RU2298544C1 - Method for preparing substituted n-adamantyl-para-nitrosoarylamines - Google Patents

Abstract

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of N-adamantyl-p-nitrosoamines of the formula:

wherein R¹ means methyl (Me), phenyl (Ph); R² means hydrogen atom (H); R³ means compounds of the formula

Proposed compounds can be used as biologically active substances. Invention provides synthesis of substituted N-adamantyl-p-nitrosoarylamines that have not been described early.

EFFECT: improved method of synthesis.

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Description

The invention relates to the field of organic chemistry, and in particular to methods for producing N-adamantyl-p-nitrosoarylamines of the formula

where R ¹ = Me, Ph; R ² = H, Me; R ³ =

which can find application as biologically active substances.

Currently, several methods are known for producing N-adamantyl-p-nitrosoarylamines. In them, the aryl ring is introduced into the compound without changing the carbon skeleton.

A known method of obtaining based on benzaldehyde. In this method, aminoadamantyl-N-benzylidene PhCH = N-Ad is obtained from 1-aminoadamantane and benzaldehyde, hydrogenation of which gives PhCH ₂ -NH-Ad [US Pat. Australia Cl. 09.6, 87.1; 34.2, 09.10. (C 07 s, A 61k, A 23k), No. 276243. Paulshock Marvm, Watts Yohn Conway. Aminoadamantanes with therapeutic activities and their prepation. declared 7.05.63., Publ. 06/29/67.]

Known for the synthesis of N-2-adamantyl diamines in two stages. The first stage: reductive amination of 2-adamantanone with nitroanilines. Second stage: reduction of the nitro group in N- (2-adamantyl) nitroanilines [Voloboev S.N., Butenko L.N., Novakov I. A. // Chemistry and technology of organoelement monomers and polymeric materials: Collection of scientific works / Volgogr. state tech. un-t - Volgograd, 1999. - p.3-10].

The reaction of Leykart is known (the interaction of aldehydes or ketones with ammonium formate, formamide or their substituted derivatives). By the interaction of adamantan-2-one with benzamide or with aniline in formic acid, N-2-adamantylaniline is obtained [Lavrova L.N., Klimova N.V. and others ZhORKh, issue 4, 1974, S. 761-765].

The disadvantages of the known methods is that all the above methods for producing N-adamantylarylamines allow you to get only the simplest representatives of the compounds of this class. This is due to the fact that all existing production methods are based on the use of aromatic compounds as starting materials.

The closest method for the same purpose to the claimed invention is a method for producing N-aryl-N- (1-adamantylmethyl) amines [Voloboev SN, Butenko LN, Novakov IA // Chemistry and technology of organoelement monomers and polymeric materials: Collection of scientific papers / Volgogr. state tech. un-t - Volgograd, 1999. - p.3-10.]. In this method, N-aryl-N- (1-adamantylmethyl) amines are prepared by reductive N-alkylation of aromatic amines with 1-adamantylaldehyde by the Wallach reaction. The reaction is carried out without solvent in the presence of a 4-fold molar excess of absolute formic acid.

The disadvantages of this method are the use of absolute formic acid and the possibility of obtaining only the simplest representatives of the compounds of this class.

The invention solves the problem of creating a method for producing substituted N-adamantyl-p-nitrosoarylamines with a wider range of substituents.

The technical effect of the proposed method of obtaining is to obtain previously not described substituted N-adamantyl-p-nitrosoarylamines.

The specified technical result in the implementation of the invention is achieved by the fact that the method of producing N-adamantyl-p-nitrosoarylamines of the formula

where R ¹ = Me, Ph; R ² = H, Me; R ³ =

of amines, is carried out in one stage by cyclocondensation of isonite-rose-β-diketones with ketones and N-adamantylamines H ₂ NR, where a) R = Ad, b) R = CH (CH ₃ ) -Ad in the presence of an organic solvent at room temperature .

The method of obtaining N-adamantyl-p-nitrosoarylamines is as follows.

Isonitrozo-β-diketones are mixed with ketones and N-adamantylamines in an organic solvent in the presence of zeolites at room temperature. The resulting N-adamantyl-p-nitrosoarylamines are purified from the starting materials, extracted and isolated after evaporation of the extractant.

In this way, substances not previously described are obtained:

3,5-dimethyl-N-adamantyl-p-nitrosoaniline.

Green crystals are soluble in acetone, ethanol, chloroform, So pl. 170 ° C. Electronic spectrum, λ _max , nm (ε), ethanol: 410 (32000), 690 (75). Found,%: C 75.73; H, 9.29; N, 9.55. C ₁₈ H ₂₄ N ₂ . Calculated,%: C 75.99; H 8.44; N, 9.85.

2,3,5-trimethyl-N-adamantyl-p-nitrosoaniline.

Green crystals are soluble in acetone, ethanol, chloroform, So pl. 135 ° C. Electronic spectrum, λ _max , nm (ε), ethanol: 410 (26000), 700 (59). Found,%: C 76.23; H, 9.11; N, 9.96. C ₁₉ H ₂₆ N ₂ . Calculated,%: C 76.45; H, 8.72; N, 9.39.

3-methyl-5-phenyl-N-adamantyl-p-nitrosoaniline.

Green crystals, soluble in acetone, ethanol, chloroform, mp 125 ° C. Electronic spectrum, λ _max , nm (ε), ethanol: 410 (21500), 700 (60). Found,%: C 78.83; H 6.95; N, 7.71. C ₂₃ H ₂₅ N ₂ . Calculated,%: C 79.71; H 7.51; N, 8.09.

3,5-dimethyl-N- (1-adamantyl) ethyl p-nitrosoaniline.

Green crystals, soluble in acetone, ethanol, chloroform, mp 145 ° C. Electronic spectrum, λ _max , nm (ε), ethanol: 410 (29000), 690 (67). Found,%: C 76.90; H 8.53; N, 8.91. C ₂₀ H ₂₆ N ₂ . Calculated,%: C 76.84; H 8.96; N, 8.96.

3-methyl-5-phenyl-N- (1-adamantyl) ethyl-p-nitrosoaniline.

Green crystals, soluble in acetone, ethanol, chloroform, mp 120 ° C. Electronic spectrum, λ _max , nm (ε), ethanol: 410 (23000), 690 (74). Found,%: C 79.09; H, 8.77; N, 8.06. C ₂₅ H ₃₀ N ₂ . Calculated,%: C 80.16; H, 8.02; N, 7.48.

Example 1. Obtaining 3,5-dimethyl-N-adamantyl-p-nitrosoaniline.

A mixture of 0.01 mol of isonitrosoacetylacetone, 0.07 mol of acetone, 0.009 mol of 1-aminoadamantane and 2-2.5 g of zeolite in 20 ml of cyclohexanol was incubated for 168 hours at 20 ° C, then poured into 250 ml of ice water and extracted with diethyl ether (2 × 15 ml) . The extract is washed twice with 15 ml of 5% HCl solution, then twice with 15 ml of 5% NaOH solution, and then with 50 ml of water. The ether was evaporated, the oily residue which separated was washed with petroleum ether until green crystals formed. Yield 60%. Mp 170 ° C. Electronic spectrum, λ _max , nm (ε), ethanol: 410 (32000), 690 (75). Found,%: C 75.73; H, 9.29; N, 9.55. C ₁₈ H ₂₄ N ₂ . Calculated,%: C 75.99; H 8.44; N, 9.85.

Example 2. Obtaining 2,3,5-trimethyl-N-adamantyl-p-nitrosoaniline.

A mixture of 0.01 mol of isonitrozoacetylacetone, 0.07 mol of methyl ethyl ketone, 0.009 mol of 1-aminoadamantane and 2-2.5 g of zeolite in 20 ml of ethylene glycol was incubated for 168 hours at 20 ° C, then poured into 250 ml of ice water and extracted with diethyl ether (2 × 15 ml) . The extract is washed twice with 15 ml of 5% HCl solution, then twice with 15 ml of 5% NaOH solution, and then with 50 ml of water. The ether was evaporated, the oily residue which separated was washed with petroleum ether until green crystals formed. Yield 30%. Mp 135 ° C. Electronic spectrum, λ _max , nm (ε), ethanol: 410 (26000), 700 (59). Found,%: C 76.23; H, 9.11; N, 9.96. C ₁₉ H ₂₆ N ₂ . Calculated,%: C 76.45; H, 8.72; N, 9.39.

Example 3. Obtaining 3-methyl-5-phenyl-N-adamantyl-p-nitrosoaniline.

A mixture of 0.01 mol of isonitrosobenzoylacetone, 0.07 mol of acetone, 0.009 mol of 1-aminoadamantane and 2-2.5 g of zeolite in 30 ml of pyridine is held for 240 hours at 20 ° C, then poured into 250 ml of ice water and extracted with diethyl ether (2 × 15 ml). The extract is washed twice with 15 ml of 5% HCl solution, then twice with 15 ml of 5% NaOH solution, and then with 50 ml of water. The ether was evaporated, the oily residue which separated was washed with petroleum ether until green crystals formed. Yield 20%. Mp 125 ° C. Electronic spectrum, λ _max , nm (ε), ethanol: 410 (21500), 700 (60). Found,%: C 78.83; H 6.95; N, 7.71. C ₂₃ H ₂₅ N ₂ . Calculated,%: C 79.71; H 7.51; N, 8.09.

Example 4. Obtaining 3,5-dimethyl-N- (1-adamantyl) ethyl-p-nitrosoaniline.

A mixture of 0.01 mol of isonitrosoacetylacetone, 0.07 mol of acetone, 0.009 mol of N- (1-adamantyl) ethylamine and 2-2.5 g of zeolite in 20 ml of cyclohexanol is held for 240 hours at 20 ° C, then poured into 250 ml of ice water and extracted with diethyl ether (2 × 15 ml). The extract is washed twice with 15 ml of 5% HCl solution, then twice with 15 ml of 5% NaOH solution, and then with 50 ml of water. The ether was evaporated, the oily residue which separated was washed with petroleum ether until green crystals formed. Yield 20%. Mp 145 ° C. Electronic spectrum, λ _max , nm (ε), ethanol: 410 (29000), 690 (67). Found,%: C 76.90; H 8.53; N, 8.91. C ₂₀ H ₂₈ N ₂ . Calculated,%: C 76.84; H 8.96; N, 8.96.

Example 5. Obtaining 3-methyl-5-phenyl-N- (1-adamantyl) ethyl-p-nitrosoaniline.

A mixture of 0-01 mol of isonitrosobenzoylacetone, 0.07 mol of acetone, 0.009 mol of N- (1-adamantyl) ethylamine and 2-2.5 g of zeolite in 20 ml of ethylene glycol is held for 240 hours at 20 ° C, then poured into 250 ml of ice water and extracted with diethyl ether (2 × 15 ml). The extract is washed twice with 15 ml of a 5% solution of HCl, then twice with 15 ml of a 5% solution of NaOH, and then 50 ml of water. The ether was evaporated, the oily residue which separated was washed with petroleum ether until green crystals formed. Yield 15%. Mp 120 ° C. Electronic spectrum, λ _max , nm (ε), ethanol: 410 (23,000), 690 (74). Found,%: C 79.09; H, 8.77; N, 8.06. C ₂₅ H ₃₀ N ₂ . Calculated,%: C 80.16; H, 8.02; N, 7.48.

Obtained by the authors, not previously described, substituted N-adamantyl-p-nitrosoarylamines can be used as biologically active substances in medical preparations.

Claims (1)

The method of obtaining substituted N-adamantyl-p-nitrosoarylamines of the General formula

where R ¹ = Me, Ph; R ² = H, Me; R ³ =

of amines, characterized in that the isonitrozo-β-diketones are subjected to cyclocondensation with ketones and N-adamantylamines H ₂ NR ³ , where a) R ³ = Ad, b) R ³ = CH (Me) -Ad in the presence of an organic solvent.