SU761475A1 - Method of preparing phosphorilated benzimizoles - Google Patents

Description

The invention relates to the chemistry of phosphorus-containing imidazoles, namely to an improved method for producing phosphorylated benzimidazoles of the general formula

(K0) ₂ PCH ₂ - / - That)

² β

where K is CH ₃ , C ₂ H ₅ , C ₃ H 7.

These compounds can be used as potential physiologically active substances, as well as intermediates of organic synthesis.

Known methods for producing phosphorylated benzimidazoles by condensation of o-phenylenediamine with phosphonooacetic acid esters [1] and with phosphorylated acetals [2].

The disadvantages of these methods are low yields of the target product and the process at high temperature (150-170 ° C).

5 The closest in technical essence to the proposed method is a method for producing phosphorylated benzimidazoles by reacting o-phenylenediamine with an organophosphorus compound, namely, phosphonoiminoacetic acid methyl ester hydrochlorides [3].

The reaction is carried out by mixing the reagents in anhydrous methanol, followed by boiling for 1 h at

15 80 ° C. The reaction complex is decomposed with water upon cooling and the product is isolated by recrystallization. Output 60-80% · The process proceeds according to the scheme:

Р (СНВ) п (= "· НС1) 0К II 0

- ^ (ρΥ- ^Η > _{+ №Ε} ')

The disadvantages of the method described above are carrying out condensation at an elevated temperature in an environment of a highly flammable liquid (methanol), the low yield of the target product and the labor

II

P R (S) ₂ + NON + KNTS.e.1

the capacity of obtaining the initial methyl ester of phosphonoiminoacetic acid.

The aim of the invention is to increase the yield of the target product and simplify the process.

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The goal is achieved by the fact that o-fsnilepdiamine is reacted with an organophosphorus compound, namely, chloroacetylenephosphonate, in an organic solvent at a temperature from 0 to 25 ° C, followed by treatment of the reaction product with ammonia.

As an organic solvent, it is desirable to use lower chlorinated hydrocarbons.

. ·. / ... 'four

Distinctive features of the method are the use of phonate as an organophosphorus compound chloroacetylenephos ⁵ and carrying out the process at a temperature of from 0 to 25 ° C, followed by treatment of the reaction product with ammonia. · The reaction proceeds according to the following scheme:

[θ! GB1 (! = <! G (0V) ₂

ή and. "

II (B

/! - <! n ₂ p (ok) ₂ + MN ₄ <! 1 ΝΗ And

ABOUT

where K is CH ₃ , C ₂ H ₅ , C ₃ H ₇ .

Example 1. To a solution of 2.9 g (0.02 mol) of chloroacetylenephosphonic acid diethyl ether in 20 ml of chloroform is added a suspension of 2.2 g (0.02 mol) of o-phenylenediamine in 10 ml of chloroform at 20 ^s C. After stirring in for 0.5 h at room temperature, a white crystalline precipitated precipitate (2-benznmidazolylmethanephosphonate hydrochloride) is treated with ammonia gas. Then ammonium chloride is filtered off, the chloroform filtrate is kept in a vacuum created with the HELP of a water-jet pump (Height 20 mm Hg) until the chloroform is completely removed. 5.0 g (93% yield) of the crystalline residue (2-benzimidazolylmethanephosphonic acid diethyl ester) is recrystallized from hexane; m.p. 68-69 ° C.

Hnr spectrum: b _{P] 1} ~ 7.00; δ (CH ₉ ) 3.45; δ (OSI) 3,98; δ (CH ₃ ) 1.12; I (CH ₂ , P) 22.0 Hz; I (GSP ,, P) 15.0 Hz; I (N, N)

6.5 Hz.

IR spectrum, cm ^-1 : 1250 (P == O), 1120, 1125 (DEW); 3100-3150 (ΝΗ), 1620-1670

(imidazole ring).

Found,% ': C 53.2; H 6.31; N 10.00; R 11.2.

С ^ НпМгОЗР.

Calculated,%: C, 53.70; H 6.35; N 10.45; R 11.60.

Example 2. To a solution of 4.3 g (0.02 mol) of dipropyl chloroacetylenephosphonic acid ester in 20 ml of carbon tetrachloride is added a suspension of 2.2 g (0.02 mol) of o-phenylenediamine in 10 ml of carbon tetrachloride at 25 ° C. After stirring for 0.5 h at room temperature, the precipitated white precipitate (2-benzimidazolyl methanephosphonate hydrochloride) is treated with gaseous ammonia. Then ammonium chloride is filtered off, the filtrate is kept in a vacuum created with the help of a water-jet pump.

(Ro _ST 20 mm Hg. Art.) Until complete removal of the solvent. 5.5 g (yield 97%) of the crystalline residue (2-bispropyl ether dipropyl ether methane phosphonic acid) was recrystallized from hexane. Hnr spectrum: b _# ~ 7.0; δ (CH ₂ ) 3.50;

b (OCH ₂ ) 3.87; δ (CH ₃ ) 0.78; 1 (CH ₂ , P) 22.0 Hz; I (OCH ₂ , P) 12.0 Hz; I (N, N)

6.5 Hz.

20 IR spectrum, cm ^-1 : 1254 (P = O), 1035, 1063 (DEW), 3140–3180 (ΝΗ), 1620-1630 (imidazole ring).

Found,%: C 56.20; H 6.98; P 9.90; N 9.20.

25 0ΐ4Η ₂ ιΝ ₂ Ο ₃ Ρ.

Calculated,%: C 56.70; H 7.09; P 10.52; N 9.45.

Example 3. To a solution of 3.1 g (0.02 mol) dimethyl ester of 2-benzimidazolyl 30 taiphosphonic acid in 20 ml of chloroform is added a suspension of 2.2 g (0.02 mol) of o-phenylenediamine in 10 ml of chloroform at 0 ° C. After stirring for 0.5 h at room temperature, the precipitated white

35 crystalline precipitate (2benzimidazolylmethanephosphonate hydrochloride) is treated with gaseous ammonia. Then, ammonium hydrochloride is filtered off and the filtrate is kept in vacuum at a constant pressure of 20 mm Hg. Art. until complete removal of the solvent. 4.6 g (yield 95%) of the crystalline residue (2-benzimidazolylmethanephosphonic acid dimethyl ester) is recrystallized from

45 hexane; m.p. 92 ° C.

PMR spectrum: b _P C - 7.0; δ (CH ₂ ) 3.36;

b (OCH ₃ ) 3.56; I (CH ₂ , P) 22.0 Hz; I (CH ₃ , P) 13.0 Hz.

IR spectrum, cm ^-1 : 1256 (P = O), 3Ί40–3160

50 (ΝΗ), 1620–1640 (benzimidazole ring).

Found,%: C 50.52; H 5.45; R 12.68. 3ιοΗι ₃ 0 ₃ Ν ₂ Ρ.

Calculated,%: C 50.10; H 5.43; R 12.94.

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Thus, the proposed method allows to obtain phosphorylated benzimidazoles in good yield (up to 97%). The method is characterized by simple processability, does not require the use of flammable solvents and high temperatures.

Claims (2)

Claim A method of producing phosphorylated benzimidazools by the interaction of o-phenylenediamine with an organophosphorus compound in an organic solvent medium, characterized in that chloroacetylenephosphonate is used to increase the yield of the target product and simplify the process and Perurature from 0 to 25 ° C, followed by treatment of the reaction product with ammonia. 2. The way pop. 1, characterized in that lower chlorinated hydrocarbons are used as the organic solvent 5.