Organic compounds -- part of the class 532-570 series – Organic compounds – Nitriles
Reexamination Certificate
1999-08-26
2001-02-27
McKane, Joseph K. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitriles
Reexamination Certificate
active
06194600
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a new method of producing aminocyanoacetamide which can be employed industrially. Aminocyanoacetamide is an intermediate which is of interest for the production of imidazoles, pyrazines, purines or pteridines for example.
BACKGROUND OF THE INVENTION
Various methods of producing aminocyanoacetamide are known. Those which should be mentioned in particular are that of Smith Jr. et al., who in
J. Am. Chem. Soc.,
76, 6080 (1954) describe a method of producing aminocyanoacetamide from hydroxyiminocyanoacetamide by hydrogenation with aluminium amalgam, and various methods of producing aminocyanoacetamide from esters of cyanoacetic acid via esters of aminocyanoacetic acid such as that according to EP 0 342 616, which discloses the production of aminocyanoacetamide by the nitrosylation of an ester or cyanoacetic acid by means of an alkali nitrite, hydrogenation of the resulting ester of hydroxyiminocyanoacetic acid with platinum/hydrogen and the subsequent liberation of aminocyanoacetamide with aqueous ammonia. The method of Smith Jr. et al. cannot be employed industrially due to the problems of using a mercury catalyst. Methods of producing aminocaynoacetamide from esters of cyanoacetic acid via esters of aminocyanoacetic acid such as that described in EP 0 342 616 are methods which are costly on an industrial scale and which are based on the cumbersome reaction of cyanoacetic acid which is protected by an ester function to form an ester of aminocyanoacetic and the subsequent liberation of aminocyanoacetamide.
SUMMARY OF THE INVENTION
With the present method, a process which can be employed industrially can be used for the first time for the direct production of aminocyanoacetamide. The method is based on the reaction of cyanoacetamide with nitrites at a pH below 2.6 and of preferably around 2 to form nitrosocyanoacetamide and the subsequent catalytic hydrogenation of nitrosocyanoacetamide to form aminocyanoacetamide. By “around 2” is meant 1.5-2.5 and narrower ranges, e.g. 1.6-2.4 or 1.8-2.2.
Cyanoacetamide is a starting material which is commercially available on large scale. Cyanoacetamide is nitrosylated with nitrites at a pH of preferably around 2 to form nitrosocyanoacetamide. An alkali nitrite is preferably used for nitrosylation, and is preferably added to an acidic solution or suspension of cyanoacetamide. The pH is preferably held at around 2 during nitrosylation. This procedure prevents the formation of very large amounts of by-products, reduces the amount of nitrous gases which are formed and yields a product which can readily be centrifuged.
The customary nitrites for nitrosylation are alkali nitrites, preferably sodium nitrite. The nitrite is used in an amount of 1-5 equivalents with respect to cyanoacetamide, preferably 1-2 equivalents with respect to cyanoacetamide. Nitrosylation is conducted in acidic media, preferably in strong, concentrated mineral acids, and in particular is preferably conducted in hydrochloric acid at a pH of around 2. The reaction takes placed in a concentrated solution or preferably in a suspension, at temperatures between 0° C. and 50° C., preferably between 0° C. and 5° C. In particular, a pH of preferably around 2 within this reaction step results in a direct crystallization of nitrosocyanoacetamide. At higher pH values, namely above 2.6, which is the pH of an aqueous solution of nitrosocyanoacetamide, the undesired semi-sodium salt precipitates. This undesired semi-sodium salt is obtained in a very fine form and therefore on an industrial scale the product is hardly separable and washable. Such a product will always also contain high amounts of sodium chloride and by-products of the reaction. Another drawback of the precipitation of the semi-sodium salt is that it is a highly exothermal reaction forcing the hydrolysis of cyanoacetamide. Thus, the reaction is conducted at a pH lower than 2.6 under conditions wherein essentially no undesired semi-alkali metal (especially sodium) salt precipitates.
The nitrosocyanoacetamide which is thus obtained is reacted by catalytic hydrogenation to form aminocyanoacetamide. Hydrogenation is effected with hydrogen in the presence of a catalyst. Suitable catalysts are preferably noble metal catalysts such as platinum, which is finely divided in amounts of 1% to 20% on conventional support materials such as carbon, alumina, silica, barium sulphate or calcium carbonate, or platinum oxide. Platinum in an amount of 2% to 10% on carbon is preferably used as the catalyst.
The catalyst is advantageously used in amounts of 1% to 30% with respect to the nitrosocyanoacetamide, most preferably 2% to 10% with respect to the nitrosocyanoacetamide.
Hydrogenation is conducted either in aqueous media such as water, or is preferably conducted in what are predominantly nonaqueous media, e.g. in low molecular weight, water-miscible alcohols such as methanol or ethanol, in low molecular weight, water-miscible carboxylic acids such as formic acid or acetic acid, or in tetrahydrofuran. A little sodium hydrogen phthalate can be added to buffer aqueous hydrogenation solutions. Other additives can be added to the hydrogenation solution, such as iron sulphate to prevent the formation of gaseous hydrogen cyanide, Raney nickel to prevent poisoning of the catalyst, etc.
Even when working in nonaqueous media, the use of hydrous catalysts does not give rise to problems. After the reaction is complete, the catalysts used can easily be worked up again and used for the next reactions.
Hydrogenation is effected at a pressure of 1 bar to 100 bar, preferably 1 bar to 10 bar, and at temperatures between 0° C. and 80° C., preferably between 20° C. and 50° C. The time of hydrogenation can vary between 30 minutes and 20 hours depending on the pressure, temperature, medium and amount of catalyst.
After the completion of hydrogenation in aqueous media the pH of the reaction solution can be lowered by the addition of an acid such as acetic acid. This procedure prevents the formation of very large amounts of by-products.
Another aspect of the invention is the single step process of producing nitrosocyanoacetamide from cyanoacetamide and the resultant compound.
Still another aspect is the single step of hydrogenation of the nitrosocyanoacetamide to aminocyanoacetamide.
In the foregoing and in the following examples, all temperatures are set forth uncorrected in degrees Celsius and unless otherwise indicated, all parts and percentages are by weight.
The entire disclosures of all applications, patents and publications, cited above, and of Swiss Application No. 2907/97, filed Dec. 18, 1997, are hereby incorporated by reference.
REFERENCES:
patent: 0 342 616 (1989-11-01), None
Smith, Jr. et al., Journal of the American Chemical Society, vol. 76, No. 23, (1954), pp. 6080-6084.
Bollinger Heinrich
Kurz Martin
Muller Hans Rudolf
Schwaninger Peter
Eprova A.G.
McKane Joseph K.
Millen, White, Zrlano & Branigan, P.C.
Murray Joseph
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