RU2163591C2 - Method of synthesis of 1-adamantylaldehyde - Google Patents

Abstract

FIELD: organic chemistry, chemical technology. SUBSTANCE: invention relates to the field of synthesis of 1-adamantylaldehyde that can be used as a semiproduct for synthesis of functional adamantanes and biologically active substances also. Method involves the use of 1-adamantane carboxylic acid nitrile as the functional derivative that is reduced with product obtained by interaction of tin (II) chloride with hydrogen chloride in the presence of diethyl ether to yield 1-adamantylaldimine hexachlorostannic salt. The latter is treated with water excess to yield 1-adamantylaldehyde in the mole ratio of 1-adamantane carboxylic acid, tin chloride and diethyl ether = 1: (1.5-2.0): (6.2-7.0), respectively. EFFECT: simplified process, increased yield, absence of polymer in reaction products. 1 tbl, 8 ex

Description

 The invention relates to the field of synthesis of derivatives of adamantane, and in particular to a method for producing 1-adamantylaldehyde, which can be used as intermediates for the synthesis of functional adamantanes, as well as biologically active substances.

 A known method of producing 1-adamantylaldehyde by reduction of the acid chloride of 1-adamantanecarboxylic acid with lithium aluminum hydride in the presence of aziridine with a yield of 24%. Basically, a polymer product is obtained. (Netherlands patent N 6613232, 1967, Chem. Abst. 68, N 68538, 1968).

 There is also a known method for producing 1-adamantylaldehyde from 1-adamantylmethanol by oxidation with lead tetraacetate in a yield of 52%. (N.L.Dovgan, F.N. Stepanov "Abstracts of the 10th Ukrainian Republican Conference on Organic Chemistry". Kiev: Naukova Dumka, 1969, p. 79).

 1-Adamantylaldehyde is also obtained by dry distillation of a mixture of the Ca-salt of 1-adamantanecarboxylic acid with a large excess of formic acid calcium. The yield of crude product is 70%. The resulting aldehyde is purified through a bisulfite derivative (F.N. Stepanov, N.L. Dovgan, MLC No. 4, 277, 1968).

(AdCOO) ₂ Ca + (HCOO) ₂ Ca ---> 1-Ad-CHO
A common disadvantage of the considered methods for producing 1-adamantylaldehyde is the insufficiently high yield of the final product, most of the reaction products are the product of polymerization of 1-adamantylaldehyde. These factors reduce the effectiveness of methods for producing 1-adamantylaldehyde.

The closest solution to the claimed technical essence is a method for producing 1-adamantylaldehyde (USSR Author's Certificate N 438249 MKI C 07 C 47/44, 1977) by reacting adamantane with carbon monoxide in methylene chloride in the presence of aluminum chloride with a stepwise increase in the temperature of the reaction mixture from -10 ^o C to 25 ^o C for two hours. In the middle of the process, pentane is added to the reaction mixture before passing carbon monoxide. Aldehyde is distinguished by standard techniques of step extraction. Yield 1-AdCHO-75%.

 The described process has the following disadvantages: the complex composition of the reagents, the need for a temperature program, the difficult isolation of the reaction products, most of the reaction products are the product of the polymerization of 1-adamantylaldehyde, the yield of the target product is not high enough.

 The objective of the invention is to provide an effective method for the synthesis of 1-adamantylaldehyde.

 The technical result of the invention is to improve the processability of the process, increase yield, the absence of polymer in the reaction products.

 The presented technical result is achieved by the fact that, in the preparation of 1-adamantylaldehyde, the nitrile of 1-adamantanecarboxylic acid is used as a functional derivative, which is reduced by the product of the interaction of tin (II) chloride with hydrogen chloride in the presence of diethyl ether to obtain 1-adamantylaldehyme hexachloride salt, which is treated with excess water to obtain 1-adamantylaldehyde at a molar ratio of nitrile of 1-adamantanecarboxylic acid, tin chloride, diethyl ether 1: 1.5-2.0: 6, 2-7.0.

SnCl ₂ + 2HCl ---> H ₂ SnCl ₄ .

2AdCN + 2H ₂ SnCl ₄ + 2HCl ---> [AdCH = NH ₂ ] ₂ · SnCl ₆ + SnCl ₄ .

[AdCH = NH ₂ ] ₂ · SnCl ₆ + 2H ₂ O ---> 2AdCHO + SnCl ₄ + 2NH ₄ Cl.

 The use of 1-adamantanecarboxylic acid nitrile, which has a high reactivity, allows it to be reduced by the product of the interaction of tin (II) chloride with hydrogen chloride to obtain a hexachlorotin salt of 1-adamantyl aldimine, which is not prone to polymerization in the presence of an organic solvent, which increases the yield and purity of the final product. 1-Adamantylaldehyde is isolated in an aqueous medium, which avoids the rapid polymerization of 1-adamantylaldehyde, as a result of which the polymer is absent in the reaction products.

 The developed method allows to obtain 1-adamantylaldehyde with a high yield of 93-95%.

The selection of the indicated ratios of the reagents is due to the following:
- a decrease in the concentration of tin chloride below the indicated intervals leads to a decrease in the yield of the target product due to a decrease in the conversion of adamantanecarboxylic acid nitrile, and an increase in the concentration of tin chloride leads to an unjustified overspending of this reagent without leading to an increase in the yield of 1-adamantylaldehyde;
- a decrease in the concentration of diethyl ether leads to a decrease in the yield of 1-adamantylaldehyde, and an increase in the concentration of diethyl ether leads to an increase in the duration of the reaction.

 The analysis of the prior art by the applicant, including a search by patent and scientific sources of information, and the identification of sources containing information about analogues of the claimed invention, allowed to establish that the applicant did not find an analogue characterized by features identical to all the essential features of the claimed invention set forth in the claims.

 Therefore, the claimed invention meets the requirement of "novelty" under applicable law.

 To verify the conformity of the claimed invention to the requirement of "inventive step", the applicant conducted an additional search for known solutions in order to identify features that match the distinctive features of the claimed invention, the results of which show that the claimed invention does not explicitly follow from the prior art defined by the applicant, the influence of the transformation provided for by the essential features of the claimed invention on the achievement of a technical result is revealed.

 Therefore, the claimed invention meets the requirement of "inventive step" under applicable law.

The method is as follows: absolute diethyl ether and tin (II) chloride are sequentially loaded into the reactor. With stirring, the suspension is cooled to 0-5 ^o C and at this temperature saturated with hydrogen chloride until a true solution is formed. Without stopping stirring, 1-adamantanecarboxylic acid nitrile is added in portions, ensuring that the temperature of the reaction mass does not exceed 5 ^° C. After the addition of the total amount of nitrile, the reaction mass is stirred at a temperature of 0-5 ^° C for 2 hours, then kept without stirring for 20 hours at a temperature of 20-25 ^o C. During this time, precipitated 1-adamantyl aldimine hexachlorotannate. The aldimine salt is filtered off and treated with excess water at a temperature of 60 ^o C. In this case, 1-adamantyl aldimine is completely hydrolyzed to 1-adamantyl aldehyde. The suspension of the aldehyde in water is cooled to 20-25 ^o C, the precipitate is filtered off, washed with water and dried.

 The method is tested in laboratory conditions, the following are specific examples of the method.

 Example 1

40 ml (0.385 mol) of absolute diethyl ether, 17.6 g (0.093 mol) of tin (II) chloride are sequentially charged into a four-necked reactor equipped with a stirrer, a thermometer, a bubbler and a reflux condenser with a chlorine tube. With stirring, the suspension is cooled to 0 - 5 ^o C and at this temperature saturated with hydrogen chloride until a true solution is formed. Without stopping stirring, 10 g (0.062 mol) of adamantanecarboxylic acid nitrile are added in portions, ensuring that the temperature of the reaction mass does not exceed 5 ^° C. After the addition of the total amount of nitrile, the reaction mass is stirred at 0-5 ^° C for 2 hours, then kept without stirring for 20 hours at a temperature of 20-25 ^o C. During this time, 1-adamantyl aldimine hexachlorotin sulphate precipitates. The aldimine salt is filtered off and transferred to a glass with 200 ml of water. With stirring, the suspension is heated to 60 ^o C. In this case, 1-adamantylaldimine is completely hydrolyzed to 1-adamantylaldehyde. A suspension of the aldehyde in water is cooled to 20-25 ^° C, the precipitate is filtered off and washed twice with 20 ml of water, dried. The molar ratio of 1-AdCN: SnCl ₂ : (C ₂ H ₅ ) ₂ O = 1: 1.5: 6.2. The yield of 1-adamantylaldehyde is 9.5 g (93%). T _pl = 139-141 ^o C. Found,%: C 80.21; H 9.83; C ₁₁ H ₁₆ O. Calculated,%: C 80.48; H 9.75; C ₁₁ H ₁₆ O. IR spectrum (in liquid paraffin), cm ^-1 : 1728 (C = O), 1376 (CH).

 Example 2

40 ml (0.385 mol) of absolute diethyl ether, 18.8 g (0.099 mol) of tin (II) chloride are successively charged into a four-necked reactor equipped with a stirrer, thermometer, bubbler and reflux condenser with a calcium chloride tube. With stirring, the suspension is cooled to 0-5 ^o C and at this temperature saturated with hydrogen chloride until a true solution is formed. Without stopping the stirring, 10 g (0.062 mol) of adamantanecarboxylic acid nitrile are added in portions, ensuring that the temperature of the reaction mass does not exceed 5 ^° C. After the addition of the total amount of nitrile, the reaction mass is stirred at a temperature of 0-5 ^° C for 2 hours, then kept without stirring for 20 hours at a temperature of 20-25 ^o C. During this time, 1-adamantyl aldimine hexachlorotin sulphate precipitates. The aldimine salt is filtered off and transferred to a glass with 200 ml of water. With stirring, the suspension is heated to 60 ^o C. In this case, 1-adamantylaldimine is completely hydrolyzed to 1-adamantylaldehyde. A suspension of aldehyde in water is cooled to 20-25 ^o C, the precipitate is filtered off and washed twice with 20 ml of water, dried. The molar ratio of 1-AdCN: SnCl ₂ : (C ₂ H ₅ ) ₂ O = 1: 1.6: 6.2. The yield of 1-adamantylaldehyde was 9.6 g (94%).

 Example 3

40 ml (0.385 mol) of absolute diethyl ether 20.0 g (0.105 mol) of tin (II) chloride are successively charged into a four-necked reactor equipped with a stirrer, thermometer, bubbler and reflux condenser with a calcium chloride tube. With stirring, the suspension is cooled to 0-5 ^o C and at this temperature saturated with hydrogen chloride until a true solution is formed. Without stopping the stirring, 10 g (0.062 mol) of adamantanecarboxylic acid nitrile are added in portions, ensuring that the temperature of the reaction mass does not exceed 5 ^° C. After the addition of the total amount of nitrile, the reaction mass is stirred at a temperature of 0-5 ^° C for 2 hours, then kept without stirring for 20 hours at a temperature of 20-25 ^o C. During this time, 1-adamantyl aldimine hexachlorotin sulphate precipitates. The aldimine salt is filtered off and transferred to a glass with 200 ml of water. With stirring, the suspension is heated to 60 ^o C. In this case, 1-adamantylaldimine is completely hydrolyzed to 1-adamantylaldehyde. A suspension of aldehyde in water is cooled to 20-25 ^o C, the precipitate is filtered off and washed twice with 20 ml of water, dried. The molar ratio of 1-AdCN: SnCl ₂ : (C ₂ H ₅ ) ₂ O = 1: 1.7: 6.2. The yield of 1-adamantylaldehyde was 9.6 g (94%).

 Example 4

In a four-necked reactor equipped with a stirrer, a thermometer, a bubbler, and a reflux condenser with a calcium chloride tube, 40 ml (0.385 mol) of absolute diethyl ether of 21.2 g (0.112 mol) of tin (II) chloride are successively charged. With stirring, the suspension is cooled to 0-5 ^o C and at this temperature saturated with hydrogen chloride until a true solution is formed. Without stopping the stirring, 10 g (0.062 mol) of adamantanecarboxylic acid nitrile are added in portions, ensuring that the temperature of the reaction mass does not exceed 5 ^° C. After the addition of the total amount of nitrile, the reaction mass is stirred at a temperature of 0-5 ^° C for 2 hours, then kept without stirring for 20 hours at a temperature of 20-25 ^o C. During this time, 1-adamantyl aldimine hexachlorotin sulphate precipitates. The aldimine salt is filtered off and transferred to a glass with 200 ml of water. With stirring, the suspension is heated to 60 ^o C. In this case, 1-adamantylaldimine is completely hydrolyzed to 1-adamantylaldehyde. A suspension of aldehyde in water is cooled to 20-25 ^o C, the precipitate is filtered off and washed twice with 20 ml of water, dried. The molar ratio of 1-AdCN: SnCl ₂ : (C ₂ H ₅ ) ₂ O = 1: 1.9: 6.2. The yield of 1-adamantylaldehyde is 9.7 g (95%).

 Example 5

40 ml (0.385 mol) of absolute diethyl ether, 22.3 g (0.118 mol) of tin (II) chloride are successively charged into a four-necked reactor equipped with a stirrer, a thermometer, a bubbler and a reflux condenser with a calcium chloride tube. With stirring, the suspension is cooled to 0-5 ^o C and at this temperature saturated with hydrogen chloride until a true solution is formed. Without stopping the stirring, 10 g (0.062 mol) of adamantanecarboxylic acid nitrile are added in portions, ensuring that the temperature of the reaction mass does not exceed 5 ^° C. After the addition of the total amount of nitrile, the reaction mass is stirred at a temperature of 0-5 ^° C for 2 hours, then kept without stirring for 20 hours at a temperature of 20-25 ^o C. During this time, 1-adamantyl aldimine hexachlorotin sulphate precipitates. The aldimine salt is filtered off and transferred to a glass with 200 ml of water. With stirring, the suspension is heated to 60 ^o C. In this case, 1-adamantylaldimine is completely hydrolyzed to 1-adamantylaldehyde. A suspension of aldehyde in water is cooled to 20-25 ^o C, the precipitate is filtered off and washed twice with 20 ml of water, dried. The molar ratio of 1-AdCN: SnCl ₂ : (C ₂ H ₅ ) ₂ O = 1: 1.9: 6.2. The yield of 1-adamantylaldehyde is 9.7 g (95%).

 Example 6

40 ml (0.385 mol) of absolute diethyl ether, 23.5 g (0.124 mol) of tin (II) chloride are successively charged to a four-necked reactor equipped with a stirrer, thermometer, bubbler and reflux condenser with a calcium chloride tube. With stirring, the suspension is cooled to 0-5 ^o C and at this temperature saturated with hydrogen chloride until a true solution is formed. Without stopping the stirring, 10 g (0.062 mol) of adamantanecarboxylic acid nitrile are added in portions, ensuring that the temperature of the reaction mass does not exceed 5 ^° C. After the addition of the total amount of nitrile, the reaction mass is stirred at a temperature of 0-5 ^° C for 2 hours, then kept without stirring for 20 hours at a temperature of 20-25 ^o C. During this time, 1-adamantyl aldimine hexachlorotin sulphate precipitates. The aldimine salt is filtered off and transferred to a glass with 200 ml of water. With stirring, the suspension is heated to 60 ^o C. In this case, 1-adamantylaldimine is completely hydrolyzed to 1-adamantylaldehyde. A suspension of aldehyde in water is cooled to 20-25 ^o C, the precipitate is filtered off and washed twice with 20 ml of water, dried. The molar ratio of 1-AdCN: SnCl ₂ : (C ₂ H ₅ ) ₂ O = 1: 2.0: 6.2. The yield of 1-adamantylaldehyde is 9.7 g (95%).

 Example 7

42.5 ml (0.410 mol) of absolute diethyl ether, 22.3 g (0.118 mol) of tin (II) chloride are successively charged into a four-necked reactor equipped with a stirrer, thermometer, bubbler and reflux condenser with a calcium chloride tube. With stirring, the suspension is cooled to 0-5 ^o C and at this temperature saturated with hydrogen chloride until a true solution is formed. Without stopping the stirring, 10 g (0.062 mol) of adamantanecarboxylic acid nitrile are added in portions, ensuring that the temperature of the reaction mass does not exceed 5 ^° C. After the addition of the total amount of nitrile, the reaction mass is stirred at a temperature of 0-5 ^° C for 2 hours, then kept without stirring for 20 hours at a temperature of 20-25 ^o C. During this time, 1-adamantyl aldimine hexachlorotin sulphate precipitates. The aldimine salt is filtered off and transferred to a glass with 200 ml of water. With stirring, the suspension is heated to 60 ^o C. In this case, 1-adamantylaldimine is completely hydrolyzed to 1-adamantylaldehyde. A suspension of aldehyde in water is cooled to 20-25 ^o C, the precipitate is filtered off and washed twice with 20 ml of water, dried. The molar ratio of 1-AdCN: SnCl ₂ : (C ₂ H ₅ ) ₂ O = 1: 1.9: 6.6. The yield of 1-adamantylaldehyde is 9.7 g (95%).

 Example 8

45.0 ml (0.434 mol) of absolute diethyl ether, 22.3 g (0.118 mol) of tin (II) chloride are successively charged into a four-necked reactor equipped with a stirrer, a thermometer, a bubbler and a reflux condenser with a calcium chloride tube. With stirring, the suspension is cooled to 0-5 ^o C and at this temperature saturated with hydrogen chloride until a true solution is formed. Without stopping the stirring, 10 g (0.062 mol) of adamantanecarboxylic acid nitrile are added in portions, ensuring that the temperature of the reaction mass does not exceed 5 ^° C. After the addition of the total amount of nitrile, the reaction mass is stirred at a temperature of 0-5 ^° C for 2 hours, then kept without stirring for 20 hours at a temperature of 20-25 ^o C. During this time, 1-adamantyl aldimine hexachlorotin sulphate precipitates. The aldimine salt is filtered off and transferred to a glass with 200 ml of water. With stirring, the suspension is heated to 60 ^o C. In this case, 1-adamantylaldimine is completely hydrolyzed to 1-adamantylaldehyde. A suspension of aldehyde in water is cooled to 20-25 ^o C, the precipitate is filtered off and washed twice with 20 ml of water, dried. The molar ratio of 1-AdCN: SnCl ₂ : (C ₂ H ₅ ) ₂ O = 1: 1.9: 7.0. The yield of 1-adamantylaldehyde is 9.7 g (95%).

 Comparative characteristics of the proposed and known methods for producing 1-adamantylaldehyde are shown in table 1.

 As follows from the table, the proposed method has significant advantages over the prototype: higher manufacturability, higher yield, simpler methods for isolating the final product, the absence of polymer in the reaction products.

Thus, the above information indicates the fulfillment of the following set of conditions when using the claimed invention:
- a tool embodying the invention in its implementation, is intended for use in various sectors of the chemical and pharmaceutical industries;
- for the claimed invention in the form described in the claims, the possibility of its implementation using the methods 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 achieve the technical result.

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

Claims (1)

 A method of producing 1-adamantylaldehyde from functional derivatives of adamantane, characterized in that the functional derivative is nitrile 1-adamantanecarboxylic acid, which is reduced by the product of the interaction of tin chloride II with hydrogen chloride in the presence of diethyl ether to obtain the hexachloro tin salt of 1-adamantyl aldimine, which is treated with excess water to obtain 1-adamantylaldehyde at a molar ratio of nitrile of 1-adamantanecarboxylic acid, tin chloride, diethyl ether 1 : 1.5 - 2.0: 6.2 - 7.0.

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