PROCESS FOR PRODUCING 2-TERT.-BUTYL-4,5-DICHLORO-3(2H)-PYRIDAZINONE

Abstract: Novel processes for producing 2-tert.-butyl-4,5-dichloro-­ 3(2H)-pyridazinone comprise reacting tert. -butylhydrazine with mucochloric acid in an aromatic hydrocarbon and/or chlorinated hydrocarbon solvent. A novel compound, mucochloric acid-tert.-butylhydrazone, is also provided as an intermediate product.

Description: PROCESS FOR PRODUCING 2-TERT.-tJTn.-415- DICHLORO-3 (2H)-PYRIDAZINONE BACKGROUND OF THE INVENTION (a) Field of the Invention This invention relates to a process for producing 2tert.-butyl-4,5-dichloro-3 (2H)-pyridazinone (hereinafter, referred to as TDCP) which is useful as an intermediate of an active ingredient compound of agricultural drugs, particularly insecticides, acaricides, hematicides, and fungicides. (b) Description of the Prior Art Generally, in the synthesis of 2-alkyl-4, 5-dichloro- 3(2H)-pyridazinone t3) from alkylhydrazine [1] and mucochloric acid (2) starting materials according to the following reaction: EMI1.1 a good yield is resulted by subjecting the reaction mixture to fluxing in an aqueous solution of a mineral acid such as hydrochloric acid or sulfuric acid. For example, 2methyl-4,5-dichloro-3(2H)-pyridazinone can be obtained in a high yield by reflexing a mixture of methylhydrazine and mucochloric acid in an aqueous solution of hydrochloric acid According to the above-mer.tioned method, however, reaction of tert.-butylhydra2ine with mucochloric acid provides a low yield of intended TDCP, and a large amount of by-products such as 4,5-dichloro-3(2N)-pyri8azinone of the formula 14) above and the like is produced. On the other hand, in the method described in U.c.P. No. 4,356,15S, TDCP is produced by neutralizing tert.-buwylhyd-azinf hydrochloride with potassium hydroxide in water-ethanol, reacting the tert. -butylhydrazine with mucochloric acid, distilling off the solvent, adding acetic acid and acetic anhydride to replace the solvent therewith, and refluxing the reaction mixture for about 20 hours to conduct reaction again. Also in this method, however, the yield of TDCP has been low. Thus, there have been problems in conventional methods with respect to separation and purification of TDCP from a large amount of by-products, disposal of by-products, recovery of water-soluble solvents, etc. in addition to practical production of TDCP. As mentioned above, conventional methods for producing TDCP have not been satisfactory for industrial mass production of TDCP. SUMMARY OF THE INVENTION An object of the present invention is to provide a process for producing 2-tert.-butyl-4,5-dichloro-3(2N)- pyridazinone in a good yield. Another object of the invention is to provide a process for producing 2-tert .-bua:yl-4, 5-dichloro-3 (2R)-pyridazinone, in which the aimed product can be readily separate8 from the solvent used and readily purified. Other objects of the invention will be apparent to those skilled in the art from the description given below. The present invention provides a process for producing 2-tert.-butyl-4 ' 5-dichloro-3 (2H)-pyridazinone, which comprises reacting tert.-butylhydra2ine with mucochloric acid in a solvent of an aromatic hydrocarbon and/or a halogenated hydrocarbon. The present invention also provides mucochloric acidtert. -butylhydrazone which is an intermediate of the present process. DETAILED DESCRIPTION OF TRE INVENTION The process according to the invention is represented by the following reaction schemes: EMI4.1 The process represented by the Reaction (1) is a onestage method which comprises cyclization reaction of tert.butylhydrazine with mucochloric acid in a solvent of an aromatic hydrocarbon and/or a halogenated hydrocarbon to give TDCP in a high yield by one stage. The process according to the Reaction (2) is a twostage method which comprises subjecting tert.-butylhydrazine and mucochloric acid to dehydration-condensation reaction to synthesize a novel intermeciate, mucochloric acid-tert.- butylhydrazone1 and then subjecting the intermediate product to dehydration-cyclization reaction in a solvent of an aromatic hydrocarbon and/or a halogenated hydrocarbon to give TDCP in a high yield. The process according to the Reaction (3) comprises reacting, in a solvent of an aromatic hydrocarbon and/or a halogenated hydrocarbon, tert.-butylhydrazine with crude mucochloric acid which has been obtained through oxidative chlorination of furfural or 1,4-butynediol, to give TDCP in a high yield. This process can employ one-stage method or two-stage method as in the process according to the Reactions (1) and (2), respectively. The present inventors have also found that the yield of TDCP can be further increased by aiding a specific organic acid to the reaction mixture in each of Reactions (1), (2)() and (3). The present invention will be explained in detail below. As a tert.-butylhyerazine material to be used in the Reactions ( through (3), can be used tert.-butylhydrazine itself or a mineral acid salt thereof such as the hydrochloride or the sulfate. When such mineral acid salt is to be used, it is preferable to previously treat the salt with a base (such as aqueous Na0H, SOH, Na2CC3 or NaHCO solution, organic acid alkali salt such as sodium formate, sodium acetate, potassium propionate and sodium benzoate or the like), which constitutes one of the important features of the invention. It has also been found that TDCP can be obtain8 in a high yield in the case where a specific organic acid salt of tert.-butylhydrazine such as the formate or acetate salt thereof is used even without pre-treatment. As the mucochloric acid to be used as a starting maternal, commercial available products can be used as they are. Alternatively, crude mucochloric acid obtained through oxidative chlorination of furfural or 1,4-butynediol as shown in the Reaction (3) can be used directly. A tert.butylhydrazine is reacted with preferably about an equal mol of mucochloric acid, and the reaction may be carried out with an excess amount of either one. The most important feature of the invention resides in using an oil-soluble solvent as illustrated below as a solvent in the cyclization reaction in each of the Reactions (1), (2)(B) and (3). Namely, particularly preferred oilsoluble solvents include aromatic hydrocarbons represented by benzene, toluene, xyiene, ethylbenzene, isopropylbenzene, cymene, tert.-butylbenzene, etc.; and halogenated hydrocarbons represented by chloroform, dichloromethane, carbon tetrachloride, dichloroethane, trichloroethane, tetrachloroethane, dibromomethane, bromoetbane, dibromoethane, bromochloromethane, etc. Moreover, can be also used substituted benzenes represented by chlorobenzene, dichlorobenzene, nitrobenzene, benzonitrjle, etc. On the other hand, it is not preferred to use as the solvent alcohols such as methanol, ethanol, propanol, etc.; ethers such as diethylether, tetrahydrofuran, etc.; esters¯such as methyl acetAte, ethyl acetate, etc.; ketones such as acetone, methylethyl ketone, etc.; and amides such as N,N-dimethylformamide (Mr), ,-dimethylacetamidé (DMA), etc., since the yield of the intented TOCP is decreased. The reaction temperature for the cyclization in each of the Reactions (1), (2)(B) and (3) is desirably in the range of approximately 0 0C to 1500C, especially in the range of approximately 100C to 1000C. It is one of the features of the present invention that addition of the specific organic acid is effective in the cyclization reaction shown in the Reactions (1), t2)(B) and (3). Examples of the specific organic acid include formic acid, acetic acid, propionic acid, benzoic acid, p-toluene- sulfonic acid etc. Among them, fatty acids such as formic acid, acetic acid, propionic acid and the like are preferred. A satisfactory result can be obtained by the addition of a trace amount of such organic acid in the case where there is no water in the reaction system, and such acid is effective in an amount of about 0.01 time or more the molar amounts of te .-butylhydrazine or mucochloric acid starting materials. In the synthesis of the intermediate (HKZ) by the two-stage method according to the Reaction (2), it is preferable to use as the solvent lower alcohols typically exemplified by methanol, ethanol, propanol and the like. However, ethers such as tetrahydrofuran, dioxane, etc. may be also used. The reaction temperature is desirably about room temperature or lower. Under such conditions, the intermediate (MHZ) can be synthesized in a high yield. The intermediate (MHZ) can be separated by adding water to the reaction liquid to precipitate crystals and then filtering off and drying the crystals. The intermediate is stable at room temperature in some degree and changes with elapse of time during storage or on heating to gradually color. Accordingly, it is practically advantageous to conduct the two-stage reactions shown in the Reactions (2)(A) and (B) according to a one-pot method wherein the reactions are carried out in the same vessel by exchanging a solvent. Such one-pot method is also possible in the present invention. The process according to the invention is advantageous also in that the end product can be obtained in a higher yield compared with conventional methods and that the end product can be readily purified. The present invention will be explained specifically by way of the following examples and comparative examples. Incidentally, these examples are merely illustrative and are not to restrict the invention. Example 1 To a solution of 5.4 g of 42 % aqueous potassium hydroxide solution and 48 g of benzene was added 5.0 g (0.04 mol) of tert. -butyihydrazine hydrochloride. The resulting mixture was stirred at room temperature for 15 minutes, added with 6.S g (0.04 mol) of mucochloric acid, and then stirred at 40 to 450C for 5 hours to complete the reaction. Then, water was added to the reaction mixture, and benzene layer was separated, washed successively with 30 % aqueous sodium hydroxide solution, 35 t hydrochloric acid solution and water, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give 6.9 g of 2-tert.-butyl-4,5.dichloro-3(2H)-pyridazinone (TDCP) having a melting point of 63 - 65 C as pale yellow crystals (yield: 78 %). Example 2 To a solution of 4.9 g of 33 % aqueous sodium hydroxide solution and 60 g of dichioromethane was added 5.0 g (0.04 mol) of tert.-butylhydrazine hydrochloride. The resulting mixture was stirred at room temperature for 15 minutes, added with 6.8 g (0.04 mol) of mucochloric acid, and then stirred at 40 to 450C for 6 hours to complete the reaction. Then the following procedures were carried out as in Example 1 to give 66 g of the end product (TDCP) as pale yellow crystals (yield: 75 %). Example 3 To a solution of 4.9 a of 33 t aqueous sodium hydroxide solution and 48 g of benzene was added 5.0 g (0.04 mol) of tert.-butylhydrazine hydrochloride. The resulting mixture was stirred at room temperature for 15 minutes, added with 6.8 g (0.04 mol) of mucochloric acid, and then stirred for 30 minutes. Then, 3.6 g of acetic acid was added thereto and the reaction mixture was stirred at 35 to 45 C for 4 hours. After completion of the reaction, the following procedures were carried out as in Example 1 to give 7.4 g of the end product (TDCP) as pale yellow crystals (yield;84 t). Example 4 To a solution of 3*5 g (0.04 mol) of tert.-butylhydazine and 48 g of benzene was added 6.8 g (0.04 mol) of mucochloric acid at 10 to 1SOC. The resulting mixture was stirred for 30 minutes, added with 2.4 g of acetic acid and then stirred at 35 to 400C for 4 hours. After completion of the reaction, the following procedures were carried out as in Example 1 to give 7.4 g of the end product TDCP as pale yellow crystals (yield:84 t). Example 5 The same procedures as in Example 4 were carried out by using 5.9 g (0.04 mol) of tert.-butylhydrazine acetate instead of the tert.-butylhydrazine starting material in the example to give 7.7 g of the end product TDCP as pale yellow crystals (yield: 87 t). Example 6 To a solution of 4.9 g of 33 % aqueous sodium hydroxide solution and 48 g of benzene was added 5.0 g (0.04 mol) of tert.-butylhydra:ine hydrochloride. The resulting mixture was stirred at room temperature for 15 minutes, added with 6.8 g (0.04 mol) of mucochloric acid, and then stirred for 30 minutes. Then, 3.0 g.of propionie acid was added thercto and the reaction mixture was stirred at 35 to 45 C for 4 hours. After completion of the reaction, the following procedures as in Example 1 were repeated to give 7.1 g of the end product (TDCP) as pale yellow crystals (yicld: 80 %). Example 7 To a solution of 4.9 g of 33 t aqueous sodium hydroxide solution and 48 g of toluene was added 5.0 g (0.04 mol) of tert .-butylhydrazine hydrochloride. The resulting mixture was stirred at room temperature for 15 minutes, added with 6.6 g (O.OC mol) of mucochioric acid, and then stirred for 30 minutes. Then, 2.4 g of acetic acid was added thereto and the reaction mixture was stirred at 35 to 45 C for 4 hours. After completion of the reaction, the following procedures as in Example l were repeated to give 7.1 g g of the end product (TDCP) as pale yellow crystals (yield: 80 %). Example 8 The same procedures as in Example 1 were carried out by using 3.3 g (0.04 mol) of sodium acetate as base and toluene as solvent to give 7.2 g of the end product TDCP yield: 81 %). Comparative Example 1 To a mixed solution of 24 g of acetic acid and 24 5 of acetic anhydride were added 3.5 g (0.04 mol) of tert.- butylhydrazine and 6.8 c (0.04 mol) of mucochloric acid at 10 to 1ZOC and the resulting mixture was stirred at 40 to 450C for 5 hours. After the reaction, the reaction mixture was concentrated and then added with water and benzene. The following procedures were carried out as in Example 1 to give û.9 g of the end product (TDCP) as pale yellow crystals (yield: 10 t). Comparative Example 2 To a solution of 4.9 g of 33 t aqueous sodium hydroxide solution and 48 g of ethanol was added 5.0 g (0.04 mol) of tert.-butylhydrazine hydrochloride. The resulting mixture was stirred at room temperature for 1S minutes, added with 6.8 g (0.04 mol) of mucochloric acid, and then stirred at 40 to 450C for 6 hours. After completion of the reaction, the ethanol was distilled off under reduced pressure and then water was added. The reaction liquid was extracted with benzene. Then the following procedures were carried out as in Example 1 to give 1.0 g of the end product TDCP as pale yellow crystals (yield: 11 t). Comparative Example 3 The same procedures as in Comparative Example 2 were carried out by replacing the ethanol with ethyl acetate to give 1.1 g of the end product TDCP as pale yellow crystals (yield: 12 %). Example 9 (Synthesis of mucochloric acid-tert.-butylhydrazone) EMI14.1 In 120 g of S b aqueous sodium hydroxide solution was dissolved 18.7 g (0.15 mol) of tert.-butylhydrazine hydrochloride. Then a solution of 25.4 g (0.15 mol) of mucochloric acid dissolved in 25 ml of methanol at 0 to SOC was added thereto. The resulting mixture was stirred at 5 C for 30 minutes and then at 10 to 15 C for 30 minutes. After completion of the reaction, water was added thereto, and the resulting crystals were filtered off, washed with water and dried under reduced pressure at room temperature to give 31.2 g of white crystals, i.e. the title-compound which decomposes around 1180C (yield:87 %). The compound thus obtained was confirmed to be the title compound by 1H-NMR spectroscopy and mass spectroscopy which provided the following results: ÚH-NMR (acetone-d6 ) #(ppm) 1.26. tert.-C4 }'9 8.44 2 CH mass spectrum (m/e (t 238(M+l0O), 194(28), 57(3) Example 10 A mixture of 3.0 g (0.0125 mol) of the mucochloric acid-tert.-butylhydrazone obtained in Example 9 and 15 g of benzene was stirred at 400C for 5 hours. After completion of the reaction, the following procedures were carried Out as in Example 1 to give 2.3 g of the end product TDCP (yield: 83 %). Example 11 A mixture of 3.0 g (0.0125 mol) of the mucochloric acid-tert.-butylhydrazone obtained in Example 9, 15 g of benzene and 0.5 g of acetic acid was stirred at 35 to 450C for 4 hours. After completion of the reaction, the following procedures were carried out as in Example 1 to give 2.7 g of the end product TDCP (yield: 98 %). Example li The same procedures as in Example 11 were carried out by using toluene instead of the benzene to give 2.6 g of the end product TDCP (yield: 94 t). Example 13 The same procedures as in Example 11 were carried out by using 0.4 g of formic acid instead of the 0,5 g of acetic acid additive to give 2.6 g of the end product TDCP (yield: 94 %). Example 14 The same procedures as in Example 11 were carried out by using l.2-dichloroethane as a solvent instead of the benzene to give 2.5 g of the end product TDCP (yield: 91 %). Comparative Example 4 Reaction was carried out similarly as in Example 1D except that a mixed solvent of 8 g of acetic acid and 8 g of acetic anhydride was used instead of the benzene used 2S a solvent. After completion of the reaction, the reaction mixture was concentrated and the solvent was distilled off. Then the following procedures were carried out as in Example 10 to give 1.2 g of the end product TDCP (yield: 42 t) Comparative Example 5 The same procedures as in Example 10 were carried out by using ethanol instead of the benzene to give 0.5 g of the end product TDCP (yield: 18 8). Comparative Example 6 The same procedures as in Comparative Example 5 were carried out by using ethyl acetate instead of the ethanol to give 0.5 g of the end product TDCP (yield. 18 %). Example 15 To a mixed solution of 8 g of. 25 % aqueous sodium hydroxide solution and 50 g of methanol was added 6.2 g (0.05 mol) of tert.-butylhydrazine hydrochlorìde at 150C. After starting for 30 minutes, S.S g (0.05 mol) of mucochloric acid was added thereto. The resulting mixture was stirred for 1 hour and then concentrated by distilling off methanol and water at 40 C or lower to give pale yellow crystals. The crystals thus obtained was added with 60 g of benzene and 2 g of acetic acid and then stirred at 35 - 45 C for 4 hours. After completion of the reaction, the following procedures were carried out as in Example 10 to give 10.4 g of the end product TDCP (yield: 94 t), Comparative Example To mixed solution of 8 g of 25 % aqueous sodium hydroxide solution and 50 g of methanol was added 6.2 g (0.05 mol) of tert. -butylhydrazine hydrochloride at 150C. After stirring for 30 minutes, 8.5 g (0.05 mol) of mucochloric acid was added thereto. The resulting mixture was stirred for 1 hour and then concentrated by distilling away methanol and water at 40 0C or lower to give pale yellow crystals. The crystals thus obtained was added with a mixed solution of 30 g of acetic acid and 30 g of acetic anhydride and then refluxed for 20 hours. After completion of the reaction, the reaction mixture was concentrated by distilling off the solvent and then added with water and benzene. Thereafter, the treatment as in Example 1 was carried out to give 3.9 g of the end product TDCP (yield: 35 %). Example 16 Furfural (9.6 g) and 8 z aqueous hydrochloric acid (200 ml) were taken into a 500 ml cylindrical gas-absorption tube, and chlorine gas was introduced thereto at a rate of 500 ml/min. for 5 hours at 900C. After completion of the introduction, the redaction liquid was concentrated, extracted with toluene and concentrated again to give 15.1 g of crude crystalline mucochloric acid of 94 % in purity. Then 10.4 g of tert. -butyl hydrochloride was dissolved in an aqueous solution of 3,4 g of sodium hydroxide in 10 g of water, and the resulting solution was added successively with 100 g of toluene and 15.1 g of the crude crystalline mucochloric acid. The resulting reaction mixture was stirred at 40 to 450C for S hours to complete reaction. The following procedures were carried out as in Example 1 to give 13.7 g of the end product TPCP as crystals. Example 17 Furfural (9.6 g) and 8 % aqueous hydrochloric acid (200 ml) were taken into a S00 ml cylindrical gas- absorption tube, and chlorine gas was introduced thereto at a rate of 500 ml/min. for 5 hours at 900C. After completion of the introduction, the reaction liquid was concentrated to give 17.8 g of crude crystals of mucochloric acid. Then 10.4 g of tert.-butyl hydrochloride was dissolved in an aqueous solution of 3.! g of sodium hydroxide in 10 g of water, and the resulting solution was added successively with 100 g of benzene and l7.8g of the crude crystals of mucochloric acid. The resulting reaction mixture was stirred at 40 to 450C for 5 hours to complete reaction. The following procedures were carried out as in Example 1 to give 13.1 g of the end product TDCP as crystals. Example 18 1,4-butynediol (8.8 g) and 10 % aqueous hydrochloric acid (200 ml) were taken into a 500 ml cylindrical gasabsorption tube, and chlorine gas was introduced thereto at a rate of 500 ml/min. for 7 hours at 90 C. After completion of the introduction, the reaction liquid was concentrated, extracted with toluene and concentrated again to give 9.2 g of crude crystals of mucochloric acid of 83 % in purity. Then 5.6 g of tert. -butyl hydrochloride was dissolved in an aqueous solution of 1.8 g of sodium hydroxide in 10 g of water, and the resulting solution was added successively with 100 g of methylene chloride and 9.2 g of the crude crystals of mucochioric acid. The resulting reaction mixture was stirred at 40 to 4fOC for 5 hours to complete reaction. The following procedures were carried out as in Example 1 to give 7.9 g of the end product TDCP as crystals.

Claims: SQUAT I S CLAIMED IS: 1. A process for producing 2-tert.-butyl-4,5-dichloro- 3(2g)-pyridazinone which comprises reacting tert.-butylhydrazine with mucochloric acid in a solvent selected from aromatic hydrocarbons, halogenated hydrocarbons and mixtures thereof. 2. The process according to Claim 1, wherein the solvent is selected from benzene, toluene, xylene, ethylbenzene, isopropylbenzene, cymene, tert.-butylbenzene1 chloroform, dichloromethane, carbon tetrachloride, dichloroethane, trichloroethane, tetrachloroethane, dbromomethane, bromoethane, dibromoethane, bromochloromethane, and a mixture thereof. 3. The process according to Claim 1 or 2, wherein a specific organic acid is added to the reaction mixture. 4, The process according to Claim 3, wherein the organic acid is selected from formic acid, acetic acid, propionic acid and a mixture thereof. 5. A process for producing 2-tert.-butyl-4,5-dichloro- 3(2H)-pyridazinone, which comprises subjecting tert. butyihydrazine and mucochloric acid to dehydration-condensation reaction to produce mucochloric acid-tert.-butylhydrazone of the formula (I): EMI22.1 and then subjecting the product of the formula (I) to dehydration-cyclization reaction in a solvent selected from aromatic hydrocarbons, halogenated hydrocarbons, and mixtures thereof. 6. The process according to Claim 5, wherein the solvent is selected from benzene, toluene, xylene, ethylbenzene, isopropylbenzene, cymene, tert.-butylbenzene, chloroform, dichloromethane, carbon tetrachloride, dchloroethane, trichloroethane, tetrachloroethane, dibromomethane, bromoethane, dibromoethane, bromochloromethane, and a mixture thereof. 7. The process according to Claim 5 or 6, wherein a specific organic acid is added to the reaction mixture. 8. The process according to Claim 7, wherein the organic acid is selected from formic acid, acetic acid, propionic acid and a mixture thereof. 9. A process for producing 2-tert.-butyl-4,5-dieloro- 3(2H)-pyridazinone, which comprises oxidatively chlorinating a compound selected from furfural, 1,4-butynediol and a mixture thereof to produce crude mucochloric acid, and then reacting the crude mucochloric acid with tert.-butyl- hydrazine in a solvent selected from aromatic hydrocarbons, halogenated hydrocarbons and mixtures thereof. 10. The process according to Claim 9, wherein the solvent is selected from benzene, toluene, xylene, ethylbenzene, isopropylbenzene, cyrnene, tert-butylbenzene, chloroform, dichloromethane, carbon tetrachloride, dichloroethane, trichloroethane, tetrachloroethane, dibromomethane, bromoethane, dibromoethane, bromochloromethane, and a mixture thereof. 11. The process according to Claim 9 or 10, wherein a specific organic acid is added to the reaction mixture. 12. The process according to Claim 11, wherein the organic acid is selected from formic acid, acetic acid, propionic acid and a mixture thereof. 13. Mucochloric acid-tert.-butylhydrazone represented by the structural formula: EMI23.1

Inventors: KAWAMURA, YASUO C/O CENTRAL RESEARCH INSTITUTE, OGURA, TOMOYUKI C/O CENTRAL RESEARCH INSTITUTE, SUZUKI, HIDEO C/O CENTRAL RESEARCH INSTITUTE
Applicants: NISSAN CHEMICAL INDUSTRIES LTD.
Application year: 1985
Main classification: C07D237
IPC codes: C07D237