SU1120003A1 - Method of obtaining adamantilacetic acids - Google Patents

Abstract

A METHOD FOR OBTAINING ADAMANTULE ACID ACIDS using nitric acid by reacting a compound containing, in its structure, an adamantyl cycle with 1,1-dichloroethylene in a sulfuric acid medium at 5-15 seconds with subsequent release of the target product by planting in water, in order to reduce, of the byproducts of oxidation and the increase in the yield of adamantht-acetic acids, the initial adamantane-containing compound is pretreated with 98-100% nitric acid until complete dissolution at a molar ratio of the starting produk (A and that of nitric acid 1: 10-71 and a temperature of 25-30 C, the resulting mixture was vshivayut onto ice, the precipitate is separated and then subjected to sulfuric acid ob-: rabotke with 1,1-dichloroethylene of 00.

Description

The invention relates to the chemistry of organic polyhedra, specifically to an improved method for producing adamantylacetic acids used in the synthesis of biologically active substances, pesticides, polymeric materials with improved performance properties, such as {thermal stability, hydrophobic properties, thermal-oxidative stability, mechanical properties, and others. Known as the synthetic methods of adamantiluyuksusnyh acids from the hell man from halogenyl oxyadmantane with 1,1-dichlorostilane in sulfuric acid 5. However, the known methods are complex, multistage, based on hard-to-reach starting compounds this limits the possibilities of their use on a large scale. The closest to the invention in technical essence and the achieved result is the method of obtaining adamantylacetic acids by the interaction of compounds containing in their structure an adamantyl cycle with 1,1-dichloroethylene or a mixture of nitric and sulfuric acids or oleum at -5. The end products are planted in water. The yield of adamantyl acetic acid is 54-86% 16. However, the use of an acid mixture of the composition: 50% nitric acid, 98% sulfuric acid and 60% oleum, not only complicates the technological process, but also requires significant labor and time spent on its preparation. This acidic mixture is a strong oxidation of the body, since the derivatives of nitrogen in acidic media have a high redox potential, and therefore the yields of adamantylacetic acids are low and amounted to 5pot in some cases about 50%. This is due to the occurrence of side reactions of oxidation of both the initial and final products. It is known, for example, that under the action on 1-adamantyluxus nougo acid specified above acid 3–11 ° C, a mixture is obtained at –– hydroxyhydroxy oxidant oxidation with a yield of up to 40–45.2% 7J. Under similar conditions, 1-adyl mlntancarboxylic acid is converted into hydroxy derivative in about 40% yield. Formed hydroxypropoidic acids contain an OH group at a nodal (tertiary) atom, carbon, are capable of further chemical transformations in an acidic medium, reduce the yield and contaminate the desired reaction products. I Application in a known method as a raw material for hard-to-reach halogen-producing adamantane naturally limits its use on a large scale. The aim of the invention is to reduce the amount of oxidation by-products and increase the yield of adamantylacetic acids. The goal is achieved by the fact that according to the method of obtaining adamantylacetic acids by pretreatment of the starting adamantane-containing compounds with 98-100% nitric acid until they are completely dissolved at 25-30 ° C and the molar ratio of the raw material and nitric acid is 1: 10-71, followed by pouring the reaction mixture on ice, separating the precipitate that has formed, which is then reacted with 1,1-dichloroethylene in a medium of sulfuric acid at 5-15 ° C and spent on the desired product by planting in water. Distinctive features of the proposed method are the use of pretreatment of adamantane-containing compounds with 98-100% nitric acid until completely dissolved at 25-30 seconds and a molar ratio of the starting compound and nitric acid 1: 10-71 (i.e., until complete dissolution), with Then pouring the obtained reaction mass on ice, separating the precipitate that has formed, which is then subjected to a sulfuric acid treatment with 1,1-dichloroethylene, Thus, the oxidation side reactions are significantly reduced. However, although it is known that nitroesters of the adamantane series are successfully used in organic synthesis instead of the hard-to-reach hydroxy and halogen derivatives of adamantane, for example. in adamantylation reactions of aromatic compounds 8 for the synthesis of the antiviral drug midanthan C91 based on the ritter reaction, but in the reactions of adamantane and its derivatives with olefins of various systems and cycloalkenes in an acidic medium, the process proceeds with the formation of the corresponding adamantylamine, alkenylmethane, cyclic alkanes, cyclic alkenes, and the cycloalkenes in the acidic medium with the formation cycloalkenyladenthanes, but not the carboxylic acids of the adamantane range of the invention, for the first time discovered that adamantylnitrates, such as 1-hydroxyadamantane nitrate, 3-hydroxy-1-adamantanecarboxylic nitrate The notes nitrate. 3-hydroxy-1-adamantylacetic acid and 1,3-dioxyadamantane dinitrate, interact with 1,1-dichloroethylene in concentrated sulfuric acid, forming the corresponding adamantylacetic acids in high yields (90-95%). The structure of the synthesized acids was established by identification with known acid samples by analytical and spectral methods. The proposed method for the preparation of mantiluacetic acid ada is universal, since it allows the use of all adamantane-containing compounds capable of producing nitroesters when treated with nitric acid. This method successfully produces 1,3-adamantanediuceric acid from both adamantane itself. and from nitrate of 3-hydroxy-adamantylacetic acid. In Examples 1-4, the process — is conducted in a reactor flask equipped with a stirrer, a thermometer, a reflux condenser, and an addition funnel. Example 1. Getting 1-adamantylamine acid. To 45 ml of 98-100% (67.5 g) nitric acid was added 13.6 g of adamantane (molar ratio 10: 1) at such a rate that the reaction temperature did not exceed 2530 ° C. After the dissolution of the adamantate. the mixture was poured into ice. The precipitate was separated, dried on air and at 5-15 ° C was dissolved in 100 ml (184 g) of 98% concentrated sulfuric acid. 50 ml (62.5 g) of 151-dichloroethylene are added dropwise to the solution obtained at the same temperature for 1 hour. The reaction mixture is stirred for 0.5 hours and then consumed in ice water. The precipitated acid is filtered, rinsed with water and a slat. The yield of purified acid is 17.6 g (90.97 „). T; pl. 135-13bS (from hexane). Found.%: C 73.83, H 9.69. Calculated,%: C, 74.18; H, 9.33. Example 2. Getting 1,3-adamantylamine acid. To 300 ml of 98-100% (450 g) nitric acid, 35 g of 1-adamantylacetic acid (40: 1 molar ratio) are added at such a rate that the temperature of the reaction mixture does not exceed 25-30 ° C. After 1-adamantylacetic acid is dissolved, the mixture is poured into ice. The precipitate is separated, dried in air and at 5–15 ° C dissolved in 140 ml (257 g) of 98% concentrated sulfuric acid, and then 80 ml (100 g) of 1,1-dichloroethylene are added dropwise. The reaction mass is stirred for 0.5 h and poured into ice water. The precipitate formed is filtered off, washed with water and dried. The yield of purified acid is 43.5 g (94.6%). M.p. 235-236 C (from acetone). Found, I: C, 66.86; H, 7.79. Ls4 Vrtisleno,%: C 66.64, H 7.99. Example 3. Getting 1,3-adamantylamine acid. To 275 ml of 98-100% (412.5 g) nitric acid, 13.6 g of adamantane (molar ratio 65: 1) were added at 1015 ° C. The reaction mixture is stirred for 3 hours and poured onto ice. The precipitate is separated, dried in air and at 5-15 ° C, dissolved in 1600 ml (2944 g) of 98% concentrated sulfuric acid, and then 200 ml (250 g) of 1,1-dichloroethylene are added dropwise. The reaction mass is stirred for 1 h and poured into ice water. The precipitated acid is filtered off, washed with water and dried. The yield of purified acid is 22.7 g (90.4%). M.p. 235-236 C (from acetone). Found,%: C 66.36, H 8.13 SA, P4 Calculated,%: C 66.64, H 7.99. PRI me R 4. Preparation of 3-carboxy-1-adamantylacetic acid. To 300 ml of 98-100% (450 g) nitric acid, 18 g of 1-adamantylcarboxylic acid (71: 1 molar ratio) are added at such a rate that the temperature of the reaction mixture does not exceed 25-30 ° C. The mixture is stirred for 5 hours and drunk on ice. The precipitate formed is filtered, dried in air and dissolved in 200 ml (368 g) of 98% concentrated sulfuric acid, and then 60 ml (75 g) of 1,1-dichloroethylene are added dropwise. The reaction mixture is stirred for 1 h and drunk in ice water. The precipitated acid is filtered off, washed with water and dried. The yield of purified acid is 21.2 g

(93.2%). T.iin. 230-232 0 (smash, acetic acid).

Found,%: C 64.71, H 7.38

uh

Calculated,%: C 65.52, H 7.61.

The table shows the comparative data on the amount of by-products formed during the synthesis of adamantylacetic acids.

1-adamantylamine

acid

1,3-adamantyldiacetic acid

(from adamantan)

1,3-adamantyldiacetic acid

(from 1-anadmantilucetic acid)

3-Carboxy-1-admanedacetic acid

As can be seen from the table, the amount of by-products is lower by more than two times according to the proposed method, by the well-known one.

Thus, the use of the proposed method of obtaining acetic acid of acetic acids provides, in comparison with the known ones, the possibility of obtaining various adamantylacetic acids in higher yields without complicating the technology of their production 9 .1

9.6

5.4

6.8

Most importantly, with the presence of adamantane production, as well as the possibility of parallel use of intermediate nitroesters of the adamantane range (adamantylnitrates) for the synthesis of other adamantane-containing compounds, including intermediates for the production of such antiviral drugs as midantane and rimantadine, a cura-like dyadony.

Claims (1)

METHOD FOR PRODUCING ADAMANTILUXE ACIDS using nitric acid by reacting a compound containing an 'adamantyl cycle in its structure _? with 1,1-dichloroethylene in a sulfuric acid medium at 5-15 ° C, followed by precipitation of the target product by precipitation in water, characterized in that, in order to reduce the amount of oxidation by-products and increase the yield of adamantyl acetic acids, the initial adamantane-containing compound is pretreated with 98- 100% nitric acid _ until they are completely dissolved at a molar ratio of the starting product and nitric acid of 1: 10-71 and a temperature of 25-30 ° С, the resulting mixture is drunk on ice, the precipitate is separated and then subjected to sulfate tnoj ob-: rabotke with 1,1-dichloroethylene. eleven