SU914549A1 - Process for producing secondary amides - Google Patents

Description

The invention relates to organic chemistry, and more particularly to a method for producing secondary amides, which are used in the chemical and chemical-pharmaceutical industry.

A known method of producing secondary amides by the interaction of tertiary alcohol or ether with acetonitrile in the presence of acid in a solvent medium, followed by hydrolysis of the resulting product.

According to the known method, the process is conducted with an excess of nitrile in glacial acetic acid at room temperature for 20 hours in the presence of sulfuric acid (13.

The disadvantages of this method are the difficulty of regenerating the excess of the original nitrile and a large amount of acidic wastewater.

The purpose of the invention is to increase the efficiency of the process and the exclusion of acid * waste acid.

The goal is achieved by the method of producing secondary amides of the General formula

AYANSOK, O) where A is a tertiary hydrocarbon residue;

I - alkyl, possibly substituted, aryl, aralkyl, ^3_ pyridyl, · by the interaction of a tertiary alcohol or ether of the general formula

ΑΟΚφ, (II) · where A is indicated above;

hydrogen or acyl with nitrile of the general formula

NFM, (And I) where K is indicated above, in the presence of an acid and a solvent, followed by hydrolysis of the obtained product, according to which the process is carried out in the presence of trifluoroacetic acid, and the unreacted nitrile and trifluoroacetic acid are distilled off before the hydrolysis stage.

914549 4

In this case, trifluoroacetic acid also acts as a solvent.

As the tertiary alcohol or ester, 1-adamantanol or its alkyl derivatives or their esters can be used.

The process can be carried out at 50 “150 at atmospheric and overpressure.

The proposed method allows to obtain compounds that are widely used in medicine.

The method is easily feasible on an industrial scale, the target products are obtained in high yield and high purity,

Example 1. Ν- (1-adamantyl) acetamide.

A mixture of 12.0 g (0.079 M) of 1-adamantanol, 28.2 ml of trifluoroacetic acid and 16.5 ml of acetonitrile is boiled for 7 hours, and unreacted trifluoroacetic acid and acetonitrile are distilled off. 150 ml of ether and 50 ml of water are added to the residue. the organic layer was washed with saturated soda solution, water and dried over sodium sulfate. The ether is evaporated and get 12.9 g (85%) of the target product with so pl. 147-148 ° C. Literature data: so pl. 149 ° C (3), mp 148 ° C (6).

PRI me R 2. Ν- (1-adamantyl) acetamide. ...

A mixture of 4.5 g (0.018 M) of 1-adamantyl trifluoroacetate, 6 ml of trifluoroacetic acid and 3.5 ml of acetonitrile is refluxed for 12 hours and the reaction mixture is treated analogously to Example 1. 1.3 g of the expected product is obtained (38%) , mp 147-148 ° C.

The starting 1-adamantyl trifluoroacetate is prepared by reacting 1-adamantanol with trifluoroacetic anhydride in a yield of 92% _? t.kip. 122 ° C / 30 mmHg

Example). Ν- (G-adamantyl) acetamide.

A mixture of 1.0 g of 1-adamantanol,

1.88 ml of trifluoroacetic acid and 1.0 ml of acetonitrile is at room temperature overnight (yield 86% amide · GLC) followed reaktsi- ⁵⁵ onnuyu mixture was refluxed for 2 hours.

According to GLC, the yield of the target product is · 88%.

PRI me R 4. Ν- (1-adamantyl) benzamide.

A mixture of 5.0 g (0.033. M) of 1-adamantanol, 12 ml of trifluoroacetic acid and 15 ml of benzonitrile is held for 10 hours at 90-100 ° and the unreacted trifluoroacetic acid and benzonitrile are distilled off.

100 ml of ether 10 and 100 ml of water are added to the residue, the organic layer is washed with 10% potash solution and water. It is dried over sodium sulfate and the ether is evaporated. The rest of the residue is recrystallized from petroleum ether 15 and 6.0 g is obtained (. 79 ^ of the desired product with a melting point of 148-149 ° C. Literature data: 149150 ° C (4).

PRI me R 5 · Ν- (tert - butyl) acetamide.

A mixture of 4.85 g (0.065 P) of tert-butanol, 20 ml of trifluoroacetic acid and 14 ml of acetonitrile is maintained at 90-100 ° for 10 hours and treated analogously to example 4. After recrystallization from petroleum ether, 4.3 g (57 %) of the target product with 7.pl. 97 ~ 98 ° C. Literature data: 97 “98 ° С (2).

. P. p and me 6. Ethyl ether

Ν- (1-adamantyl) carboxamidoacetic acid.

A mixture of 5.0 g (0.033. M) of 1-adamantanol, 18.6 g of ethyl cyanoacetic acid and 17 ml of trifluoroacetic acid 35 is kept at 90-100 ° C for 12 hours and treated analogously to Example 1. After recrystallization from aqueous alcohol 6.1 g (70%) of the expected product are obtained with 40 mp. 103 ~ 104 ° C. Literature data: 103 -10 ° C (4).

PRI me R 7. (1- (1-Adamantyl) chloracegamide.

A mixture of 2.5 g (0.016 M) of 1-adamant45 nolau 6 ml of trifluoroacetic acid and 5.6 g of chloroacetonitrile is maintained at 80-90 ° for 10 hours and treated analogously to example 1. After recrystallization from aqueous alcohol 50, 3.1 g are obtained (83%) of the target product with so pl. 120-121 ° С. Literature data: so pl. 122 ° C (12).

Example 8. Ν-0-adamantyl) diethylamino-cetamide hydrochloride.

A mixture of 5.0 g (0.033 M) of 1-adamantanol, '18, 5 g of diethylaminoacetonitrile and 25 ml of trifluoroacetic acid is maintained at 90-100 ° С for 10 h.

and excess trifluoroacetic acid is distilled off. 100 ml of ether and 50 ml of water are added to the residue, a saturated potash solution is added until the reaction is very alkaline, and extracted with ether. 5 The ether extract is dried over sodium sulfate, the ether is evaporated, and the excess amount of the initial nitrile is distilled off from the residue in vacuo. The residue was dissolved in ether and an ethereal solution of hydrogen chloride was added until acidic. The precipitate formed is filtered off and crystallized from propanol (petroleum ether). Obtain 5.0 g (50%) of the target product with so pl. 208-209 ° C. Literature data: so pl. 205 “207 ° C (18).

Calculated,%: C 63.87; H 9.72; m 9.31. " C1 11.78.

0 ₁₆ ^Η 2 _θ Ν ₂ o no

Found,%: C 63.8; 63.9; H. 9.6;

9.7; N, 9.1 .; 9.2;

C1 11.8; 11.8.

, PRI me R 9 · M- (3,5 ^- dimethyl-1- /. Adamantyl) acetamide.

A mixture of 5.0 g (0.028 M) of 3,5 ^- dimethyl-1— -adamantanol, 7.5 ml of acetonitrile and 16 ml of trifluoroacetic acid is maintained at 90-100 ° C for 10 hours and treated analogously to example 4. After recrystallization from aqueous alcohol receive 5.1 g (85%) of the target product with so pl. 109 “1 ° C. Literature data: sublimation temperature 80-82 ° C (19). Calculated,%: C 75.97; H 10.4 ?;

N, 6.33.

С _1Ц Н _% Н0

Found,%: C 75.8; 75.7; H 10.7; 10.3; N, 6.4; 6.5.

Example. N- (1-adamantyl) phenylacetamide.

A mixture of 10.0 g (0.67 Μ) of 1-adamantanol, 30 g of benzyl cyanide and 30 mp * trifluoroacetic acid is maintained at 90-100 ° for 7 hours and treated analogously to example 4. After recrystallization from aqueous alcohol, 15.3 g (86%) of the target product 1 with so pl. 182-183 ° C. Literature data: 177-178.5 ° С (5), 184185 ° С (20).

Calculated,%: C 80.26; H, 8.61;

Ν_5 ^ 20. ^; 'C _{1 &} H, N0

Found,%: C 80.4; 80.4; H 8.5; . '8.7; N 5.3? 5,6.

PRI me R 11. Η- (1-adamantyl) nicotinamide.

A mixture of 1.67 g (0.011 M) of 1-adamantanol _g 3.4 g of nicotinic acid nitrile and 20 ml of trifluoroacetic acid is maintained at 90-100 * C for 15 hours, the excess trifluoroacetic acid is distilled off, 50 ml of water and 100 ml of benzene are added. saturated potash solution is poured to pH 9 and the aqueous layer is extracted with benzene. The benzene extract was dried, evaporated and the residue was recrystallized from a mixture of petroleum ether and ethanol. Obtain 1.6 g (56%) of the target product, so pl. 1b0 ~ 1b2 ° C.

An ethereal solution of hydrogen chloride is added to the ethereal solution of the base until acidic and the corresponding hydrochloride is obtained with mp 238-240 ° C. Literature data: so pl. base 1b4-1b7 ° C.

Calculated,%: N 9.56; C1 12.11.

C ₁₆ / y) _r 0, HC1

Found,%: N 9.8; 9.5; C1 12.1; 12.0.

Example 12. Ν- (1-adamantyl) ~ 3 ”(2-hydroxyethylamino) propioamide chloro, hydrate.

A mixture of 5.0 g (0.033 M) of 1-adamantanol, 20 ml of trifluoroacetic acid and 16.0 g of 3- (2-hydroxyethylamino) propionitrile is held for.

h at 100 ° C. Excess trifluoroacetic acid and nitrile are distilled off. 150 ml of ether and 100 ml of water are added to the residue, the organic layer is washed with a 10% potash solution, water and dried over anhydrous sodium sulfate. An ethereal solution of hydrogen chloride was added until acidic in methyl orange. The precipitate formed is filtered, and after recrystallization from isopropyl alcohol, 6.0 g (60%) of the expected product are obtained with mp. 147-149 ° C. Calculated,%: C 59 ·, 49; H 8.99; N.9.25.5 C1 11.71 * ^s 15- ⁿ 2nd ^m y ° C "C!

. Found,%: C 58.8; 58.9; H 9.0;

9.1; N, 9.2; 9.1;

C1 11.7; 11.6.

The proposed method allows you to re- ·, generate nitrile and acid and · · exclude acidic wastewater ..

Claims (3)

Claim 1. A method for producing secondary amides of the general formula I • ΑΝΗΟΟΚ, where A is a tertiary hydrocarbon residue; K is alkyl, possibly substituted, aryl, aralkyl, 3-pyridyl, by reacting tertiary alcohol 5 or an ester of general formula II A01C, where A is as defined above; hydrogen or acyl, with nitrile of the general formula III KSI, where K is indicated above, in the presence of acid in a solvent medium, followed by hydrolysis of the resulting product, characterized in that, in order to increase the efficiency of the process and eliminate acidic wastewater, as an acid and a solvent use trifluoroacetic acid and before 914549 8 by hydrolysis of the obtained reaction product, the unreacted nitrile and trifluoroacetic acid are removed. 2. The method of pop. 1, characterized in that 1-adamantanol or its alkyl derivatives or their esters are used as a tertiary alcohol or ester of the general formula II. 3. The method according to claims 1 and 2, characterized in that the process is carried out at 50-150 ° C.