JPS6046105B2 - Method for hydrolyzing cyano compounds - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for hydrolyzing cyano compounds.

More specifically, the present invention provides a cyano compound in a polar solvent containing a required amount of water, hydrogen peroxide and one or more selected from molybdic acid, tungstic acid, telluric acid, vanadic acid, and selenic acid. The present invention relates to a method for producing a carboxamide compound, characterized in that hydrolysis is carried out in the presence of an alkali metal salt, alkaline earth metal salt, or ammonium salt of a transition metal oxide. Conventionally, methods for synthesizing carboxamide compounds by hydrolyzing the cyano group of a cyano compound can be broadly classified into four known methods.

Of these, the first method using a strong acid and the second method using a strong alkali can only be applied to cyano compounds whose other moieties in the molecule are stable under these conditions, and the cyano group does not react with carboxylic acids. It is often hydrolyzed to A third method involves partial decomposition of a transition metal compound and a cyano compound [for example, S. Pwraskewas9Synt
hesis574 (1974)], the target cyano compounds are extremely limited, and many of the processing conditions are special, so it cannot be said to be a general method.

A fourth method using hydrogen peroxide under basic conditions is Rad
Known as the 2is2ewsky reaction, rapid hydrolysis rates can be achieved under mild conditions.

[For example, S. R. Sandler, W. Karo,'
OrganicFunctionalGroupPre
parations9' AcademicPress
, New York (1968), p. 295], but even in this method, the desired results are often not achieved because the cyano compound is treated under basic conditions. For example, these conventional methods cannot be sufficiently applied to the hydrolysis of one of the cyano groups of the Schiff base of diaminomaleonitrile (Toshiaki Takagi et al., JP-A-49-127921), which has useful uses as a physiologically active substance.

An example of benzylidene aminomaleonitrile, which is a typical Schiff base, is shown in Comparative Examples 1 to 3. Hydrogenation of benzylidene aminomaleonitrile using hydrogen peroxide under neutral basic and acidic conditions Neither decomposition gives the desired product in good yield. The present inventors have sought to eliminate these drawbacks and have discovered a new hydrolysis method that can be applied over a wide range of areas. That is, as shown in Examples 1 to 7, the method of the present invention can not only selectively hydrolyze one of the Schiff bases of diaminomaleonitrile with good yield, but also hydrolyze the benzene ring as shown in Example 8. It is possible to selectively hydrolyze only one of the two adjacent cyano groups, but this is difficult to obtain the desired product because in normal methods, cyclization reactions between adjacent groups proceed. It is something that cannot be obtained.

The method of the present invention can of course be applied to monocyano compounds, but it is also suitable for selectively hydrolyzing only one cyano group of compounds having other active moieties in the molecule, especially dicyano compounds such as those mentioned above. This is the most effective method for Yang-hei. Compounds to which the method of the present invention can be applied include alkyl cyano compounds such as acetonitrile;
Unsaturated cyano compounds such as acrylonitrile, aromatic cyano compounds such as cyanobenzene, heterocyclic cyano compounds such as nicotinonitrile, malononitrile, etc. It can be applied to alkyl dicyano compounds such as succinonitrile, aromatic dicyano compounds such as phthalonitrile, heterocyclic dicyano compounds such as dicyapyrazine, and polycyano compounds such as tetracyanoethylene. It may also contain other functional groups that are stable under the conditions of the invention. According to the present invention, for example, cyanopyrazinecarboxamide, which is an intermediate for the synthesis of 2,4-dihydroxypteridine, which has useful applications in the pharmaceutical field, is
It can be easily produced from cyanopyrazine.

In addition, the method of the present invention is carried out by dissolving or suspending the cyano compound in a polar solvent and in the presence of water. Water may be added in advance to the polar solvent, but the transition metal oxide It is extremely convenient and industrially advantageous to add these as an aqueous solution when adding the hydrogen peroxide, or as a hydrogen peroxide solution when adding the hydrogen peroxide.

Examples of the polar solvent used in the present invention include alkanols such as ethanol and propanol, ketones such as acetone and methyl ethyl ketone, cyclic ethers such as tetrahydrofuran and dioxane, dimethylacetamide, dimethylformamide, and nitromethane. The operability is particularly good when using ethanol or acetone. The amount of solvent used is 3 to 3 for the cyano compound.
A suitable amount is 10 times the amount of heel, but preferably 5 to 5 times the amount of saliva. Although there is no problem even if the amount of solvent is large, the reaction will require a long time because the catalyst concentration will be relatively reduced. On the other hand, if the amount of solvent is too small, the catalyst concentration will become too high, which will cause the reaction to proceed significantly and cause side reactions, which may lower the yield or reduce the purity of the product, which is not preferable. Therefore, it goes without saying that the amount of polar solvent should be selected in consideration of these various conditions and the most industrially advantageous conditions. In the present invention, the reaction is carried out in the presence of an alkali metal salt, alkaline earth metal salt, or ammonium salt of a transition metal oxide, that is, molybdic acid, tungstic acid, telluric acid, vanadic acid, and selenic acid as a catalyst as described above. The hydrolysis reaction was significantly accelerated and
If cyano groups are present, only one of them is selectively hydrolyzed. Examples of alkali metal salts, alkaline earth metal salts, or ammonium salts of transition metal oxides include sodium, potassium, calcium, or ammonium salts of tungstic acid, sodium or potassium salts of telluric acid, sodium molybdate, Examples include, but are not limited to, potassium salt or ammonium salt, sodium or potassium salt of selenate, sodium salt of vanadate, sodium or potassium salt of chromic acid, potassium or sodium salt of antimonic acid, and the like. In particular, sodium molybdate and ammonium exhibit excellent effects in the method of the present invention and are easily available industrially. The amount of catalyst used is 0 for the cyano compound.
．． 01 to 100% by weight, preferably 0.1 to 5% by weight. The concentration of hydrogen peroxide added during the reaction of the present invention is not particularly limited, but it is usually convenient to use 30% since water necessary for the reaction is added.

Hydrogen peroxide is preferably added to the reaction solution containing the cyano compound, reaction solvent, and catalyst solution at a selected concentration.
The amount of hydrogen peroxide added is preferably 0.1 to 1, and preferably 0.3 to 3, times the amount of the cyano compound in terms of pure content. The amount used may be greater than the above range, but if the amount is too large, it is not only uneconomical but also causes side reactions, which is not preferable. Furthermore, if the amount used is less than the above range, the desired effect may not be expected. When carrying out this reaction, the reaction proceeds even if only hydrogen peroxide is used without using a catalyst, but the yield is lower than when a catalyst is used in combination (see Comparative Example below). The reaction temperature is not constant depending on the solvent used, the amount of catalyst and its type, etc., but it is usually 5 to 5
0°C, most preferably 15-30°C. If the reaction temperature is too high, side reactions other than the original reaction will proceed, leading to a decrease in yield and the quality of the product, which is undesirable. Reaction times are generally between 2 and 5 screams.

Although it depends on the set conditions, if the reaction time is too short, unreacted substances will remain, which is not preferable. By appropriately combining the above conditions, when carrying out the method of the present invention, a product with such high purity that no special purification is required can be obtained, and nuclear magnetic resonance spectra and mass spectra can be measured immediately after drying. . If a product of even higher quality is to be obtained, the purpose can be easily achieved by recrystallizing it from a suitable solvent if desired. The method of the present invention will be explained in more detail below with reference to Examples and Comparative Examples.

Example 1 Benzylidene amino maleonitrile 6.0 Da (30.6
mmol) in 600 ml of ethanol solution, add sodium molybdate aqueous solution (a). 2y/40ml water) was added.

To this solution, 25 ml of 30% hydrogen peroxide solution was added dropwise at room temperature. After stirring at room temperature for an hour, the precipitated crystals were collected by filtration, thoroughly washed with water, and dried. 4.7 g of the obtained yellow crystals (yield 71.2%) were recrystallized from ethanol to obtain yellow microcrystals with a melting point of 205-206°C (decomposed). IR (KBr): 3390, 3290, 3170
and 1680c7n-1 (amide group) 2190
c7n-1 (nitrile group) mass spectrometry: 214 (M,
196 ([M-H2O)+, 26.6%) 137
([M-C6FI5]+,100%) etc. NM
R (dimethyl sulfoxide Db solution δ): 7.7-7
．． 8 and 8.22-8.34 (phenyl H) 8.
50 (Azomethine H) Elemental analysis value: Actual value, C, 62. O5: H, 4.72; N, 26.3
Calculated value as 3% CllHlON4O, C,
6l. 67; H, 4.7l; N, 26. Based on the results of 16% or more, the product has the following structure.

Example 5 3.0 y of α-phenylbenzylidene amino maleotrile was dissolved in 80 ml of ethanol, and a solution of 0.1 y of ammonium molybdate dissolved in 20 ml of water was added thereto.

Furthermore, 15 mt of 30% hydrogen peroxide solution was added to this, and the mixture was stirred at room temperature for 2 hours. Thereafter, the insoluble solution was filtered off, and water was added to the filtrate to obtain 0.8y of precipitated crystals (yield: 25%). Recrystallized from ethanol, melting point 183-185℃ (
It was yellow microacicular crystals (decomposition). Infrared spectrum (K
Br): 3420, 3280, 3175, 1678 and 1656 cm-1 (acid amide group), 2180c! n″′
1 (cyano group) mass spectrum (Mle): 290 (M
NMR spectrum (dimethyl sulfoxide Db solution δ): 7.5-7.6,
7.75-7.85 and 7.95-&05 (phenyl H
).

Elemental analysis value: Actual value C, 7O. 27; H, 4.69; N, l9.29% Cl
Calculated value C as 7Hl4N4O, 7O. 33:H, 4
．． 86; N, l From the results of 9.30% or more, the structure of the product is as follows.

Example 6 The same procedure as in Example 1 was carried out except that paramethoxybenzylidenemalononitrile was used instead of benzylidenemalononitrile, to obtain a yellowish white powdery solid with a yield of 78%.

Recrystallized from acetonitrile, melting point 213-216℃
It was (decomposition). Infrared spectrum (KBr): 342
0,3380,3280,317 Moxibustion 1689d-1
(acid amide group) and 2180-1 (cyano group).

NMR spectra (δ in dimethylsulfoxide Db solution): 8.30, 8.20, 7.37 and 7.27 (rose-substituted phenyl H) and 8.46 (azomethine H).

Elemental analysis value: Actual value C, 59.38; H, 4.94; N
, calculated value C as 22.95% Cl2Hl2N4O2
,59. Ol; H, 4.95; N, 22.94% or more. Based on the results, the structure of the product is as follows.

Example 7 The following compound with a melting point of 208 to 209.5°C (decomposed) was obtained in a yield of exactly the same procedure as in Example 1, except that paramethylbenzylidene diamino maleonitrile was used instead of benzylidene amino maleonitrile. 86.2%
I got it.

Infrared spectrum (KBr): 3380, 3280, 31
60 and 1698 cm-1 (acid amide group), and 219
0c7! -1 (cyano group) elemental analysis value: Actual value C, 63.24; H, 5.36; N, 24.5l% Cl
.

Calculated value C as Hl2ON4, 63. l4:H,5.
3O; N, 24.55% Example 8 Phthalonitrile 1.2
A mixture of 100 ml of 8f1 ethanol, 10 ml of 0.5% sodium molybdate and 15 ml of 30% hydrogen peroxide was stirred at room temperature for 1 hour.

Thereafter, a small amount of water was added and concentrated under reduced pressure (bath temperature 40°C) until the total volume was about 30 ml. When cooled, orthocyanobenzamide had a melting point of 171°C (literature value 172-3°C).
was obtained with a yield of 58%. Example 9 Phenylacetonitrile 2.5f1 ethanol 200m
t,. 0.5% sodium molybdate 15ml and 3
A mixture of 15 ml of 0% hydrogen peroxide solution was stirred at room temperature for 4 hours.

Thereafter, the same operations as in Example 8 were performed to obtain phenylacetamide with a melting point of 156°C (literature value: 155°C) in a yield of 34%. Example 10 2,3-dicyanopyrazine 3 in a 4-necked 200ml flask
．． 0q (0.023M0L) and 150ml of ethanol were added and completely dissolved at room temperature.

Next, a solution of 0.3 g of sodium molybdate dissolved in 30 mL of water was added to form a homogeneous solution. While cooling the reaction solution with water, 15 ml of 30% hydrogen peroxide was added dropwise to about 1 drop. There was some heat generation during the first drop, but no heat generation was observed thereafter. When hydrogen peroxide was added dropwise, the reaction solution turned yellow, but the yellow color gradually became lighter and needle-shaped crystals gradually precipitated. After being left at room temperature for a day and night, the precipitated white needle crystals were filtered and washed with 10 mt of water.
It was dried at 120°C for 8 hours to obtain 2.85f of 2-dicyanopyrazine-3-carboxamide. Yield 83.6
% Mp27O~273°C (yellowing at around 230°C) decomposition. The 2-cyanopyrazine-3-carboxamide produced by this method has the following characteristic values. (1
) Elemental analysis value (%) 2-cyanopyrazine-3-carboxamide C6H4
N,O(2) infrared absorption spectrum (estimated attribution) Cm-
1 (3) Nuclear magnetic resonance spectrum 9.0 in DMSO-D6
0ppm2H(S) Ring proton 8.30ppm
-NH2(BrOad)amide proton (4) Mass spectrum M+148 (5) Ultraviolet absorption spectrum (maximum absorption: Nnl) (6) Thin layer chromatography Rf=1.
82 (n-C4lll9OH, CH3COOH, H2O
=4:1:1) (7) Melting point: 270-273lC (decomposition) Turns yellow around 230°C.

(8) Appearance White needle-like crystals Example 11 The reaction and post-treatment were carried out in the same manner as in Example 10, except that the ingredients in Example 10 were changed to 50 mt of acetone, 0.2 g of sodium molybdate, and 20 m1 of water. 3.19y of 3-carboxamide was obtained.

The yield was 93.5%. Example 12-24 The reaction was carried out in the same manner as in Example 10 or 11, and the yield of Example 10 was as follows by changing the solvent, catalyst, etc.
A product identical to that was obtained.

Test Example 3.0 g of 2-cyanopyrazine-3-carboxyamide obtained in Example 10 was dissolved in 60 nt of methanol solution, 6 y of 48% caustic soda solution was added, and chlorine was gradually blown in while cooling to below 0°C with stirring. , and reacted for 4 hours.

Thereafter, it was neutralized to pH 7 with a 20% aqueous hydrochloric acid solution. This liquid was concentrated under reduced pressure, and to the precipitated yellow crystals, 5.35 dah of a 28% aqueous sodium hydroxide solution and 30 ml of water were added, and the mixture was heated under reflux for 3 hours.

Claims (1)

[Claims] 1. A cyano compound in a polar solvent containing the required amount of water,
In the presence of hydrogen peroxide and an alkali metal salt, alkaline earth metal salt, or ammonium salt of one or more transition metal oxides selected from molybdic acid, tungstic acid, telluric acid, vanadic acid, and selenic acid. A method for producing a carboxamide compound, characterized by carrying out hydrolysis.