WO2022091014A1 - Industrial method of producing benzisothiazolinone - Google Patents
Industrial method of producing benzisothiazolinone Download PDFInfo
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- WO2022091014A1 WO2022091014A1 PCT/IB2021/060017 IB2021060017W WO2022091014A1 WO 2022091014 A1 WO2022091014 A1 WO 2022091014A1 IB 2021060017 W IB2021060017 W IB 2021060017W WO 2022091014 A1 WO2022091014 A1 WO 2022091014A1
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- WIPO (PCT)
- Prior art keywords
- acid
- formula
- ortho
- chloro
- chloride
- Prior art date
Links
- DMSMPAJRVJJAGA-UHFFFAOYSA-N benzo[d]isothiazol-3-one Chemical compound C1=CC=C2C(=O)NSC2=C1 DMSMPAJRVJJAGA-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 claims abstract description 28
- 239000002904 solvent Substances 0.000 claims description 42
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- 229910052751 metal Inorganic materials 0.000 claims description 20
- 239000002184 metal Chemical class 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 16
- 239000003054 catalyst Substances 0.000 claims description 16
- IBSQPLPBRSHTTG-UHFFFAOYSA-N 1-chloro-2-methylbenzene Chemical compound CC1=CC=CC=C1Cl IBSQPLPBRSHTTG-UHFFFAOYSA-N 0.000 claims description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 15
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 14
- PXZSANDJGNKIIA-UHFFFAOYSA-N 2-methylsulfanylbenzonitrile Chemical compound CSC1=CC=CC=C1C#N PXZSANDJGNKIIA-UHFFFAOYSA-N 0.000 claims description 13
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 13
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 235000019270 ammonium chloride Nutrition 0.000 claims description 11
- 125000004001 thioalkyl group Chemical group 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- 239000003377 acid catalyst Substances 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- 239000003999 initiator Substances 0.000 claims description 9
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- 239000012320 chlorinating reagent Substances 0.000 claims description 7
- 238000000746 purification Methods 0.000 claims description 7
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 239000004215 Carbon black (E152) Substances 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 6
- 229930195733 hydrocarbon Natural products 0.000 claims description 6
- 150000002430 hydrocarbons Chemical class 0.000 claims description 6
- 239000004246 zinc acetate Substances 0.000 claims description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 5
- 235000011054 acetic acid Nutrition 0.000 claims description 5
- 235000019253 formic acid Nutrition 0.000 claims description 5
- 235000006408 oxalic acid Nutrition 0.000 claims description 5
- 235000019260 propionic acid Nutrition 0.000 claims description 5
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 4
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 claims description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 3
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 2
- JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 claims description 2
- 229910021592 Copper(II) chloride Inorganic materials 0.000 claims description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 claims description 2
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical group [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 229940117389 dichlorobenzene Drugs 0.000 claims description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 2
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 claims description 2
- ZPFBCFAPICAMJZ-UHFFFAOYSA-M potassium;ethanethiolate Chemical compound [K+].CC[S-] ZPFBCFAPICAMJZ-UHFFFAOYSA-M 0.000 claims description 2
- BEBPTRYPELOERP-UHFFFAOYSA-M potassium;methanethiolate Chemical compound [K+].[S-]C BEBPTRYPELOERP-UHFFFAOYSA-M 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical group [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 claims description 2
- QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 claims description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 2
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- 235000011167 hydrochloric acid Nutrition 0.000 claims 1
- 239000001384 succinic acid Substances 0.000 claims 1
- 235000011044 succinic acid Nutrition 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 3
- 239000011541 reaction mixture Substances 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 18
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- MFHPYLFZSCSNST-UHFFFAOYSA-N 1-chloro-2-(trichloromethyl)benzene Chemical compound ClC1=CC=CC=C1C(Cl)(Cl)Cl MFHPYLFZSCSNST-UHFFFAOYSA-N 0.000 description 10
- 238000010926 purge Methods 0.000 description 10
- 239000012535 impurity Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 6
- -1 caulks Substances 0.000 description 6
- 238000003556 assay Methods 0.000 description 5
- 239000003513 alkali Substances 0.000 description 4
- 238000005660 chlorination reaction Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- NHWQMJMIYICNBP-UHFFFAOYSA-N 2-chlorobenzonitrile Chemical compound ClC1=CC=CC=C1C#N NHWQMJMIYICNBP-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 230000000711 cancerogenic effect Effects 0.000 description 2
- 231100000315 carcinogenic Toxicity 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- XEMRAKSQROQPBR-UHFFFAOYSA-N (trichloromethyl)benzene Chemical class ClC(Cl)(Cl)C1=CC=CC=C1 XEMRAKSQROQPBR-UHFFFAOYSA-N 0.000 description 1
- VUWCWMOCWKCZTA-UHFFFAOYSA-N 1,2-thiazol-4-one Chemical class O=C1CSN=C1 VUWCWMOCWKCZTA-UHFFFAOYSA-N 0.000 description 1
- LWJQGKJCZOGGPJ-UHFFFAOYSA-N 2-methylsulfanylbenzoic acid Chemical group CSC1=CC=CC=C1C(O)=O LWJQGKJCZOGGPJ-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000003139 biocide Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000005553 drilling Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000002979 fabric softener Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 239000000976 ink Substances 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 230000003641 microbiacidal effect Effects 0.000 description 1
- 229940124561 microbicide Drugs 0.000 description 1
- 239000002855 microbicide agent Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000003090 pesticide formulation Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007100 recyclization reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000005201 scrubbing Methods 0.000 description 1
- 238000001577 simple distillation Methods 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Definitions
- the present invention relates to an industrial method for the preparation of Benzisothiazolinone (BIT) of formula (I) in an environment friendly and commercially viable manner with high yield and high chemical purity.
- BIT Benzisothiazolinone
- Benzisothiazolinone also known as l,2-benzisothiazol-3(2H)-one belongs to the class of isothiazolinones is a used as a biocide.
- Benzisothiazolinone acts as microbicide and/or fungicide and widely used as a preservative in: emulsion paints, caulks, varnishes, adhesives, inks, and photographic processing solutions home cleaning and car care products; laundry detergents, stain removers and fabric softeners; industrial settings, for example in textile spin-finish solutions, leather processing solutions, preservation of fresh animal hides and skins; agriculture in pesticide formulations; gas and oil drilling in muds and packer fluids preservation.
- Benzisothiazolinone is first disclosed in J. Chem. Soc., Trans., 1923,123, 3310-3315 and J. Chem. Soc., 1926,129, 92! -925.
- T e U.S. Patent No.5,633,384 discloses the synthesis of BIT starting from ortho-chlorobenzo nitrile using sodium thiamethoxide in presence of tetra-n-butylammonium bromide and monochlorobenzene and further carried-out chlorination and cyclization.
- the preparation of 2-chlorobenzotrichloride discloses in U.S. Patent No.
- CN101947468 discloses the preparation of composite catalyst and its application in chlorination of 2-chlorotoluene for the preparation of 2-chlorobenzotrichloride.
- the composite catalyst is expensive, and it is not easy to prepare.
- CN108129255A discloses the device and its process of manufacturing ortho-chlorotrichlorotoluene from chlorination of ortho-chlorotoluene using mercury lamp, illumination initiator and compressed air at 10 to 120°C. The drawback of the process is involving benzoyl peroxide which generates free-radicals and explosive.
- Orthro-chloro benzonitrile is prepared from benzo trichlorides using ammonium chloride [i. EP 441004; ii. JACS, 52, 2951 (1930)].
- OCBN Orthro-chloro benzonitrile
- the drawback of the process involves elevated temperature conditions and it demands expensive temperature-controlled jacket and metal oxides or salts belong to the groups 8, 11, 12 and 13.
- the inventors of the present invention have come-up with an improved industrial process which involves sequential reaction such as photochlorination, benzonitrile preparation, thioalkylation and cyclization in two steps, minimum/no-use of solvents, friendly available reagents and reuse of solvents, reagents and isolation or purification technique to remove reaction impurities with increase yield and purity of B enziso thiazo lino ne .
- Benzisothiazolinone (BIT) of formula (I) which comprises the steps: a) obtainingortho-chloro benzonitrile formula (V) by photo chlorination of orthochlorotoluene formula (II) in presence of light, with or without initiator followed by nitrilation using ammonium chloride, metal salts and with or without suitable catalystor solvent; b) obtaining Benzisothiazolinone (BIT) formula (I) by reacting ortho-chloro benzonitrile formula (V) with thioalkyl metal salt with or without catalyst, in presence or absence of solvent and further cyclization in presence of acid catalyst, using chlorinating agent followed by addition of a base.
- Benzisothiazolinone (I) where the purity by HPLC is greater than 90%; in this embodiment, Benzisothiazolinone (I) is obtained with more than 82% yield.
- Benzisothiazolinone formula (I) provides an industrial method for the preparation of Benzisothiazolinone formula (I), which comprises the steps: a) obtaining ortho-chloro benzonitrile formula (V) by photochlorination of orthochloro toluene formula (II) in presence of light, with or without initiator followed by nitrilation using ammonium chloride, metal salts and with or without catalyst, or solvent; b) obtaining Benzisothiazolinone (BIT) formula (I) by reacting ortho-chloro benzonitrile formula (V) with thioalkyl metal salt with or without catalyst, in presence or absence of solvent and cyclization in presence of acid catalyst, using chlorinating agent followed by addition of a base; c) purifying Benzisothiazolinone formula (I).
- ortho-chloro benzonitrile formula (V) by nitrilation of ortho-chloro benzotrichloride formula (III) using ammonium chloride, metal salts and with or without ortho-chloro benzo icacid formula (IV); where the said ortho-chloro benzoic acid formula (IV) is obtained by reacting a ortho-chloro benzo trichloride formula (III) in presence of acid catalyst;
- ortho-chloro benzo trichloride formula (III) 2- (methylthio)benzonitrile formula (VI) and ortho-chloro benzoic acid formula (IV)are proceeded directly into subsequent steps or isolated.
- purification of Benzisothiazolinone (I) comprises treating a crude compound of step (b) with alkali solution and adjusting pH of clear solution to the pH 4.0 ⁇ 1.0; filtering, washing with a solvent to obtain pure compound with HPLC purity greater than 98 %.
- the solvent used for purification is selected from chlorinated solvent or hydrocarbon solvents.
- Benzisothiazolinone (I) is obtained further to the purification meets “standard specification”; where the “standard specification” is meeting HPLC purity greater than 99%; single unknown impurity less than 0.1%; assay purity greater than 80% and moisture content by KF is in range of 10 to 20%.
- solvent refers to one or more solvents.
- step (a) involves the photochlorination and nitrilation reaction.
- photochlorination involves UV light of 350 to 500nm wave length at temperature from 60°C to 140°C.
- step (a) wherein photochlorination reaction in step (a) is carried out by purging chlorine gas 3.5 to 4.0 equivalent.
- the said initiator in photochlorination in step (a) is selected from water, azobisisobutyronitrile (AIBN), dibenzoyl peroxide, sulfuric acid, formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, orthro- chloro benzoic acid and the like or mixture thereof.
- AIBN azobisisobutyronitrile
- dibenzoyl peroxide sulfuric acid, formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, orthro- chloro benzoic acid and the like or mixture thereof.
- the suitable initiator is 0.1 to 7.0% w/w.
- the said metal salts in nitrilation is preferably selected from the groups 8, 11, 12 and 13.
- metal salts is selected from zinc acetate, zinc chloride, copper (II) acetate, copper (II) chloride, nickel (II) chloride, iron chloride, and the like. In certain embodiments, wherein said metal salts is 0.001 to 0.003 equivalent.
- said catalyst for nitrilation is selected from formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, orthro- chlorobenzoic acid and the like or mixture thereof.
- said solvent for nitrilation is selected from the group consisting of hydrocarbon solvents and chlorinated solvents.
- step (b) step (3) and step (4) is selected from hydrocarbon solvents, chlorinated solvents and the like.
- hydrocarbon solvents is preferably selected from the group consisting benzene, toluene, xylene and the like or mixture of solvents thereof.
- chlorinated solvent(s) is preferably selected from the group consisting of monochlorobenzene, ethylene dichloride, dichlorobenzene and the like or mixture of solvents thereof.
- reaction temperature for photochlorination and nitrilation is 60°C to 200°C.
- cycle time of photochlorination and nitrilation is 8 to 24 hours.
- compound ortho-chloro benzonitrile formula (V) is isolated by adding minimum amount of solvent, filtering, adjusting the pH 7 to 9 using alkali solution; and adding minimum amount of base and separating the organic layer.
- the said ortho-chloro benzonitrile (V) may be isolated by extraction in solvent or by simple distillation.
- a preparation of ortho-chloro benzo trichloride formula (III) is achieved with GC purity greater than 97% and chemical assay greater than 95%, yield 90 to 94% and the content of ortho-chloro toluene (II) is less than 0.1%.
- said thioalkyl metal salt is preferably selected from the group consisting of sodium thiomethoxide, potassium thiomethoxide, sodium thioethoxide, potassium thioethoxide and the like.
- said catalyst is preferably selected from sodium acetate, tetra butyl ammonium bromide (TBAB), tetra butyl ammonium chloride (TBAC), and the like or mixture thereof.
- step (b) and step (4) is preferably selected from thionyl chloride, chlorine gas and the like.
- chlorinating agent is selected from chlorine gas, sulfuryl chloride, thionyl chloride, iron chloride, methane sulfonyl chloride, tert-butyl hypochlorite, methoxy acetyl chloride, oxalyl chloride, A-chloro succinimide and the like.
- said base of step (b) is selected from group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate and the like.
- unreacted thioalkyl metal salt from reaction mixture is recovered by acidification, solvent extraction and treating with an alkali up to 14 to 18%.
- recovery and reuse of thioalkyl metal salt is achieved from mother liquor by dissolving methyl chloride gas in solvent, adding phase transfer catalyst; treating with sodium hydrosulfide, extracting with solvent and further treating with an alkali in 44 to 48%.
- acid impurity is 2-(methylthio)benzoic acid.
- concentrated HC1 is prepared by scrubbing HC1 gas generated in step (a) into water and reused in process.
- the 2-chlorobenzotrichloride (0.91 Kg), ammonium chloride (2.32 Kg), ortho-chloro benzoic acid (61.88 g) and zinc acetate (1.66g) were charged at room temperature.
- the reaction mixture was heated tol80°C to 200°C for 8.0 hours.
- the reaction mixture was cooled to room temperature and monochlorobenzene (0.1 to 0.3V) was added.
- the reaction mixture was filtered, and pH of reaction mass was adjusted to neutral pH using sodium carbonate.
- the organic layer was separated and neutralized with aqueous ammonia under stirring. The organic layer separated to obtain compound ortho-chloro benzonitrile (90% yield).
- reaction mixture was heated at 50°C to 70°C.
- the chlorine gas (7.2 Kg) purging was started and reaction mixture was heated at 140°C to 150°C and chlorine gas purging was maintained for 20 to 24 hours.
- the UV light was switched off and chlorine gas purging was stopped, and reaction mixture was cooled to room temperature.
- the air was purged for 2.0 hour and ammonium chloride (1.13 Kg), ortho-chlorobenzoic acid (299.6 g), and zinc acetate (8.1 g) were charged at room temperature.
- the reaction mixture was heated to 180°C to 200°C for 8.0 hours.
- reaction mixture was cooled to room temperature and monochlorobenzene (1320 mL) was added.
- the reaction mixture was filtered, and pH of reaction mass was adjusted to neutral by using aqueous sodium carbonate.
- the organic layer was separated and neutralized with aqueous ammonia under stirring. The organic layer was separated to obtain compound ortho-chloro benzonitrile (84.63% yield).
- the ortho-chloro benzonitrile 100 g) monochlorobenzene (1.0V), tetra butyl ammonium bromide (0.017 eq), 25% sodium thiamethoxide (1.5 eq) were added at room temperature.
- the reaction mixture was heated to 90°C to 100°C for 2.0 to 4.0 hours.
- the reaction mixture was cooled to 60°C to 70°C and aqueous layer separated.
- the aqueous layer extracted with monochlorobenzene at 60°C to 70°C and separated the organic layer to obtain 2-methylsulfanyl -benzonitrile (323.3g) with HPLC purity 97.59%.
- the ortho-chloro benzonitrile (1.0 eq), monochlorobenzene (1.0V), tetra butyl ammonium bromide (0.017 eq), 25% sodium thiamethoxide (1.5 eq) were added at room temperature.
- the reaction mixture was heated to 90°C to 100°C for 2.0 to 4.0 hours.
- the reaction mixture was cooled to 60°C to 70°C and aqueous layer separated.
- the aqueous layer extracted with monochlorobenzene at 60°C to 70°C and organic layer separated to obtain 2-methyl sulfanyl benzonitrile with HPLC purity 97.59%.
- the compound (I) was treated with water, basified with aqueous sodium hydroxide and heated at 40°C to 50°C for 0.5 to 1.0 hour.
- the reaction mass was filtered and cooled to room temperature and acidified with concentrated hydrochloride till pH 4 to 5.
- the reaction mass was filtered, washed with water and dried under vacuum to obtain white powder pure Benzisothiazolinone compound (83% yield, HPLC purity 99.98%, assay by HPLC 80%, Moisture content 15.56% and single unknown impurity less than 0.1%).
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Abstract
The present invention relates to an industrial method for the preparation of Benzisothiazolinone formula (I), which is simple, economical, efficient, user and environment friendly, moreover commercially viable with higher yield and chemical purity.
Description
INDUSTRIAL METHOD OF PRODUCING BENZISOTHIAZOLINONE
RELATED APPLICATION
This application claims the benefit to Indian provisional application no. 202021047473, filed on October 30, 2020, the contents of which are incorporated by reference herein.
FIELD OF THE INVENTION
The present invention relates to an industrial method for the preparation of Benzisothiazolinone (BIT) of formula (I) in an environment friendly and commercially viable manner with high yield and high chemical purity.
BACKGROUND OF THE INVENTION
Benzisothiazolinone (BIT) also known as l,2-benzisothiazol-3(2H)-one belongs to the class of isothiazolinones is a used as a biocide. Benzisothiazolinone acts as microbicide and/or fungicide and widely used as a preservative in: emulsion paints, caulks, varnishes, adhesives, inks, and photographic processing solutions home cleaning and car care products; laundry detergents, stain removers and fabric softeners; industrial settings, for example in textile spin-finish solutions, leather processing solutions, preservation of fresh animal hides and skins; agriculture in pesticide formulations; gas and oil drilling in muds and packer fluids preservation.
The Benzisothiazolinone (BIT) is first disclosed in J. Chem. Soc., Trans., 1923,123, 3310-3315 and J. Chem. Soc., 1926,129, 92! -925. T e U.S. Patent No.5,633,384 discloses the synthesis of BIT starting from ortho-chlorobenzo nitrile using sodium thiamethoxide in presence of tetra-n-butylammonium bromide and monochlorobenzene and further carried-out chlorination and cyclization.
The preparation of 2-chlorobenzotrichloride discloses in U.S. Patent No. 2,132,361from 2-chlorotoluene by chlorinating in presence of light of a mercury vapor lamp at 100 °C to 150°C. The patent is silent on purity, impurity profile and yield. Another reference, DE 2,139,779 discloses the preparation of 2-chlorobenzotrichloride from 2- chlorotoluene using chlorinating in diffuse daylight in presence of pyridine compound. The major drawback of this process is the use of corrosive, carcinogenic 2,4,6- triphenylpyridine compound and the process does not disclose the removal of impurities and reaction time. Another reference, CN101947468 discloses the preparation of composite catalyst and its application in chlorination of 2-chlorotoluene for the preparation of 2-chlorobenzotrichloride. However, the composite catalyst is expensive, and it is not easy to prepare. In yet another reference, CN108129255A discloses the device and its process of manufacturing ortho-chlorotrichlorotoluene from chlorination of ortho-chlorotoluene using mercury lamp, illumination initiator and compressed air at 10 to 120°C. The drawback of the process is involving benzoyl peroxide which generates free-radicals and explosive.
Orthro-chloro benzonitrile (OCBN) is prepared from benzo trichlorides using ammonium chloride [i. EP 441004; ii. JACS, 52, 2951 (1930)]. However, the drawback of the process involves elevated temperature conditions and it demands expensive temperature-controlled jacket and metal oxides or salts belong to the groups 8, 11, 12 and 13.
The aforesaid references did not disclose a process for the preparation of Benzisothiazolinone (BIT) in a single reference. Further the references did not provide an easy process to manufacture and from an easily available ortho-chlorotoluene. Additionally, these processes involve longer cycle time, unfriendly reaction conditions such as the use of expensive, carcinogenic reagents, expensive temperature controlled jacketed device. Thus, achieving the desired compound in a less number of steps (two steps), using economic solvents, catalyst; recyclization, reuse of solvent or catalyst; isolation or purification techniques to remove reaction impurities and to achieve acceptable regulatory standard of Benzisothiazolinone formula (I) remains a need. Therefore, the inventors of the present invention have come-up with an improved
industrial process which involves sequential reaction such as photochlorination, benzonitrile preparation, thioalkylation and cyclization in two steps, minimum/no-use of solvents, friendly available reagents and reuse of solvents, reagents and isolation or purification technique to remove reaction impurities with increase yield and purity of B enziso thiazo lino ne .
SUMMARY OF THE INVENTION
In one aspect of present invention provides an industrial method for the preparation of Benzisothiazolinone (BIT) of formula (I), which comprises the steps:
a) obtainingortho-chloro benzonitrile formula (V) by photo chlorination of orthochlorotoluene formula (II) in presence of light, with or without initiator followed by nitrilation using ammonium chloride, metal salts and with or without suitable catalystor solvent; b) obtaining Benzisothiazolinone (BIT) formula (I) by reacting ortho-chloro benzonitrile formula (V) with thioalkyl metal salt with or without catalyst, in presence or absence of solvent and further cyclization in presence of acid catalyst, using chlorinating agent followed by addition of a base.
In one embodiment, the industrial method for the preparation of Benzisothiazolinone (I) where the purity by HPLC is greater than 90%.
In another embodiment, the industrial method for the preparation of Benzisothiazolinone (I) where the purity by HPLC is greater than 90%; in this embodiment, Benzisothiazolinone (I) is obtained with more than 82% yield.
In another aspect of present invention provides an industrial method for the preparation of Benzisothiazolinone formula (I), which comprises the steps:
a) obtaining ortho-chloro benzonitrile formula (V) by photochlorination of orthochloro toluene formula (II) in presence of light, with or without initiator followed by nitrilation using ammonium chloride, metal salts and with or without catalyst, or solvent; b) obtaining Benzisothiazolinone (BIT) formula (I) by reacting ortho-chloro benzonitrile formula (V) with thioalkyl metal salt with or without catalyst, in presence or absence of solvent and cyclization in presence of acid catalyst, using chlorinating agent followed by addition of a base; c) purifying Benzisothiazolinone formula (I).
In one embodiment, the industrial method for the preparation of Benzisothiazolinone (I) where the purity by HPLC is greater than 97%.
In another embodiment, the industrial method for the preparation of Benzisothiazolinone (I) where the purity by HPLC is greater than 99%.
In yet another embodiment, the industrial method for the preparation of Benzisothiazolinone (I) where the purity by HPLC is greater than 99% and a single unknown impurity is less than 0.5%, preferably less than 0.1%.
In another aspect of present invention provides an industrial method for the preparation of Benzisothiazolinone formula (I), which comprises the steps:
1) obtaining ortho-chlorobenzotrichloride formula (III) by photochlorination of ortho - chlorotoluene formula (II) in presence of light, with or without initiator;
2) obtaining ortho-chloro benzonitrile formula (V) by nitrilation of ortho-chloro benzotrichloride formula (III) using ammonium chloride, metal salts and with or
without ortho-chloro benzo icacid formula (IV); where the said ortho-chloro benzoic acid formula (IV) is obtained by reacting a ortho-chloro benzo trichloride formula (III) in presence of acid catalyst;
3) obtaining 2-(methylthio) benzonitrile formula (VI) by reacting ortho-chloro benzonitrile formula (V) using thioalkyl metal salt, with or without catalyst, in presence or absence of solvent;
4) obtaining Benzisothiazolinone formula (I) by cyclising 2-(methylthio) benzonitrile formula (VI) with chlorinating agent, base, in presence of acid catalyst, with or without catalyst or solvent.
In an embodiment, wherein ortho-chloro benzo trichloride formula (III), 2- (methylthio)benzonitrile formula (VI) and ortho-chloro benzoic acid formula (IV)are proceeded directly into subsequent steps or isolated.
In certain embodiments, wherein purification of Benzisothiazolinone (I) comprises treating a crude compound of step (b) with alkali solution and adjusting pH of clear solution to the pH 4.0 ± 1.0; filtering, washing with a solvent to obtain pure compound with HPLC purity greater than 98 %.
In certain embodiment, wherein the solvent used for purification is selected from chlorinated solvent or hydrocarbon solvents.
In certain embodiment where Benzisothiazolinone (I) is obtained further to the purification meets “standard specification”; where the “standard specification” is meeting HPLC purity greater than 99%; single unknown impurity less than 0.1%; assay purity greater than 80% and moisture content by KF is in range of 10 to 20%.
In certain embodiment where Benzisothiazolinone (I) is obtained with around 89% yield.
DETAILED DESCRIPTION OF THE INVENTION
The present invention now will be described more fully hereinafter. The invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. As used in the specification, and in the appended claims, the singular forms “a”, “an”, “the”, include plural referents unless the context clearly indicates otherwise.
The term “solvent” used herein, refer to one or more solvents.
In certain embodiment of the present invention, wherein step (a) involves the photochlorination and nitrilation reaction.
In certain embodiments, wherein photochlorination involves UV light of 350 to 500nm wave length at temperature from 60°C to 140°C.
In certain embodiments, wherein photochlorination reaction in step (a) is carried out by purging chlorine gas 3.5 to 4.0 equivalent.
In certain embodiments, wherein the said initiator in photochlorination in step (a) is selected from water, azobisisobutyronitrile (AIBN), dibenzoyl peroxide, sulfuric acid, formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, orthro- chloro benzoic acid and the like or mixture thereof.
In certain embodiments, wherein the suitable initiator is 0.1 to 7.0% w/w.
In certain embodiments, wherein the said metal salts in nitrilation is preferably selected from the groups 8, 11, 12 and 13.
In certain embodiments, wherein said metal salts is selected from zinc acetate, zinc chloride, copper (II) acetate, copper (II) chloride, nickel (II) chloride, iron chloride, and the like.
In certain embodiments, wherein said metal salts is 0.001 to 0.003 equivalent.
In certain embodiments, wherein said catalyst for nitrilation is selected from formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, orthro- chlorobenzoic acid and the like or mixture thereof.
In certain embodiments, wherein said solvent for nitrilation is selected from the group consisting of hydrocarbon solvents and chlorinated solvents.
In certain embodiments, wherein the said solvent used in step (b) step (3) and step (4) is selected from hydrocarbon solvents, chlorinated solvents and the like.
In certain embodiments, wherein said hydrocarbon solvents is preferably selected from the group consisting benzene, toluene, xylene and the like or mixture of solvents thereof.
In certain embodiments, wherein chlorinated solvent(s) is preferably selected from the group consisting of monochlorobenzene, ethylene dichloride, dichlorobenzene and the like or mixture of solvents thereof.
In certain embodiments, wherein the reaction temperature for photochlorination and nitrilation is 60°C to 200°C.
In certain embodiments, wherein the cycle time of photochlorination and nitrilation is 8 to 24 hours.
In certain embodiments, wherein compound ortho-chloro benzonitrile formula (V) is isolated by adding minimum amount of solvent, filtering, adjusting the pH 7 to 9 using alkali solution; and adding minimum amount of base and separating the organic layer.
In certain embodiment, wherein the said ortho-chloro benzonitrile (V) may be isolated by extraction in solvent or by simple distillation.
In certain embodiments, wherein a preparation of ortho-chloro benzo trichloride formula (III) is achieved with GC purity greater than 97% and chemical assay greater than 95%, yield 90 to 94% and the content of ortho-chloro toluene (II) is less than 0.1%.
In certain embodiment, wherein said thioalkyl metal salt is preferably selected from the group consisting of sodium thiomethoxide, potassium thiomethoxide, sodium thioethoxide, potassium thioethoxide and the like.
In certain embodiment, wherein said catalyst is preferably selected from sodium acetate, tetra butyl ammonium bromide (TBAB), tetra butyl ammonium chloride (TBAC), and the like or mixture thereof.
In certain embodiment, wherein said acid catalyst in step (b) and step (4) is preferably selected from thionyl chloride, chlorine gas and the like.
In certain embodiment, wherein said chlorinating agent is selected from chlorine gas, sulfuryl chloride, thionyl chloride, iron chloride, methane sulfonyl chloride, tert-butyl hypochlorite, methoxy acetyl chloride, oxalyl chloride, A-chloro succinimide and the like.
In certain embodiment, wherein said base of step (b) is selected from group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate and the like.
In certain embodiment, wherein unreacted thioalkyl metal salt from reaction mixture is recovered by acidification, solvent extraction and treating with an alkali up to 14 to 18%.
In certain embodiment, wherein recovery and reuse of thioalkyl metal salt is achieved from mother liquor by dissolving methyl chloride gas in solvent, adding phase transfer catalyst; treating with sodium hydrosulfide, extracting with solvent and further treating with an alkali in 44 to 48%.
In certain embodiment, wherein overall recovery of thioalkyl metal salt is 58 to 60% from input of thioalkyl metal salt.
In certain embodiment, wherein Benzisothiazolinone formula (I) is recovered from solvent mother liquor by concentration and filtration; and acid impurity is recovered from solvent mother liquor by acid base treatment.
In certain embodiment, wherein acid impurity is 2-(methylthio)benzoic acid.
In certain embodiment, wherein concentrated HC1 is prepared by scrubbing HC1 gas generated in step (a) into water and reused in process.
In certain embodiment, wherein the solvents are recovered and reused in process by distillation from the mother liquor.
The following examples serve to illustrate the invention, but they are not intended to limit it thereto:
EXPERIMENTAL
Example 1: Preparation of 2-chlorobenzotrichloride (III)
In presence of UV light, an ortho-chlorotoluene (1.72Kg) and AIBN(5.2 g) were added and reaction mixture was heated at 50°C to 70°C. The chlorine gas (4.3 Kg) purging was started and reaction mixture was heated at 140 to 150°C and chlorine gas purging was continued for 20 to 24 hours. After completion of reaction, the UV light and chlorine gas purging were stopped, and reaction mixture was cooled to room temperature. The air was purged for 2.0 hour and the compound 2-
chlorobenzotrichloride was isolated as a clear pale-yellow liquid (2.95 Kg, 90% yield, GC Purity 97.05% and Assay Purity 94.92%w/w), LCMS:230.92 [M+H] +
Example 2: Preparation of 2- Chlorobenzonitrile (V)
In presence of UV light, an ortho-chlorotoluene (0.5 Kg) and AIBN (2.5 g) were added and reaction mixture was heated at 50°C to 70°C. The chlorine gas purging was started, and reaction mixture was heated to 140°C to 150°C and the chlorine gas purging continued for 28 hours. After completion of reaction, the UV light was switched off and chlorine gas purging was stopped, and the reaction mixture was cooled to room temperature. The air was purged for 2.0 hour and to the reaction mixture ammonium chloride (232.4 g), ortho-chlorobenzoic acid (61.83 g), and zinc acetate (1.66 g) were added at room temperature. The reaction mixture was heated at 180°C to 200°C for 8.0 hours and 2-chlorobenzonitrile was isolated by high vacuum distillation with 78% yield and GC 99% purity.
Example 3: Preparation of ortho-chloro benzonitrile (V)
The 2-chlorobenzotrichloride (0.91 Kg), ammonium chloride (2.32 Kg), ortho-chloro benzoic acid (61.88 g) and zinc acetate (1.66g) were charged at room temperature. The reaction mixture was heated tol80°C to 200°C for 8.0 hours. The reaction mixture was cooled to room temperature and monochlorobenzene (0.1 to 0.3V) was added. The reaction mixture was filtered, and pH of reaction mass was adjusted to neutral pH using sodium carbonate. The organic layer was separated and neutralized with aqueous ammonia under stirring. The organic layer separated to obtain compound ortho-chloro benzonitrile (90% yield).
Example 4: Preparation of ortho-chloro benzonitrile (V)
The 2-chlorobenzotrichloride (0.5 Kg), ammonium chloride (139.58 Kg), water (2.75 g), sulfuric acid (0.5g) and zinc acetate (0.92 g) were charged at room temperature. The reaction mixture was heated to 180°C to 200°C for 16.0 hours. The reaction mixture was cooled to 60-70 °C and filtered reaction mass at the same temperature and collected unreacted solid ammonium chloride (33.0 g; assay 95.23% w/w; 23.6% recovery). Crude ortho-chloro benzonitrile (filtrate) 252 g (85% yield; GC Purity - 96.01).
Example 5: Preparation of ortho-chloro benzonitrile (V)
In presence of UV light, an ortho-chlorotoluene (2.5 Kg) and AIBN (3.75 g, 0.15%) were added and reaction mixture was heated at 50°C to 70°C. The chlorine gas (7.2 Kg) purging was started and reaction mixture was heated at 140°C to 150°C and chlorine gas purging was maintained for 20 to 24 hours. After completion of reaction, the UV light was switched off and chlorine gas purging was stopped, and reaction mixture was cooled to room temperature. The air was purged for 2.0 hour and ammonium chloride (1.13 Kg), ortho-chlorobenzoic acid (299.6 g), and zinc acetate (8.1 g) were charged at room temperature. The reaction mixture was heated to 180°C to 200°C for 8.0 hours. The reaction mixture was cooled to room temperature and monochlorobenzene (1320 mL) was added. The reaction mixture was filtered, and pH of reaction mass was adjusted to neutral by using aqueous sodium carbonate. The organic layer was separated and neutralized with aqueous ammonia under stirring. The organic layer was separated to obtain compound ortho-chloro benzonitrile (84.63% yield).
Example 6: Preparation of 2-methylsulfanyl-benzonitrile (VI)
The ortho-chloro benzonitrile (100 g) monochlorobenzene (1.0V), tetra butyl ammonium bromide (0.017 eq), 25% sodium thiamethoxide (1.5 eq) were added at room temperature. The reaction mixture was heated to 90°C to 100°C for 2.0 to 4.0 hours. The reaction mixture was cooled to 60°C to 70°C and aqueous layer separated. The aqueous layer extracted with monochlorobenzene at 60°C to 70°C and separated the organic layer to obtain 2-methylsulfanyl -benzonitrile (323.3g) with HPLC purity 97.59%.
Example?: Preparation of Benzisothiazolinone (I)
The 2-methylsulfanyl-benzonitrile (323 g), monochlorobenzene (100g) concentrated hydrochloride (26.26 g) and water (15.54 g) were added at room temperature. The reaction mixture was heated to 40°C to 45°C and chlorine gas (56.92 g) was purged for 1.0 to 2.0 hours. The reaction mixture was heated to 60°C to 70°C for 2.0 to 4.0hour and aqueous sodium hydroxide solution (61 g) was added. The reaction mass was cooled to room temperature and pH of reaction mass was adjusted using aqueous sodium hydroxide. The reaction mass was filtered, washed with monochlorobenzene and water and dried under vacuum to obtain compound (I) (105 g,96% yield).
Example 8: Preparation of Benzisothiazolinone (I)
The ortho-chloro benzonitrile (1.0 eq), monochlorobenzene (1.0V), tetra butyl ammonium bromide (0.017 eq), 25% sodium thiamethoxide (1.5 eq) were added at room temperature. The reaction mixture was heated to 90°C to 100°C for 2.0 to 4.0 hours. The reaction mixture was cooled to 60°C to 70°C and aqueous layer separated. The aqueous layer extracted with monochlorobenzene at 60°C to 70°C and organic layer separated to obtain 2-methyl sulfanyl benzonitrile with HPLC purity 97.59%. To organic layer, monochlorobenzene (1.0V), concentrated hydrochloric acid (0.3eq), water (1.2eq) were added and heated to 35°C to 45 °C. The chlorine gas was purged for 1.0 to 2.0 hours and reaction mixture was heated to 65°Cto 70°C for 2.0 to 4.0 hours. The aqueous NaOH solution (l.Oeq) was added for 30 minutes and cooled to 25°C to 30°C.The pH was adjusted to 4.0 ± 1.0 and maintained for 30 minutes. The reaction mixture was filtered, and wet cake was washed with monochlorobenzene, water and dried under vacuum to obtain Benzisothiazolinone (I) with 85% yield.
Example 9: Purification of Benzisothiazolinone (I)
The compound (I) was treated with water, basified with aqueous sodium hydroxide and heated at 40°C to 50°C for 0.5 to 1.0 hour. The reaction mass was filtered and cooled to room temperature and acidified with concentrated hydrochloride till pH 4 to 5. The reaction mass was filtered, washed with water and dried under vacuum to obtain white powder pure Benzisothiazolinone compound (83% yield, HPLC purity 99.98%, assay by HPLC 80%, Moisture content 15.56% and single unknown impurity less than 0.1%).
Example 10: Preparation of ortho-chloro benzoic acid (IV)
To a mixture of ortho-chloro benzonitrile (250 g) and water (562.5 g), concentrated hydrochloric acid (187.5 g) was added under stirring for 15 to 30 minutes and mixture was heated to 100°C to 110°C for 6 to 8 hours. The reaction mixture was cooled to room temperature and stirred for 1 to 2 hours. The precipitated solid was filtered, washed with water and dried under vacuum to get ortho-chloro benzoic acid compound (168 g, 98%, HPLC purity 99.79%).
Claims
CLAIM:
1) An industrial method for preparation of Benzisothiazolinone formula (I), which comprising the steps of:
a) obtaining ortho-chloro benzonitrile formula (V) by photochlorination of ortho - chloro toluene formula (II) in presence of light, with or without initiator followed by nitrilation using ammonium chloride, metal salts, with or without catalyst and solvent;
(II) (V) b) obtaining Benzisothiazolinone formula (I) by reacting ortho-chloro benzonitrile formula (V) with thioalkyl metal salt with or without catalyst, in presence or absence of solvent and further cyclization in presence of acid catalyst, using chlorinating agent followed by addition of base; c) optionally purifying Benzisothiazolinone formula (I).
2) An industrial method for the preparation of Benzisothiazolinone of formula (I), which comprising the steps of: a) obtaining ortho-chloro benzo trichloride formula (III) by photochlorination of ortho-chloro toluene formula (II) in presence of light, with or without initiator;
(II) (III) b) obtaining ortho-chloro benzonitrile formula (V) by nitrilation of ortho-chloro benzo trichloride formula (III) using ammonium chloride, metal salts and with or without formation of ortho-chloro benzoic acid formula (IV); where the said ortho-chloro benzoic acid formula (IV) is obtained by reacting a ortho-chloro benzo trichloride formula (III) in presence of acid catalyst;
(V) (IV) c) obtaining 2-(methylthio)benzonitrile formula (VI) by reacting ortho -chloro benzonitrile formula (V) using thioalkyl metal salt, with or without catalyst, in presence or absence of solvent;
d) obtaining Benzisothiazolinone formula (I) by cyclizing 2 -(methylthio) benzonitrile formula (VI) with chlorinating agent, base, in presence of acid catalyst, with or without catalyst or solvent. ) The process as claimed claim lor 2, wherein the said initiator is selected from water, azobisisobutyronitrile (AIBN), dibenzoyl peroxide, sulfuric acid, formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, and orthro -chloro benzoic acid. ) The process as claimed claim 1 or 2, wherein the said metal salts is selected from zinc acetate, zinc chloride, copper (II) acetate, copper (II) chloride, nickel (II) chloride, and iron chloride. ) The process as claimed claim 1 or 2, wherein the said acid catalyst is selected from formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, hydrochloric acid, sulfuric acid, orthro-chlorobenzoic acid, thionyl chloride, chlorine gas; and catalyst is selected from sodium acetate, tetra butyl ammonium bromide (TBAB), and tetra butyl ammonium chloride (TBAC). ) The process as claimed claim 1 or 2, wherein the said solvent used is selected from hydrocarbon solvent, which is selected from benzene, toluene, xylene; and chlorinated solvent, which is selected from monochlorobenzene, ethylene dichloride, dichlorobenzene and the like.
) The process as claimed claim 1 or 2, wherein said thioalkyl metal salt is selected from sodium thiomethoxide, potassium thiomethoxide, sodium thioethoxide, and potassium thioethoxide. ) The process as claimed claim 1 or 2, wherein said chlorinating agent is selected from chlorine gas, sulfuryl chloride, thionyl Chloride, iron chloride, methane sulfonyl chloride, tert-butyl hypochlorite, methoxy acetyl chloride, oxalyl chloride, and N- chloro succinimide . ) The process as claimed claim 1 or 2, wherein said base is selected from group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, and sodium bicarbonate. 0) The process as claimed claim 1, wherein purification of compound (I) is carried out in chlorinated solvent or hydrocarbon solvents; base which is selected from potassium hydroxide, sodium carbonate, sodium bicarbonate; and acid which is selected from hydrochloric acid, sulfuric acid, formic acid, acetic acid, propionic acid, oxalic acid, and succinic acid.
15
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CN115594563A (en) * | 2022-12-15 | 2023-01-13 | 山东道可化学有限公司(Cn) | Method for preparing o-chlorotrifluoromethane by micro-reaction continuous photocatalysis of o-chlorotoluene |
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