oxacyclotridecan-2-one

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

Procedure: Cyclododecanone was treated with trifluoroacetic acid to form the lactone (Huisgen, R. et al., ibid), dodecanolid (yield 75%; bp 111°-115° C. at 8 mm). The lactone was hydrolyzed to form 12-hydroxydodecanoic acid (Smissman, E. et al., ibid) (yield 92%; mp 82°-4° C.). The hydroxy acid was converted to 12-bromododecanoic acid (VI) with 48% HBr in the presence of H2SO4 (Jocelyn, P. et al., ibid) (yield 88%; mp 52°-55° C.).

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

Procedure: Concentrated H2SO4 (0.2 mL) was added to a solution of oxacyclotridecan-2-one (850 mg, 4.3 mmol) in 20 mL of methanol and stirred for 1 day. Methanol was removed under reduced pressure and the aqueous residue was extracted with diethyl ether 3 times. The combined organic layers were washed with saturated NaHCO3, saturated NaCl, and then dried over MgSO4. The diethyl ether was removed under reduced pressure to yield 874 mg (88%) of 14c as a white solid. 1H-NMR (400 MHz, CDCl3, δH ppm): 3.65 (3H, s, CO2CH3), 3.63 (2H, t, 3JH—H=6.6 Hz, HO—CH2), 2.29 (2H, t, 3JH—H=7.6 Hz, CH2CO2), 1.50-1.66 (4H, m, 2CH2), 1.22-1.38 (14H, m, 7CH2). HRMS (EI): m/z calcd 231.1955 ([M+H]+, C13H27O3), found 231.1954 [M+H]+. Methanol was removed under reduced pressure the aqueous residue was extracted with diethyl ether 3 times The combined organic layers were washed with saturated NaHCO3, saturated NaCl dried over MgSO4 The diethyl ether was removed under reduced pressure

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

Procedure: Concentrated H2SO4 (0.2 mL) was added to a solution of oxacyclotridecan-2-one (850 mg, 4.3 mmol) in 20 mL of methanol and stirred for 1 day. Methanol was removed under reduced pressure and the aqueous residue was extracted with diethyl ether 3 times. The combined organic layers were washed with saturated NaHCO3, saturated NaCl, and then dried over MgSO4. The diethyl ether was removed under reduced pressure to yield 874 mg (88%) of 14c as a white solid. 1H-NMR (400 MHz, CDCl3, δH ppm): 3.65 (3H, s, CO2CH3), 3.63 (2H, t, 3JH—H=6.6 Hz, HO—CH2), 2.29 (2H, t, 3JH—H=7.6 Hz, CH2CO2), 1.50-1.66 (4H, m, 2CH2), 1.22-1.38 (14H, m, 7CH2). HRMS (EI): m/z calcd 231.1955 ([M+H]+, C13H27O3), found 231.1954 [M+H]+. Methanol was removed under reduced pressure the aqueous residue was extracted with diethyl ether 3 times The combined organic layers were washed with saturated NaHCO3, saturated NaCl dried over MgSO4 The diethyl ether was removed under reduced pressure

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

Procedure: Cyclododecanone was treated with trifluoroacetic acid to form the lactone (Huisgen, R. et al., ibid), dodecanolid (yield 75%; bp 111°-115° C. at 8 mm). The lactone was hydrolyzed to form 12-hydroxydodecanoic acid (Smissman, E. et al., ibid) (yield 92%; mp 82°-4° C.). The hydroxy acid was converted to 12-bromododecanoic acid (VI) with 48% HBr in the presence of H2SO4 (Jocelyn, P. et al., ibid) (yield 88%; mp 52°-55° C.).

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

Procedure: 16-Methyloctadecanoic acid was synthesized by the same operation, except that in the step (a) of the synthesis process for 14-methylhexadecanoic acid described above, 12-dodecanolide was changed to 15-pentadodecanolide, and in the step (b), 2-methylbutylmagnesium bromide was changed to sec-butylmagnesium bromide. Thus, 16-methyloctadecanoic add was obtained from 15-pentadodecanolide at a total yield of 84%. The purity was 95%. Thus, 16-methyloctadecanoic add

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

Procedure: 11.9 g (60.0 mmol) of 12-dodecanolide and 24.3 g (96.0 mmol, 1.6 equivalents) of a 32% (hydrogen bromide)/(acetic acid) solution were introduced into a 100-mL autoclave protected with Teflon (registered trademark), and the autoclave was purged with nitrogen and then sealed. The content in the autoclave was stirred with a magnetic stirrer for 16 hours by using an oil bath at 60° C. After cooling the mixture, 14 mL of water was added thereto, and the mixture was transferred into a separatory funnel by using 200 mL of hot hexane. The mixture was washed with ion-exchanged water, dried over magnesium sulfate, filtered, and crystallized from n-hexane. Thus, 14.4 g (yield: 86%) of 12-bromododecanoic acid was obtained. the autoclave was purged with nitrogen sealed at 60° C After cooling the mixture, 14 mL of water was added the mixture was transferred into a separatory funnel The mixture was washed with ion-exchanged water dried over magnesium sulfate filtered crystallized from n-hexane

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

Procedure: Concentrated H2SO4 (0.2 mL) was added to a solution of oxacyclotridecan-2-one (850 mg, 4.3 mmol) in 20 mL of methanol and stirred for 1 day. Methanol was removed under reduced pressure and the aqueous residue was extracted with diethyl ether 3 times. The combined organic layers were washed with saturated NaHCO3, saturated NaCl, and then dried over MgSO4. The diethyl ether was removed under reduced pressure to yield 874 mg (88%) of 14c as a white solid. 1H-NMR (400 MHz, CDCl3, δH ppm): 3.65 (3H, s, CO2CH3), 3.63 (2H, t, 3JH—H=6.6 Hz, HO—CH2), 2.29 (2H, t, 3JH—H=7.6 Hz, CH2CO2), 1.50-1.66 (4H, m, 2CH2), 1.22-1.38 (14H, m, 7CH2). HRMS (EI): m/z calcd 231.1955 ([M+H]+, C13H27O3), found 231.1954 [M+H]+. Methanol was removed under reduced pressure the aqueous residue was extracted with diethyl ether 3 times The combined organic layers were washed with saturated NaHCO3, saturated NaCl dried over MgSO4 The diethyl ether was removed under reduced pressure

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

Procedure: Cyclododecanone was treated with trifluoroacetic acid to form the lactone (Huisgen, R. et al., ibid), dodecanolid (yield 75%; bp 111°-115° C. at 8 mm). The lactone was hydrolyzed to form 12-hydroxydodecanoic acid (Smissman, E. et al., ibid) (yield 92%; mp 82°-4° C.). The hydroxy acid was converted to 12-bromododecanoic acid (VI) with 48% HBr in the presence of H2SO4 (Jocelyn, P. et al., ibid) (yield 88%; mp 52°-55° C.).