RU2241710C1 - Method for preparing substituted pyrido[1,2-a][1,3]-benzimidazoles - Google Patents

Abstract

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention describes a method for preparing substituted pyrido[1,2-a][1,3]-benzimidazoles of the general formula:

wherein (1): R is NO₂; R1 is hydrogen atom (H); (2): R is CF₃; R1 is hydrogen atom (H); (3): R is CN; R1 is hydrogen atom (H); (4): R = R1 is CN that can be used as intermediate compounds in synthesis of fluorescent and biologically active substances. Method involves interaction of 2-nitro-4-R-5R1-halogenbenzene with pyridine and reducing the prepared salt of N-(2-nitro-4-R-5-R1-phenyl)pyridinium wherein interaction of 2-nitro-4-R-5-R1-halogenbenzens with pyridine is carried out at temperature 20⁰C and in the mole ratio 2-nitro-4-R-5-R1-halogenbenzene : pyridine = 1:7 and salt alcoholic solution is subjected for reduction with SnCl₂ x 2 HO solution in 3% HCl in the mole ratio N-(2-nitro-4-R-5-R1-phenyl)-pyridinium salt : SnCl₂ x 2 H₂O = 1:3 at temperature 20⁰C for 0.12 h. Method provides preparing the end product with high yield and purity from available raw at room temperature and for short time interval.

EFFECT: improved preparing method.

2 cl, 2 tbl, 8 ex

Description

The invention relates to a method for the synthesis of nitrogen-containing heterocyclic compounds, in particular to the production of substituted pyrido [1,2-α] [1,3] benzimidazoles of the general formula

where 1 R = NO ₂ , R1 = H;

2 R = CF ₃ , R1 = H;

3 R = CN, R1 = H;

4 R = R1 = CN.

which can be used as intermediates in the synthesis of fluorescent and biologically active substances. The claimed compounds include:

7-nitropyrido [1,2-α] [1,3] benzimidazole (1):

7- (trifluoromethyl) pyrido [1,2-α] [1,3] benzimidazole (2):

pyrido [1,2-α] [1,3] benzimidazole-7-carbonitrile (3):

pyrido [1,2-α] [1,3] benzimidazole-7,8-dicarbonitrile (4):

A known method of producing substituted pyrido [1,2-α] [1,3] benzimidazoles based on the interaction of picryl chloride or 2,4-dinitrochlorobenzene with 2-aminopyridine in benzene at 20 ° C and cyclization of the compounds obtained by boiling at a temperature of 190 ° C N, N-dimethylaniline 2.5 hours under nitrogen (Morgan SG, Stewart J. // J. Chem. Soc., 1938, No. 8, p. 1057).

where R = H, NO ₂

The disadvantages of the known method for the synthesis of substituted pyrido [1,2-α] [1,3] benzimidazoles are: the use of expensive 2-aminopyridine as a starting reagent, as well as relatively stringent conditions, which are unacceptable for components of nucleic acids.

The purpose of the invention is to reduce the cost of synthesis, reduce the time and temperature of the process, increase the purity and yields of target products.

This goal is achieved by the fact that instead of 2-aminopyridine, cheaper pyridine is used as the starting reagent, the interaction of pyridine with 2-nitro-4-R-5-K1-halogenbenzene is carried out at a temperature of 20 ° C and a molar ratio of 2-nitro-4- R-5-R1-halogenbenzene: pyridine = 1: 7, for 1 hour, the restoration of the alcohol solution of the salt of N- (2-nitro-4-R-5-R1-phenyl) pyridinium is carried out with a solution of SnCl ₂ · 2H ₂ O in 3% hydrochloric acid and a molar ratio of salt of N- (2-nitro-4-R-5-R1-phenyl) pyridinium: SnCl ₂ · 2H ₂ O = 1: 3 at a temperature of 20 ° C for 0.12 h that allows you to reduce those perature cyclization reaction from 190 ° C to 2.0 ° C and reduce the process time from 2.5 hours to 0.12 hours.

where X = Cl, Br

1 R = NO ₂ , R 1 = H;

2 R = CF ₃ , Rl = H;

3 R = CN, Rl = H;

4 R = Rl = CN.

The structure and purity of the intermediate compounds and the desired pyrido [1,2-α] - [1,3] benzimidazoles were analyzed by means of 1H NMR, determination of the melting temperature and elemental composition.

The invention is illustrated by the following examples.

Example 1. N- (2-nitro-4-trifluoromethylphenyl) pyridinium chloride 5 g (0.022 mol) of 2-nitro-4-trifluoromethylchlorobenzene was added to 11.7 ml (0.154 mol) of pyridine and stirred at a temperature of 20 ° C for 1 hours. The precipitate formed is filtered off and washed with 30 ml of ethyl croipia. Get 6.43 g (96% of theory) of M- (2-nitro-4-trifluoromethylphenyl) pyridinium chloride - white powder, So pl. 260-262 ° C.

Found,%: C 46.9; H 2.6; N 9.3

Calculated,%: C 47.3; H 2.6; N 9.2

¹ H NMR (DMSO-d6) δ, ppm: 9.57 (d, 2H, J = 8.1), 8.98 (t, 1H, J = 15.2), 8.67 (s, 1H) 8.6 (d, 1H, J = 8.0), 8.48 (d, 1H, J = 8.2), 8.42 (t, 2H, J = 13.3)

Examples 2-4. Salts of N- (2-NO ₂ -4-R-5-R1-phenyl) pyridinium are obtained analogously to example 1. Physicochemical characteristics of salts of N- (2-NO ₂ -4-R-5-R1-phenyl) pyridinium are given in table 1.

Example 5. 7- (Trifluoromethyl) pyrido [1,2-α] [1,3] benzimidazole

To 5 g (0.016) of the salt of N- (2-NO ₂ -4-trifluoromethylphenyl) pyridinium in 20 ml of ethyl alcohol is added with stirring 11.13 g (0.048 mol) of SnCl ₂ · 2H ₂ O in 20 ml of 3% hydrochloric acid acids. After 0.12 hours, the reaction mixture was basified with a 25% aqueous ammonia solution to pH = 7-8 and extracted with several portions of chloroform (Σ = 200 ml). After distillation of chloroform, 3.7 g (98% of theory) of 7- (trifluoromethyl) pyrido [1,2-α] [1,3] benzimidazoles — white powder, mp. 233-235 ° C.

Found,%: C 60.7; H 3.3; N 12.0

Calculated,%: C 61.0; H 3.0; N 11.9

¹ N PMP (DMSO-d6) δ, ppm: 9.16 (d, 1H, J = 7.80), 8.53 (d, 1H, J-8.0), 8.15 (s, 1H) 7.74 (d, 1H J = 7.9), 7.66 (m, 2H), 7.09 (t, 1H, J = 14.8)

Examples 6-7. Substituted pyrido [1,2-α] [1,3] benzimidazoles (1,3,4) are obtained analogously to example 5. The physicochemical characteristics of the substituted pyrido [1,2-α] [1,3] benzimidazoles are shown in Table 2 .

Example 8. Condensation 4 with rhodamine 123. In a flask equipped with a stirrer, a thermometer, a reflux condenser and a capillary for introducing argon, load C ₁₂ H ₇ N ₃ 2.2 g (0.01 mol) 4, 3.8 g 01 mol) of rhodamine 123 and 10 g of phenol. The resulting mixture is slowly heated with stirring to 175 ... 185 ° C. The resulting melt is kept under stirring in a stream of argon until the evolution of ammonia ceases. After completion of the reaction, the reaction mixture was poured into 20 ml of ethanol, the precipitated precipitate was filtered off, washed with 3 ml of ethanol and dried at T = 60 ° C for 2 hours. 10.3 g (94% of theory) of hexazocyclan are obtained.

Found,%: C 74.86; H 3.81; N, 12.65

Calculated,%: C 74.58; H 3.87; N 12.79: (C ₆₈ H ₄₂ N ₁₀ O ₆ )

In the IR spectrum of hexazocyclan there is no band 2220 cm ^-1 - C = N, there is a band 680 cm ^-1 - C = N-.

The structural formula of hexazocyclan obtained on the basis of 4 and rhodamine 123:

The macroheterocycle obtained on the basis of 4 and rhodamine 123 has the following spectral characteristics: the maximum of the emission spectrum is 578, 621, 709 nm and the maximums of the absorption spectrum are 301, 343, 430 nm.

Claims (4)

The method of obtaining substituted pyrido [1,2-a] [1,3] benzimidazoles of General formula I

where 1. R is NO ₂ , R1 is H; 2. R is CF ₃ , R1 is H; 3. R is CN, R1 is H; 4. R = R1 - CN, consisting in the fact that 2-nitro-4-R-5-R ₁ -halogenbenzene is reacted with pyridine at a temperature of 20 ° C and a molar ratio of 1: 7, followed by reduction with simultaneous cyclization of the resulting salt of N- (2-nitro-4 -R-5-R ₁ -phenyl) pyridinium of the general formula II

where X is Cl, Br; R and R ₁ have the above meanings, by treating an alcoholic solution of the above salt with a solution of SnCl ₂ · 2H ₂ O in 3% hydrochloric acid and a molar ratio of N- (2-nitro-4-R-5-R1-phenyl) pyridinium salt: SnCl ₂ · 2H ₂ O = 1: 3 at a temperature of 20 ° C for 0.12 hours