1-ethynylcyclohexene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 21.5 g of ethynylcyclohexene are added dropwise to a suspension of 6 g of 80% strength sodium hydride in 200 ml of tetrahydrofuran under reflux, and the reaction mixture is kept under reflux conditions until no further gas is evolved. 28 g of 2,3,6-trimethyl-cyclohexanone are then added dropwise at room temperature and the mixture is left overnight, whilst being stirred, in order to complete the reaction. Water is added to the reaction mixture, the reaction product is taken up in ether and the ether solution is washed with water, dried and concentrated. Fractional distillation gives 9 g of unconverted ethynylcyclohexene, 8 g of starting ketone, and 22 g of 1-(2,3,6-trimethyl-1-hydroxy-cyclohexyl)-2-(cyclohex-1-en-1-yl)-acetylene of boiling point 120° C/0.1 mm Hg and refractive index nD25 = 1.5143. This corresponds to a yield of 68% of theory, based on trimethylcyclohexanone converted. Fragrance note: faint, tart, herbaceous. under reflux the reaction the ether solution is washed with water dried concentrated Fractional distillation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: First, the appropriate alkynyl alcohols are synthesized. To produce the particular compositions disclosed herein, 1-Ethynylcyclohexene, for example, is deprotonated with butyl lithium and then condensed with paraformaldehyde (Brandsma and Verkruijsse). By this process, 3-Cyclohexenyl-2-propyn-1-ol was produced in 82% yield (Baudouy, et al.). This compound had been reported previously without complete spectroscopic data (Baudouy). 1-Ethynylcyclohexene (3.00 g, 28.6 mmol) was dissolved in diethyl ether (125 mL) and cooled to −78° C. 2.5 M n-butyllithium in hexane (12.4 mL, 31.1 mmol) was added dropwise. The solution was allowed to stir at −78° C. for 1.5 h and then paraformaldehyde (1.70 g, 56.5 mmol) was added. The reaction mixture was allowed to warm to 25° C. overnight. The mixture was poured into sat. NH4Cl solution (125 mL) and then extracted with diethyl ether (3×50 mL). The ether extracts were dried with MgSO4 and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica gel using 1:1 diethyl ether/pentane to yield a light yellow oil (3.17g, 23.3 mmol, 82.4%). 1H NMR (CDCl3): 6.09 (m, 1 H), 4.35 (s, 2 H), 2.07 (m, 4 H), 1.62-1.57 (m, 5 H). EI HRMS (m/e) called for (M+)(C9H12O) 136.0888, found 136.0894. To produce the particular compositions

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Anhydrous ZnCl2 (5.0 g, 37 mmol) was dissolved in TBF (25 mL) and the solution cooled to 0° C. in an ice bath. In another flask 1-ethynylcyclohexene (4.3 mL, 36.3 mmol) was dissolved in THF (25 mL), cooled to 0° C. in an ice bath, and treated with n-butyllithium (15.7 mL of a 2.2M solution in hexane, 34.5 mmol). After 20 minutes the cyclohexenylethynyllithium solution was added via cannula to the ZnCl2 solution. After an additional 20 minutes Pd(PPh3)4 (620 mg, 0.54 mmol) was added to the alkynylzinc solution. The resulting yellow solution was treated with chloroacetyl chloride (4.2 mL, 55 mmol) dropwise over 10 minutes. After 2 h at 0° C. the reaction mixture was quenched by the addition of saturated aqueous NH4Cl (500 mL), and diluted with ethyl acetate. The aqueous phase was extracted with ethyl acetate (3.times.200 ml) and the combined organic layers were washed with water (200 ml), brine (200 ml), dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo to afford a dark brown oil that was purified by column chromatography eluting with hexane, then 99:1 hexane:ethyl acetate to afford 1-chloro-4-(1-cyclohexen-1-yl)-3-buty-n-2-one (4.4 g, 67% yield) as an orange oil. 1H NMR (CDCl3, 300 MHz) Δ6.56 (m, 1H), 4.23 (s, 2H), 2.19 (m, 4H), 1.68-1.62 (m, 4H). MS (EI ionization) 182 (35Cl M+), 184 (37Cl M+). The material was carried on to the next step without further purification. cooled to 0° C. in an ice bath After 2 h at 0° C. the reaction mixture was quenched by the addition of saturated aqueous NH4Cl (500 mL) diluted with ethyl acetate The aqueous phase was extracted with ethyl acetate (3.times.200 ml) the combined organic layers were washed with water (200 ml), brine (200 ml) dried over Na2SO4 filtered The filtrate was concentrated in vacuo to afford a dark brown oil that was purified by column chromatography eluting with hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This product was prepared from toluene-4-sulfonic acid 4-trifluoromethoxy-phenyl ester and 1-ethynyl-cyclohexene following the general procedure for the Sonogashira cross-coupling process described above. Chromatography eluent: heptane; yield (110 mg, 83%); 1H NMR δ (CDCl3): 7.41 (d, J=8.38 Hz, 2H), 7.21 (d, J=8.37 Hz, 2H), 6.28 (m, 1H), 2.17 (dm, 4H), 1.63 (dm, 4H); LCMS m/z: 266. yield (110 mg, 83%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This product was prepared from toluene-4-sulfonic acid 4-trifluoromethoxy-phenyl ester and 1-ethynyl-cyclohexene following the general procedure for the Sonogashira cross-coupling process described above. Chromatography eluent: heptane; yield (110 mg, 83%); 1H NMR δ (CDCl3): 7.41 (d, J=8.38 Hz, 2H), 7.21 (d, J=8.37 Hz, 2H), 6.28 (m, 1H), 2.17 (dm, 4H), 1.63 (dm, 4H); LCMS m/z: 266. yield (110 mg, 83%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This product was prepared from toluene-4-sulfonic acid 4-formyl-phenyl ester and 1-ethynyl-cyclohexene following the general procedure for the Sonogashira cross-coupling process described above. Chromatography eluent: heptane/DCM 1:1; yield (71 mg, 68%); 1H NMR δ (CDCl3): 9.99 (s, 1H), 8.02 (d, J=8.51 Hz, 2H), 7.52 (d, J=8.60 Hz, 2H), 6.31-6.27 (m, 1H), 2.14-2.22 (m, 4H), 1.58-1.73 (m, 4H); LCMS m/z: 210. yield (71 mg, 68%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This product was prepared from toluene-4-sulfonic acid 3-trifluoromethyl-phenyl ester and 1-ethynyl-cyclohexene following the general procedure for the Sonogashira cross-coupling process described above. Chromatography eluent: heptane; yield (106 mg, 85%); 1H NMR δ (CDCl3): 7.68 (s, 1H), 7.6-7.7.49 (m, 2H), 7.46-7.37 (m, 1H), 6.28 (m, 1H), 2.31-2.12 (m, 4H), 1.73-1.57 (m, 4H); LCMS m/z: 250. yield (106 mg, 85%)