DE1445796A1 - Process for the preparation of triazolone derivatives - Google Patents

Description

Process for the preparation of triazolone derivatives Bs has been found that triazolone derivatives of the general formula in which R1 stands for B, an aliphatic or optionally substituted aromatic radical, R2 stands for H or an optionally substituted aromatic radical and R3 stands for II or the group where R is an aliphatic radical substituted by electron-withdrawing atoms or groups or an optionally substituted aromatic radical Boll, is obtained when the reaction products of cyanic acid stars of the general formula R - OCN. II where R has the meaning given above, and semicarbazides of the general formula where R1 and R2 have the meaning given above, in a molar ratio of 1: 1 or 2: 1, which, according to a separate, older proposal (German patent. ... ... (note P 42 737 IVb / t2 o) and German Patent. ... (Note F 44 636 IVb / 12 o)), preferably converted into the ring compounds according to the invention in a liquid medium at temperatures of 100 to 20,000 with elimination of a radical ROH. The process is exemplified by the reaction of 4- (p-methylphenyl) semicarazide (III: R2 = 4-methyophenyl and R1 = H) with 1 or 2 moles of 3-chlorophenyl cyanate (II: R = 3-chloro) phenyl-) explained: R2RN p2 -'C = 0 0 = 0 HN - 1) II + III 1 -ROH N1 - - NH --- + BO m ' IV Ia (R2 = 4-methylphe- nyl) R2HE - 0 = 0 R2 - -BOH m 0 = 0 -RAW t HN = O c = o 2) 211 + III NN C = NH C = NH 6R OR V Ib (R2 = 4-methylphe- nyl R = 3-chlorophenyl) In general, the reaction is carried out in one stage from II and III without isolating the primary addition products IV or V. Ib can also be reached from IV by adding a further Mole II via V. The reaction temperature is 10 to 20,000, preferably 100 to 1000C. The connections with R3 are new.

Aliphatic radicals R are, for example, alkyl, alkenyl, cycloalkyl and cycloalkenyl radicals. Electron-withdrawing substituents of these radicals are, for example: Halogen, acyl, ketone, carboxylic acid, carbon ester, sulfonic acid, sulfonic acid ester, Nitro, cyano and acetylene radicals, especially in the # or 13-position to the oxygen-carrying one C atom.

The aromatic radicals R are 5- and 6-membered aromatic hydrocarbon radicals with up to 20 carbon atoms in question.

As heterocyclic radicals R there are, for example, 5- and 6-membered ones aromatic ring systems in question, one or more nitrogen, oxygen or Contain sulfur atoms.

The aromatic or heterocyclic radicals can be used as substituents for example carry: alkyl, aryl, alkylsmino, acylamino, nitro, halogen, Alkoxy, aroxy, acyloxy, arbonyl, carboxyl-S carbon ester, amide, sulfonyl, sulfonic acid ester, amide, acyl, cyano, rhodanide, alkyl mercapto, aryl mercapto or acyl mercapto residues.

The cyanic acid esters used as starting compounds can according to own older proposals by implementing hydroxyl-containing compounds with halogen cyanides at temperatures, preferably below + 650C, if appropriate be prepared in a solvent in the presence of a base.

It can be used for the inventive method, for. B. the following cyanic acid esters are used: phenyl cyanate, mono- and polyalkylphenyl cyanates such as 3-methyl-, 4-isododecyl-, 4-cyclohexyl-, 2-tert-3utyl-, 3-trifluoromethyl-, 2,4-dimethyl-, 3,5-dimethyl-, 2,6-diethyl-, 4-allyl-2-methoxyphenyl cyanate; Aryl phenyl cyanates such as 4-cyanatodiphenyl, 4,4'-biscyanatodiphenyl; Dialkylaminophenylcyanates such as 4-dimethylamino, 4-dimethylamino-3-methylphenylocyanate; Acylaminophenyl cyanates such as acetylaminophenyl cyanate; Nitrophenyl cyanates such as 4-nitro, 3-nitro, 4-nitro-3-methyl, 3-nitro-60methylphenyl cyanate; Halophenyl cyanates such as 2-chloro, 3-chloro, 4-chloro, 2,4-dichloro, 2,6-dichloro, 3-bromine, 2-chloro-6-methyl-phenyl cyanate; Cyanatophenyl carboxylic acids, esters, amides such as 4-cyanatobenzoic acid, 2-cyanatobenzoic acid ethyl ester, 2-cyanatobenzoic acid morpholide and diethylamide; Cyanatophenylsulfonic acid, esters, amides such as 4-cyanatobenzenesulfonic acid; Alkoxyphneylcyanats such as 2-Nethoxy-, 3-Methoxy-, 4-Isopropoxyphenylcyanat; Phenoxyphenyl cyanate such as 4-cyanatodiphenyl ether; Acyloxyphenyl cyanates such as 3-acetoxyphenyl cyanate; Acyl phenyl cyanates such as 4-acethylphenyl cyanate; Cyanatophenyl cyanates such as 2,3-dicyano-1,4-dicyanatobenzene; # - and ß-naphthyl cyanate, anthrachinyl cyanates such as 1,4-dicyanatoanthraquinone; Quinoline cyanates such as 5-cyanatoquinoline; cyanatopyrazoles such as 5-cyanato-1-phenyl-3-methyl-yrazole, 1,4-phenylenedicyanate, 1,5-naphthylenedicyanate, 1,3,5-tricyanatobenzene, 4,4'-biscanato-diphenyldimethylmethane, 4,4'-biscyanatodiphenyl-cyclohexane-1,1, 2,2'-biscyanatodinaphthyl, 4-methyl mercaptophenyl cyanate, 3-N, N-dimethylcarbamylphenyl cyanate, and the canic acid esters of the following alcohols: ß, ß, ß-trichloroethanol, ß, ß, ß-trifluoroethanol, ß, ß, ß-tribomethanol, butyne- (2) -diol-1,4, acetylacetone (enol form reacts), icetoacetic ester (enol form), cyclohexen- (1) -ol- (1) -one- (3), hydroxyacetone, 2Nitroethanol, ß, ß-dichloroethanol, hydroxyacetonitrile, ethyl hydroxyacetate.

As R1 come hydrogen, alkyl radicals such as Methl, ethyl, n- or isopropyl, Butyl and aryl radicals such as phenyl are possible.

R2 should mean hydrogen or aryl radicals which are also substituted can be, for example by alkyl, aryl, halogen, nitro, aroxy, alkoxy, Alkylamino, acyl, cyano, alkyl mercapto or aryl mercaptores.

For example, the following can be used for the method according to the invention Semicarbazide derivatives can be used: semicarbazide, 4-phenylsemicarbazide, 4- (2'-, 3'- or 4'-halophenyl) -seiicarbasid, halogen such as fluorine, chlorine, bromine, iodine, 4- (2'-, 3'- odor 4'-alkylphenyl-) semicarbazide, alkyl with 1 - 12 carbon atoms, 4- (2'-, 3'- or 4'-nitrophenyl) -semicarbazide, 4- (2'-, 3'- or 4'-Akoxyphenyl) -semicarbazide, Alkyl with 1 - 4 carbon atoms, 2-methyl-semicarbazide, 2-phenyl-semicarbazide, 2-methyl-4-phenyl-semicarbazide, 2,4-Diphenyl-semicarbazide.

The solvents used are water, alcohols, ethers, nitriles, bsters, Amides, aromatic and aliphatic, optionally halogenated or nitrated Hydrocarbons into consideration.

An addition of bases such as triethylamine, pyridine, diethylaniline, NaOH, NaOCH3, Na2CO3 or the corresponding potassium compounds can be used for the reaction be beneficial. The inventive method is carried out at temperatures between 10 and 2000C, preferably between 10 and 1000C. You can get the components mix in any order to carry out the process, preferably in a liquid medium. It is generally used to produce the Compounds according to the invention with R3 = H the components cyanate and semicarbazide in a molar ratio of 1: 1, for the preparation of the compounds according to the invention with R3 = C-OR the components cyanic acid ester and semicarbazide in a molar ratio of 2: 1. Instead of In the latter case, 2 moles of cyanate can also be used for 1 mole of cyanate on isolated iminocarbaroxy (or alkoxy) semicarbazide (from 1 mol of oyanoic acid ester and 1 mole of semicarbazide (German patent. ... ... (note F 42 737 IVb / 12 o) produced) let absorb. The products of the process are mostly, if necessary after concentration of the solvent, isolated by suction. Are the not ring-closed ones created Products IV or V with, these are removed by suitable solvents.

The compounds I according to the invention are slightly off in the IR spectrum A distinction should be made between normal 1: 1 and 2: 1 addition products IV and V, respectively. You wise a characteristic band at 5275 except for, which is absent at IV and V, respectively.

Example 1: To a mixture of 4.95 g (0.03 mol) 4- (p-methylphenyl) -semicarba @ id and 30 ml of ethanol are added 9.18 g (0.06 Hol) of 3-chlorophenyl cyanate at room temperature. When heated up to about 40 - 500C, solution occurs temporarily, then solidifies the mix largely.

After suctioning off, 8.3 g (= 83% of theory) are obtained crude yield of: which melts after cleaning by boiling with ether at 1630C. The IR spectrum shows a strong band at 5.75-5.80 u. analysis: C16H14ClN5O2 (343.5) calc. : C 55.9% H 4.08% E 20.4% 0 9.32% C1 10.35% Found: C 55.23% H 4.06% N 2046% 0 9.39% Cl 10, 20% Example 2: 4.53 g (0.03 mol) of 4-phenyl-seimcarbazide are placed in 30 ml of methanol. After adding 9.18 g (0.06 mol) of 3-chlorophenylycanate, the temperature rises to 65 ° C. despite ice cooling. After 30 minutes, the precipitated product is filtered off with suction and washed with ether. 7.4 g des are preserved in this way. After concentrating the filtrate, 6.3 g of oily product remain (predominantly m-chlorophenol), from which a further 0.7 g of the reaction product are precipitated with ether.

Total yield: 8.1 g (= 82% of theory). Mp. After purification: 180-181 ° C. IR: strong band at 5.75-5.80 μ Analysis: C15H12ClN5O2 (329.5) molar weight calculation . : c 5496% H 3.64% N 21.3% 0 9.72%% Cl 10.8% 329.5 found: C 54.61% H 3.93% N 21.00% 0 9.90 % Cl 10.60% 325 Example 3: Analogously to Example 1, 4- (p-methylphenyl) semicarbazide hydrochloride and 2,4-dimethyphenylcyanate in an alcohol / water mixture in addition to 1-iminocarb- (2,, 4-Dimethyphenoxy) -4- (p-tolyl) -semicarbazid in a smaller amount the 909804/1312 by fp. 2080C.

The latter product precipitates directly in the reaction and can be isolated by suction.

IR: strong band at 5.75 - 5.80 # analysis: C18H19N5O2 (337) calc .: C 64.2% H 5.6% N 20.7% 0 9.5% found: C 64.53% H 5.82% N 20.72% 0 9.70% Example 4:, 2.5 g of that according to the German patent. ... ... (Note F 42 737 IVb / 12 o) obtained from phenyl cyanate and 4-phenyl semicarbazide are dissolved in 50 ml of alcohol, treated with 1.1 g of phenyl cyanate and slowly heated to about 6000. 1.5 g of the fall from the melting point 178 ° C /, which are isolated by suction.

IRt Strong band at 5.75 -5.80 µ Analysis: C15H13H5O2 (295) Calc .: C 61.0% H 4.4% X 23.7% 0 10.85% Found: C 61.21% H 4.53% X 23.37% 0 11.46% example 5: 1 g of 2-methyl-4-phenyl-semicarbazide is mixed with 1 g of ß, ß, ß-trichloroethyl cyanate in 7.5 ml of alcohol refluxed for one hour.

0.35 g des with a melting point of 164 ° -167 ° C. precipitate and are isolated by filtration with suction.

Another 0.25 g are precipitated from the filtrate with ether.

Total yield: 52% of theory

IR: Strong band at 5.8 to 5.9μ Analysis: C9H10N4O (19G) Calc .: C 56.8% H 5.25% N 29.5% 0 8.42% Found: C 56.82% H 5.52% N 29.11% 0 8.96% Example 6: Analogously to Example 5, 2,4-diphenyl-semicarbazide is used instead of 2-methyl-4-phenyl-semicarbazide of m.p. 219-221 ° C.

IR: strong band at 5.8 to 5.9 µ analysis: C14H12N4O (252) calc .: C 66.6% H 4.77% N 22.2% 0 6.35% found: C 66.64% H 5.03% N 22.00% 0 6.71% Example 7: Analogous. Example 5 is obtained from 2-phenyl-semicarbazide hydrochloride and 1 equivalent of 4-methyl-phenylcyanate in alcohol at 80 ° C. in addition to 1-imino-carb- (4-methylphenoxy) -2-phenylsemicarbazide in a small amount. of melting point 271 ° C II: Strong band at 5.8-5.9 µ Analysis: C8H8N40 (176) calc .: C 54.5% H 4.55% N 31.8% 0 9.1% Gef. : C 54.33% H 4.77% N 31.21% 0 9.78% Example 8: Analogously to Example 5, 4-phenyl-semicarbazide and phenyloyanate give the from the raw Fp. 231 ° C calc .: X 31.8 7 found: N 30.96%

Claims (1)

Claim: 4 process for the preparation of triazolone derivatives of the general formula in which R1 is H, an aliphatic or optionally substituted aromatic radical, R2 is H or an optionally substituted aromatic radical and R3 is H or the grouping NH -C-OR, where R is an aliphatic or substituted by electron-attaching atoms or groups optionally substituted aromatic radical, characterized in that 1 or 2 mol of a cyanic acid ester of the general formula R - OCN where R has the meaning given above, with 1 xol of a semicarbazide of the general formula in which R1 and R2 have the meaning given above, optionally in a liquid medium and optionally with the addition of a base at temperatures from 10 to 2000C. Triazolone derivatives of the general formula in which R1 stands for H, an aliphatic or optionally substituted aromatic radical, R2 stands for H or an optionally substituted aromatic radical and R3 stands for the grouping stands, where R is intended to mean an aliphatic radical or an optionally substituted aromatic radical substituted by electron-withdrawing atoms or groups.