DD240887A1 - PROCESS FOR PREPARING SUBSTITUTED 5-CYANPYRIMIDINES - Google Patents

Abstract

The invention relates to a process for the preparation of substituted 5-cyanopyrimidines which have as substituents in 2- and 4-positions a substituted or unsubstituted aryl or hetaryl radical and in the 6-position an alkyl radical (with C1 to C12) -, a substituted - or unsubstituted aryl or Hetarylrest- or alkyloxy (with alkyl: C1 to C12). It is the object of the invention, in addition to the already known from the literature 5-cyano-6-ethoxy-2,4-diphenyl-pyrimidine and 5-cyano-2,4,6-triphenyl-pyrimidine other, previously unknown representatives of this type of novel Way to produce. The task is to find a technically feasible synthetic route. The object is achieved by the reaction of 3,5-diaryl-1,2,4-dithiazolium salts with substituted b-iminopropionitriles. The compounds obtained are of pharmaceutical and optoelectronic interest.

Description

Title of the invention

Process for the preparation of substituted 5-cyanopyrimidines

Field of application of the invention

The invention relates to a process for the preparation of substituted 5-cyanopyrimidines. Such compounds may gain importance as biologically active preparations as well as for use in optoelectronic devices.

Characteristic of the known technical solutions

Various methods for the preparation of substituted 5-cyanopyrimidines are described in the literature. There are 3 fundamentally different production types:

1. Introduction of the cyano group by exchange or conversion of other fractional groups in the 5-position of Pyrimidinkörpers. (CCPrice, IUJ ₀ Leonard, R _a H..R itsmann _e, J. Amer, Chem Soc 68, 766 (1946);. · DJ Brown, M.TT.Paddon-Row, J. Chem ^Soc · 1967th H.Bredereck, G.Simchen, H.H. Wagner, AA Santos, Liebigs Ann. Chem., 7, 6J, 73 (1972), A. Boiler, M. Cereghetti, M. Schadt, H. Scherer, Mol.Cryst.Liqu.Cryst., 42, 215 (1977); D. Demus, DDR Pat., 1595o5 (1978).

2. Construction of the pyrimidine heterocycle by cyclization of aliphatic starting compounds. (A.R.Todd, P. Berggel,

J. Chem. 1937 , 364; Z.Fo'ldi, A. Salmonamon, Chem. 74., 1126 (1941); A. Dornow, E. Schleese, ibid. Jn, 18 "3o (1958); J. Goerdeler, J. Gnad, ibid., 98, 1531 (1965); J. Goerdeler, D. Wieland, ibid., JKX), 47 (1967), H. Graboyes, υ J. Mitch., J. Med. Chem., H, 568 (1968), H.Willitzer et al., DDR Pat., 93560 (1971), W. Kantlehner, JC Ivanov, W. Mergen, H. Bredereck, Liebigs Ann Chem., 1980 , 372; S. Robev, Dokl. Biolg. Acad, TTauk 33, 635 (1980), M. Mittelbach, H. Junk, J.Het. Chem., V, 7.1385 (1980) 3. Preparation of the Substituted 5- Cyanopyrimidines from Other Heterocycles by Ring Conversion Reactions (H. Weidinger, HJSturm, Liebigs Ann. Chem., 1616, 433 (1968); J. Liebscher, GDR Pat., 129907 (1977)). The preparation routes of types 1 and 2 have the disadvantage that the synthesis of the The preparation routes of type 3 allow only the preparation of substituted 5-cyanopyrimidines having a very specific substituent pattern. "Of the substituted 5-cyanopyrimidines according to the invention, these are 5-cyano-6-ethoxy-2,4-diphenyl-pyrimidine and the 5-cyano-2,4,6-tr iphenyl-pyrimidine known from the literature. 5-cyano-6-ethoxy-2,4-diphenyl-pyrimidine has been obtained by a Type 2 method. (RRSchmidt, Chem. Ber 98, 466 (1965) This process has the disadvantage that the 6-step synthetic route described is very complicated 5-cyano-2,4,6-triphenyl-pyrimidine was prepared by a process of type 3 ^ i-triphenyl-i ^^ oxadiazine-i-perchloroate obtained (J.Shibuya, M. Kurabayashi, Bull, Chem. Soc., 4 ^, 3902 (1973) This method has the disadvantage that only this, in the 2,4- and 6-position similarly substituted, 5-cyanopyrimidine can be represented.

Object of the invention

The aim of the invention is to produce such compounds in a simple manner.

Explanation of the essence of the invention

The object of the invention is to prepare variously substituted 5-cyanopyriinidines from readily available starting compounds in a technically applicable synthesis route in a simple manner.

According to the invention this object is achieved in that 3,5-diaryl-1,2,4-dithiazolium salts of the type II,

II

J X

where R is a substituted or unsubstituted aryl or hetaryl radical and X "is an acid residue anion such as ClO", Cl

br

or FeCl ,, with substitution

beta-iminopropionitriles of type III,

NH

III

where R ^{2 is} an alkyl radical (C ₁ to C ₁₂ ), a substituted or unsubstituted aryl or hetaryl radical or an alkoxy radical (with alkyl: C ₁ to C ₁₂ ), to the substituted 5-cyanopyrimidines of type I,

1 p

wherein R and R have the abovementioned meaning, are reacted ·

That's it. possible, the reactions using auxiliary bases, e.g. Alkali hydroxides, alkali alcoholates, tertiary amines such as triethylamine or alkali salts of weak acids, e.g. If the reaction is carried out using the indicated auxiliary bases, the substituted β-iminonitriles (III) may also be used as salts, e.g. Hydrohalides, hydrogen sulfates, sulfates or perchlorates are used ·

The invention will be explained in more detail below with reference to exemplary embodiments.

example 1

Compound I with R ¹ = C / -IL- and R ² = OC ₀ H ₁ (meaning always parts by weight)

option A

To the mixture of 20 parts of acetonitrile, 0.35 part of III (R ² = OC ₂ H ₅ ) and 0.28 part of sodium hydroxide solution (10 mol / 1), 1 part of II (R ¹ = CgH, X = ClO.) given. The mixture is stirred for 10 min. At room temperature and then filtered. The filtrate is concentrated to dryness. The residue obtained is washed with Y / a and recrystallized from acetonitrile. This gives 0.34 parts (40 %) of the final product, which has a melting range of 126 - 127 ⁰ C (acetonitrile).

efe »" "« "#

Analogously to variant A, but instead of sodium hydroxide solution, 0.56 parts of methylal sodium metatate solution (5 mol / l) are used. The yield is 0.53 parts (63 %).

Variant C ^

Analog variant A, but instead of sodium hydroxide Ό, 4ο parts of triethylamine are used. The yield is 0.29 parts (35 %).

Variant D

0.46 parts III (R = OC ₂ H ₅ ) hydrochloride are reacted analogously to variant A. However, instead of sodium hydroxide, 1 part of sodium acetate is used. The yield is 0.33 parts (39 ^) ..

Variant ^ E

Analog variant A, but the reaction is carried out without sodium hydroxide solution. The yield is 0.55 parts (66%)

Example 2

Compound I with R ¹ = C ₆ H ₄ (P) CH ₃ and R ²

To the mixture of 20 parts of acetonitrile and 0.34 part of III (R ² = OC ₂ H ₅ ) is added with stirring 1 part II (R ¹ = CgH ₄ (P) CH ₃ , X = ClO ₄ ). The mixture is stirred for 10 min. At room temperature and then filtered.

The filtrate is concentrated to dryness. The residue is washed with water and recrystallized from acetonitrile. This gives 0.51 parts C 59 %) of the final product, which has a melting range of 121 - 126 C (benzene / gasoline).

Example 3

Compound I with R ¹ = CgH ₄ Cm) GH ₃ and R ² = OG ₂ H ₅

1 part II (R ¹ = C ₆ H ₄ Cm) CH ₃ , X = GlO ₄ ) is analogous to Example

2 implemented. This gives 0.39 parts (45 %) of the final product, which has a melting range of 112 - 116 ° C (benzene / gasoline).

Example 4

Compound I with R ¹ = C ₆ H ₄ Cp) OCH ₃ and R ² = OC ₂ H ₅

To the mixture of 20 parts of acetonitrile and 0.34 part of III CR ² = OC ₂ H ₅ ) is added with stirring 1 part II CR ¹ = C ₆ H ₄ Cp) OCH ₃ X = ClO ₄ ). The mixture is stirred for 10 min. At room temperature and then concentrated to dryness. The residue is washed with water and recrystallized from acetonitrile. This gives 0.49 parts (56%) of the final product, which has a melting range of 15o - 152 ⁰ C (benzene / gasoline).

Example 5

Compound I with R ¹ = C ₆ H ₄ Cp) Cl and R ² = OC ₃ H ₅

1 part II (R ¹ = G ₆ H ₄ Cp) Cl, X = J ₃ ) is reacted with 0.18 parts III (R ² = OC ₂ H ₅ ) in 40 parts of acetonitrile analogously to Example 2 to. This gives 0.25 parts (48 %) of the final product, which has a melting range of 193-198 ⁰ C (benzene / gasoline).

Example 6

Compound I with R ¹ = CgH ₅ and R ² = CH ₃

To the mixture of 0.26 parts of III (R ² = CH ₃ ) and 1 part of ITatriumacetat in 10 parts of dimethylformamide 1 part II (R ¹ = CgH ₅ , X = ClO.) Is added with stirring • The approach is 10 min. At Room temperature is stirred. 10 parts of water are added to the batch and the product is filtered off with suction. This gives 0.54 parts (71 %) of the final product, which has a melting range of 170 172 ⁰ C (chlorobenzene).

2 0.7 parts of III (R = CH ₃ ) are reacted analogously to variant A. The yield is 0.62 parts (81%).

Example 7

Compound I with R ¹ = R ² = CH ₁ -

0.44 parts of III (R ² = CgH ₅ ) are reacted analogously to Example 6, variant .A. This gives 0.39 parts (42 %) 'of the final product, which has a melting range of 259 - 261 ⁰ C (chlorine benzene).

Example 8

Compound I with R ¹ = CrH, - and R ² = Cz-H ₇₁ (D.

0.50 parts of III (R ² = CgH ₄ (P) CH ₃ ) are reacted analogously to Example 6, variant A. This gives 0.55 parts (57 %) of the final product, which has a melting range of 229-230 ° C. (chlorobenzene).

Claims (3)

-J Erfindungsansprüehe 1. A process for the preparation of substituted 5-cyanopyrimidines, characterized in that 3,5-diaryl ~ 1,2,4-dithiazolium salts of the type II, II where R is a substituted or unsubstituted aryl or hetaryl radical and X is an acid radical anion, such as CIOT, Cl "", Br "~, jT or PeCl7, with substituted β-iminopropionitriles of type III, which can each be present in the form shown here or as isomers (enamines) - MH Il III where R is an alkyl radical (C ₁ -C ₂ ), a substituted or unsubstituted aryl or hetaryl radical or an alkyloxy radical (with alkyl: C ₁ to C ₁₂ ), to the substituted 5-cyanopyrimidines of type I, wherein R and R have the meaning given above, are reacted. 2. Method according to item 1, characterized in that the reaction using auxiliary bases, such. Alkali hydroxides, alkali alcoholates, tertiary amines, e.g. Triethylamine or alkali salts of weak acids, such as. TTatriumacetat or sodium carbonate is performed. Method according to item 2, characterized in that the substituted β-iminopropionitriles (III) are used as salts, e.g. Hydrohalides, hydrogen sulfates, sulfates or perchlorates are used.