SU435237A1 - Method of producing 5-keto-5,6,7,8-tetrahydroquinoline derivatives - Google Patents

Description

one

The invention relates to a method for producing 5-keto-5,6,7,8-tetrahydroquinoline derivatives, namely 2-methyl- (or 2,7,7-trimethyl) 5-keto-5, 6,7,8-tetrahydroquinoline, which can be used in the synthesis of biologically active drugs.

A two-stage process for the preparation of 2-methyl-5-keto-5,6,7,8 - tetrahydroquinoline by the condensation of dihydroresorcinol with methyl vinyl ketone and the subsequent reaction of the formed triketone with ammonia is known. The disadvantages of this method are the duration (5 days) of the first stage, the reaction in the second stage under very severe conditions, for example, with prolonged (40 hours) heating at 150 ° C in an autoclave under high pressure, as well as relatively low (28%) tetrahydroquinoline ketone yield.

In order to simplify the production of tetrahydroquinoline ketone or its 7,7 dimethyl-substituted analogue, as well as to increase the yield of the target product by the proposed method, dihydroresorcin or dimedone is subjected to interaction with the calculated amount of ammonia rather than methyl vinyl ketone, which allows to obtain crystalline products with a yield of up to 90% for very short time (15-20 min). The second stage is condensation.

The resulting imipov with methyl vinyl ketone is carried out in an alcohol medium at 70-80 ° C for 7 hours. A mixture of tetrahydro and hexahydroquinoline ketones is formed, from which the tetrahydroquinoline ketone, as the lower boiling fraction, is easily separated by vacuum distillation. The yield of ketones is 37 and 52%, respectively.

Individuality of the compounds obtained

proved by physico-chemical methods and elemental analysis data. Example 1. Imin dihydroresorcinol. 140 g (2 mol) are poured into 207.17 g (1.85 mol) of dihydroresorcinol (mp 104-105 ° C)

24.5% aqueous ammonia solution. The mixture is very hot, and dihydroresorcinol is partially dissolved; complete dissolution of the substance occurs after heating for min. The water is then removed from the reaction mixture under vacuum created by a water jet pump, and the remaining yellow precipitate is washed with cold acetone. Obtain 184 g (89.6%) of the desired product in the form of a light yellow powder, so pl. 127-128 ° C.

Found,%: N 12.15, 12.23.

SbNDOY.

Calculated,%: N 12.60. Example 2. Imin Dimedone. Analogously to example 1 of 84 g (0.6 mol) of dimedone and 62 1 l of 25% ammonia after recrystallization of the residue from alcohol and ether, 72 g (86.3%) of imine dimedone are obtained, t. Pl. 163-164 ° C (from alcohol and ether). Found,%: N 9.96, 9.89. CgHisON. Calculated,%: N 10.06. Example 3. 2-Methyl-5-keto - 5,6,7,8-tetrahydroquinoline. A mixture of 184 g (1.65 mol) of imine dihydroresorcinol (mp. 127-128 ° C), 171.4 g (2.45. Mol) of methyl vinyl ketone and 500 ml of ethanol are heated with stirring at 75-77 ° C for 7 hour. Then ethanol was distilled off from the reaction mixture, and the residue was distilled in vacuo. 98.25 g (36.8%) of the desired product is obtained in the form of a colorless mobile liquid. -. T. kip J12-114 ° C / 2 mmHg Art., 1.500, df 1.1166. Found,%: C 74.27, 74.20; H 6.80, 6.71; N 8.23, 81.1.MRD 45.99. C.oHiiON. H 6.88; N 8.69. Calculated,%: C, 74.51; MRD 46.01. Ketone hydrochloride is obtained in quantitative yield in the form of small needles, so pl. 208-209 ° С (from alcohol). Found,%: N 6.70, 6.68. CioHiiON-HCl. Calculated,%: N 7.09. After distillation of the ketone obtained, a thick yellow liquid begins to be distilled, i.e. bale. 200-218 ° C / 2 mmHg Art. consisting essentially of 2-methyl-5-keto-hexahydroquinoline. The yield is 123.6 g (46.3%). Example 4. 2,7,7-Trimethyl-5-keto-5,6,7,8 tetrahydroquinoline. A mixture of 11.5 g (0.08 mol) of imine dimedone (mp. 163-164 ° C), 9.31 g (0.13 mol) of methyl vinyl ketone and 100 ml of ethanol with stirring is heated for 7 hours with 80 ° WITH. After removal of the solvent, the residue is distilled in vacuo. 8.21 g (52.5% of theory) of 2.7,7-trimethyl-5-keto-5,6,7,8-tetrahydrochipoline are obtained (ie, kit. 116-118 ° C / 2 mm Hg. Art. .) in the form of a yellowish liquid which, on standing, completely turns into crystals, m.p. 48-49 ° C. Found,%: C 76.06, 76.25; H 7.92, 8.07; N 7.12, 7.18. CisHisON. Calculated: 1%: C 76.15; H 7.99; N 7.39. Ketone hydrochloride is obtained in the form of white small crystals, t. Il. 231-232 ° C (from alcohol). The yield is 100%. Found,%: N 5.99, 5.80. CisHisON-HCl. Calculated,%: N6,20. The subject of the invention. A method for producing 5-keto5,6,7,8-tetrahydroquinoline derivatives using dihydroresorcinol, methyl vinyl ketone and ammonia, characterized in that, in order to simplify the process and increase the yield of the target product, dihydroresorin or dimedop are affected by ammonia with subsequent condensation. product with methyl vinyl ketone in an alcohol environment of 70-80 ° C alcohol and isolation of the target product by known methods.