DD149666A1 - PROCESS FOR THE PREPARATION OF 6-AMINO AND 6-HYDROXY-1-ARYL-5-CYAN-2 (1H) -PYRIDINONE AND THIONES - Google Patents

Abstract

The title compounds which can be used as intermediates are made available according to the invention by a simple process by adding the addition compounds of enamines with isocyanates and isothiocyanates (substituted beta-aminoacrylic acid amides and thioamides) with malononitrile to substituted 6-amino-1-aryl-5 -cyan-2 (1H) -pyridones and -thionen IV and be reacted with Cyanessigsaeureester to substituted 6-hydroxy-1-aryl-5-cyano-2 (1H) -pyridinonen.

Description

Title of the invention

Process for the preparation of 6-amino and 6-hydro: -; y-1-aryl-5-cyano-2 (1H) -pyridinones and -thiones

Field of application of the invention

The invention relates to a process for the preparation of substituted 6-amino and 6-hydroxy: 7-1-aryl-5-cyano-2 (11I) -pyridines and -thiones. Such compounds may become important as intermediates, e.g. for the production of pharmaceuticals or dyes.

Characteristic of the known technical solutions

It is known that after J. prakt. Chen. 312 , 533 (1970) substituted 6-amino-1-aryl-5-cyano-2 (1H) -pyridinethiones can be prepared by addition of arylsenefins to Xlidenmalonitrile, but a generalization of the synthesis is limited. Furthermore, the same compounds according to J. prakt, Chem. Ss1 ^ _t 679 O973) also arise from special Thiopyranthionen and prim. amines; but H ₂ S is released. Of the substituted 6-amino-1-phenyl-2 (1H) -pyridinones, the 4-, 5-yetramethylene compound according to J. prakt. Chem. 312 , 537 (1970) has only been prepared in many stages via the corresponding thione in small amounts , Also known are the 4-methyl compound according to Austr. J. Chera. 28, 531 (1975) and the 4-, 5-trimethylene according to Pol. J. Chem. 2, 295 (1973), they are made of malononitrile and the corresponding ß-keto acid anilides, which must be synthesized in the latter example only over several stages, for example from an enamine. In addition, a. Generalization of these syntheses, which include other products

220066

can arise, be difficult. Furthermore, the structures formulated in the latter citation do not agree with the actual experimental results. "Simple 1-position unsubstituted 6-hydroxy-5-cy, 2-pyridinones are known for simple preparation processes (compare Heterocyclic Compounds, Vol 14-, Supplement 3, pp. 625, 879 and the literature cited therein), these are obviously not suitable for the synthesis of 1-aryl derivatives.

Object of the invention

The aim of the invention is, substituted amino and hydroxypyridinones u. -thione in a simple manner.

Explanation of the invention of the invention

The object of the invention is to produce new, as well as already known 6-amino and 6-hydroxy-2-pyridones and -thiones by a simple process. ^In accordance with the invention, the object is achieved by reacting the addition compounds of enamines and isocyanates as well as isothiocyanates, which are substituted .beta.-aminoacrylamides and thioamides of the general formula I,

R ₀ N -C = CCHH-R ³ I

^ά L Ιο Il

R 'R ^ X

Ί 2

wherein R and R represent a hydrogen atom, an Alley I, aryl or cyclic linking alkyl group and NR _{3 represents} a pyrrole

3 rolidino-, morpholino-, piperidino- or dialkylamino radical, R is an aryl group or X is an oxygen or sulfur atom, with malononitrile II

NC - CH ₂ - CN II

in a solvent at 60-120 ° to the 6-amino-1-aryl-5-cyano-2 (1H) -pyridinones and -thiones of general formula III,

_ 3_ 220 0 68

Where Y is an acyno group and R, R, R and X have the abovementioned meaning, are reacted under identical conditions .beta.-aminoacrylic acid amides of the formula I in which

1 2 3

R, R, R have the abovementioned meaning and X represents an oxygen atom, with cyanoacetic esters IV

HC - CH ₂ - CO ₂ alkyl ^; * IV

be implemented, resulting in 6-hydroxy-1-aryl-5-cyano-2 (1H) -pyridinone of the general formula III. in the X an oxygen atom. Y

1 2 3

represents a hydroxy group and R, R, R ^ have the abovementioned meaning.

The starting materials I are prepared according to known, e.g. in progress Chem. Forsch. 14, 235 (1970).

embodiments

Example 1: 6-Amino-3- ^Z- 1-pentamethylene-1-phenyl-5-cyano-2 (1H) -pyrinthine-thione

0.01 mol of 2-morpholino-cyclohepten- (1) -thiocarbonsäureanilid be together with 0.015 mol of malononitrile in 15-20 ml abs. Ethanol heated for 2 hours under reflux. After cooling and trituration, the product crystallizes out. It is filtered off, washed with a little cold ethanol and recrystallized from ethanol. Yield 63%, Schrap. 234-237 ⁰ C.

Example 2: 6-Amino-3-ethyl-1-phenyl-5-cyano-2 (1H) -pyridinethione

0.01 mol of 1-pyrrolidino-n-butene-1-thiocarboxylic acid (2) -anilide are refluxed for 2 hours together with 0.011 mol of malononitrile in 10 ml of n-propanol. After 10 hours The precipitate is filtered off with suction, washed with water and recrystallized from acetonitrile. Yield 78 % _t m.p. 202-203 ⁰ C.

_4- 220068

Example 3? 6-Amino-1,4-diphenyl-5-cyano-2 (1H) -pyridinethione

0.01 mol of β-morpholino-thiocinnamic anilide and 0.015 mol of malononitrile are heated to boiling in 40 ml of methanol with the addition of 2 ml of glacial acetic acid and 1 ml of piperidine for 1 hour. Thereafter, the reaction mixture is treated with 20 ml of 4N KOH and again

1 min. Heated to a low boil. After cooling, it is stirred with 50 ml of water, filtered off, washed with water and recrystallized from glacial acetic acid. Yield 61% \ mp, 232-236 ⁰ G.

Example 4: 6-Amino-3, ^/ ! -Tetraniethylene-1-phenyl-5-cyano-2 (1H) -pyridinethione

0.01 mol of 2-morpholino-cyclohexene-1-thiocarboxylic acid anilide are heated to boiling for 2 hours together with 0.014 mol of malononitrile in 15 ml of n-propanol. After cooling, the mixture is diluted with 50 ml of water, filtered off with suction, washed with water and converted from Mtroniethan umkr istall. Yield 60%, mp. 261-264 ⁰ C.

Example 5: 6-Amino-3,4-trimethylene-1-phenyl-5-cyano-2 (1H) -pyridinethione

0.01 mol of 2-morpholino-cyclopenten- (1) -thiocarboxylic acid anilide and 0.012 mol of malononitrile are dissolved in 15 ml of n-propanol

2 hours to boiling. After cooling, it is stirred with 50-60 ml of water and filtered with suction. The product is heated to boiling point in 5 l of ethanol with the addition of 5 l of 4N KOH for 5 min. After cooling, 20 ml of 7 / asser are added, filtered off with suction and recrystallized from ethanol. Yield 60 % _t m.p. 263-266 ⁰ C.

Example 6: 6-Amino-3,4-trimethylene-1-phenyl-5-cyano-2 (1H) -pyridinone

A solution of 0.01 mol of 2-morpholino-cyclopenten- (1) -carboxylic acid anilide, 0.011 mol of malononitrile and 3 ml of piperidine in 20 ml of n-propanol is heated to boiling for 1 hr. After cooling, the product is filtered off with suction, washed with water and recrystallized from ethanol. Yield 71%, mp. 279-283 ⁰ C.

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Example 7: 6-Amino-3 »4-tetramethylene-1-phenyl-5-cyano-2 (1H) -py'ridinone

0.01 mol of 2-morpholinocyclohexene (1) -carbonsäureanilid and 0.014 mol of malononitrile are heated together with 15 ml of n-propanol with the addition of 2 ml of piperidine for 1.5 hours under reflux. After trituration, the product crystallizes out, which after washing with suction is washed with water and recrystallized from nitromethane. Yield 62%, mp 276-278 ⁰ C.

Example 8: 6-Amino-3 »4-pentamethylene-1-phenyl-5-cyano-2 (1H) -pyridinone

0.01 mol of 2-morpholinocyclohepten- (1) -carbonsäureanilid be heated together with 0.014 mol of malononitrile in 15 ml of n-propanol for 1 hr. Reflux. The precipitate which has already precipitated out in the heat is filtered off with suction after cooling and recrystallised from ethanol. Yield 83% \ mp. 254-257 ⁰ C.

Example 9: 6-Amino-1,4-diphenyl-5-cyano-2 (1H) -pyridinone

0.01 mol of β-morpholino-zirate acid anilide and 0.011 mol of malononitrile are heated to boiling point in 40 ml of n-propanol for 2 hours. It is then evaporated in vacuo to near dryness, the residue is filtered off with suction and recrystallized from ethanol. Yield 51% »mp 288-290 ⁰ G.

Example 10: 6-Amino-3,4-tetramethylene-1- (p-tolyl) -5-cyano-2 (1H) -pyridinethione

0.01 mol of 2-morpholino-cyclohexene (1) -thiocarboxylic acid p-toluidite are heated to boiling with 0.014 mol of malononitrile in 10 ml of n-propanol for 2 hours. After 2-3 days. Standing precipitate precipitate, which is filtered off and recrystallized from ethanol. Yield 59%, ⁰ CMp. 238-241 ⁰ C.

Example 11: 6-Amino-3,4-tetramethylene-1- (oC-naphthyl) -5-cyano-2 (1H) -pyridinethione

0.01 mol of 2-morpholino-cyclohexene (1)-carbothioic acid 0 £ naphthylamide are heated with 0.014 mol of malononitrile in 10 ml n-propanol, 2 h _e boiling. After standing overnight, the

220 068

decanted off the precipitated oil, the oil with 10 ml of ethanol and 5 4N KOH and boiled for 10 min. After cooling, it is diluted with 100 ml of water and the precipitate is filtered off with suction and recrystallized from ethanol. Yield 66%, mp 229-232 ⁰ C.

Example 12: 6-Hydroxyt-3 _> 4-trimethylene-1-phenyl-5-cyano-2 (1H) -pyridinone

0.01 mol of 2-morpholino-cyclopenten- (1) -carbonsäureanilid and 0.012 mol of ethyl cyanoacetate are heated for 2 hrs. In 15 ml of n-propanol to boiling. After cooling to about 60 °, a solution of 0.23 g of sodium in 10 ml of abs. Ethanol to and heated for 30 min. To boiling. The reaction mixture is allowed to cool and diluted with 75 ml of water. From a slight greasy precipitate is separated and with half konz. Hydrochloric acid acidified. To. 12 h, the precipitate is filtered off with suction and recrystallized from acetonitrile. Yield 59%, mp 276-279 ⁰ C.

Example 13: 6-Hydroxy-3,4-tetramethylene-1-phenyl-cyano-1- (IH) -pyridinone

0.01 mol of 2-morpholino-cyclohexene (1) -carbonsäureanilid be heated with 0.012 mol of cyanoacetic acid ester 1.5 h in 15 ml of n-propanol to boiling. The precipitated after standing for several hours morpholine salt is filtered off with suction and recrystallized from nitromethane, yield 57%, mp. 219-222 ⁰ C. The free hydroxy compound is obtained by dissolving the morpholinium salt in a little water and displacing the solution with dilute sulfuric acid. Schmp. 264-267 ⁰ C

Claims (1)

_ ₇ _ 22 0 0 68 E _r claim entitlement A process for the preparation of substituted 6-amino- and 6-hydroxy-5-cyano-2-pyridinones and -thionen., Geken η characterized in that substituted ß-Aminoacrylsäureamide and thioamides of the formula I ,. , RN -C = GCR ³ I R ¹ ir x v / orin RoN is a morpholino, pyrrolidino, piperidino or dialkyl 1 ~ 2
kylaminogruppe, R and R is an aryl or alkyl group, a cyclic linking alkyl group or a V / asserstoffatom, R ^ is an aryl radical and X is an oxygen or sulfur atom, in a solvent, preferably an alcohol or dimethyl. formamide, with GO-120 ⁰ with malononitrile II NC - CH ₂ - CN II to the substituted 6-amino-1-aryl-5-cyano-2 (1H) -pyridinones and -thiones of the general formula III, R ¹
R ² ' III X 1 2 ^ in which Y represents an amino group and R, R, R ^J and X have the abovementioned meaning and ß-Aminoacrylsäurearnide of the formula I, wherein X is an oxygen atom and R, R ^ ", R ^ have the meaning given under the same conditions with cyanoacetic esters IV NC - CH ₂ - CO ₂ alkyl IV to the 6-HydroAy-1-aryl-5-cyano-2 (1H) -pyridinone of the general formula III in which X represents an oxygen atom, Y represents a hydroxy group and R, R, R ^ have the meaning indicated above, are reacted _e