SU1131871A1 - Process for preparing amides of adamantane carboxylic acids - Google Patents

Abstract

METHOD OF OBTAINING AMIDES OF ADAMANTANKARBONIC ACIDS of general formula O 0, # WHERE, S tm .. H bond, CH2 5 interaction of corresponding carboxylic acids adamantane with acetamide during boiling of the reaction medium, which is different (in order to increase the yield of the target products , the process is carried out in the presence of manganese acetate as a catalyst with a molar ratio of the starting acid: catalyst 1: (O, 027-0.278).

Description

The invention relates to organic synthesis, specifically to an improved method for the preparation of amides, adamantanecarboxylic acids of the general formula: WHERE, Gf bH 2 R BOND, CH 2 which are used as pharmaceuticals, and also as intermediates for. synthesis of biologically active substances, plasticizers, polymers There is a known method for producing carboxylic acid amides by thermal dehydration of the ammonium salts of the corresponding acids i. This method is ineffective for adamantane derivatives due to the fact that when heated to 200 s, the reaction practically does not proceed, and at higher temperatures destroys with adamantane nuclei ;. A known method for producing carboxylic acid amides by reacting carboxylic acids with a chlorinating agent, such as thionyl chloride or phosphorus pentachloride, and the subsequent treatment of the resulting acid chloride with ammonia 2. The disadvantage of this method is the use of highly toxic and fire dangerous products such as thionyl chloride, tetrahydrofuran. In addition, carboxylic acid chlorides are highly toxic and decompose when heated in the presence of moisture. The closest to the proposed technical essence and the achieved result is a single-stage method of producing amides-adamantane-1-carboxylic acids, which involve the interaction of adamantane-1 carboxylic acids with an excess of acetames and at the boiling point after last (216 seconds) for 5 hours. Adamantane-1-carboxylic acid amide is 63-69% 3j. The disadvantage of this method of obtaining amides of adamantanecarboxylic acids is a relatively low yield of the target products, which is significant, since the cost of the starting adamantane-containing compounds is rather high. Therefore, increasing the yields in the reactions for the preparation of adamantane derivatives, in particular, amides of adamantanecarboxylic acids, is an important task. The aim of the invention is to increase the yield of the target products - amides of adamantanecarboxylic acids. The goal is achieved by the method of obtaining the amides of adamantanecarboxylic acids of the general formula. WHERE, its SNGC K bond, W., by the interaction of the corresponding carboxylic acids adamantane with acetamide in the presence of manganese acetate as a catalyst at a molar ratio of the starting acid: catalyst 1: (0.027-0.278). According to the proposed method, the yield of amides of adamantanecarboxylic acids reaches 75-97%, depending on the chemical nature of the starting adamantanecarboxylic acid. With both less and more than the specified amount of catalyst in the reaction mixture, the yield of the target products practically does not increase. In comparison with the known method 3j, where the yield of the amide of adamantane-1-carboxylic acid is 65%, the same amide under similar conditions (temperature, time, reagent ratio, but in the presence of manganese acetate in an amount of 0.098 mol per 1 mole of the starting acid is obtained with 87% yield (Table 1). The table shows the comparison of the known and proposed methods for the preparation of amides of adamantanecarboxylic acids in the interaction of acetamide with carboxylic acids of the adamantane series, the synthesis time is 5 hours, the temperature is 216 ° C. mono- or diamides and adamantanecarboxylic acids differ stage isolation of the final products. As mono- and diamides adamantankarbonovyk acids synthesized by reacting m-1zbytka

acetamide with the corresponding adamantanecarboxylic acid in the presence of manganese acetate as a catalyst. All reagents are refluxed into the reactor. The reaction mixture is heated to the boiling point of acetamide (216 ° C) and held under these conditions for 5 hours. Then, in the case of monoamides, the reaction mixture after cooling to 80 ° C is poured into a cold alkali solution. In this case, acetamide and unreacted acid goes into solution, and the amide adamantanecarboxylic acid precipitates the unreacted acid from the alkaline solution upon acidification, and the amide of adamantanecarboxylic acid is recrystallized from ethanol.

In the case of diamonds of the adamantine, the desired products are isolated as follows: after the reaction of the adamantane-containing diacid with acetamide in the presence of manganese acetate, the excess of acetamide is distilled off under vacuum, and the distillation residue is recrystallized from acetone / water (1,3-dicarboxymethyladanamine dylamide water diamide 1,3 dicarboxyadmanthan.

Example. Synthesis of amide 1 carboxymethyladamantane.

30 g (o, 154 mol) 1-carboxymethyl-. adamantane, 120 g (2.03 mol) of dry acetamide and 1 g (0.00408 mol of acetic acid manganese kilt t 5 h in a 250 ml reactor under reflux at 216 ° C. After cooling, not less than 80 ° C is poured into stirring 1.2 g of potassium hydroxide solution. After stirring the resulting suspension for 1 h, the precipitate is filtered, washed with water, dried and reprecipitated from etapol to water to give 2 g of 1-carboxymethyladamantane amide, 77% yield.

Upon acidification of the aqueous base solution, after separation of the amide precipitate, 7 g of the starting 1-cyboxymethyladamantane is released. Melting point of amide of I-carboxy-admantane is 180-181 ° C.

S ,, ,,, ЫО

Calculated,%: C 74.62; H 9.84; N 7.25.

Found,%: C 74.42; H 9.84; N 7.25.

PRI mme R 2. Synthesis of amide 1 carboxymethyladamantane. ,

: 30 g of 0.154 mol of 1-carboxymethyladamantane, 120, 03 mol) of dry acetamide and 4 g (0.0133 mol) of manganese acetate are boiled for 5 hours in a 250 ml reactor with reverse coolant at. Analogously as in Example 1. 29 g of 1-carboxymethyladamantane amide are obtained, yield 96% and 1 g of the starting 1-carboxymethyladamantane.

5 Example. Synthesis of 1-carboxymethyladamantane amide.

30 g (0.154 mol) of 1-carboxymethyl-adamantane, 120 g (2.03. Mol) of dry acetamide. -5 g (0.0204 mol) of acetate

0 manganese is boiled for 5 hours in the reactor

volume of 250 ml under reflux at 216 C. Allocated analogously to example 1. 25 g of amide 1carboxymethyladamantane are obtained, yield 97%

5 and 3 g of the original 1-carboxymethyladamantane,

PRI me R 4. Synthesis of 1,3-dicarboxy-admantane diamide.

30 g (o, 118 mol) of 1,3-dicarboxy-adamptan, 120 g (2.03 mol) of dry .acetamnda and 8 g (0.0326) mol of manganese acetate are boiled for 5 hours in a 250 ml reactor with a reflux condenser at 216 C. Then, under a vacuum of distillation, an excess of acetamide, and the VAT residue is recrystallized from a mixture of ethanol and water. The yield of diamide 1, 3-dicarboxy amide of 22.4 g (75%). 255-256 ° C.

Calculated,%: C, 64.86; .H, 8.11;

N 12.61.

Cl2 "lftN202

Found,%: C 64.58; H 8.03; N 1, .51.

PRI me R 5. Synthesis of 1,3-d11 carboxymethyladamantane diamide.

30 g (0.134 mol) 1,3-dicarboxymethyladamantane, 120 g (2.03 mol)

dry acetamide and 8 g of 0.0326 mol of manganese acetate are boiled in a 250 ml reactor under reflux at 216 C for 5 h, then the excess acetamide is distilled off under vacuum, and the distillation residue is recrystallized from acetone / water. The yield of 1,3-dicarboxymethyladamant diamide is 25.9 g (87%). M.p. 169-170s.

five

Calculated,%: C, 67.20; H 8.80; N 11.20.

Found,%: C 67,12; H 8.76; N 10.72.

PRI me R 6. Synthesis of amide Icarboxyamide.

30 g (0.166 mol) of 1-carboxy-adamantane 60 g (|, 015 mol) of dry acetamide and i g / 0.0163 mol) of manganese acetate are boiled for 5 hours in a 150 ml reactor under reflux at 216 C. In a similar way at 311816

measure I. Obtain 26.5 g of amide Icarboxyadamantane, yield 87%, and 1 g of the starting 1-carboxy-malemantane. M.p. 180-181 0.

5 Calculated,%: C 73.74; H 9.50; N 7.82.

C H,; NO.

Found,%: C73.54; H 9.32; At 7.58. ten

Thus, the proposed

way let u get targeted

products with a higher yield.

Claims (1)

METHOD FOR PRODUCING ADAMANTANCARBOXYLIC ACID AMIDES of general formula Λ jO-RC ^ °. / x7 ing WHERE x = n, s <, sn ₂ sC; ΝΗβ R = CBfl3b, CH2> by the interaction of the corresponding carboxylic acids of adamantane with acetamide when the reaction medium is boiling, characterized in that, in order to increase the yield of the target products, the process is carried out in the presence of manganese acetate as a catalyst at a molar ratio of the initial acid: catalyst 1 : (0.027-0.278). S_U 0,, 1131871> 1 and 31871