Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2003-02-06
2004-04-20
Vollano, Jean F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S057000, C564S056000
Reexamination Certificate
active
06723875
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a process for the preparation of alkyl-ureas, starting from O,S-dimethyl dithiocarbonate.
BACKGROUND OF THE INVENTION
Alkyl-ureas are a family of well-known compounds. They are important intermediates in the production of isocyanates, drugs, phytomedicines and are used in colouring agents' chemistry, as plasticizers and stabilisers (see Ulmann's Encyclopaedia of Industrial Chemistry, Fifth Edition, 1996, Vol. A27, 355).
There are various processes for preparing monoalkyl-ureas. Among these, the main, long-known processes are the following reactions: i) the reaction of ammonia with a suitable carbamoyle chloride, obtainable by phosgenation of a suitable amine; ii) the reaction of a salt of a suitable amine with a cyanate of an alkaline metal; iii) the reaction of a suitable isocyanate with ammonia; iv) the reaction of a suitable amine with nitro-urea; v) the reaction of transamidation of urea with a suitable amine (see Houben-Weyl, Georg Thieme Verlag, Stuttgart 1952, Vol. VIII, 153). The starting materials used in the first four processes are fairly expensive, highly toxic and/or difficult to obtain. The fifth process does not exhibit the same disadvantages of the first four processes. The transamidation of urea with amines is carried out under pressure in an aqueous or anhydrous medium, as described in DE-C-8 555 551 and in U.S. Pat. No. 3,937,727, or, more easily, in a solvent at atmospheric pressure (see U.S. Pat. No. 4,310,692). The transamidation reaction uses, as a starting material, urea, which is an innocuous, non-toxic and inexpensive compound. However, the yields of the reaction products are fairly limited (they normally reach about 80%) and, at the same time, as results from their physical properties (melting point), their purity is low.
Similarly, the main processes for synthesising di- and tri-alkyl-ureas may be related to the above-described processes for monoalkyl-substituted ureas, i.e.: (i) the reaction of a suitable amine with a suitable carbamoyle chloride, obtainable by phosgenation of a suitable amine; (ii) the reaction of a suitable isocyanate with a suitable amine; (iii) the transamidation reaction of the ureas with suitable amines. The disadvantages of all these processes are the same as those mentioned above, i.e.: as regards the synthetic processes (i) and (ii), the toxicity, difficulty to obtain and/or very high costs of the raw materials; as regards process (iii), the yield and purity problems; on this subject, see for example U.S. Pat. No. 6,281,170, wherein the preparation of N,N,N′-trialkyl-ureas starting from N,N′-dimethyl-urea, with a yield of only 61% is disclosed.
Symmetric and asymmetric N,N′-dialkyl-ureas have been recently prepared also starting from S,S-dimethyl dithiocarbonate (see Man-kiti Leung et al, J. Org. Chem., 1996, 61, 4175). O,S dimethyl dithiocarbonate is an industrially accessible compound (I. Degani, R. Fochi, V. Regondi, Synthesis, 1980, 375 and I. Degani, R. Fochi, V. Regondi, Synthesis, 1980, 149); however, the processes described for its conversion into symmetric and asymmetric N,N′-dialkyl-ureas are not suitable for industrial exploitation, due to the long reaction times, the usually poor yield and, referring in particular to asymmetric ureas, due to the sophisticated operation conditions and the fairly high cost of the reagents.
Concerning symmetric dialkyl-ureas only, it is also possible to synthesise them from carbon dioxide and a suitable monoalkyl-amine at high temperatures and pressures, but with no more than a 75% conversion, which implies the need to recover and purify the gaseous effluents before being able to recycle them in the reaction, as described by U.S. Pat. No. 4,178,309.
SUMMARY OF THE INVENTION
The object of the present invention is a process for preparing mono-, di- and trisubstituted ureas that may solve the disadvantages of the known processes, i.e. a process which may provide high yields of the said ureas, in fair conditions and at a low cost. Such an object is brilliantly solved by the present invention, which relates to a process for preparing alkyl-ureas starting from O,S-dimethyl dithiocarbonate, represented by the following formula (1):
characterised in that is provides the following steps:
A) causing the O,S-dimethyl dithiocarbonate (1) to react with a primary amine of general formula R
1
NH
2
in order to obtain an O-methyl thiocarbamate of formula (2), wherein R
1
is an alkylic, cyclo-alkylic or aryl-alkylic radical
B) isomerising the O-methyl thiocarbamate of formula (2) in order to obtain a S-methyl thiocarbamate of formula (3)
C) causing the S-methyl thiocarbamate of formula (3) to react with a compound of general formula R′R″NH, wherein R′ and R″ may be equal or different one in respect of the other and may be H, R
2
and R
3
, wherein R
2
and R
3
are alkylic, cyclo-alkylic or aryl-alkylic radicals and may be equal to or different from R
1
, in order to obtain one of the alkyl-ureas (4), (5) or (6)
BEST WAY OF CARRYING OUT THE INVENTION
The present invention relates to the preparation of monoalkyl-ureas (4), N,N′-dialkyl-ureas (5) and trialkyl-ureas (6) starting from O,S-dimethyl dithiocarbonate (1), through the intermediate formation of O-methyl thiocarbamates (2) and S-methyl thiocarbamates (3), wherein R
1
, R
2
and R
3
represent alkylic, cyclo-alkylic or aryl-alkylic radicals which may be equal or different one in respect of the other and wherein R
2
and R
3
may also be H.
The first step provides causing the O,S-dimethyl dithiocarbonate (1) to react with a primary amine R
1
NH
2
, wherein an alkylic, cyclo-alkylic or aryl-alkylic radical is bound to the nitrogen atom, which reaction results in yields between 99% and 99.9% of O-methyl thiocarbamate (2), wherein R
1
represents the same radicals of the primary amine; the molar ratio R
1
NH
2
/(1) lies between 1.1 and 1.2; the reaction temperature is between 20° C. and 30° C.; the reaction time is between 2 and 3 hours. The O-methyl thiocarbamate (2) thus obtained is highly pure and may be employed directly in the following step. During the formation of the O-methyl thiocarbamate (2), a mole of methanthiol is produced, which is a product of a certain industrial value and is recovered under the form of sodium salt in aqueous solution, with a 94-98% yield.
The second step consists in isomerising the O-methyl thiocarbamate (2) into S-methyl thiocarbamate (3), wherein R
1
represents the same radicals of the primary amine and of the corresponding O-methyl thiocarbamate (2). The isomerisation reaction is made at a temperature between 40° C. and 60° C., in an organic solvent, preferably toluene, in amounts between 0.05 and 4.50 parts in weight per part in weight of (2), using, as initiator, a quantity of dimethyl sulphate between 4% and 8% of the weight of the reagent; the reaction time is between 0.5 and 4 hours; the reaction yields are between 94% and 98%. Dimethyl sulphate may be replaced by a protic organic acid, preferably by methansulphonic acid, used as catalyst. When the reaction is carried out using a protic organic acid, the reaction temperature is about 100° C.; the reaction time is between 2 and 3.5 hours; yields are around 98%. The S-methyl thiocarbamate (3) thus obtained is extremely pure and may be employed directly in the following step.
The third step provides causing the S-methyl thiocarbamate (3), wherein R″ represents the same radicals of the primary amine R
1
NH
2
and of the corresponding O-methyl thiocarbamate (2), to react with a compound of general formula R′R″NH, wherein R′ and R″ may be equal or different one in respect of the other and they may be H or an alkylic, cyclo-alkylic or aryl-alkylic group. In case a monoalkyl-urea of formula (4) is to be obtained, R′=R″=H and the compound reacting with the S-methyl thiocarbamate is aqueous ammonia. The reaction is carried out at a temperature between 60° C. and 70° C.; the reaction ti
Cadamuro Silvano
Carvoli Gianni
Degani Jacopo
Fenoglio Claudia
Fochi Rita
Oxon Italia S.p.A.
Vollano Jean F.
Young & Thompson
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