HU187275B - Process for producing 2-bracket-4-substituted-phenyl-bracket closed-5-cyano-pyrimidines - Google Patents

Abstract

The invention relates to a novel process for the preparation of 5-cyano-2- [4-substituted-phenyl] -pyrimidines which, owing to their favorable crystalline-liquid properties, e.g. can be used in optoelectronic devices. The object of the invention is the simple production of 5-cyano-2- [4-substituted-phenyl] -pyrimidines in high yields. It has been found that crystalline-liquid 5-cyano-2 [4-substituted-phenyl] -pyrimidines of the general formula, by condensation of 4-subst.-Benzamidinhydrochloriden with alpha-cyano-beta-dimethylamino-acrolein in pyridine and / or triethylamine or other strong organic bases with very good yield in a reaction step can be produced. formula

Description

Object of the invention

SUMMARY OF THE INVENTION It is an object of the present invention to provide high yields of 2- (4-substituted-phenyl) -5-cyanopyrimidines.

187 275

Field of the Invention

The present invention relates to a novel process for the preparation of 2- (4-substituted-phenyl) -5-cyanopyrimidines of the formula (I). Because of their favorable properties, these compounds can be used, for example, in the manufacture of optoelectronic components.

Features of the prior art

Various processes for the preparation of substituted 5-cyanopyrimidines are described in the literature. These include 5-bromo or 5-iodo-pyrimidines with copper (I) cyanide [C. C. Price, et al., J. Am. Chem. Soc. 68, 766 (1946); D. J. Brown et al., J. Chem. Soc. (C) 1967, 903] or pyrimidine alkoxymes with thionyl chloride or acetic anhydride [H. Bredereck et al., Liebigs Ann. Chem. 766, 73 (1972)]. However, in these cases the synthesis of the starting compounds is very complicated.

2- (4-Substituted phenyl) -5-cyanopyrimidines have been prepared so far [A. Boller et al., Mol. Cryst. Liqu. Cryst. 42, 215 (1977)]:

In Scheme (a), a 4-substituted benzamidine hydrochloride is condensed with ethyl ethoxymethylenemalonic acid diethyl ester to give 2- (4-substituted-phenyl) -5-ethoxycarbonyl-6-hydroxypyrimidine, followed by the addition of the hydroxyl group of the compound to and in the fourth step, the ethoxycarbonyl group is converted to the cyano group.

This synthesis route consists of four steps. As a result, it is costly and generates relatively low yields, since the yield of each step is not quantitative. The same authors disclose a very time-consuming process for the synthesis of these compounds in the alkali salts of the alkali metal salts of 4-substituted-benzamidine hydrochlorides and acetalized hydroxymethylenecyanoacetaldehydes in U.S. Patent No. 124,734 and German Patent Publication No. 2,547,737. by. These patents, however, do not include yield data. Column chromatography of the bama oily product obtained in Example 6 also shows that this process is not problem-free, and the authors also strive to find a new synthesis route.

The reaction in aqueous solution is expected to lead only partially to nitrile. Detailed studies by W. D. Kermer (Dissertation, Marburg 1972) and H. Zaschke (Dissertation, Halle 1977) have shown that in the presence of water the corresponding acid amides are formed instead of nitriles.

BRIEF DESCRIPTION OF THE INVENTION

It is an object of the present invention to provide a novel process for the preparation of these compounds.

We have found that the 2- (4-substituted-phenyl) -5-cyanopyrimidines of formula (1)

R is C _n H _{2n +)} O, C _n H _{2n + 1} , C _n H _{2n + 1} S, C ₁ H _{2n + (} NH, C 1-4 CH / N, C 1-3, OCOO, CH ₂ CO, OH, NH _2). , 4-R ¹ -C ₆ H ₄ COO, 4-C.Hj, ₊₁ cyclo-C ₆ H, _o -COO wherein

R ¹ is C _n H _{2n + l,} C "H _{2n + l} O, C _n H _{2n + l} COO, C" H _{2n + 1} OCOO, C _{n H} HFC F; and n is an integer from 1 to 10 - in very good yields, can be prepared in one step by reaction of 4-substituted benzamidine hydrochlorides with a-cyano-P-dimethylaminoacrolein in pyridine and / or triethylamine and / or other strong organic condensation in the presence of bases. This transformation proceeds according to Scheme b).

Example I

Preparation of 2- (4-Hydroxyphenyl) -5-cyanopyrimidine

This compound is prepared according to Scheme b), R is hydroxy.

ml abs. triethylamine, 50 mL abs. pyridine,

A mixture of 17.3 g (0.1 mol) of 4-hydroxybenzamidine hydrochloride and 11 g (0.1 mol) of α-cyano-β-dimethylaminoacrolein is heated with stirring at 80 ° C for 6 hours. The dark brown reaction mixture was poured into a mixture of 500 g of ice and 50 ml of concentrated sulfuric acid, the precipitate was filtered off, washed thoroughly with water and recrystallized from methanol in the presence of activated carbon. Yield: 12.8 g (65%), m.p. 260-262 ° C (sublimal).

Example 2

Preparation of 2- (4-Acyloxyphenyl) -5-cyanopyrimidines

These compounds are prepared by reaction of 2- (4-hydroxyphenyl) -5-cyanopyrimidine with acid chlorides according to Scheme c), according to Einhom or Schotten-Baumann type.

2.97 g (0.01 mol) of 2- (4-hydroxyphenyl) -5-cyanopyrimidine, 0.015 mol of the corresponding acid chloride and 25 ml of abs. The pyridine mixture was stirred at room temperature for 6 hours, then refluxed for 5 minutes and allowed to stand overnight. The reaction mixture was 22

Table 2

Data for compounds of formula (1)

187.275 beets are poured into 300 g of ice and 20 ml of concentrated sulfuric acid, extracted with ether, and the ether phase is washed with 1 N potassium brine, then with water, dried over sodium sulfate, evaporated on a rotary evaporator, and the residue is evaporated several times. Yield 70-90%.

Table I

Data for compounds of formula 2

R ² KSNI

c ₅ h " 107 - _ . 123 c ₄ h ₉ o 121 - _ . 129 . 15 c ₆ h ₁₃ o 83 96 . 121 C _e H ₁₃ - c ₆ H ₄ - 106 112 . 249 CH 3 O - C ₆ H ₄ . 224 - . 334 C, H _U O — c ₆ h ₄ . 130 - . 278 . 20 CjHj | - C _Ö H _1O . 117 192 . 248

Example 3 &

Preparation of 2- (4-Alkyl- and 4-alkyloxyphenyl) -pyrimidines

These compounds are prepared according to Scheme b): R is C _n H _{2fl +} , or C 1 H _{2n t} , O.

40mlabsz. A mixture of triethylamine, 1.1 g (0.01 mol) of α-cyano-dimethylaminacrolein and 0.01 mol of substituted benzamidine hydrochloride or free base was heated at 80 ° C for 6 hours with stirring. The cooled reaction mixture was poured into 150 g of ice and 30 ml of concentrated sulfuric acid, the precipitate was filtered off with suction, washed well with water and then recrystallized several times from n-hexane. Yield 75-95%.

R K S _A N I C ₄ H ₉ O . 119 139 C ₅ H _u O . 97 102.5. 133 c ₆ h ₁₃ o . 92.5 122. 134.5. c ₇ h ₁₅ o . 102 127. 129 c ₄ h ₉ . 109 - - / · 101 /. C.H ,, . 94 / · 93.5 /. 109 c ₇ h ₁₃ . 94 107 - - c ₉ h ₁₂ . 90 107 - -

A patent claim

Claims (1)

Process for the preparation of 2- (4-substituted-phenyl) -5-cyanopyrimidines of formula (1) R is C 2 H _{2n + 1} , C _n H _{2n + 1} O, C _n H _{2n + 1} S, C 1 H _{2n (} , NH, CH ₂ H _{2n + 1} COOO, C _n H _{2n + 1} COO, OH, _NH2, 4-R ¹ -COO-C _e H _4, C-4 "H _{2n +,} cyclo-C _e H ₀ -COO wherein R is C _n H _{2n +} ¹ C _n H _{2n +} ,,, O, C _n H _{2n + l} COO, C _n H ,, _ln OCOO, C _n H _{2n + 1} F; and n is an integer from 1 to 10, characterized in that the 4-substituted-benzamidine hydrochlorides are condensed with α-ω-dimethylamino-acrolein in pyridine and / or triethylamine and / or in the presence of other strong organic bases.