SU1728214A1 - Method of 1-bromo-2-alkyl(aryl)cyclopropanes synthesis - Google Patents

Abstract

The invention relates to halo-substituted hydrocarbons, in particular, to a process for the preparation of 1-bromo-2-alkyl (aryl cyclopanes of the general formula Br n CH 2 CHR, where R is Cs-Se-alkyl, phenyl, benzyl, which are used in quality of synthons in organic synthesis. The goal is to increase the yield of the target product and simplify the technology. The goal is achieved by restoring the corresponding 1,1-dibromo-2-alkyl (aryl) cyclopropanes with diisobutyl aluminum hydride in the presence of tetrabutoxy titanate at room temperature and the molar ratio of reagents 1: 1.9-2.2: 0.01-0.02 in diethyl ether. Yield 95-98% (in the prototype 85-90%). Lowering the synthesis temperature to room temperature instead of heating to 80 ° C prototype. 1 table. E

Description

The invention relates to organic chemistry, specifically to a method for producing 1-bromo-2-alkyl (aryl) cyclopropanes, which are used as synthons in organic synthesis, are precursors of practically useful compounds, primarily with physiological activity.

Among cyclopropane-containing hydrocarbons, herbicides, fungicides, antifungals, as well as drugs with the properties of antidepressants, antispasmodics, and analgesics have been found.

A known method for producing monobromalkylcyclopropanes, based on the reduction reaction (obtained by Makosha from olefins and bromoform) with 1,1-dibromo-2-alkylcyclopropanes with tributyltin hydride (p-Viz5pN) with a yield of 70-85%. The method is carried out as follows. A mixture of 0.25 mol of p-VizPn and 0.25 mol of hemdibromide is heated in an argon atmosphere at 40 ° C for 4 h. After distillation, 0,, 213 mol (70-85%) of monobromoalkylcyclopropane is obtained.

The disadvantages of this method are the use of hard-to-reach tributyltin hydride, the high cost of imported tributyltin hydride, and the complex synthesis of the main reagent — tributyltinhydrideXJ

Yu

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Yes - with the use of expensive lithium aluminum hydride.

There is also known a method for producing bromeliccyclopropanes, based on the reduction reaction with zinc in methanol (Zn (MeOH) with a yield of 80-93%.

The method is carried out as follows. 65.38 g (1 mol) of zinc dust in 300 ml of methanol (MeOH) are placed in a flask, and 2.2 ml (0.01 mol) of concentrated HC are added. Then, at a temperature of 0 ° C, 0.25 mol of 1,1-dibromo-2,2-dimethylcyclopropane was added, stirred at 0 ° C for 2 hours. Excess Zn was filtered off, washed with MeOH, and added to the methanol solution. 200 ml of pentane, 500 ml of water are washed, the organic layer is washed with water, dried with CaCte, the solvent is distilled off, the residue is distilled and 30.2 g (80%) of 1-bromo-2,2-dimethylcyclopropane are obtained.

However, this method has the following disadvantages: a large (fourfold) excess of a reducing agent, the use of a poisonous solvent, methanol, the need to carry out the reaction while cooling to 0 ° C.

The closest to the present invention is a method based on the use of diisobutyl aluminum hydride (i-BuaAIH) for the reduction of hemdibromoalkyl- and hemdibromo-cyclopropanes in the presence of transition metal complexes in dioxane at 80 ° C in 4 hours to obtain a mixture of 1-bromo-2-alkyl (aryl) cyclopropane (10-15%) and alkyl (aryl) cyclopropane (85-90%). The method is carried out as follows. In a stream of argon, a mixture of 0.01 mol of 1,1-dibromo-2-hexylcyclopropane, 0.015 mol of i-BuaAIH, 0.16 mol (p-ViOKP in 25 ml of dioxane was heated at 80 ° С for 4 h in a thermostatically controlled reactor, decomposed with 30 ml of 10% HCI, extracted with diethyl ether, dried with sodium sulfate, the solvent was evaporated, distilled in vacuum, a mixture of 10% 1-bromo-2-hexylcyclopropane and 90% hexyl cyclopropane was obtained. Under similar treatment 1 , 1-dibromo-2-phenylcyclopropane gave a mixture of 15% 1-bromo-2-phenylcyclopropane and 85% phenylcyclopropane.

. BT / ri-Biiffl.Ti uI + I-BU ™ .Л / + w

VT80 dh., 95/0 ЈT

10-15% 85-90%

The disadvantages of this method are the low yield of the target product (10-15%), the need to carry out the reaction when heated to 80 ° C, the difficulty from MA-BT + C

dividing the products from the high boiling solvent; a complex, hardly separable mixture of the products obtained, requiring repeated distillation, which leads to losses of the target product,

The aim of the invention is to increase the yield of the target product and simplify the technology

This goal is achieved by the reaction of 1,1-dibromo-2-alkyl (aryl) cyclopropane (PC3N3Br) with diisobutylaluminium hydride (i-BuaAIH) in the presence of tetrabutoxytitanium (p-CIO)) in diethyl ether (EtaO) ) at room

temperature, with a molar ratio of reagents equal to 1: (1.9-2.2) :( 0.01-0.02). The yield of the target product 95-98%

9T

K + 2l-BuzAlHp

BTVDYuchv

95-98% 69% 31%

, CeHi3,, CgHig, PhCHa, Ph

Example 1, In a glass reactor,

equipped with a reflux condenser mounted on a magnetic stirrer, 2.84 g (10 mmol) of 1,1-dibrom-2-hexylcyclopropane, 0.034 g (0.1 mmol) are placed

(n-BuO) 4 Ti and 20 ml of diethyl ether. In a stream of argon, 2.84 g (20 mmol) of i-BuaAIH are added dropwise with stirring, stirred at room temperature for 3 hours. The resulting re-mass is decomposed by cooling with 10% hydrochloric acid, extracted with diethyl ether three times with 30 ml each time, the solvent is evaporated, distilled under vacuum to obtain 2.79 g (98%) of 1-bromo-2-hexylcyclopropane. Other examples confirming the method are listed in the table under the reaction conditions: 10 mmol of 1,1-dibromo-2-alkyl (aryl) cyclopropane, 20 ml of diethyl ether, 20 ° С, 3 h.

Claims (1)

Invention Formula 50 The method of obtaining 1-bromo-2-alkyl (aryl) cyclopropane of the general formula BrCHC% -CHR where R is C5-Cd-alkyl, phenyl, benzyl, by reducing the corresponding 1,1-dibromo-2-alkyl (aryl) cyclopropanes with diisobutyl aluminum hydride in the presence of tetrabutoxytitanium in an oxygen-containing organic solvent, characterized in that, in order to increase the yield of the target product and simplification of the technology, the process is carried out at room temperature and the molar ratio of reagents is 1: 1.9-2.2: 0.01-0.02 and diethyl ether is used as a solvent.