Continuous methods of hydrolysis of cyanopyridines in adiabatic conditions

 

(57) Abstract:

The invention relates to a continuous method of hydrolysis of cyanopyridines in adiabatic conditions, which is a continuous Association of two or more of the supplied flow with formation of a reaction mixture containing cyano, water and a base, heating it to a temperature sufficient to initiate the hydrolysis of the cyano. Another variant of the invention consists in combining a first stream containing cyano, with the second stream containing water and a base, and at least one of the threads is heated to a temperature that provides a consolidated stream temperature sufficient to initiate hydrolysis of cyano, transmission flows after the mergers through the reaction zone and the reaction of hydrolysis in almost adiabatic conditions. This process of hydrolysis cyanopyridines leads to increased rates of formation of products with high yield and selectivity. 4 C. and 36 C.p. f-crystals, 2 tab.

The present invention relates to a continuous method of hydrolysis cyanopyridines and, in particular, to such a method, carried out in essentially Adia products amides, carboxylic acid, or a mixture thereof.

Some of the products formed in the hydrolysis of cyanopyridines are well known commercial products. For example, pyridylamine amides and carboxylic acids are important vitamins, precursors of medical and chemical intermediates. Among the amides of the most well-known example includes Niacinamide (also known as nicotinamide and 3-pyridinecarboxamide), and among the carboxylic acids, the most well-known example includes Niacin (also known as nicotinic acid and 3-piridinkarbonovaya acid). Niacinamide and Niacin, which belong to the vitamin B3are members of vitamin b complex and precursors of coenzymes I and II and are an important Supplement to the diet (diet) of humans and animals. The number of deaths from pellagra in the United States, caused by deficiency of vitamin B3fell from 7358 in 1929 to 70 in 1956, primarily due to the fact that vitamin B3became more accessible. In animals receiving the diet with the addition of vitamin B3have a higher growth rate, and in the case of ruminants also has a higher production of milk. In 1985, the market Niazi the dia of Cnemical technology, Third Edition, Vol. 24, pages 59-93. By hydrolysis of 4-cyanopyridine can be obtained isonicotinoyl acid, the precursor of the hydrazide of isonicotinic acid (isoniazid) and related drugs used in the treatment of tuberculosis.

As for the methods of obtaining these compounds are frequently carried out by hydrolysis of cyanopyridines in batch and continuous methods with an excess of the base amount from catalytic to stoichiometric. Most of the described methods is a periodic processes. For example, it is reported that 4-cyanopyridine in the presence of sodium hydroxide at a molar ratio of 1: (0,03-0,075) and 120-170oC gives isonicotinamide (see Patent USSR SU 1553531 (1990); CA:113:78174f (1990)). Similarly, it is reported that 2-cyano interacts with sodium hydroxide at a molar ratio of 1: (0,03-0,20) and in the temperature range of 100-130oC with the formation of 2-picolylamine (see Patent USSR SU 1553530 (1990); CA:113:e (1990)). It was reported that at a molar ratio of 4-cyanopyridine to sodium hydroxide of 1: (1,5-1,75) and the temperature of the hydrolysis 50-80oC hydrolysis product is isonicotinoyl acid (see Patent USSR SU 1288183; CA:106:176187n (1987)). Reported that the hydrolysis of 3-canopied the 256-7 (1943)). In one embodiment, the reported hydrolysis of 3-cyanopyridine polymer base Dowex 1X4 (hydroxide form) with the formation of nicotinamide (see patent Application Holland N 7706612-And; CA:90: 186814e).

In U.S. Patent N 4314064 describes the continuous hydrolysis of 3-cyanopyridine with a hydroxide of an alkali metal in an amount of from 0.3 to 3.0 moles per 100 moles of cyanopyridine at pressures from 0.3 to 2 MPa, and when heating or cooling to maintain the prescribed reaction temperature. Similarly, it is reported that 3-cyanopyridine interacts in a continuous way with liquid ammonia at a molar ratio of 1:0.5 and contact time 40-50 minutes at 200-260oC with the formation of nicotinamide see Journal of applied chemistry of the USSR (English translation: 45:2716-2718 (1972)).

Alternatively, the processes of hydration of cyanopyridines in the presence of bases were investigated processes of bacterial and enzymatic hydrolysis. In U.S. Patent N 5395758 transferred to the company Sumitomo Chemical Company Ltd. describes the conversion of 2-, 3 - and 4-cyanopyridine in their corresponding amides using culture broths of bacteria Agrobacterium. In the Japan Patent N 9300770000, transferred to the firm of Nitto Chemical Ind. Co. Ltd, describes the hydration aromaticheskiye corresponding aromatic amides with high selectivity.

Due to these assumptions, there remains a need and a demand for continuous way hydrolysis cyanopyridines, which provides increased speed of production of the product, while at the same time, high yields and selectivity of the product. In addition to this continuous method should be such that it can be performed with the use of original substances, which are readily available, and simple equipment requiring minimal supervision. The present invention is designed to meet these needs.

Summary

A feature of the present invention is the discovery that continuous hydrolysis of cyanopyridines can be carried out in the presence of a base and in an essentially adiabatic conditions to ensure vigorously flowing reaction, which, surprisingly, leads to increased rates of formation of products with high yields and selectively. Thus, one preferred embodiment of the present invention provides a continuous method of hydrolysis of the cyano (e.g., 2-, 3 - or 4-cyanopyridine) by combining two or more incoming flows with the formation of a reaction mixture containing cyanobacteria reaction of the reaction mixture in a substantially adiabatic conditions. The methods according to the present invention can be carried out in a number of systems of continuous action, including, for example, a simple flow tube, does not require temperature control, except for the temperature of initiation of the reaction, and can be essentially completed in less than a minute.

For specific cyanopyridine desired initiation temperature is a function of the reactivity of cyano to hydrolysis and concentration, and applied Foundation and the ratio of the base to the number of cyano. The ratio of the base to the cyanopyridine is also influenced by whether the main product amide or carboxylic acid. You can control the preferred direction of the hydrolysis of 2-cyanopyridine, 3-cyanopyridine and 4-cyanopyridine to get picolinate, Pikalyovo acid, nicotinamide, Niacin, isonicotinamide or isonicotinoyl acid with a surprisingly high speeds for products at unexpected selectivity and surprisingly short reaction times.

Another preferred embodiment of the present invention provides a method that includes the stage of combining the first stream containing cyanopyridine from about 20oC to approximately 300oC, and transmission flows are aggregated through the reaction zone to cause the flow of hydrolysis in essentially adiabatic conditions. The first stream may contain only cyanopyridine in the form of a melt or may further comprise water and/or other not interact solvent. Although to provide a suitable reaction zone can several reactor designs, including the sequence of reactors in cascade reactor with circulation or flow tubular reactor, it is preferable flow tubular reactor. Preferred hydrolysis include the hydrolysis of 3-cyanopyridine hydroxides of alkali metals such as sodium hydroxide or potassium, getting nicotinamide or Niacin in high yields and degrees of conversion with minimum contamination.

Description

To facilitate the understanding of the principles of the present invention will be made reference to some of the implementation options and their descriptions will be used a special language. However, it should be understood that not thereby assume any restriction of the scope of the invention, and qualified personnel in this PA the present invention.

As indicated above, the present invention offers unique methods of continuous hydrolysis of cyanopyridines in the presence of a base in an essentially adiabatic conditions, which, surprisingly, lead to increased rates of formation of products with high yields and selectively. In this regard, the term "essentially adiabatic conditions" is meant to include the conditions in which essentially all of the heat released by the reaction of hydrolysis, is retained in the reaction mixture during the interaction period. In other words, essentially does not attempt to cool the combined reactants within the reaction zone during the period of interaction. In the result, the heat generated by the reaction of hydrolysis, usually produced faster than it can dissipate into the environment, and the temperature of the reaction mixture within the reaction zone reaches essentially temperatures caused by uncontrolled exothermic hydrolysis reaction. Typically, the temperature of the reaction mixture rises at least approximately on 20oC. Assumes that the term "reaction zone" includes the area inside the reactor continuous action, which cyanopyridine, the Association is positive from the point of view of the applicant's method can be carried out in a number of systems of continuous action, requires only a control flow rates and temperatures of the initiation and completed within a time less than thirty seconds after held initiation.

Continuous hydrolysis of cyanopyridines, according to the options the implementation of the preferred method, gives mainly amides, carboxylic acids or mixtures thereof. 2-, 3 - and 4-cyanopyridines hydrolyzed using preferred from the point of view of the applicant's method with the formation of picolinamides, pikolinos acid, nicotinamide, Niacin, isonicotinamide and isonicotinic acid. In addition, a wide range of substituted and unsubstituted cyanopyridines is also suitable for use in this invention. Typical substituents include groups such as alkyl containing up to about 9 carbon atoms, aryl, cyano, amino, alkylamino, hydroxy and halogen (for example, -Cl, -Br), etc., Suitable substituents can result in hydrolysis to remain unchanged or may in the process of hydrolysis is converted into a new Deputy. Preferred cyanopyridines for use in the method of hydrolysis include the unsubstituted cyanopyridines (2-cyanopyridine, 3-cyanopyridine and 4-cyanopyridine) and substituted cyanopyridines is a, and either commercially available or can be obtained using methods known in the field of art and literature. The preferred cyanopyridines are unsubstituted 2-cyanopyridine, 3-cyanopyridine and 4-cyanopyridine, for example, manufactured by the companies Reilly Industries, Inc., of Indianapolis, Indiana and Cambrex Corporation, East Rutherford, New Jersey. While it is not necessary for the present invention, it is preferred to use the cyanopyridines had a high purity of, for example, from about 95 to about 99.9 percent or more pure.

Known for a number of reasons, which facilitate the hydrolysis and the choice of the used base is not critical in the broad aspects of the present invention. Suitable bases for use in the present invention typically include those foundations that are compatible with the aqueous hydrolysis system, which accelerate the hydrolysis of cyanopyridines. Preferred bases for use in this invention are ammonia, hydroxides of alkali metals such as sodium hydroxide or potassium hydroxide, and carbonates of alkali metals such as sodium carbonate or potassium. Although not required, the base is usually used in solution, more predpochtitel who I am.

The methods according to the present invention can be carried out with various amounts of water relative to the cyano thus, in order to control the reaction product, to improve the flow of products through the reactor and to affect the magnitude of the temperature increase caused by uncontrolled exothermic hydrolysis reaction. The preferred amount of water to control the reaction product depends on the number of cyano groups in the cyanopyridine subjected to hydrolysis, and whether the desired amide groups or carboxylic acid group. In the case of hydration of each cyano reacts with one (1) of the water molecule with the formation of amide groups and two (2) water molecules with the formation of the carboxylic acid group. In the result, the preferred number of moles of water per mole of cyano, used to control the product can be determined for each cyanopyridine by adding (a) the number of cyano groups, you need to to hydrolyze amide groups, multiplied by one (1), and (b) the number of cyano groups, which is necessary to hydrolyze to carboxylic acid groups, multiplied by two (2). In the case of the preferred methods is typically used at the output combination. Typically, water is added as cyano and basis for filing in the methods according to the present invention. Preferred solutions cyano contain from about 20% to about 85% by weight of the cyano in the water, with the preferred solutions contain from about 35% to about 70% by weight of the cyano for the formation of amide and carboxylic acid.

In preferred methods cyanopyridine at least one base and a sufficient amount of water together in a continuous mode with obtaining the reaction mixture at an initial temperature sufficient to initiate and maintain hydrolysis without additional heating and sufficient to cause rapid hydrolysis of the cyano. This initial temperature is called in this specification, the temperature of initiation. To initiate the hydrolysis when heated, at least one stream of reagent may be pre-heated to a temperature sufficient to make the reaction mixture reached a temperature of initiation, and the hydrolysis was started immediately after combining streams of reagents. The total amount of heating is a function of the quantities and Teploenergetika, in the range from about 20% to about 85% by weight of the cyano enough to be the initiation temperature from about 20oC to approximately 300oC.

For the formation of amide most preferred are temperatures of the initiation of from about 60oC to about 140oC, whereas for the formation of carboxylic acids, the most preferred are temperatures of the initiation of from about 60oC to approximately 200oC. In a favorable way hydrolysis is rapid and exothermic, causing a rapid temperature rise of the United streams of the reactants in the reaction zone. For example, in more favorable ways hydrolysis reaction led to an increase in the temperature of the reaction mixture at a value of at least about 20oC, and the reaction was completed within the time less than about 30 seconds and typically less than about 5 C.

The choice of the basis and its quantity in relation to the cyanopyridine can be adjusted in such a manner as to cause the product that contains mainly preferred amide or preferred carboxylic acid. When using stronger bases, such as hydroxy is s, such as ammonia, requires a large number of reasons. The control of these parameters to achieve the desired products or mixtures of products will be fully within the competence of a qualified professional bound by the provisions of the present description. Since the base can be either monobasic or dibasic, and cyanopyridines can have more than one cyano, relative amounts of these reagents can be usefully defined in terms of equivalents. The number of equivalents can be determined by multiplying the number of moles of base (defined in the usual way) by the number of protons, which will react mol this reason. The number of equivalents of cyanopyridine can be determined by multiplying the number of moles of cyanopyridine (defined in the usual way) on the number of cyano groups. The ratio of the base to the cyano will represent the ratio of the number of equivalents of base to the number of equivalents of the cyanopyridine. In a preferred method, the ratio of the base to the cyano will vary depending on the desired product of the hydrolysis, the forces applied to the Foundation and the amount of water present. In General, amide formation b is kerno (from 0.01 to 50): 100, and the formation of acid favors the ratio of the number of equivalents of base to the number of equivalents of cyano, approximately (50 to 200): 100.

While the present continuous hydrolysis can be carried out in a number of conventional devices continuous process, such as cascades of reaction vessels, reactors with circulating or flowing pipe, it is preferable flow tubular reactor. In a preferred method, at least two streams of reagents containing together cyano, water and base, are fed into the reactor with a sufficient amount of heat, filed by at least one of the streams of reactants, which leads to the fact that the combined flow reach the temperature of initiation. Although not required, the flow of the reactants may be passed through the mixing region directly in front of the entrance to the reactor or representing the initial stage of the reactor. The mixing region may include a static mixer, the area containing the nozzles or other mechanical forms, known in the art. The reactor may also be equipped for operation at ambient pressure or at a predetermined pressure above atmospheric Yes what are you under pressure above atmospheric, in the General case is equipped with a safety pressure valve, and a discharge liquid in the trap is set below the limiting pressure in the reactor. After hydrolysis of the reaction products leave the reactor and can be held in the receiving tank for further processing or can be sent directly to the allocation system product.

For the preferred continuous processes are usually achieved high rate of products formation, selectivity and outputs. For example, upon receipt of nicotinamide by hydrolysis of 3-cyanopyridine can be achieved of the speed varying from about 200 to several thousand kg per hour per liter of reactor volume, and the applicant conducted to date, the systems are easily achieved speeds from about 200 to about 1000 kg per hour per liter and, more often from about 400 to about 900 kg per hour per liter. Similar speed can be and have been obtained for the hydrolysis of 3-cyanopyridine to Niacin. The outputs of amides and carboxylic acids when using the preferred continuous method typically varied in the range from about 95% to about 99.5% pure with remainder unreacted nitrile, usually from about 0 is rule from about 1 to about 5%.

Products continuous method of hydrolysis can be isolated using standard methods. These methods include known methods periodic or continuous crystallization, periodic or continuous evaporation techniques or combinations thereof. Niacinamide, suitable for food quality applications can be obtained through continuous dehydration or drying of the hydrolysis mixture with the use of the evaporator falling film and technology cooling belt, for example as described in U.S. Patent N 434064. The products of carboxylic acids may be selected by first interaction basic salts of acid and allocation of free carboxylic acid using standard methods such as crystallization. The products of hydrolysis obtained using the method according to the present invention, useful as vitamins (namely, Niacinamide and Niacin), as chemical intermediates in the production of, for example, products used in the agricultural and pharmaceutical industries.

With the aim to contribute to the further understanding of the present invention and its preferred features and options for implementation are the following examples. The

Examples 1-10 were carried out in an autoclave of 1 liter, in order to simulate the first stage of the cascade of reaction vessels. Examples 11-14 were carried out in a flow tube reactor. Hydrolysis with getting pyridylamine carboxylic acids gave similar results in both reactors. However, the best selectivity to obtain the amide was achieved in a flow tube reactor. For all examples, the compositions of the solutions are given in mass percent.

Examples 1-10

Examples 1-10 are shown in table. 1, was performed using the following procedure. An aqueous solution of the specified cyanopyridine (shortly denoted by CN) was heated in a stirred autoclave of stainless steel, equipped with a heating jacket, to a temperature of initiation, the heating was stopped and was quickly injectible aqueous solution of the specified radix (usually for a time less than 5 seconds). When the temperature of the reaction mixture began to fall, said maximum temperature, dumped the heater casing and the autoclave was rapidly cooled in cold water. The reaction mixture was analyzed with HPLC (liquid chromatography high resolution) measuring the amount of the corresponding amidst adiabatic conditions can be adjusted concentration cyano, the choice of the basis, the number of bases and the temperature initsiirovaniya to get pyridylamine amides and carboxylic acids. The choice of conditions produces high outputs pyridinemethanol amide or carboxylic acid.

Examples 11-14

Continuous hydrolysis of 3-cyanopyridine was performed in isolated flow tubular reactor having a length of 1.68 m and inner diameter 26,64 mm and with no means of cooling. From one end of the reactor was successively connected with a static mixer, a heater and a pump for introducing a solution of 3-cyanopyridine. Between the static mixer and the pump had the inlet pipe for introducing an aqueous solution of sodium hydroxide. Thermocouples were placed: (a) between the heater and the static mixer, (b) at the entrance to the reactor, and (c) near the reactor exit. From the outlet side of the reactor was connected with the receiving tank equipped with a condenser water. Between the reactor and the receiver tank was located: (a) closer to the reactor safety valve pressure and (b) closer to the receiving tank regulator back pressure set pressure of approximately 200 psi (1379 kPa), or alternatively, ball valve, limited to create W the ez heater with constant speed 537,5 liters per hour, increasing the temperature to 115oC. 7% Aqueous sodium hydroxide solution is metered introduced into a stream of 3-cyanopyridine with a constant speed of 18.9 liters per hour and the combined streams are fed into the reactor through a static mixer. United reagents included in the flow-through tubular reactor at a temperature of 116oC, was reached temperature in 156,9oC for a time of about 4 seconds and immediately came out from the reactor and sent to the storage tank. The ratio of sodium hydroxide to cyanopyridine was 1.1: 100. Sample hydrolysis product was analyzed and it was found that it contains calculated on a dry basis, (a) 96,04% nicotinamide; (b) to 0.23% of 3-cyanopyridine and (C) of 3.73% sodium nicotinate. Table 2 summarizes the results of examples 11 to 14, held in flow-through tubular reactor using the above method. Other substituted cyanopyridines, including 2-cyanopyridine and 4-cyanopyridine, can be either hydrolyzed in tubular flow reactors with obtaining amides, carboxylic acids or mixtures. In the case of the hydrolysis of 2-cyanopyridine or its derivatives with obtaining carboxylic acids should be avoided maximum temperatures above about 135oC to prevent Pirovano and described in detail in the foregoing description, the latter should be considered as illustrative and not restrictive in character, and it is clear that was illustrated and described only the preferred embodiment and which is desired to be protected all changes and modifications that are within the invention.

All publications cited here are indicative of the level of qualified professionals and, thus, introduced as a reference, as if each piece was individually entered as a reference, and it would be fully set forth.

1. Continuous hydrolysis of cyano, including continuous joining of two or more of the supplied flow with formation of a reaction mixture containing cyano, water and base, by heating it to a temperature sufficient to initiate the hydrolysis of the cyano and the interaction of the reaction mixture in almost adiabatic conditions.

2. The method according to p. 1, in which the cyano selected from the group consisting of 2-cyanopyridine, 3-cyanopyridine and 4-cyanopyridine.

3. The method according to p. 2, in which this interaction is initiated at a temperature of at least primers the clients of cyano.

4. The method according to p. 3, which includes the interaction of from about 0.01 to about 10 equivalents of base per 100 equivalents of cyanopyridine, and this interaction is initiated at a temperature of from about 60 to about 140oWith, and form a product containing pyridylamine amide.

5. The method according to p. 4, in which the specified radix is the ammonia.

6. The method according to p. 5, wherein said cyanopyridine is a 3-cyanopyridine, and the specified pyridylamine amide represents Niacinamide.

7. The method according to p. 4, in which the indicated base is a hydroxide of an alkali metal.

8. The method according to p. 7, in which the cyano is a 3-cyanopyridine, the alkali metal hydroxide is a hydroxide of sodium or potassium, and the product contains Niacinamide.

9. The method according to p. 4, in which the indicated base is a carbonate of an alkali metal.

10. The method according to p. 9, in which the cyano is a 3-cyanopyridine, carbonate of alkaline metal is sodium carbonate or potassium, and the product contains Niacinamide.

11. The method according to p. 10, wherein said method comprises the extraction is pyridine, 3-cyanopyridine and 4-cyanopyridine.

13. The method according to p. 12, in which this interaction is initiated at a temperature of at least about 20oWith, and the specified radix is present in amount of at least 50 equivalents of base per 100 equivalents of cyano.

14. The method according to p. 13, which includes the interaction of from about 50 to about 200 equivalents of base per 100 equivalents of cyanopyridine, and this interaction is initiated at a temperature of from about 60 to about 200oWith, and form a product containing pyridinemethanol carboxylic acid.

15. The method according to p. 14, in which the specified radix is the ammonia.

16. The method according to p. 15, wherein said cyanopyridine is a 3-cyanopyridine, and the product contains Niacin.

17. The method according to p. 14, in which the indicated base is a hydroxide of an alkali metal.

18. The method according to p. 17, in which the cyano is a 3-cyanopyridine, the alkali metal hydroxide is a hydroxide of sodium or potassium, and the product contains Niacin.

19. The method according to p. 14, in which the indicated base is a carbonate sealoch metal is sodium carbonate or potassium, the product contains Niacin.

21. Continuous hydrolysis of cyano, including stage:

combining the first stream contains the specified cyano, with the second stream containing water and a base, and at least one of the threads is heated to a temperature that provides a consolidated stream temperature sufficient to initiate hydrolysis of the cyano, and

bandwidth flows after the mergers through the reaction zone and the reaction of hydrolysis in almost adiabatic conditions.

22. The method according to p. 21, where the first stream contains from about 20 to about 85% by weight of the cyano and the second stream contains from about 5 to about 50% by weight of the specified radix.

23. The method according to p. 22, which includes the interaction of from about 0.01 to about 10 equivalents of base per 100 equivalents of cyanopyridine, and this interaction is initiated at a temperature of from about 60 to about 140oWith, and form a product containing a substituted amide.

24. The method according to p. 23, which represents a cyano 3-cyanopyridine, the base is a hydroxide of sodium or potassium, and the product contains the cation per 100 equivalents of cyano, moreover, this interaction is initiated at a temperature of from about 60 to about 200oWith, and form a product containing substituted carboxylic acid.

26. The method according to p. 25, in which the cyano is a 3-cyanopyridine, the base is a hydroxide of sodium or potassium, and the product contains Niacin.

27. The method according to p. 21, wherein said first stream contains 3-cyanopyridine, and indicated the hydrolysis reaction is carried out in a flow tube reactor.

28. The method according to p. 27, wherein said first stream contains from about 20 to about 85% by weight of 3-cyanopyridine.

29. The method according to p. 28, in which the specified radix is chosen from the group consisting of ammonia, sodium hydroxide, sodium carbonate, potassium hydroxide and potassium carbonate.

30. The method according to p. 29, in which the hydrolysis reaction initiated at a temperature of from about 20 to about 300oWith, and the base is sodium hydroxide or potassium.

31. The method according to p. 30, in which the specified radix is present in an amount of less than about 50 equivalents of base per 100 equivalents of 3-cyanopyridine, the hydrolysis reaction initiated at a temperature of from about 60 to about 140oWith, and form a product containing Niacin.

33. Continuous hydrolysis of cyano, including continuous interaction of the reaction mixture containing cyano, water and ground, and this interaction is initiated at a temperature of at least 100oWith and receive the temperature rise specified reaction mixture, at least on the 20oWith almost adiabatic process conditions.

34. The method according to p. 33, in which the cyano is a 3-cyanopyridine, and this method involves reacting from about 0.01 to about 10 equivalents of base per 100 equivalents of 3-cyanopyridine, and form a product containing Niacinamide.

35. The method according to p. 34, in which the specified radix is chosen from the group consisting of ammonia, sodium hydroxide, sodium carbonate, potassium hydroxide and potassium carbonate.

36. The method according to p. 35, in which the cyano is a 3-cyanopyridine, and this method involves the interaction of at least 50 equivalents based the first base selected from the group consisting of ammonia, sodium hydroxide, sodium carbonate, potassium hydroxide and potassium carbonate.

38. The method according to p. 33, in which this interaction is essentially completed within a time less than about 30 C, and 30 s the temperature rises specified reaction mixture, at least about 20oC.

39. The method according to p. 33, in which essentially all of the heat generated in the specified interaction is retained in the reaction mixture during this interaction.

40. Continuous hydrolysis of cyano, including stage: continuing education and passing through the reaction zone the reaction mixture containing cyano, water and a base; the initiation of the exothermic hydrolysis reaction mixture in the reaction zone by heating this mixture to a temperature sufficient to initiate hydrolysis of the cyano, and retention specified in the reaction mixture during the hydrolysis reaction, essentially, just heat released in the reaction of hydrolysis.

 

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