SU637083A3 - Method of obtaining derivatives of 5-nitroimidazole - Google Patents

Description

b ml of ethanol; 4.68 g (20 mmol) of 1- (2-bromoethyl) -2 are added. methyl 5-nitroimidazole (CgHgBrNsOs, mol. weight 234.07, mp. 78-80 ° C) is heated to 60-65 ° C, stirred for 12 hours and 1.26 g of sulfite is added at 60-65 ° C on three . After 2 hours, the reaction is complete. The reaction mixture is evaporated to dryness, the highly hygroscopic residue (mixture of inorganic salts (and sodium salt of the product) is dried by double evaporation with 50 ml of acetoiitrile and immediately used further. which: It heated up to 250 ° C. decomposes .The yield is 55-58% calculated on the barium salt.

Calculated,%: Ba 22,68. Ci2Hi6N6OioS2Ba. Found%: Ba 22.20.

(Ethylsulfonyl) - ethyl. 2-methyl5-nitroimidazole.

To 7.5 g of dry barium salt, 50 ml of thionyl chloride and 2 ml of DMF are added, the mixture is heated under reflux for 4 hours, thionylchloride is evaporated and the residual T1-chloro-chlorine is removed by double evaporation from 20 ml of benzene. The residue is treated with 200 g of ice water and extracted with 3X100 L1L chloroforma, the extract is dried over sodium sulfate, filtered | And evaporated. The residue - pure chlorine anhydride (2.95 g) is dissolved in Minimum amount of inert solvent, mixed; suspended with water, for example, in dioxane, while cooling with a mixture of ice and salt is added dropwise to a suspension of 3.2 g of zinc dust in 5 ml of water and 5 g of ice, maintained at a temperature of 5 ° C. After 3 hours, the reaction is complete. The reaction mixture is added dropwise within 1 hour to a solution of 3.5 g of sodium carbonate heated to 85 ° C in 15 ml of water. The hot solution is filtered and the filter residue is washed well with warm water. The clear filtrate is evaporated to dryness in a vacuum created by a water-jet pump. To a solid residue, add 20 ml of DMSO to 7 ml of ethyl bromide, heat to 120 ° C (oil bath) for 3 hours under reflux. The solvent is evaporated to dryness, the residue is suspended in a small amount of water and filtered. The residue is recrystallized from ethanol to obtain 1.72 g of the desired compound, m.p. 124- 126 ° C.

Similarly, the reaction is carried out using potassium, calcium and barium salts instead of sodium carbonate, and identical results are obtained.

The output is higher if you do not use sylf, but a clear salt.65

Example 2. 5.83 g (25 mmol) of 1- (2bromoethyl) -2-methyl-5-S1troyimidazole is dissolved in 50 ml of DMSO and 5.48 g (30 mmol) of ethylase sulphinate ' weight 116,16), incubated for 2.5 hours at 100-110 ° C, the solvent is evaporated in vacuo, the solid residue is washed with water and recrystallized from ethanol. Yield (ethylsulfonyl) -eth.yl -2-methyl-5-nitro-IMidazole 2.28 g (57%), so pl. 124-126 ° C.

Calculated,%: C 38.86; H 5.30; N 16.99; S 12.97.

CgHisNsO S (247.3).

Found,%: C .38,69; H 5.42; N 18.21; S 13.02.

The structure of the product is confirmed by IR and NMR spectroscopy.

Starting from 6.2 g of calcium ethanesulfinate

in 58 ml of acetonitrile or from 7.1 g of barium ethanesulfinate in 100 ml of dioxane, get the target product, so l. 123-125 ° C or 123-126 ° C, with a yield of 40 or 43-45%, respectively.

Example 3. As In Example 2, using instead of sodium ethanesulfinate sodium butyl sulfate, 1- (2-ethylsulfonylbutyl) -2-methyl-5-n-nitroimidazole is obtained, which is recrystallized from toluene, m.p. 93-94.5 ° C. Yield 60-62%.

EXAMPLE 4 1 - (2-Ethylsulfonylethyl j 2-ethyl-5-n "Tray midazol, mp 138-140 ° C., Is prepared like 1, from 1- (2-bromoethyl ) -2-ethyl-5-nitroimidazole. Output 56-

58%.

Example 5. 2.25 g (8 mmol) of 1- (2 iodoethyl) -2-methyl-5-nitro-imidazole (CbN3O2, mol. Weight 280.98) is dissolved in 40 ml of dry DMF and with stirring and 60 ° C, 2.79 g (24 mmol) of sodium ethanesulfinate is added in portions over 2.5.

The reaction mixture is stirred at 60 ° C for 3 hours, the DMF is removed at 24-25 ° C / 0.7 mm Hg. the residue is dissolved in 40 ml of water and extracted with 4X40 ml of ethyl acetate. The extract is dried with sodium sulfate.

and evaporated. The oily residue is crystallized immediately. The crystals are suspended in benzene and sucked off. Yield (ethylsulfon-11l) -ethyl -2-methyl-5-nitroimidazole, 1.174 g (59.2%), m.p. 122-

126 ° C. After recrystallization from 96% ethanol, t. Il. 124.5-126.5 ° C, yield 40-45%.

Calculated,%: C 38.86; H 5.30; 16.99. C8Hi5N304S (247.27). Found,%: C .39,10; H 5.60; X 16.82.

Ph o o m V l and invented. And

The method of obtaining derivatives of 5-ntroimidazole total FSUE

gk

CK2CH2 -.- K1

about

where R-C | -C4-alkyl;

, Ri-hydrogen, Ci-C4-alkyl, o tl and h a y y and the fact that, in order to increase the yield of the target product, the combination of the formula

(

Jta

-.,

Ojn

CHjCHj-B where R. Has the above value;

B is a halogen, is subjected to an action with a compound of the general formula Z-R, where Z is M-SO, is lly if B is S02-M, is reacted with a compound of the general formula Zi-Ri, where b is a halogen; RI has a high value, the values everywhere being M are alkali metal or alkaline earth metal, at 60–120 ° C in an inert organic solvent medium — dimethyl sulfoxide or dimethylformamide.

Sources of information taken into consideration and expertise:

1. South Africa Patent 6607466, CA 71, 3384e, 1969.

2. US patent 3376311, cl. 260-309 02.04.68.