RU2330013C1 - Method of obtaining adamantyl containing derivatives of 1,4-diketones - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to the method of obtaining new adamantly containing derivatives of symmetric 1,4-diketones with the general formula:

where R₁=H or CH₃,

R₁-H or CH₃, which are potentially biologically active materials. The method consists of connecting to 1,3-dehydroadamantan or 5,7-dimethyl-1,3-dehydroadamantan symmetrical 1,4-diketone: 2,5-hexanedione or 1,4-cyclohexanedione with their molar relation equal to 1:1 at the temperature of 80°C for a period of 5 hours.

EFFECT: it makes it possible to obtain new compounds with a high output.

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Description

The invention relates to the chemistry of adamantane derivatives, and in particular to a new method for producing adamantyl-containing derivatives of symmetric 1,4-diketones of the general formula:

where R ₁ = N or CH ₃ ,

R ₁ = H or CH ₃ ,

which are potentially biologically active substances.

A known method of producing adamantyl-containing β-diketones [RF Patent No. 2187493 C07C 49/15, 49/792, 45/45, 45/61, C07D 307/46, 333/16. Publ. BI No. 23, 2002], consisting in the interaction of 1,3-dehydroadamantane with some β-diketones.

However, this method does not lead to the production of substances of the claimed structural formula. In addition, γ-diketones, unlike β-diketones, are not strong CH acids, have several reaction centers and the formation of substances of the claimed structural formula during the interaction of γ-diketones with 1,3-dehydroadamantane and 5,7-dimethyl-1,3 β-dehydroadamantane is not obvious.

A known method of producing adamantyl-containing γ-diketones, for example 1,4-di- (1-adamantyl) butane-1,4-dione by the interaction of (1-adamantylacetyl) malonate with sodium [Stetter H., E. Rauscer // Chem. Ber. 1960. Bd. 93. No. 9. S.2054-2057].

A significant disadvantage of this method is, first of all, multi-stage, low yield of the target products and the preparation of a diadamantyl-containing compound.

The task of the invention is to develop a technologically advanced one-stage method for the synthesis of adamantyl-containing derivatives of symmetric 1,4-diketones, proceeding in high yield.

The technical result is the expansion of the arsenal of chemical compounds obtained in high yield in a new way.

The technical result is achieved in a new method for producing adamantyl-containing derivatives of symmetric 1,4-diketones of the general formula:

where R ₁ = N or CH ₃ ,

R ₁ = H or CH ₃ ,

consisting in the addition of the corresponding symmetric 1,4-diketone to the adamantane derivative, 1,3-dehydroadamantane or 5,7-dimethyl-1,3-dehydroadamantane being used as the adamantane derivative, and 2 as the initial symmetrical 1,4-diketones , 5-hexanedione or 1,4-cyclohexanedione, and the process is carried out at a molar ratio of 1: 1 at a temperature of 80 ° C. for 5 hours.

The essence of the method is the reaction of addition of symmetric 1,4-diketones to 1,3-dehydroadamantane (1,3-DHA) and its 5,7-dimethyl derivative (5,7-DM-1,3-DHA):

where R ₁ = H or CH ₃ .

The high nucleophilicity of 1,3-dehydroadamantane and its 5,7-dimethyl derivative allows to obtain the products of the addition of these symmetrical 1,4-diketones with high yields in fairly mild conditions in one stage.

The advantage of this method is a high yield (≈80%), as well as the possibility of obtaining almost any homologues of this series, which are also potentially biologically active substances.

In the interaction of 1,3-DHA or 5,7-DM-1,3-DHA with 2,5-hexanedione or 1,4-cyclohexanedione, the only reaction direction is C-adamantylation at the α-carbon atom of the starting γ-diketone. Moreover, the interaction of 1,3-DGA or 5,7-DM-1,3-DGA with 1,4-cyclohexandine due to its complete symmetry produces one target product. In the interaction of 1,3-DHA or 5,7-DM-1,3-DHA with 2,5-hexanedione, one target product is formed - in the CH ₂ group, the amount of addition products in the CH ₃ group is small, which is explained by the thermodynamic the stability of the formed secondary radicals. The products of O-adamantylation are completely absent, which is due to the low degree of enolization of the initial γ-diketones.

As studies have shown, the reaction is sensitive to temperature. It was found that with a decrease in the reaction temperature from 80 to 35–40 ° C, the yield decreases, since the interaction in a boiling diethyl ether did not lead to the desired reaction products. A further increase in temperature (more than 80 ° C) leads to a decrease in the yield of the target products, which is apparently associated with the occurrence of a side reaction of the recombination of adamantyl radicals.

A suitable molar ratio of 1,3-DGA reagents (or 5,7-dimethyl-1,3-DGA): symmetric 1,4-diketone is 1: 1, since it yields a high yield of target compounds.

Reducing the duration of the reaction less than 5 hours, ceteris paribus, leads to some decrease in the yield of the target products. The increase in the duration of the reaction over 5 hours does not lead to a significant change in the yield of the target products.

The method is as follows.

A solution of 1,3-dehydroadamantane (or 5,7-dimethyl-1,3-dehydroadamantane) in absolute diethyl ether is added to an equimolar amount of symmetric 1,4-diketone. The ether is distilled off and a mixture of 1,3-dehydroadamantane (or 5,7-dimethyl-1,3-dehydroadamantane) and symmetric 1,4-diketone is heated for 5 hours at a temperature of 80 ° C. The synthesized adamantyl-containing derivatives of symmetric 1,4-diketones are sent to the purification step. The yield of target products is 80%.

The invention is illustrated by the following examples.

Example 1

Synthesis of 3- (1-adamantyl) hexane-2,5-dione.

To 1.1414 g (0.01 mol) of 2,5-hexanedione in a dry nitrogen atmosphere at room temperature, a solution of 1.34 g (0.01 mol) of freshly-digested 1,3-DGA in 20 ml of absolute diethyl ether is pinned.

The solvent is distilled off, after which the temperature of the reaction mixture is brought to 80 ° C, maintained without stirring for 5 hours. At the end of the reaction, the mass is evacuated and 1.99 g (0.008 mol, 80%) of 3- (1-adamantyl) hexane-2,5-dione, which are colorless crystals with a _{mp of} 70-73 ° C, are obtained.

Mass spectrum, m / e: 248 (5%) M ⁺ , 205 (5%) [M-CH ₃ CO] ⁺ , 135 (100%) Ad ⁺ .

Example 2

Synthesis of 3- (3,5-dimethyl-1-adamantyl) hexane-2,5-dione.

Similarly, from 1.1414 g (0.01 mol) of 2,5-hexanedione and 1.62 g (0.01 mol) of freshly-digested 5,7-DM-1,3-DGA, 2.2 g (0.008 mol, 80%) 3- (3,5-dimethyl-1-adamantyl) hexane-2,5-dione, which is a viscous liquid with T _bale = 210 ° C / 20 mmHg

Mass spectrum, m / e: 276 (3%) M ⁺ , 233 (3%) [M-CH ₃ CO] ⁺ , 163 (100%) (CH ₃ ) ₂ Ad ⁺ .

Example 3

Synthesis of 2- (1-adamantyl) cyclohexane-1,4-dione

Similarly, from 1.1213 g (0.01 mol) of 1,4-cyclohexanedione and 1.34 g (0.01 mol) of freshly-digested 1,3-DHA, 1.97 g (0.008 mol, 80%) of 2- ( 1-adamantyl) cyclohexane-1,4-dione, which is a colorless crystal with T _PL = 125-128 ° C.

Mass spectrum, m / e: 246 (1%) M ⁺ , 135 (100%) Ad ⁺ .

Example 4

Synthesis of 2- (3,5-dimethyl-1-adamantyl) cyclohexane-1,4-dione

Similarly, from 1.1213 g (0.01 mol) of 1,4-cyclohexanedione and 1.62 g (0.01 mol) of freshly extracted 5.7-DM-1,3-DGA, 2.19 g (0.008 mol, 80%) 2- (3,5-dimethyl-1-adamantyl) cyclohexane-1,4-dione, which is a colorless crystal with a _mp = 68-70 ° C.

Mass spectrum, m / e: 274 (1%) M ⁺ , 163 (100%) (CH ₃ ) ₂ Ad ⁺ .

Claims (1)

The method of obtaining adamantyl-containing derivatives of symmetric 1,4-diketones of the General formula

, where R ₁ is H or CH ₃ , R ₂ is

R ₁ is H or CH ₃ ; R ₂ is

consisting in the addition of the corresponding symmetric 1,4-diketone to the adamantane derivative, 1,3-dehydroadamantane or 5,7-dimethyl-1,3-dehydroadamantane being used as the adamantane derivative, and 2 as the initial symmetrical 1,4-diketones , 5-hexanedione or 1,4-cyclohexanedione, and the process is carried out at a molar ratio of 1: 1 at a temperature of 80 ° C. for 5 hours.