RU2309932C1 - Method for preparing adamantyl-containing aromatic compounds - Google Patents

Abstract

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of adamantyl-containing aromatic compounds of the general formula:

, wherein R¹ = R² = R³ = R⁴ means hydrogen atom (H); R⁵ means Ad (1); R¹ means -CH₃; R² = R³ = R⁵ means H; R⁴ means Ad (2); R¹ means -C₂H₅; R² = R³ = R⁵ means H; R⁴ means Ad (3); R¹ means i-C₃H₇; R² = R³ = R⁵ means H; R⁴ means Ad (4); R¹ = R² means -CH₃; R³ = R⁵ means H; R⁴ means Ad (5); R¹ = R³ means -CH₃; R² = R⁵ means H; R⁴ means Ad (6); R¹ = R⁴ means -CH₃; R² = R³ means H; R⁵ means Ad (7) that are intermediate products for synthesis of biologically active substances. Method involves adding aromatic compounds to a adamantine derivative wherein 1,3-dehydroadamantane is used as a adamantine derivative, and compounds chosen from the following order: benzene, toluene, ethylbenzene, isopropylbenzene (cumene), o-, m-, p-xylene are used as aromatic compounds in the mole ratio of reagents = 1:(2-4) in diethyl ether medium, at temperature 30-35°C, or in the parent aromatic compound medium at their boiling point (80-110°C) for 30 min, in the presence of catalytic amounts of sulfuric acid. Method provides preparing the claimed compounds with the high yield.

EFFECT: improved method of synthesis.

7 ex

Description

The invention relates to the chemistry of adamantane derivatives, and in particular to a new method for producing adamantyl-containing aromatic compounds of the general formula

where R ¹ = R ² = R ³ = R ⁴ = H, R ⁵ = Ad (1); R ¹ = CH ₃ , R ² = R ³ = R ⁵ = H, R ⁴ = Ad (2); R ¹ = C ₂ H ₅ , R ² = R ³ = R ⁵ = H, R ⁴ = Ad (3); R ¹ = iC ₃ H ₇ , R ² = R ³ = R ⁵ = H, R ⁴ = Ad (4); R ¹ = R ² = CH ₃ , R ³ = R ⁵ = H, R ⁴ = Ad (5); R ¹ = R ³ = CH ₃ , R ² = R ⁵ = H, R ⁴ = Ad (6); R ¹ = R ⁴ = CH ₃ , R ² = R ³ = H, R ⁵ = Ad (7),

which are intermediates for the synthesis of biologically active substances.

A known method for producing derivatives of adamantane-containing aromatic compounds, consisting in the interaction of halogenated adamantane and aromatic hydrocarbons or their derivatives in the presence of Lewis acids (N. Stetter, M. Schwartz, A. Hirschorn, Chem. Ber., 92, 1629 (1959).

The main disadvantage of this method is the difficulty of separating the obtained compounds from the catalyst and purification of the product. In addition, aluminum chloride is explosive when water enters.

There is a method for producing adamantyl-containing aromatic compounds based on hydroxy derivatives of adamantane in the presence of phosphoric anhydride followed by hydrogenation on alkaline nickel [L.A. Zosim, A.G. Yurchenko. JORH, vol. XVI, vol. 4 (1980)].

The disadvantages of this method are the relatively low yield of products (60%), leading to the loss of expensive raw materials, a multi-stage process, difficulties and losses during isolation.

Closest to the proposed invention is a method in which para- (adamantate-1-yl) isopropylbenzene is obtained by alkylation of isopropylbenzene with 1-bromadamantane, 1-hydroxyadamantane and adamantan-1-ol nitrate in the presence of protic and aprotic acids. The process was carried out in the bulk of the initial isopropylbenzene, the temperature ranged from 25 to 154 ° C (the boiling point of isopropylbenzene) (B.I. No, G.M.Butov, S.M. Ledenev, R.A. Zhulite // Basic organic synthesis and petrochemistry. - Yaroslavl, 1989. - Issue 25. - P.79-87; B.I. No, G.M.Butov, S.M. Ledenev // ZhORKh. - Volume 30. - Issue 2 - S.315-316).

The disadvantages of this method are multi-stage synthesis and relatively low yields (26-86%).

The objective of the invention is to develop a technologically advanced low-stage method for the synthesis of adamantyl-containing aromatic compounds, proceeding in high yield in the initial adamantane under mild conditions.

The technical result is the expansion of the arsenal of chemical compounds obtained in high yield, increasing the yield of the claimed compounds, reducing the reaction time and simplifying the production method.

The technical result is achieved in a new method for producing adamantyl-containing aromatic compounds of the General formula

where R ¹ = R ² = R ³ = R ⁴ = H, R ⁵ = Ad (1); R ¹ = CH ₃ , R ² = R ³ = R ⁵ = H, R ⁴ = Ad (2); R ¹ = C ₂ H ₅ , R ² = R ³ = R ⁵ = H, R ⁴ = Ad (3); R ¹ = iC ₃ H ₇ , R ² = R ³ = R ⁵ = H, R ⁴ = Ad (4); R ¹ = R ² = CH ₃ , R ³ = R ⁵ = H, R ⁴ = Ad (5); R ¹ = R ³ = CH ₃ , R ² = R ⁵ = H, R ⁴ = Ad (6); R ¹ = R ⁴ = CH ₃ , R ² = R ³ = H, R ⁵ = Ad (7),

which consists in adding aromatic compounds to the adamantane derivative, 1,3-dehydroadamantane being used as an adamantane derivative, and compounds from the series benzene, toluene, ethylbenzene, isopropylbenzene (cumene), o-, m-, p- are used as aromatic compounds xylene, with molar ratios of reactants equal to 1: (2-4), in diethyl ether at a temperature of 30-35 ° C or in the medium of the starting aromatic compound at a boiling point of 80-110 ° C for 30 min in the presence of catalytic amounts sulfuric acid .

The essence of the method is the catalytic reaction of the addition of 1,3-dehydroadamantane to a number of aromatic compounds:

where R ¹ = R ² = R ³ = R ⁴ = H, R ⁵ = Ad (1); R ¹ = CH ₃ , R ² = R ³ = R ⁵ = H, R ⁴ = Ad (2); R ¹ = C ₂ H ₅ , R ² = R ³ = R ⁵ = H, R ⁴ = Ad (3); R ¹ = iC ₃ H ₇ , R ² = R ³ = R ⁵ = H, R ⁴ = Ad (4); R ¹ = R ² = CH ₃ , R ³ = R ⁵ = H, R ⁴ = Ad (5); R ¹ = R ³ = CH ₃ , R ² = R ⁵ = H, R ⁴ = Ad (6); R ¹ = R ⁴ = CH ₃ , R ² = R ³ = H, R ⁵ = Ad (7).

The advantage of this method is a high yield (83-91%), a short reaction time (30 min), ease of isolation of products, and the possibility of obtaining almost any homologues of this series, many of which are intermediates for the synthesis of biologically active substances.

There are two ways to carry out the reaction.

The first is the interaction of 1,3-dehydroadamantane with an aromatic compound in an inert solvent (diethyl ether) in the presence of a catalyst (sulfuric acid), followed by neutralization of the reaction mass and distillation of the solvent. The reaction is carried out in an inert solvent if the boiling point of the aromatic compound exceeds 110 ° C. The reaction is carried out in diethyl ether at a temperature of 30-35 ° C.

The second is the interaction of 1,3-dehydroadamantane with an aromatic compound in the presence of a catalyst (sulfuric acid), followed by neutralization of the reaction mass and distillation of the excess aromatic component. The reaction is carried out in bulk aromatic compounds without solvent, which is possible if its boiling point does not exceed 110 ° C.

The reaction is carried out within 30 minutes By reducing the reaction time, a high yield of the main product is not achieved. The increase in the duration of the reaction is impractical and economically disadvantageous.

It was found that the optimal condition for the reaction of addition of aromatic compounds to 1,3-dehydroadamantane is its implementation with a molar ratio of 1,3-dehydroadamantane: aromatic compound 1: 2-4. A smaller excess led to a slight decrease in the yield of the target products. A further increase in the content of aromatic compounds did not affect the yield of the target products and was impractical.

The regenerated aromatic compound does not contain any impurities and is suitable for repeated similar synthesis. The synthesized compounds after distillation of the excess of the starting reagents are sent to the purification step.

The invention is illustrated by the following examples.

Example 1

(Adamant-1-yl) benzene.

The molar ratio of 1,3-dehydroadamantane and benzene is 1: 2.

To 4.68 g (0.06 mol) of benzene in the presence of 0.03 g (0.0003 mol) of sulfuric acid in a dry nitrogen atmosphere at room temperature, a solution of 4 g (0.0298 mol) of freshly hatched 1,3-dehydroadamantane 20 ml of benzene, the mixture is incubated for 30 minutes at a temperature of 80 ° C. At the end of the reaction, the mixture is neutralized with sodium carbonate, filtered off, excess benzene is distilled off. The product is isolated by recrystallization from alcohol.

Yield 5.65 g (89%); so pl. 82 ° C. Found,%: C 90.55; H, 9.41. C ₁₆ H ₂₀ . Calculated,%: C 90.51; H, 9.49. Mass spectrum, m / z (intensity): 212 (M ⁺ , 14%), 135 (Ad ⁺ , 100).

Example 2

4- (Adamantyl-1) toluene.

The molar ratio of 1,3-dehydroadamantane and toluene is 1: 2.

To 5.52 g (0.06 mol) of toluene in the presence of 0.03 g (0.0003 mol) of sulfuric acid in a dry nitrogen atmosphere at room temperature, a solution of 4 g (0.0298 mol) of freshly hatched 1,3-dehydroadamantane 20 ml of toluene, the mixture is incubated for 30 minutes at a temperature of 110 ° C. At the end of the reaction, the mixture is neutralized with sodium carbonate, filtered off, excess toluene is distilled off. The product is isolated by recrystallization from alcohol.

Yield 5.63 g (83%); so pl. 98-99 ° C. Found,%: C 90.28; H, 9.75. C ₁₇ H ₂₂ . Calculated,%: C 90.20; H, 9.80. PMR spectrum (δ, ppm): 1.70, 1.4, 2.03, 2.21, 6.9-7.18.

Example 3

4- (1-Adamantyl) ethylbenzene.

The molar ratio of 1,3-dehydroadamantane and ethylbenzene is 1: 2.

To 6.36 g (0.06 mol) of ethylbenzene in the presence of 0.03 g (0.0003 mol) of sulfuric acid in a dry nitrogen atmosphere at room temperature, a solution of 4 g (0.0298 mol) of freshly hatched 1,3-dehydroadamantane 20 ml of diethyl ether. The mixture is incubated for 30 minutes at a temperature of 30-35 ° C. At the end of the reaction, the mixture is neutralized with sodium carbonate, filtered off, the excess ether and ethylbenzene are distilled off. The product is isolated by recrystallization from alcohol.

Yield 6.34 g (87%). Found,%: C 90.01; H, 9.98. C ₁₈ H ₂₄ . Calculated,%: C 89.94; H, 10.06. PMR spectrum (δ, ppm): 1.24, 1.69, 1.87, 2.03, 2.60, 7.05-7.24.

Example 4

4- (1-Adamantyl) isopropylbenzene.

The molar ratio of 1,3-dehydroadamantane and isopropylbenzene is 1: 2.

To 7.21 g (0.06 mol) of isopropylbenzene in the presence of 0.03 g (0.0003 mol) of sulfuric acid in a dry nitrogen atmosphere at room temperature, a solution of 4 g (0.0298 mol) of freshly-digested 1,3-dehydroadamantane 20 ml of diethyl ether. The mixture is incubated for 30 minutes at a temperature of 30-35 ° C. At the end of the reaction, the mixture is neutralized with sodium carbonate, filtered off, excess ether and isopropylbenzene are distilled off. The product is isolated by distillation.

Yield 6.60 g (86%); so pl. 86 ° C; t.kip. 185 ° C (5 mmHg). Found,%: C 89.77; H, 10.25. C ₁₉ H ₂₆ . Calculated,%: C 89.70; H, 10.30. PMR spectrum (δ, ppm): 1.76, 1.88, 2.04; 7.04, 7.20; 1.10, 1.18, 2.68-2.92.

Example 5

4- (Adamant-1-yl) -o-xylene.

The molar ratio of 1,3-dehydroadamantane and o-xylene is 1: 4.

To 12.74 g (0.12 mol) of o-xylene in the presence of 0.03 g (0.0003 mol) of sulfuric acid in a dry nitrogen atmosphere at room temperature, a solution of 4 g (0.0298 mol) of freshly 1.3- dehydroadamantane in 20 ml of diethyl ether. The mixture is incubated for 30 minutes at a temperature of 30-35 ° C. At the end of the reaction, the mixture is neutralized with sodium carbonate, filtered off, excess ether and o-xylene are distilled off. The product is isolated by recrystallization from alcohol.

Yield 6.37 g (88%); so pl. 109-112 ° C. Found,%: C 90.03; H, 10.01. C ₁₈ H ₂₄ . Calculated,%: C 89.94; H, 10.06. PMR spectrum (δ, ppm): 1.68, 1.84, 2.03, 2.13, 2.20, 6.9-7.20.

Example 6

4- (Adamant-1-yl) -m-xylene.

The molar ratio of 1,3-dehydroadamantane and m-xylene is 1: 4.

To 12.74 g (0.12 mol) of m-xylene in the presence of 0.03 g (0.0003 mol) of sulfuric acid in a dry nitrogen atmosphere at room temperature, a solution of 4 g (0.0298 mol) of freshly 1.3- dehydroadamantane in 20 ml of diethyl ether. The mixture is incubated for 30 minutes at a temperature of 30-35 ° C. At the end of the reaction, the mixture is neutralized with sodium carbonate, filtered off, excess ether and m-xylene are distilled off. The product is isolated by recrystallization from alcohol.

Yield 6.22 g (86%); so pl. 108-110 ° C. Found,%: C 90.03; H, 10.01. C ₁₈ H ₂₄ . Calculated,%: C 89.94; H, 10.06. PMR spectrum (δ, ppm): 1.70, 1.82, 2.02, 2.15, 6.9-7.18.

Example 7

2- (Adamant-1-yl) -p-xylene.

The molar ratio of 1,3-dehydroadamantane and m-xylene is 1: 4.

To 12.74 g (0.12 mol) of p-xylene in the presence of 0.03 g (0.0003 mol) of sulfuric acid in a dry nitrogen atmosphere at room temperature, a solution of 4 g (0.0298 mol) of freshly 1.3- dehydroadamantane in 20 ml of diethyl ether. The mixture is incubated for 30 minutes at a temperature of 30-35 ° C. At the end of the reaction, the mixture was neutralized with sodium carbonate, filtered off, excess ether and p-xylene were distilled off. The product is isolated by recrystallization from alcohol.

Yield 6.30 g (88%).

Found,%: C 90.03; H, 10.01. C ₁₈ H ₂₄ . Calculated,%: C 89.94; H, 10.06. PMR spectrum (δ, ppm): 1.73, 1.88, 2.03, 2.35, 6.70-6.85.

Thus, the above information indicates the fulfillment of the following set of conditions when using the claimed invention:

- a tool embodying the claimed invention in its implementation, is intended for use in various industries;

- for the claimed invention in the form described in the independent clause of the claims below, the possibility of its implementation using the means and methods described above or known prior to the priority date is confirmed;

- a tool embodying the claimed invention in its implementation, is able to ensure the achievement of a technical result.

Therefore, the claimed invention meets the requirement of "industrial applicability".

findings

A new low-stage method for producing adamantyl-containing aromatic compounds and their derivatives has been developed, which allows to obtain compounds of the claimed structural formula with fairly high yields. The structure of the obtained compounds was confirmed by PMR spectroscopy and elemental analysis.

Claims (1)

The method of obtaining adamantyl-containing aromatic compounds of General formula

where R ¹ = R ² = R ³ = R ⁴ = H, R ⁵ = Ad (1); R ¹ = CH ₃ , R ² = R ³ = R ⁵ = H, R ⁴ = Ad (2); R ¹ = C ₂ H ₅ , R ² = R ³ = R ⁵ = H, R ⁴ = Ad (3); R ¹ = iC ₃ H ₇ , R ² = R ³ = R ⁵ = H, R ⁴ = Ad (4); R ¹ = R ² = CH ₃ , R ³ = R ⁵ = H, R ⁴ = Ad (5); R ¹ = R ³ = CH ₃ , R ² = R ⁵ = H, R ⁴ = Ad (6); R ¹ = R ⁴ = CH ₃ , R ² = R ³ = H, R ⁵ = Ad (7), consisting in joining aromatic compounds to an adamantane derivative, characterized in that 1,3-dehydroadamantane is used as an adamantane derivative, and compounds from the series: benzene, toluene, ethylbenzene, isopropylbenzene (cumene), o-, m- are used as aromatic compounds , n-xylene, at molar ratios of reagents equal to 1: (2-4) in diethyl ether at a temperature of 30-35 ° C or in the medium of the starting aromatic compound at a boiling point of 80-110 ° C for 30 min in the presence of catalytic amounts of sulfuric isloty.