DE2433692A1 - PROCESS FOR THE PREPARATION OF 5 (4) AMINOMIDAZOLE-4 (5) CARBOXAMIDE - Google Patents

Description

The invention "relates to a method of manufacture of ^^ O- ^ i ^ oimidazol - ^^^ oarboxamid (im following mostly abbreviated as "AlGA") by hydrolysis of the novel compound 4- (5) -Cyanoiinidaz, ol-5 (4 -) - alkylcarbaina t (in the following mostly abbreviated as "ClAC"); the latter connection is established by the Hofmann reaction of 4 (5) ™ cyanoidazole-5 (4 -) - carboxamide (hereinafter generally abbreviated as "CICA") in alcohol.

The connection AICA has the structure:

N

LjL

-C-NH ₂

NH2

and is a valuable intermediate for synthesis of various imidazole and purine derivatives that are used in the field of medicine and veterinary medicine, as a flavoring agent stronger and hardening accelerator.

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So far, AICA has been produced by reducing 4 (5) -nitroiniidazole-5 (4) -carboxamide / ~ Ber. 55, 683 (1923) _7, ■ by cyclization of 2-amino-2-amidinoaeetaniid /~J.Am. Chem. Soc. 82, .3144 (196O) _7, and by hydrolysis of 5 (4) -amino-4 (5) -cyancimidazole (JA-PS 6911/1967). However, the manufacturing processes given in the literature are unsatisfactory from a technical and economic point of view. The process mentioned last above is economically superior to the "two preceding in terms of starting material, mode of operation and yield, but not yet, completely" satisfactory. If the starting material 5 (4) -Ainino- ^/ 1- (5) -cyanoimida3oi is produced by the Hofmann reaction of 4 (5) ™ cyanoiraidazole-5 (' ^: 0-carboxamide in an aqueous alkaline solution. , the alkali metal concentration is limited to the range from 0.2 to 0.5 N. If the concentration exceeds 0.5, a side reaction predominates.

The amount of water present as a solvent is therefore very large, which affects the separation of the product or the alkali made difficult and makes the process expensive.

The invention is based on the object of overcoming the difficulties and disadvantages mentioned above and to provide an improved process for the preparation of 5 (4) aminoimidazole-4 (5) carboxamide (AICA).

It has been found that the new compound 4 (5) -cyanoimidazole-5 (4) -alkylcarbamate (CIAC) with the help of the Hofmann reaction of 4 (5) -cyanoimidazole-5 (4) -carboxamide (CICA) in alcoholic Solution can be produced in good yield and that the compound CICA can be hydrolyzed to AICA by alkali with likewise good yield

40 9-8 85/1429

According to the invention, a halogenating agent is added to a solution or mixture of CICA in alcohol which contains an alkaline compound, such as a lower alkyl alcoholate or an alkali hydroxide, and the Hofmann reaction is carried out, in which CIAC is obtained, which is then finally hydrolyzed with alcohol to AICA v. ^r ird.

The "boiro process according to the invention as an intermediate product available CIAC has the structure:

- ^ "• - KIICOOR
N

vroj.-in R is a lower alkyl group, such as the methyl, Is ethyl or Prcpylgruppe.

Zar manufacture of CIAC usable, alkaline compounds are the hydroxides of the alkali and alkaline earth metals and the lower alkyl alcoholates, e.g. Methyl, ethyl or propyl alcoholate of alkali or alkaline earth metals.

As alkali metals, Na or K are primarily suitable, and Ba or Ca as alkaline earth metals. The alkali metals mentioned are preferred over the alkaline earth metals in terms of yield and reaction time. The alkaline earth hydroxides are used in solution or suspension in a small amount of water, preferably as an aqueous solution.

The amount of alkali used for the Hofmann reaction

409885 / U29

hydroxides or alcoholates depend on the halogenating agent used and other reaction conditions.

When the halogenating agent is a halogen, that per mole of the starting material is CICA Required amount of alkaline compound twice the equivalent weight in grams, preferably twice up to G times the equivalent weight in grams, the upper limit is not critical, but a large amount is advantageous from an economic point of view from ui: ·. The theoretical amount of alkaline compound is twice the equivalent amount per CICA; in grams, however, an excess of alkaline compound, e.g. three times the equivalent weight in green nm; advantageous, us! to speed up the response. One uses hu little alkaline compound, the reaction takes place of course, but the yield is poor.

A gram equivalent weight is in the case of alkali alcoholate or hydroxide is equal to 1 mol and in the case of alkaline earth alcohol ate or hydroxide equal to 1/2 mole.

When the halogenating agent is a hypohalite Alkyl hypohalite or an organic bleach powder the theoretical amount of alkaline compound is one gram equivalent per 1 mole of CICA; the amount of alkaline compound per mole of CICA can therefore in this case be one gram equivalent less than the amount used for the reaction when halogen is used as the halogenating agent. Be like that e.g. 2 gram equivalents 1 or more and 2 to 6 gramia equivalents become 1 to 5-

The concentration of the alkaline compound in alcohol is 0.01 to 5μ, preferably 0.3 to J> n. The higher concentration is preferred in order to reduce the amount of alcohol and the reaction time, but the solubility is

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The ability of the alkaline compounds in alcohol is limited and, for example, the solubility of sodium hydroxide in methanol at 28 ° C is 19.3 ° / °, which corresponds to about 5n. The alcoholates dissolve well in alcohol. However, the solubility of alkali or alkaline earth salts of the CIGA, which is formed in the Hofmann reaction, is limited. The concentration of the alkaline compound is therefore, generally speaking, from 0.01 to 5n and preferably from 0.3 to 3%, although these values are not critical. If the concentration is closer to the upper solubility then it takes time for the alkaline to dissolve Link; in alcohol excessively long.

The halogenating agent can also be added to a mixture be, in which CICA or alkali only partially is dissolved in alcohol, but then the yield drops and the reaction time becomes long.

The alcohol in the process according to the invention is the lower alkyl alcohols are suitable, e.g. methyl, ethyl or propyl alcohol. Dex * alcohol can be with one be mixed with other solvents inert to the reactants and the product. Methyl- and ethyl alcohol are preferred for economic reasons .

Suitable halogenating agents are halogens, e.g. chlorine and bromine, inorganic hypohalites, e.g. Hypochlorite and hypobromite, organic bleaching powder, e.g. trichloroisocyanuric acid, and alkyl hypohalites, e.g. methyl hypochlorite and ethyl hypochlorite. Chlorine, bromine and inorganic hypohalites such as sodium and calcium hypohalite are preferable and give as halogenating agents from an economical point of view the best yields. For technical processes, in particular

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- 6 special chlorine preferred as halogenating agent.

Inorganic kypohalites are in the form of or suspensions in a little water are used.

The amount of halogenating agent per hol CIOA is 1 to 2, preferably Λ to 1.3 gram equiv. The theoretical amount is 1 green equivalent per mole of CIOA, and if less is used, the yield naturally falls. On the other hand, if there is an excess of halogenating agent, there is a close explosion of the halogenating agent by oxidation, which also increases the yield.

In the case of halogen, alkali hypochloxite and ilkylhjijoohj.or corresponds to Ί grass equivalent of the halogenating agent corresponds to one mole and in the case of alkaline earth hypochlorite 1 gray equivalent of half a mole.

In the case of organic bleaching powder, the value for 1 gram equivalent depends on how many halogen atoms there are Contains halogenating agents.

If the alkaline compound is an alkaline earth hydroxide or the halogenating agent is an inorganic hypohalite, a small amount of water is used, as already mentioned. The total amount of water can be between 5 and. 30 % by weight of the amount of alcohol.

The reaction temperature depends on your halogenating agent and other reaction conditions. if the

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Temperature high when the halogenating agent is added. the risk of the imidazole ring being burst increases. The halogenating agent is therefore expediently added at low temperature, for example at -10 to 15 ° C., preferably -10 to 5 ° C. The ring can burst even at temperatures below -10, but this reaction is then extremely slow,

The speed at which the halogenation agent becomes zv ~ p. £ fLeu is not critical as long as the temperature is kept within the above limits, ie not too much heat is released.

With the addition of the halogenating agent, the reaction is continued at a temperature between -5 ¹ C and the boiling point of the reaction mixture. Preferably, this is done in two stages, ie operates first one-half to 15 hours, preferably 1 to 8 hours at -5 *> is +20 ⁰ C, the halogenation reaction leading to the end and the Hofmann rearrangement, and the addition of alcohol to drive forward, whereupon the temperature is increased to 50 ° C to the boiling point of the reaction mixture and this preferably keeps boiling for two minutes to an hour so that the entire CIAC forms.

The mentioned temperature increase to 5O ⁰ C to the boiling point is not always necessary as long as the reaction time is up to +20 ⁰ C is sufficient at -5 ..

The reaction at -5 to +20 ⁰ C can be performed for more than 15 hours. The reaction at 50 ^° C. up to the boiling point can be carried out for longer than an hour as long as no water is added.

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The reaction time also varies depending on the halogenating agent, with the alkaline compound and ax its concentration as well as the functional temperature and the other reaction conditions, however, is, generally speaking, between half an hour and 20 hours is preferably 1 to 10 hours.

The CIAG generated by the Hofmann reaction like obezi can be isolated from the reaction mixture, but is srfiriduiigs its isolation and purification not always necessary. Hau can clear the residue after driving off the alcohol from the reaction mixture as raw material for hydrolysis to produce AIGA.

If the CIAG is to be isolated from the reaction mixture, so one drives off the alcohol and dissolves the residue in water. Hach! Neutralizing the remaining alkali one cools the aqueous solution to precipitate aas CIAC, which can optionally be recrystallized from a solvent such as hot water.

If you simply use the residue evaporated to dryness as the starting material for the hydrolysis, so one can determine the content of CIAC and alkali hydroxide by analysis in order to determine how much alkali hydroxide has yet to be added. However, the remaining alkali hydroxide can also simply be used as a base Calculate the excess added. For example, if the halogenating agent is a halogen and there were 3 Hol alkali hydroxide is used per mole of CICA, it can be assumed that 1 mole of alkali is left over. Is this Halogenating agent an alkali hypochlorite and 2 moles of alkali metal hydroxide were used per mole of CICA, it can be assumed that 2 moles of alkali remain.

409885/1429

The CIAC occurring as an intermediate in the process according to the invention was determined by the following analyzes and Trials identified:

(a) Elemental Analysis

(b) IR spectrum

(c) UV spectrum

(d) The product (83 ₅ g) was obtained within 3 hours at 70 to 75 ° C in a yield of. 8th? % hydrolyzed in 0.75N aqueous sodium hydroxide solution (content 12 g sodium hydroxide) to give 4 (5) -cyano-5 (4) -arainoiwidazole. The product was identified by its IR spectrum, its UV spot run and the elemental analysis.

The intermediate CIAC obtained as above is hydrolyzed to AICA in aqueous alkali. As an alkali hydroxide Sodium, potassium and lithium hydroxide are suitable.

The minimum amount to be used for the process according to the invention corresponds to the theoretical amount of 2 moles of alkali per 1 mole of CIAC. A maximum amount of alkali is harmless, but is for economic reasons to avoid an excessively large excess, that is to say one uses a maximum of 2 to 6 moles of alkali per mole of CIAC.

The concentration of the alkali is in the range from 0.5 to 5n, the lower the concentration , the longer the reaction time. The concentration and the reaction time are therefore coordinated, ie a concentration of 1.5 to 2.5 n is generally chosen.

The reaction temperature varies with the alkali and its concentration as well as the other reaction conditions

403885/1429

- ίο -

and is generally in the range of 80 ⁰ C to the boiling point of the Seaktionslösung, preferably at or near the boiling point.

At temperatures below 8O ⁰ C, the hydrolysis of the cyano group of the CIAC is difficult and the yield of 4 (5) cyano-5 ~ (^) - aminoimidazole increases.

At temp c-to doors above the boiling point, the lioaction takes place also, but the product is decomposed and love reactions occur, quite apart from that the pressure increase required for this would be technically disadvantageous.

The reaction time also depends on the reaction conditions and is, generally speaking, in the range from 2 to 20 and preferably 2 to 10 hours. For example, if CIAC in 2N aqueous sodium hydroxide solution hydrolyzed at 96 ° C, the Bep.ktion after Finished 8 1/2 hours.

In order to separate the AICA formed from the reaction mixture, this can be neutralized and evaporated to dryness, whereupon the AICA is extracted from the residue with a solvent, for example methyl alcohol or acetone. The residue is then dissolved in water / water, the pH of the solution is adjusted to 1 with hydrochloric acid and the solution is decolorized with activated charcoal. If the solution is then cooled, the hydrochloride of AICA still precipitates, which is filtered off and dried. If the aqueous solution is not neutralized, free AICA can also be obtained, but the hydrochloride separates out much more easily than the free substance.

A09885 / U29

With the aid of the method according to the invention, nan AICA is obtained in good yield and with a high degree of unity.

The examples serve to explain the invention in more detail.

Example 1

Manufacture; from CIAC j

J4v; cks Preparation of a solution of sodium methoxide in ethanol v / urder. bsi 10 to 2O ⁰ C su 400 ml of methanol 6.9 β metallic sodium was added. In the solution there were 13.6 G ^ (5) -CyaT-.oimi <? Aaol-i> (^) -. Ca, rboxainid t, whereupon with vigorous stirring at -5 to

0 ⁰ C 7.7 £ chlorine gas were introduced into the solution and this was held at 0 to + 5 ° C for a further 5 hours. The temperature was then gradually increased to the boiling point of the reaction mixture and the solution was refluxed for 5 minutes. After the methanol was removed under reduced pressure, the residue was dissolved in water and neutralized with 6N hydrochloric acid.

The aqueous solution was cooled, whereupon 14.32 g of white crystals of 4 (5) -cyanoimidazole-5 (^) - methyl carbamate separated out, which were filtered off; Yield 86.3% · The product had a melting point higher than 300 ° 0 and was easily dissolved in both cold as in hot water.

The following values were determined to identify the product:

4098 $ 5 / U29

UY spectrum

■ Λ ^ΡΗ1 24-2.0 m / rev (£ max 1.50 χ 10 ⁴ ) max '/'

λΡΗ15 ₂ 49.5 © / U (£ nax 0.98 χ 1Ο ⁴ )

K 3.x /

IR spectrum

^{2200 0} ^ ^(0Ξκ)
μ KBr 1710 approx " ¹ (COOOK _x )

JJünnschicht-CinOjnatogro.pliie

Ί1Ϊ ; 0.75 stationary phase; Üilica gel

CHCl,., Saturated with KE ₄ OH: CH, OH «0, Ö3>: 0.15

Elemental analysis: CH Ii

C H _{fi r} L0 examples .: 4.37 3.61 33.73% ^ Found .: 43.21 3.43 33.61%

Hydrolysis of C I AC:

A solution of 16.6 g of the 4 (5) -cyanoimidazole-5 (4) -methylcarbamate 5in obtained above 150 ml 2.7ji sodium hydroxide solution was refluxed with stirring for 4.5 hours. The reaction gel was neutralized and evaporated to dryness, whereupon de? " Residue

was extracted with methanol.

The methanol was evaporated and the residue was dissolved in water and adjusted to pH 1 with hydrochloric acid set. The aqueous solution was decolorized with activated charcoal. After filtering off the activated carbon, the I'il-

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occurred cooled, whereupon a precipitate separated out, which was washed on the filter with methanol. After drying, 13 _? 97 g of crystalline 5 (^) - AiHiIiO-imidazole-4- (5) -carboxamide hydrochloride (yield based on ClAC, 86%). The total conversion, based on GICA, was 74.3 % of theory.

The product decomposed at 253 to 255 ° C and was identified by infrared and ultraviolet spectra, which correspond to those of a comparative sample of 5 (- '0 ~ / uninoimidazole -''f - (^) - cai ^> boxamidhydrochlox-ii3 . complied.

At game 2.

Manufacture of CIAC :

Example 1 was worked, except that iiatrium ethylate was used instead of sodium methylate. 14.76 g of white crude crystals of ^z K5) -cyanoimidazole-5 ( ^z O-ethylcarbaiaate; yield 82.1 % were obtained.

The product decomposed at 151 C and was in cold Easily water, also soluble in warm water. The product was identified as follows.

UV spectrum

Max

Max

2V! -. 0 m / rev (£ max 1.28 χ 260.0 m / rev (£ max 0.816 χ 10 ⁴ )

IR spectrum

2200 cm- ¹ (C = *

A09885 / U29

V f ££ 1710

46 , 6G . 4th , 44 31 , 11 46 , 58 4th , 45 31 , 15

Diuin layer chromatography

Sf ₅ 0.82

stationary phase; Silica gel developing fertilizer; CHOl- ,, saturated with

EH ₄ OH: CH 1, GiI = 0.85: 0.15

El e in ejitax'aiial.y G e: _ C Π Ν

C ₇ II ₈ N ₄ Op ber.

found

Hydrolysis of J2

A solution of 8,1 g of the 4 (5) -Cyauoiniidcisol-5 (- ^ -) ~ etherealylcarbainatoc obtained as above in 150 Dl . N ll lvo lye was kept under stirring for 8.5 hours with stirring . When working up geiaäis Eeicpiel 1 eiv ^ ab the reaction mixture 14.43> g 5 (4) -aminoimida2ol ~ 4 (5) -carboxamide hydrochloride (yield 88.9%> especially on CIAC). The overall yield based on CICA was 73.0 %. The product decomposed at 253 am 255 ° 0th

The product was identified by its infrared and ultraviolet spectra.

For s ρ ie 1 3

Manufacture of CIAC:

13 g of 4 (5) -cyanoimidazole-5 (4 -) - carboxainide were dissolved in a solution of 8 g of sodium hydroxide in 400 ml of methanol. Then 8 g of sodium hypochlorite dissolved in 45 ml of water was added dropwise to the solution at -5 to 0 ° C. To. Work-up according to Example 1 was obtained

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13.2 g of crystalline ^ (5) -cyanoimidazole-5 ( ^/ <-) - 3ie "thylcarbainate in a yield of 79.2%.

The product was identified by infrared and Ultraviolet spectrum and elemental analysis according to

Example 1.

vpo from GIAC;

A solution of 16.6 g of the 4 (5) -Ov --- .: CJr: usually 7.ol-5 (A-) - 3: 3ei.} I; rlcarljur.'jiUcs in 200 al 1,5n l ^: ::: tr-ciül; -U | '-; r viuräe 15 hours /? while stirring untor Eüg] c i '± u'> ^ · εΚο.1ΐοα _Γ Kac.li ■ ' u.fr?rbeiter· according to example 1 obtained jmr.! 'i't-, 03 κ 5 (' 0 - A ' _! -ino: iraidaKol- ^/ i (5) ~ & arbüxaiui} · ../ (.'. ταchloiMcl (9I ₅ - "Ve yield, based on ClAC ).

3jj ο G-? R; ^ nt?: U; /lev.ne to product-, calculated au J'GlCA, "was 72.3 / ·: '·. The preamble disintegrates at 253 ti ? 55 ° C uud Y.-urde idi-.ntii'iziort through its infrared urd s ^ in Ultraviolet ü-Spcktraiu.

Example ^f ±

A mixture of 25.6 g of barium hydroxide, Ba (OH) ₀ * 8H ^ 30 in 1 volume of water, 25 liters of methanol and 6.8 g of 4 (5) cyanoinidazoJ-5 ( ^/ +) -carboxainide v; urde in eineiu 3OO ml flask UNTCI "Elihren etv at a 5C ° C dissolved /. in the solution at -8 vrarden. fed to -5 ° C 3.97 S chlorine. 20Gtündigem wax standing at -2 to +5 ⁰ C was the solution was refluxed for 30 minutes and then treated further as in Example 1. 5.82 g of 4 (5) -cyanoimidazole-5 (4) -diethylcarbamate were obtained in a yield of 70.2%.

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The product was identified by infrared and Ultraviolet spectrum and elemental analysis according to Example 1.

Hydrolysis of CIAC:

A solution of 15.6 g of the 4 (5) -cyanoidazole-5 (4) -methylcarbamate3 obtained above in 150 ml of 2N potassium hydroxide solution was refluxed for 8.5 hours with stirring. After working up the solution according to Example 1 received m - '. n 14.33 ε 5 (4) -Ajuinoirflida & ol-4 (5) -carbo> :: amide hydrochloride (Yield 88.2%, calculated on GIAC). The total yield, calculated on CICA, was 62.0%. The product decomposed at 253 to 255 ° C and became .identified by infrared and ultraviolet spectrum.

At s ρ i_e_ 1 £

13.6 g of 4 (5) -cyanoimi & azole-5 (4) -carboxaraid were added. according to Example 1 (manufactured by CIAC) and steamed the resulting reaction solution, the 4 (5) cyanoimidazole-5 (4) methyl carbamate contained, untex · veraiindei'tem Pressure to dryness.

The residue was mixed with 12.0 g of sodium hydroxide in 150 ml Dissolved water and the solution kept under reflux with stirring for 4.5 hours.

After working up the reaction solution as in Example 1 (hydrolysis of CIAC), 12.3 g of 5 (4) -aminoimidazole-4 (5) -carboxamide hydrochloride were obtained in a yield of 75.7%, calculated on 4 (5) -cyanoimidazole-5 (4) -carboxamide. The product decomposed at 253-255 ° C and was identified by infrared and ultraviolet spectrum .

A09885 / U29

example

To prepare a solution of sodium methylate in methanol, 6.9 g of metallic sodium were added ^{at 10 to 20 ° C. to 400 ml of methanol.} Then 13.6 g of 4 (5) -cyanoimidazole-5 ( ^/ 0-carboxainide were dissolved in the solution and 16 g of bromine were added dropwise at -5 to ⁰ ° C. After the addition of the bromine, the reaction solution was reduced to 0 for 5 hours held up to + 5 ° 0. The temperature was then slowly increased to the boiling point of the solution and this was kept under reflux for 5 minutes.

After evaporating the reaction mixture under reduced pressure, the residue along with 8 g Sodium hydroxide was dissolved in 200 ml of water and the solution was refluxed for 15 hours with stirring.

After working up according to Example 1 (hydrolysis of CIAC) 5 »63 g of 5i4) -aminoimidazole-4 (5) -carboxamide hydrochloride were obtained in a yield of 34.7% »calculated to 4 (5) -cyanoimidazole-5 (4) -carboxamide.

The product decomposed at 253 "to 255 ° 0 and became identified by infrared and ultraviolet spectrum,

Example 2.

13.6 g of 4 (5) -cyanoimidazole-5 (4) -carboxamide were dissolved in a solution of 16 g of sodium hydroxide in 400 ml of methanol and 7 ti g of chlorine gas were introduced at -5 to 0 ° with vigorous stirring, whereupon the The solution was kept at -3 to 5 ° C for 6 hours. Then the temperature was gradually raised to the boiling point and the

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- The solution is refluxed for 10 minutes.

The resulting solution was then reduced under reduced pressure Pressure evaporated and the residue dissolved together with 8 g of sodium hydroxide in 200 ml of water, whereupon the Solution was refluxed with stirring for 10 hours.

After working up as in Example 1 (hydrolysis of CIAC), but the precipitate was washed with ethanol instead of kit methanol, 12.48 g of 5 ( ⁱ 4 -) - An'iino.imida2ol-4 (5) -carboxainide- were obtained hydrochloride in a yield of 76.8%, calculated on 4 (5) - cyanoimio aa oil-5 (4 -) - carboxamide.

The product decomposed at 253 to 25? C and was identified by infrared and ultraviolet spectra

Example 8

In a solution of 16 g sodium hydroxide in 400 ml of methanol was dissolved 13 * 6 g of 4 (5) -Cyanoimidazol-5 (4) -carboxamide, whereupon to 0 ⁰ C 7.7 g of chlorine gas initiated with vigorous stirring at -5 and the solution held at 0 to 5 ° C for a further 5 hours. Then the temperature gradually increased to the boiling point of the reaction. mixture increased and this evaporated to dryness under reduced pressure. The residue was dissolved together with 4 g of potassium hydroxide in 150 ml of water and the solution was refluxed with stirring for 8.5 hours.

After working up the solution according to Example 1

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(Hydrolysis of CIAC) resulted in 12.5 6 5 (4 -) - amine- imidazole-4 (5) -car'boxamide hydrochloride in one Yield of 75.7%, calculated on 4 (5) -cyanoimidazole- -carboxamide.

Paa product decomposed at 253-255 C and became identified by infrared and ultraviolet spectra.

Bite ρ i el

A mixture of 300 ml of methanol and 6 g of metallic calcium was heated under reflux in a 500 ml flask so that the ethane contained a solution of calcium iunanet lylate in lieth.-snol. To this solution vmrd.en 6, & g ¹ I (: ') - Cyf: 7ioii! Ij.a .'- 2zol - 5 (^) - carpojrnniid added and dissolved in it while stirring for .όθ minutes ;. Kach / «ΙΛϋϊΐΙβη the solution was passed at -8 to -5 C 3j6 rgae d.ii and 15.eß the solution for 20 hours at -T: bis

+ 5 ° stand, whereupon the mixture for 30 minutes under Was held at reflux and then evaporated to dryness under reduced pressure.

The residue was dissolved together with 6 g of sodium hydroxide in 100 ml of v / water and the solution was dissolved with stirring Hours "refluxed.

After working up the reaction mixture according to Example 1 (hydrolysis of CIAC), 4.47 B 5 (4 -) - aminoiraidazole-4- (5) -carboxynide hydrochloride were obtained in a yield of 55% i calculated on 4 (5) -cyanoimidazole-5 (4) -carboxamide.

The product decomposed at 253 "to 255 ° C and became identified by infrared and ultraviolet spectrum.

PATENT CLAIMS:

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Claims (15)

PATENT CLAIMS E. Ι) Process for the preparation of 5 (4) -aminoimidazole ~ 4 (5) -carboxamide, characterized in that 4 (5) -cyanoiiaidasol-5 (4) -alkyl-carbamate in aqueous solution in the presence of an alkali hydroxide at a temperature hydrolyzed from 80 ° to the boiling point of the ResktionsgemiseOiea. 2) Method according to claim 1, characterized in that one of a 4 (5) -Cyanoimidazol- ^ C ^ O-allcylcarbaiaat goes out, in your the alkyl group is the methyl, ethyl or propyl group is. 3) A method according to Ansijruch 1 or 2, characterized in that the alkali metal hydroxide in a daji wan Ho ratio of at least 2: 1, vox'zugs-Vv ^r else from 2 to 6: 1 to 4 (5) -Cyanimidazol-5 (4) alkyl carbaate used. 4) Method according to claim 1 to 5j, characterized in that an alkali hydroxide is used whose concentration in water is in the range from 0.5 to ^ a, preferably from 1.5 to 2.5n. 5) Process according to claim 1 to 4, characterized in that the hydrolysis is carried out at carries out a temperature which corresponds to the boiling point of the reaction mixture. 40988 5 / U29 6) Method according to one of claims 1 to 5 »thereby characterized in that the hydrolysis is carried out within 2 to 20 hours. 7) Method according to one of claims 1 to 6, characterized in that one 4 (5) -Cyanoimidazole-5 (^) - alkyl carbamate used, which is made by reacting (a) 4- (5) -cyanoimidazole-5 (A) -carboxanide with (b) a halogenating agent, (c) a lower alkyl alcohol and (d) at least an alkali compound, selected from the group of alkali and alkaline earth metal alcoholates and alkali and alkaline earth hydroxides, wherein the halogenating agent (b) was added to the mixture of (a), (c) and (d). 8) Method according to claim 7 *, characterized in that the lower alkyl alcohol Is methyl, ethyl or propyl alcohol. 9) Method according to claim 7 or 8, characterized in that the halogenating agent a halogen, a hy.p ohalogenit, an alkyl hyp is ohalite or an organic bleach powder. 10) Method according to claim 9 »characterized in that the amount of halogenating agent is in the range from 1 to 2, in particular from 1 to 1.3 gram equivalent per 1 mole of 4- (5) -cyanoimidazole-5 (4 ·) -carboxamide. 11) Method according to claim 9 » characterized in that when using a halogen as halogenating agent, the amount of alkali compound (d) is at least 2, preferably 2 to 6 gram equivalents 409885/1429 per 1 mole of 4 (5) -cyanoimidazole-5 (4) -carboxamide. 12) Method according to claim 9, characterized in that when using a hypohalite, an alkyl hypohalogenite or an organic bleach powder as the halogenating agent Amount of alkali compound (d) at least 1 gram equivalent, preferably 1 to 5 gram equivalents per 1 mole 4 (5) -Gyanoimidazole-5 (4) -carboxamide is. 13) Method according to one of the preceding claims, characterized in that the consentration of the alkali compound (d) in alcohol, in the range from 0.01 to im, preferably from 0.3 to 3n lies. 14) Method according to one of the preceding claims, characterized in that the Halogenating agent at -5 to + 15 ° C-was fed, whereupon the reaction at a temperature of -5 ° C to the boiling point of the Beaktionsgemisehes carried out became. 15) The method according to claim 14, characterized in that the reaction was carried out after addition of the halogenating agent for half to 20 hours, preferably half to 15 hours at -5 to 20 ⁰ C, whereupon the reaction mixture to a temperature of 50 ° 0 has been heated to its boiling point- 409885 / U29