The preparation method of 3-amino-2,4-dimethylthiophene
A technology of dimethylthiophene and dimethyltetrahydrothiophene, which is applied in the field of preparation of 3-amino-2,4-dimethylthiophene, can solve the problems of difficult industrial preparation, long steps and low yield, and achieve Easy operation, mild reaction conditions and high yield
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[0027] The preparation method of 3-amino-2,4-dimethylthiophene provided by the invention comprises the following steps,
[0028] 1) In the presence of an acid anhydride and a base, subjecting 2,5-dimethyl-3-thiadipic acid to cyclodecarboxylation to obtain 2,4-dimethyltetrahydrothiophene-3-one;
[0029] 2) Condensate 2,4-dimethyltetrahydrothiophene-3-one with hydroxylamine or its salt and then rearrange to obtain 3-amino-2,4-dimethylthiophene.
[0030] In the prior art, the ring closure is mainly carried out by heating 2,5-dimethyl-3-thiadipic acid in the presence of iron powder, iron acetate, barium hydroxide, tertiary amine, etc., but the yield of this step is low The maximum is only 70%, and the product purity is less than 95%, the operation is complicated, the reaction conditions are harsh, the by-products are many and difficult to handle, and it is difficult to realize industrial production. In contrast to this, the inventors of the present invention have found through in...
Embodiment 1
[0060] 1) Preparation of 2,5-dimethyl-3-thiadipic acid
[0061] Put 64g of sodium hydroxide and 260g of water into a 1000mL four-necked bottle, stir to dissolve and lower to room temperature (25°C). Slowly add 84.8g of thiolactic acid dropwise with violent exotherm, control the temperature of ice water to 20-25°C, and add 68.8g of 2-methacrylic acid dropwise after the drop. Heated to 104°C and refluxed for 6 hours. Transfer to 150mL concentrated hydrochloric acid, stir evenly at 35-40°C, and extract with dichloromethane twice with 200mL each time. First recover the solvent under normal pressure, and then remove the solvent under reduced pressure to obtain 2,5-dimethyl-3-thiadipic acid with a purity of 95% and a yield of 93%. Liquid mass ESI-MS: 193 (M+H) + .
[0062] 2) Preparation of 2,4-dimethyltetrahydrothiophene-3-one
[0063] Put 197.2g of 2,5-dimethyl-3-thiadipic acid prepared in step 1) into a 500mL four-neck bottle, 160mL of acetic anhydride and 40g of sodium acet...
Embodiment 2
[0067] 1) Preparation of 2,5-dimethyl-3-thiadipic acid
[0068] According to the method of step 1) of Example 1, the difference is that the extraction solvent is methyl tert-butyl ether, and 2,5-dimethyl-3-thiadipic acid is obtained in the same way with a purity of 93.45%. The rate is 88.5%. Liquid mass ESI-MS: 193 (M+H) + .
[0069] 2) Preparation of 2,4-dimethyltetrahydrothiophene-3-one
[0070] According to the method of step 2) of Example 1, the difference is that 2,5-dimethyl-3-thiadipic acid uses the 2,5-dimethyl-3- Thiadipic acid was similarly obtained to obtain 2,4-dimethyltetrahydrothiophen-3-one with a gas phase purity of 97% and a yield of 85%. Temperament EI-MS: 130(M) + .
[0071] 3) Preparation of 3-amino-2,4-dimethylthiophene
[0072] Put 52.9g of 2,4-dimethyltetrahydrothiophen-3-one prepared in step 2), 30.1g of hydroxylamine hydrochloride and 300mL of acetonitrile into a 500mL four-necked bottle, and react under reflux for 7 hours. After the reaction w...
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