3-methylbut-2-en-1-ol

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: Although the direct conversion of dimethylallyl diphosphate to isoprene by isoprene synthase enzymes is known in the art, we have shown that isoprene can also be produced from two different alcohols, 3-methyl-2-buten-1-ol and 2-methyl-3-buten-2-ol, using linalool dehydratase-isomerase (see Example 1 and Example 2 and FIGS. 6 and 8), an enzyme isolated from Castellaniella defragrans strain 65Phen. The linalool dehydratase isomerase permits the development of novel isoprene biosynthetic pathways of either two or three steps. In a two-step isoprene biosynthetic pathway, dimethylallyl diphosphate is converted to 2-methyl-3-buten-2-ol by an enzyme such as a 2-methyl-3-buten-2-ol synthase, followed by conversion of 2-methyl-3-buten-2-ol to isoprene. In a three-step isoprene biosynthetic pathway, dimethylallyl diphosphate is converted to 3-methyl-2-buten-1-ol by either a phosphatase or a terpene synthase capable of converting dimethylallyl diphosphate to 3-methyl-2-buten-1-ol, 3-methyl-2-buten-1-ol is converted to 2-methyl-3-buten-2-ol by a 2-methyl-3-buten-2-ol isomerase, and 2-methyl-3-buten-2-ol is converted to isoprene by a 2-methyl-3-buten-2-ol dehydratase. As demonstrated in Example 1 and Example 2, the Castellaniella defragrans linalool dehydratase-isomerase functions as both a 2-methyl-3-buten-2-ol isomerase and a 2-methyl-3-buten-2-ol dehydratase.

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

Procedure: Although the direct conversion of dimethylallyl diphosphate to isoprene by isoprene synthase enzymes is known in the art, we have shown that isoprene can also be produced from two different alcohols, 3-methyl-2-buten-1-ol and 2-methyl-3-buten-2-ol, using linalool dehydratase-isomerase (see Example 1 and Example 2 and FIGS. 6 and 8), an enzyme isolated from Castellaniella defragrans strain 65Phen. The linalool dehydratase isomerase permits the development of novel isoprene biosynthetic pathways of either two or three steps. In a two-step isoprene biosynthetic pathway, dimethylallyl diphosphate is converted to 2-methyl-3-buten-2-ol by an enzyme such as a 2-methyl-3-buten-2-ol synthase, followed by conversion of 2-methyl-3-buten-2-ol to isoprene. In a three-step isoprene biosynthetic pathway, dimethylallyl diphosphate is converted to 3-methyl-2-buten-1-ol by either a phosphatase or a terpene synthase capable of converting dimethylallyl diphosphate to 3-methyl-2-buten-1-ol, 3-methyl-2-buten-1-ol is converted to 2-methyl-3-buten-2-ol by a 2-methyl-3-buten-2-ol isomerase, and 2-methyl-3-buten-2-ol is converted to isoprene by a 2-methyl-3-buten-2-ol dehydratase. As demonstrated in Example 1 and Example 2, the Castellaniella defragrans linalool dehydratase-isomerase functions as both a 2-methyl-3-buten-2-ol isomerase and a 2-methyl-3-buten-2-ol dehydratase.

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

Procedure: A 1-liter flask was charged with 43.9 g (0.51 mol) of 3-methyl-2-buten-1-ol, 51.6 g (0.51 mol) of triethylamine and 300 ml of dichloromethane, and the mixture was cooled down to 0° C. While stirring the mixture at 0° C., 45.3 g (0.50 mol) of acryloyl chloride were added dropwise over 1 hour, and the mixture was stirred additionally for 5 hours at room temperature. Solids were separated by filtration from the resultant reaction mixture, and the filtrate was washed 3 times with water and then distilled in the presence of 5 g of p-methoxyphenol to obtain 50.5 g of 3-methyl-2-butenyl acrylate. the mixture was stirred additionally for 5 hours at room temperature Solids were separated by filtration from the resultant reaction mixture the filtrate was washed 3 times with water distilled in the presence of 5 g of p-methoxyphenol

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

Procedure: The title compound was prepared according to the method of Example 335, substituting 2-(4-fluorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 2-(3-chlorophenyl)-4-tosyloxy-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone and substituting 3-methyl-2-buten-1-ol in place of isobutanol (yield: 0.1284 g, 88%). mp 128-132° C. 1H NMR (300 MHz, DMSO d6) δ 1.58 (s, 3H), 1.67 (s, 3H), 3.30 (s, 3H), 4.95 (d, J=7 Hz, 2H), 5.31 (m, 1H), 7.38 (m, 2H), 7.65 (m, 2H), 7.89 (m, 2H), 8.06 (m, 2H), 8.18 (s, 1H). MS (DCI/NH3) m/z 429 (M+H)+, 446 (M+NH4)+. Anal calc. for C22H21FN2O4S: C, 61.67; H, 4.94; N, 6.54. Found: C, 61.41; H, 4.95; N, 6.47.

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

Procedure: A mixture of 3-methyl-2-buten-1-ol (21.2 g, 0.25 mole) and anhydrous sodium acetate (0.1 g) was cooled to 0°. Diketene (36 ml, 0.3 mole) was added dropwise over a period of 1.5 to 2 hours. The reaction mixture was then heated to 75°-80°, and this temperature was maintained for one hour. The mixture was diluted with ether. The ethereal solution was washed successively with aqueous 1N hydrochloric acid, saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride, and then dried over magnesium sulfate. The ether was evaporated, leaving a residue which was distilled under vacuum, affording 3-methyl-2-butenyl acetoacetate (32.1 g, 76% yield); bp 114°-117°/18-19 mm. was cooled to 0° The reaction mixture was then heated to 75°-80° this temperature was maintained for one hour The ethereal solution was washed successively with aqueous 1N hydrochloric acid, saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride dried over magnesium sulfate The ether was evaporated leaving a residue which was distilled under vacuum

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

Procedure: A mixture of 4.3 g of 3-methyl-2-buten-1-ol and 16.2 g of ethyl orthoacetate was heated with stirring. The temperature was raised slowly over 2 hours to 120°, during which time 1.8 g of ethanol was evolved and removed. Heating was continued at 120° for 30 minutes and the reaction mixture was then distilled to give, after removal of 8.5 g of unreacted ethyl orthoacetate (b.p. 50°-65°/57 mm), 4.25 g of 1,1-diethoxy-1-(3-methyl-2-buten-1-yloxy)ethane, b.p. 75°-76°/6 mm. was heated removed Heating the reaction mixture was then distilled to give after removal of 8.5 g of unreacted ethyl orthoacetate (b.p. 50°-65°/57 mm), 4.25 g of 1,1-diethoxy-1-(3-methyl-2-buten-1-yloxy)ethane, b.p. 75°-76°/6 mm

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

Procedure: A mixture of 4.3 g of 3-methyl-2-buten-1-ol and 8.1 g of ethyl orthoacetate was heated with stirring. The temperature was increased slowly from room temperature to 165° over 2 hours, during which 2.21 g of ethanol was collected. The temperature was maintained at 165° for 26 hours, during which time an additional 1.52 g of ethanol was collected. The reaction mixture was then allowed to cool and diluted with diethyl ether. The ether solution was washed successively with dilute hydrochloric acid, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. The washed solution was dried over magnesium sulfate and distilled to give 4.03 g (52% yield) of ethyl 3,3-dimethyl-4-pentenoate, b.p. 80°-85°/52 mm. was heated was collected The temperature was maintained at 165° for 26 hours, during which time an additional 1.52 g of ethanol was collected to cool diluted with diethyl ether The ether solution was washed successively with dilute hydrochloric acid, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride The washed solution was dried over magnesium sulfate distilled