THE PATENTS ACT, 1970
COMPLETE SPECIFICATION (Section 10)

TITLE

PROCESS FOR THE PREPARATION OF -2-METHYL-5-NITROIMIDAZOLE-1-ETHANOL

NAME

Mrs. D'SOUZA PHILO BEN.

ADDRESS : 27, GANGASANGAM CO. HSG. SOC, (B-WING), VARSE, TAL: ROHA, DIST.: RAIGAD. PIN-CODE: 402 109. STATE: MAHARASHTRA, INDIA.
NATIONALITY: INDIAN.
The following specification particularly describes and ascertains the nature of this invention and the manner in which it is to be performed :-



Object
This invention relates a process for preparation of 2-Methyl-5-Nitroimidazole-1 Ethanol.as shown in formula.
The object of this invention is a method for the preparation of 2-Methyl-5-Nitroimidazole-1-Ethanol by using simple and inexpensive reactants as(1)1-(2-Hydroxyethyl)-2-Methyl lmidazole(2) sulphuric acid (H2S04)(3) oleum(H2S207) (4) nitric acid (HNC3)and (5)Liquor ammonia(NH3)in a convenient way.
Prior Art
Imidazole derivatives are claimed in prior patents-U.S Pat.2,944,061 and describe the way in which these are prepared.
These compounds have been prepared by Nitrating 2-methyl Imidazole to form 2-Methyl 5-Nitro Imidazole and 2-Methyl 5-Nitro Imidazole is reacted with ethylene oxide to form 2-Methyl-5-Nitroimidazole-1-Ethanol. Method
2-Methyl Imidazole is reacted with sulphuric acid (H2S04) to form sulphonated product. This sulphonated product is added to the mixture of oleum(H2S207) and fuming nitric acid (HNO3)at 30 o c.the product 2-mehtyl 5-Nitro Imidazole is obtained after neutralizing with liquor ammonia (NH3). 2-mehtyl 5-Nitro Imidazole is reacted with ethylene oxide to form 2-Methyl-5-Nitroimidazole-1-Ethanol.
This process suffers from many disadvantages and some of which are stated below.
Disadvantages
Use of ethylene oxide is dangerous activity in this reaction. Ethylene oxide is also carcinogenic and explosive.
In this process the intermediate 2-Methyl Imidazole is nitrated and then reacted with ethylene oxide to get final product and hence, the process is lengthy, time consuming and very expensive.
The conversion of 2-mehtyl 5-Nitro Imidazole into final i.e. 2-Methyl-5-Nitroimidazole-1-Ethanol product is only 50% and hence the yield obtained is very less.
The inputs like 2-Methyl Imidazole, ethylene oxide are costly products hence the process is not economical and versatile.
Since there is a need to obtain derivatives of imidazole which are used as an intermediate in many reactions of immense industrial application, we have formulated a simple and continent method for its preparation.

"Present invention
According to present invention, therefore there is provided a new and improvised process for the preparation of 2-Methyl-5-Nitroimidazole-1-Ethanol.
In a brief description of the process, 1-(2-Hydroxyethyl)-2-Methyl Imidazole is reacted with sulphuric acid (H2S04) to form sulphonated product. This sulphonated product is added to the mixture of oleum (H2S2O7) and fuming nitric acid (HNO3). Sulphonation of 1-(2-Hydroxyethyl)-2-Methyl Imidazole and its further nitration by fuming nitric acid. Sulphonationof 1-(2-Hydroxyethyl)-2-Methyl Imidazole and its nitration by fuming nitric acid in presence of oleum is highly exothermic and needs precise control of reaction below 30° C.
The nitrated mixture is quenched in water again by controlling temperature at 30° C. The amount of water is taken in such a way, so that the density of the reacting mass should be approximately 1.2. This highly acidic reaction mass is neutralized by addition of ammonia or sodium hydroxide solution. The process of neutralization generates heat and hence temperature has to be controlled in between 25° to 30° C. When the pH is around 2.5 to 3.00, the maximum precipitation of 2-Methyl-5-Nitroimidazole-1-Ethanol takes place. This precipitate is filtered and washed with plenty of water. This precipitate is filtered and washed with plenty of water. The crude material of 2-Methyl-5-Nitroimidazole-1-Ethanol is having MP 151-153° C. After one crystallization from methanol-ethyl acetate or toluene and drying of the product at 70° C under vacuum melted at 161° C This final product is cream colored and crystalline in nature.
Uses
The invented product ^F^^^^02-Methyl-5-Nitroimidazole-1-Ethanol has been shown to possess chemotherapeutic properities.They have very low toxicity and are especially useful for treatment of infections cause by pathogenic protozoa such as certain species of amoebae (for example Endamoeba histolytica)and trichomonas (for example Trichomonas vaginalis) drug.
2-Methyl-5-Nitroimidazole-1-Ethanol is also used as an intermediate to make metronidazole Benzoate which is veterinary drug.
Advantages of the invented process
The important practical advantage of the process of invention is that, the process steps are reduced and hence the process has become very economical. Raw material is chief and due to improved process the yields are high. The process does not carry any hazardous steps and the process is industrially useful.
This invention is now illustrated with the following example which is not intended to limit the generality of the claims.

EXAMPLE-I
Take 1110 Gms of sulphuric acid in five liter capacity flask and add to it 260 gms. of 1-(2-Hydroxyethyl)-2-Methyl Imidazole slowly in two hours at 30° C. under cooling. This is solution (A).
In another five liter flask take 225 Gms. of fuming nitric acid (98%) and add to it 600 gms. of oleum (23%). At the time of addition, control the temperature below 30° C. This is mixture (B).
Now add solution (A) to mixture (B) slowly in two hours and control the temperature below 30° C.
Take 2.5 liter of water in a ten liter flask and add to it this nitrated reaction mass in two hours time under controlled temperature of 30° C, and then add approximately 2.5 kilograms of liquor ammonia (25%) till pH is2.5 to 3.00 and maximum precipitation of 2-Methyl-5-Nitroimidazole-1-Ethanol is obtained.
Filter this precipitate and wash with 500 ml water. The wet material of 2-Methyl-5-Nitroimidazole-1-Ethanol is having M.P 152-153° C. After one crystallization from methanol-ethyl acetate and drying of the product at 70° C. under vacuum melted at 161° C.The yield was 111% based on the starting material.
2-Methyl-5-Nitroimidazole-1-Ethanol is pale yellow colored crystalline powder
The yield of this final product is 290 Gms.

I CLAIM:
1) A process for the preparation of the 2-Methyl-5-Nitroimidazole-1-Ethanol comprising the steps of,
(a) The reactant sulphuric acid and 1-(2~Hydroxyethyl)-2-Methyl Imidazole are
reacted below 30° C to form sulphonated product of 1-(2-Hydroxyethyl)-2-Methyl
Imidazole solution, this is called as solution (A).
(b) The reactant Fuming Nitric acid 98% is added to oleum 23% below 30° C to form an acid solution; this solution is called solution (B)
(c) Slow addition of solution (A) to Solution (B) at 25-30° C and reacted to form -2-Methyl-5-Nitroimidazole-1-Ethanol.
(d) Controlling the reaction temperature by circulation of cold water.
(e) Nitrated mass is quenched in the water and neutralized by dilute ammonia or sodium hydroxide. Both quenching and neutralization are carried by controlling temperature below 30° C by cold water.
(f) Maximum precipitation of 2-Methyl-5-Nitroimidazole-1-Ethanol is obtained at 2.5to3.00 pH.
(h) Wet 2-Methyl-5-Nitroimidazole-1-Ethanol is recrystalised in methanol-ethyl acetate to obtain pure product with m.p 161° C and dried under vacuum at 70° C.
2) The process as claimed in claim 1, where the purity of the compound is 99%
3) A process is according to claim 1 where 1-(2-Hydroxyethyl)-2-Methyl Imidazole starting material and this material sulphonated and nitrated to form2-Methyl-5-Nitroimidazole-1 -Ethanol.
4)The process for the preparation of 2-Methyl-5-Nitroimidazole-1-Ethanol, as shown in formula - I of the accompanying drawing in which first position is of ethanol group, second position is of methyl group and at position five is nitro group, is obtained by nitration of 1-(2-Hydroxyethyl)-2-Methyl Imidazole.
5)The process for the preparation of 2-Methyl-5~Nitroimidazole-1 -Ethanol, is substantially as herein before described.

(Mrs. D'SOUZA PHILO BEN) Name of the applicant and signature.
Dated this 8th Day of August 2001.