reduced pres- sure (kugelrohr, 0.05 Torr, 175-180°C) to yield 920 mg (78%) of a colourless liquid, which crystallises on standing and shows m.p. 39-40°C, Rf = 0.85 (dichloromethane). - I3C NMR (100.6 MHz, CDC13): 6 = 14.01 (CH,), 14.14 (CH3), 22.49 (CH,), 22.73 (CH,), 24.25 (CH,), 26.68 (CHI), 28.15 (CH,), 28.21 (CHZ), 28.62 (CH,), 30.91 (CH,), 30.99 (CH,), 31.65 (CH2), 31.94 (CH,), 31.96 (Cq), 32.23 (CHI), 37.08 (CHZ), 37.73 (CH,), 38.00 (CH), 39.48 (Cq), 40.36 (br., CH,), 40.54 (br., CH2), 123.94 (CN). - IR (KBr): C = 1450 cm-’ (s), 2229 (w), 2852 (s), 2923 (s). - MS (EI, 70 eV, 2OOOC): rnlz (%) = 317 (22) [M+], 288 (59, 260 (27). - CZ2H39N: calcd. 317.3082, found 317.3089 (MS). - (317.56): calcd. C 83.21, H 12.38, N 4.41; found C 83.03, H 12.06, N 4.66.

(RS)-9-Pentylspiro[5.5/undecan-3-ol (16): A solution of the spiro ketone 7 (2.4 g, 10 mmol) in dry THF (25 ml) is added drop- wise to a cooled and stirred suspension of lithium aluminium hy- dride (0.2 g, 5 mmol) in dry THF (50 ml). The mixture is sub- sequently stirred for 30 min at room temp. and for a further 2 h at reflux. The cooled mixture is carefully hydrolysed by dropwise addition of water and the precipitated hydroxide is dissolved by addition of the necessary amount of hydrochloric acid. After re- moval of the organic solvent under reduced pressure, the residue is treated with water and trichloromethane. The organic layer is separated and the aqueous phase extracted twice with trichloro- methane. The combined organic extracts are washed successively with dild. hydrochloric acid, water and a satd. NaCl solution and dried with Na2S04. After removal of the solvent under reduced pressure, 2.3 g (97% yield) of a colourless, viscous residue is ob- tained. This product is of sufficient purity to be used in further reactions. Crystallisation from ethanollwater 10: 1 at -40°C affords 16 as colourless crystals, m.p. 41-43°C. - I3C NMR (100.6 MHz,

28.62 (CH,), 29.25 (br., CHI), 30.43 (CH,), 30.60 (CH,), 31.80 (Cq), 32.27 (br., CH,), 33.27 (br., CH2), 37.17 (CH,), 38.10 (CH), 38.73 (br., CH,), 39.16 (br., CH2), 70.92 (CHOH). - IR (KBr): P = 1054 cm-’ (m), 1448 (m), 2850 (s), 2918 (s), 3334 (br., m). - MS (EI, 70 eV, 200°C): rnlz (YO) = 238 (<I) [M+], 220 ( 5 ) [M* - H20], 191 (9) [220 - C2H5], 149 (26), 108 (33). - C16H300: calcd. 238.2297, found 238.2302 (MS).

CDC13): 6 = 14.16 (CH3), 22.75 (CH,), 26.71 (CH,), 28.27 (CH,),

( R S ) - (9-Pen tylspiro[5.5]undec-3-y1) (all-trans) -4‘- Pen tyl- bicyclohexyl-4-carboxylate (17): To all-trans-4‘-pentylbicyclohexyl- 4-carboxylic (4.2 g, 15 mmol) thionyl chloride (1.5 ml, 20 mmol) is added and the mixture is stirred at 70°C for 1 h. Excess thionyl chloride is then removed under reduced pressure and the

residue is treated with a solution of the alcohol 16 (1.43 g, 6 mmol) in dry pyridine (10 ml). After heating of the mixture for 1 h, it is diluted with water, acidified with dild. hydrochloric acid and ex- tracted several times with trichloromethane. The combined organic layers are washed with water and a 5% NaHC03 solution, dried with Na2S04 and the solvent is evaporated. After column chroma- tography of the residue (silica gel, dichloromethane), recrystalli- sation from petroleum ether (40l60) or diethyl ether furnishes 2.34 g (780/0) of 17 as colourless crystals, C 53 SG 100 SB 109 I, Rf = 0.85 (dichloromethane). - ‘H NMR (400 MHz, CDC13): 6 = 0.75-1.59 (m, 43H) partly covering 0.85 (t, ‘ J = 7.0 Hz, 3H, CH3), 1.60-1.80(m, lOH), 1.94(mc,2H),2.13(tL3J= 12.1and3.5Hz, 1 H, CH,CO), 4.70 (tt, 3J = 8.6 and 3.9 Hz, 1 H, CH,,O). - I3C NMR (100.6 MHz, CDC13): 6 = 14.19 (2 CH3), 22.78 (2 CH3, 26.50 (CH3, 26.65 (CH,), 26.74 (2 CH?), 28.25 (CH,), 28.54 (CH,), 28.74 (CH*), 29.25 (2 CHJ, 29.42 (2 CH,), 30.04 (2 CH,), 31.79 (Cq), 32.28 (CH,), 32.31 (CH,), 33.62 (2 CH2), 34.48 (br., CHI), 37.18 (CH,), 37.52 (CH,), 37.85 (br., CH2), 37.93 (CH), 38.11 (CH), 38.16 (CH,), 42.61 (CH), 43.32 (CH), 43.99 (CH), 72.35 (OCH), 175.88 (COO). - IR (KBr): P = 1022 cm-’ (m), 1149 (m), 1178 (m), 1724 (s), 2848 (s), 2917 (s). - MS (FAB): m/z (%) =

[C,6H,f,]. - C34H6002 (500.85): calcd. C 81.54, H 12.07; found C 81.42, H 11.78.

499.4 (3) [M’ - HI, 281.1 (100) [Mf - C16H27], 221.2 (55)

[‘I Review: F. Vogtle, Supramolecular Chemistry, 2nd ed., Wiley, Chichester. 1993: Suararnolekulare Chemie. 2nd ed., Teubner, Stuttgart 1992; and ief. cited therein.

R. E;denschink. D. Erdmann, J. Krause, L. Pohl, Angew. Chem. 1978, 90, 133; Angew. Chem. Int. Ed. Engl. 1978,-17, 133. - Lzb1 R. Eidenschink, Kontakte (Darmstadt) 1979, Nr. 1, 15- 18. - I Z c ] R. Eidenschink, G. Haas, M. Romer, B. S. Scheu- ble, Angew. Chem. 1984, 96, 151; Angew. Chem Int. Ed. Engl. 1984,23, 147.

L31 L3*1 H. Minas, H.-R. Murawski, H. Stegemeyer, W. Sucrow, J Chem. SOC. Chem. Commun. 1982. 308-309. - [3b1 W. Sucrow. H. Minas, H. Stegemeyer, P. Geschwinder, H.-R. Murawski, C. Kriiaer. Chem. Ber. 1985.118. 3332-3349. - L34 D. Varech, M. J. BGenne, J. Jacques, Tetrahedron Lett. 1985, 26, 61 -64; H.-J. Deutscher, S. Richter, H. Zaschke, Mof. Cryst. Liq. Cryst. 1985, 127, 407-412; C. Tschierske, H. Zaschke, Liq. Cryst. 1989, 5,

L4] F. Reinitzer, Monatsh. Chemie 1888, 9, 421-441. L51 J. Boettcher, R. Hartmann, F. Vogtle, Chem. Bel: 1992, 125,

1865-1871; W. Calaminus, F. Vogtle, R. Eidenschink, Z. Na- turforsch. 1986, 41b, 1011-1014; H. Redlof, F. Vogtle, H. Puff, H. Reuter, P. Woller, J. Chem. Res. (S) 1984,314-315; J Chem. Res. ( M ) 1984, 2910-2929.

L61 A. I. Vogel, J Chem. Soc. 1934, 1758-1765. L71 [7a1 L. M. Rice, C. F. Geschickter, C. H. Grogan, J Med. Chem.

1963, 6 , 388-402. - [7bl L. M. Rice, M. E. Freed, C. H. Gro- gan, J Org. Chem. 1964,29, 2637-2640.

[*I Formation of the cyclic ether is almost supressed under the chosen conditions; cf. [7b1; J. N. Ashley, R. F. Collins, M. Davis, N. E. Siritt, J Chem. Soc. 1958, 3298-3313.

L91 0. Possel, A. M. van Leusen, Tetrahedron Lett. 1977, 48, 4229-4232: D. van Leusen. A. M. van Leusen. Svnthesis

191-195.

1980, 325 -326. [lo] D. G. Naae. D. J. Burton. Svnthetic Commun. 1973.3. 197-200;

S. Hayashi,’T. Nakai, G. fshikawa, D. J. Burton,’D. G. Naae, H. S. Kesling, Chem. Lett. 1979, 983-986; J. Fried, S. Kittisopi- kul, E. A. Hallinan, Tetrahedron Lett. 1984,25, 4329-4332.

[I1] 0. H. Oldenziel, D. van Leusen, A. M. van Leusen, J Org. Chem. 1977, 42, 2114-3118.

[ I 2 ] M. A. Osman, H. P. Schad, H. R. Zeller, J Chem. Phys. 1983, 78, 906-914; H. P. Schad, M. A. Osman, J Chem. Phys. 1983, 79, 5710-5717. - ZLI-4792 is a commercially available liquid crystal mixture from Merck, Darmstadt, Germany. It is com- posed of several liquid crystalline substances which are differ- ently fluorinated in the terminal phenyl unit and can be classi- fied as “medium polar” (AE = 5.2).

J. Krause, E. Poetsch, E. Merck Co., Darmstadt, Germany, personal communication, 1994. - U. Finkenzeller, E.

[ I3 ]

Liebigs Ann. 1995, 1319-1326

1326 W. Schmidt, F. Vogtle, E. Poetsch

Poetsch, K. Tarumi, Poster and Abstract of Papers, 14th Inter- national Li uid Crystal Conference, Pisa, June 21-26, 1992. -

[I4] Parameters of molecule geometry were obtained by semiempir- ical calculations (AM 1); HyperChemTM, Release 2 for Win- dows, Autodesk, Inc., 1992.

[I5] The equatorial alignment of the cyano group as well as the other substituents is indicated by the ’H-NMR spectra.

[I6] This result corresponds to the observation of liquid crystalline behaviour in esters of 9-alkylspiro[5.5]undecane-3-carboxylic acid with 4’-hydroxybiphenyl-4-carbonitrile. Presumably, in these esters the presence of the nematogenic cyanobiphenyl unit is responsible for the mesogenic properties too. - see L. A. Karamyshewa, T. A. Geivandova, K. V. Roitman, N. F. Ljukmanov, E. I. Kovshev, Mol. Cryst. Liq. Cryst. 1983, 99,

[13’1 cf. ref.[ 9 . 1, R. Eidenschink, Chem. Unserer Zeit 1984, 18, 168-176.

169-175; cf. also L. K. M. Chan, P. A. Gemmell, G. W. Gray, D. Lacey, K. J. Toyne, Mol. Cryst. Liq. Cryst. 1987, 147, 1 13- 139.

[ I 7 ] R. Frach, C. Tschierske, H. Zaschke, H.-J. Deutscher, Liq. Cryst. 1989, 5, 197-207.

[18] H. Jork, W. Funk, W. Fischer, H. Wimmer, Diinnschicht-Chro- matogrphie, vol. la, VCH, Weinheim, 1989, p. 393-396.

[191 The given values of the intensive signals are assigned to the predominant diastereomer. In addition, signals of the other diastereomer are observed.

[*O] D. A. Jager, R. E. Robertson, .l Org. Chem. 1977, 42, 3298-3301. J. Malthete. M. Leclerca. M. Dvolaitzkv. J. Ga- bard, J. Billard, V. Pontikis, J. Jacque;; Mol. Cryst. Liq. Cryst. 1973. 23. 233-260.

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Liebigs Ann. 1995, 1319-1326