SU610489A3 - Method of preparing 1-phthalazone derivatives - Google Patents

Description

(54) METHOD FOR OBTAINING 1 PHTALAZONE DERIVATIVES that the compound of the general formus is whether CUjOH where J RJ is indicated above is reacted with compounds of the General Formula Bi K-C-Y i. . where cue have the values indicated in the glitter; V-halogen, alkoxy, aryloxy, alkyl, thio or arylthio group, taken in an equimolar or effluent amount {usually an excess of 1.5 to 5 mol), in an inert solvent, sometimes in the presence of a catalyst “New acids can be called unsubstituted, N-mono- or I, N-diaberated carbamyl chlorides, alkylcarbamate, arylcarbamate, alkylthiocarbamate and arylthiocarbamate. Thus, in particular, carbamyl chlorides can be used, for example, carbamyl chloride, methylcarbamyl chloride, methylcarbamyl chloride, d dimethylcarbamyl chloride, N, N-pentamethylenecarfamyl chloride and phenylcarbamyl chloride; alkyl carbamates, for example methylcarbamate, methyl M-methylcarbamate, methyl M-isopropylcarbamate, methyl 14,4-dimethylcarbamate and methyl-, M-ethylenoxostilencarbamate, arylcarbamate, for example, phenylcarbamate, phenyl-M-methyl carbamate and phenyl-N-methyl, for example phenylcarbamate, phenyl-M-methyl carbamate and phenyl-N-methyl, for example phenylcarbamate, phenyl M-methyl carbamate and phenyl-N-methyl, for example phenylcarbamate, phenyl M-methyl carbamate and phenyl N-methyl carbamate; alkylthiocarbamates, for example, methyl-M-methylthiocarbamate, ethyl-N, N-dimethylthi-carbamate and methyl -N, f4 pyridIlthiocarbamate arylthiocarbamate, for example, Nmethylthiocarbamate and Phenyl N, N-pentamethylenic carbamate Ethyl ether tetrahydrofuran, dioxane, hexai, chloroform, benzene, toluene, mono-di- and trichlorobenzene can be used from inert organic solvents. When used as one of the starting compounds of carbamyl chloride, the reaction is carried out in the presence of a two-hydrochloride educt agent, for example, methylmethyleneiline, diethylaniline, M-methylimperidine and pyridine. When working with (carbamate or thiocarbamate, the reaction can be carried out in the presence of acetic acid, organic acid, for example, bwizol sulfonic acid or toluenesulfonic acids, organotin (coenidine), in particular dimethyl oxidol dibutyloxidol and dibutyl diacetate acate and alkali metal, as an example of sodium acetate, and llogol that now- solid metal, such as methi; ata or sodium ethylate, potassium t-butoxide, alkali metal phenol, for example, sodium nitri. In some cases, the yield of the target product can be significantly increased by using aeootropic distillation of the alcohol formed during the reaction. The process is carried out at 50-200 ° C, preferably at 60 -. The final product is isolated and purified with conventional pulses. Example I, A mixture of 4 g of 4-hydroxymethyl-2-methyl-1-phthalazone, 3 g of dimethylaniline, 2 g of methylcarbamyl chloride and 40 MJ of absolute ethyl acetate are heated with an O2 condenser for 5 hours. The reaction mixture is washed successively with water and 3% solution of hydrochloric acid and again with water. The resulting solution is evaporated, the residue is crystallized from a mixture of ethyl acetate and petroleum ether, and 2.2 g of 4- (H-1-methylcarbamoxymethyl, 5-2 g-1-methyl 1 ™) of talazone, mp 115-11 ° C, are calculated. Calculated: C 58 , 29; H 5.30; N 17.00. Found,%: C 59.02; H 5.26; N17.24, Example 2. A mixture of 2 g of 4-C1X-methyl 1-phthalazone, 1.2 g of dimethylcarbamoyl chloride and 30 ml of anhydrous pyridine was heated under reflux for 3 hours. Pyridine was distilled off under reduced pressure, the residue was diluted water and extract with ethyl ether. The extract was washed with 3% hydrochloric acid solution and with cyiuaT water over magnesium sulfate. The ether is distilled off, the residue is crystallized from a mixture of ethyl acetate - petroleum ether, and 1.6 g of 4 - (H, N-dimethylcarbamoxy methyl) -1-phthalazone are obtained, m.p. 174-176 C. Calculated,% uC 58.29; H 5.30 Ni7.00 C - iH jNjOj. Found,%: From 58.2) .; H 5, 36 MI, 22 Example 3: A mixture of 3 g of 4-hydroxymatyl-7-methoxy-1 Ftalazok, 10 g of phenyl-N-methylcarbamate, 0.5 g of sodium acetate and 20 ml of trichlorobenerl for 5 hours heated in a water bath at 80SO C. The low boiling fraction is distilled off under reduced pressure, the residue is extracted with chloroform. The extract is washed with water, the solvent is distilled off. The residue is crystallized from methanol, yielding 2.3 g of 4- {K-methylcarbamoxymethyl) -7-1 methoxy-1-phthalazone, and so on. 219-220 ° C. Calculated.,% Ss 44, 3.68; N12.88. C, jH, jN, 0 ,. Found,% c 43.85 H 3.50 N12.62. EXAMPLE 4 A mixture of 4 g of 7-chloro-4-hydroxymethyl 2-methyl-1 phthalazone, 3 g of dimethylailin, 2 g of methylcarbamoyl chloride is heated to reflux for 40 liters of ethyl ether for 5 hours. Then the reaction the mixture is sequentially water-hydrochloric acid and again with water. The ether solution was dried over magnesium sulfate and the ether was distilled off. The resulting residue was crystallized from ethyl acetate, to give 2.2 g of 7-chloro-4 ™ (M-methylcarbamoxymethyl) -2-methyl-1-phthalazone, m.p. I8-149 with. Calculated,% sC 5i, 15; H 4.26; N14.92 e, an, and NjO ,. Found,% s with 50.89; H 4.35 414.49 P. P and me 5, A mixture of 2 g of 7-bromo-4 ™ hydroxymethyl-1-phthalazone, 1.2 g of dimethyl-carbamoyl chloride and 30 ml of pyridine are heated under reflux for 3 hours. Pyridine is distilled off under reduced pressure, the residue is washed with water, extracted with ethyl acetate. The extract is successively washed with water, hydrochloric acid solution, and again with water, dried and distilled. The residue is crystallized from methanol to give if8 g of 7-5-4- (M, H-dimethylcarbamoxymethyl) -1-phthalazone, m.p. 144-215 0 Calculated: C 44, 3.68 jNl2.88 CiaH jBpNjOj. Found% s With 43.85; H 3.50; N12.62. EXAMPLE A solution of 3 g of 4-hydroxymethyl-1 phthalazone and 5 g of% dimethylaminoethylcarbamoyl chloride in 50 ml of pyridine is heated under reflux for 3 hours. Pyridine is distilled off under reduced pressure, the residue is diluted with water, sodium carbonate is added to alkaline solution and the extract is washed with chloroform. The extract is washed with water and dried. Chloroform is decanted, the rest of the crystals are comfortable with nt ethyl acetate to give 3.2 g of 4- (α-dimethylaminoethyl) -carbamoxymethicl -1 phthalazone, m.p. 148-150 0. Calculated.% Se 57.92jH 6.25fNl9.30. Ci4HieN40r Found: C 57.87; H 6.23; N19.36. EXAMPLE 7 A solution of 2 g of 4-oxnemethyl-1-phthalazone and 3 g of N, f-ethyl methylmethylaminoethyl carbamoyl chloride and 30 MP of pyridine was heated under reflux for 3 hours. Then, pyridine was distilled off under reduced pressure. Water is added to the residue, the aqueous layer is made alkaline with carbonate | 1 and three and extracted with chloroform. The extract is dried over magnesium sulphate and chromatographed on alumina. The eluate is crystallized from methanol to give 1.3 g of 4-f | H, M- (ethylene-methyl-amino-ethylene-carbamoxymethyl) -1-4 talaeona, mp. 152-154 v. C. Number of D: C 59.59; H 6.00 N18.53. t, eHi ,, Found,% i с 5, b1 n 5.89; N18.60. Examples 8-46. By analogy with Examples 1-7 (with the exception of Example 3), the desired compounds were obtained using carbamoyl chloride as one of the starting materials. The yield of the target compounds listed in table 1 reaches 40-70%. T a b l and c a I

nEtil186-188 nAllyl186-188 NCiclohexyl165-168 NBenzyl193-195 NPhenyl223-224 N -Pyridyl194-196 NY-Furfuryl182-184 Pentamethylene155-158 Hp-Picolyl180-182 Ethylene-Oxo-207-209-Ethylensthylendehyde-methylenes-157 -9-ethylenacene-benzylne-154-205-110-182 Ethylene-oxo-207-209-ethylenacene-benthylenophenyl151-158 Hp-Picolyl180-182 Ethylene-oxo-207-209- , Methyl 226-227 216-218 Ethanol-water Methanol Acetone Ethanol-water. Ethyl acetate-pvtrol “Lny ether. Ethanol-water Methanol

The temperature of the ovalat float.

Continued table.

Examples 47-67, Like Example 8 8, the desired compounds listed in Table 2 are prepared by using phenyl carbamate. The yield of the target compounds 60-80%.

EXAMPLE 68. To a solution of 3 g of 4-hydroxymethyl-2-methyl-1-phthalazone and 1.3 g of methyl M-methyl carbamate and 100 ml of n-heptane, 0.3 g of sodium methylate are added. Heptane is gradually distilled off in the reaction mixture, the distillate is fractionated using a Dean-Stark trap, and the

released methanol. (After the recovery of methanol, the reaction mixture is evaporated to approximately half of the original volume, the residue is diluted with ice-water, the heptane is separated and the aqueous layer is extracted with ethyl ether. The heptane solution and the ether extract combine the south and the solvent is distilled off. Residue crystallized from ethyl acetate-petroleum ether to give 1.7 g of 4- (M-methylcarbamoxymethyl) -2-methyl-1-phthalazone, mp 115 Ib C,

table 2

II

n p MI e p 69. A mixture of 1 g of T-chloro-4 xymethyl-1-phthalazone, 3 g of phenylthiocarbamate, 0.2 g of sodium acetate and 15 ml of dioxane is heated at 80 hours for 3 hours. Low-level substances are removed by vacuum distillation. The residue is extracted with chloroform and the extract is gnawed successively with 5% sodium hydroxide solution and water. Chloroform is distilled off and the pitch is crystallized from methanol to obtain 0.5 g of 7-gchlor 4-carboxymethyl-1-phthalaone, m.p. 243-245 С

Rychleleio,% 1C 47, 3.15g N16.56.

with "n, it, oh ,.

Found,% j with 46.88 H 3.25; Nl6.27.

Claims (1)

Invention Formula The method of obtaining lazon derivatives is of the formula   ABOUT AT , . CIHjOCNRjRj TO where H is hydrogen or alkyl H g hydrogen or alkyl, branched or undeveloped, cycloalkyl, alkenyl, aryl, aralkyl, dialkylaminoalkyl, furFURYL / picoyl or primed; Bj is aodoro g pykyl, aryl, carbamoyl, M-alkalkarvamo-35 yl N, M-dialkylcaphylone, alkylsulfonyl, or arylsulfonyl R4 hydrogen, halogen, alkyl, or alkoxyl; K - Dorod, halogen, alkylg alkxnl, amkno, acylamino, alkoxycarbo-40 NIL or carbamoyl "and g can be replaced by those mean alkylene containing or not containing a heteroatom, meaning that a compound of the general formula CHjOH where Bd 4 is indicated above, it interacts with compounds of the general formula,. Bi lf / AT, where y and cd have the indicated values f y are halogen or alkoxy, aryloxy, alkylthio or aryl group. Priority featured: 02.27.71. when R, t is hydrogen or alkyl, and yah hydrogen, straight or branched alkyl, cycloalkyl, alkoyl, aryl, aralkyl, furfuryl, picolyl or pyridyl; Bj is hydrogen, alkyl or arylt a and BS is hydrogen. 08.16.71 when H is hydrogen or alkyl; fc - hydrogen, unbranched or branched alkyl, cycloalkyl, alkenyl, aryl, aralkyl, furfuryl, picolyl or priridyl; Bj is hydrogen, alkyl or arnl; R is hydrogen or halo, alkyl or alkoxy; Bj is hydrogen, alkyl, alkoxy, amino acylamino, alkoxycarboyl, or carOgtoyl, and Ri and a can together mean alkylene, with or without a heteroatom.