EP3976578A1 - Process for preparation of bromo formimine compounds - Google Patents

Process for preparation of bromo formimine compounds

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Publication number
EP3976578A1
EP3976578A1 EP20742881.4A EP20742881A EP3976578A1 EP 3976578 A1 EP3976578 A1 EP 3976578A1 EP 20742881 A EP20742881 A EP 20742881A EP 3976578 A1 EP3976578 A1 EP 3976578A1
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EP
European Patent Office
Prior art keywords
formula
group
process according
alkyl
methyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP20742881.4A
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German (de)
French (fr)
Inventor
Anuj Kumar Mittal
Maneesh Kumar Sharma
Abhishek Jain
Mitthu Lal GURJAR
Sumit Srivastava
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PI Industries Ltd
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PI Industries Ltd
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Publication of EP3976578A1 publication Critical patent/EP3976578A1/en
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C249/16—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of hydrazones
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C249/02—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of compounds containing imino groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
    • C07C249/12—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reactions not involving the formation of oxyimino groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
    • C07C251/04—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/32—Oximes
    • C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals

Definitions

  • the present invention relates to a process for the preparation of hromo-formimine compounds or salt thereof. More particularly, the present invention relates to an improved process for the preparation of bromo-formimine compounds or salt thereof, wherein bromine anion is recycledby using a suitable oxidizing agent.
  • Bromo-formimine compounds are a commercially important class of organic compounds. Bromo-formimines are useful as intermediates in the synthesis of a wide variety of organic compounds, such as microbicides, agricultural pesticides and pharmaceutical agents.
  • Bromo-formimine bactericide are suitable for use in a variety of industries, such as, but not limited to, cooling towers; air washers; mineral slurries; pulp and paper processing fluids; paper coatings; swimming pools; spas; adhesives; caulks; mastics; sealants; agriculture adjuvant preservation; construction products; cosmetics and toiletries; shampoos; disinfectants and antiseptics; Formulated industrial and consumer products; soaps; laundry rinse waters; leather and leather products; wood, including lumber, timber, fiberboard, plywood, and wood composites; plastics; lubricants; hydraulic fluids; medical devices; metalworking fluids; emulsions and dispersions; paints, including marine paints; varnishes, including marine varnishes; latexes; odor control fluids; coatings, including marine coatings; petroleum processing fluids; fuel; oil field fluids; photographic chemicals; printing fluids; sanitizers; detergents; textiles, such as fibers; and textile products, such as clothes and carpets.
  • the present invention provides an improvedprocess for the preparation of hromo-formimine compound of Formula (I)or salt thereof,
  • X and X 1 is bromine
  • R is selected from the group consisting of CN, OH, COR 1 , and OCOCH3;
  • R 1 is selected from the group consisting of hydrogen, halogen, OR y , CN, NO2, SH, NH 2 , NH(Ci-C 6 -alkyl), N(Ci-C 6 -alkyl) 2 , NH-S0 2 -R x , Ci-C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 - C 6 -alkynyl, Ci- C 6 -alkoxy, Ci-C 6 -haloalkoxy, Ci-C 6 -alkylthio, Ci-C 6 -haloalkylthio a saturated or partially unsaturated three- to ten-membered carbocycle or heterocycle, five- or six-membered heteroaryl and aryl, wherein R x and R y are selected from the group consisting of hydrogen, Ci-C 6 -alkyl, Ci-C 6 -haloalkyl, and aryl;
  • X 3 and X 2 are independently selected from hydrogen, CO 2 R 1 , and C(0)NR 2 R 3 ;
  • R 2 and R 3 are selected from the group consisting of hydrogen, halogen, SH, Ci-C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, Ci-C 6 -alkoxy, Ci-C 6 -haloalkoxy, Ci-C 6 -alkylthio, Ci-C 6 -haloalkylthio a saturated or partially unsaturated three - to ten-membered carbocycle or heterocycle, five- or six-membered heteroaryl and aryl;
  • the purity of bromo-formimine compound of Formula (I)or salt thereofobtained according to the present invention process is more than 99 %, when measured by HPLC.
  • a condition A“or” B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B is true (or present).
  • Alkyl, alkenyl, alkynyl, carbocycle, heterocycle, aryl and heteroaryl groups, as defined herein, are optionally substituted (e.g., "substituted” or “unsubstituted” alkyl, “substituted” or “unsubstituted” alkenyl, "substituted” or “unsubstituted” alkynyl, "substituted” or “unsubstituted” carbocyclyl, "substituted” or “unsubstituted” heterocyclyl, "substituted” or “unsubstituted” aryl or “substituted” or “unsubstituted” heteroaryl group).
  • substituted means that at least one hydrogen present on a group (e.g., a carbon or nitrogen atom etc.) is replaced with a permissible substituent, e.g., a substituent which upon substitution results in a stable compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction under normal conditions (temperature, pressure, air etc.).
  • a "substituted" group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position.
  • any of the compounds according to the invention can exist in one or more optical, geometric or chiral isomer forms depending on the number of asymmetric centres in the compound.
  • the invention thus relates equally to all the optical isomers and to their racemic or scalemic mixtures (the term "scalemic” denotes a mixture of enantiomers in different proportions), and to the mixtures of all the possible stereoisomers, in all proportions.
  • the diastereomers and/or the optical isomers can be separated according to the methods which are known per se by a person ordinary skilled in the art.
  • any of the compounds according to the invention can also exist in one or more geometric isomer forms depending on the number of double bonds in the compound.
  • the invention thus relates equally to all geometric isomers and to all possible mixtures, in all proportions.
  • the geometric isomers can be separated according to general methods, which are known per se by a person ordinary skilled in the art.
  • Any of the compounds according to the invention can also exist in one or more amorphic or isomorphic or polymorphic forms, depending on their preparation, purification storage and various other influencing factors.
  • the invention thus relates all the possible amorphic, isomorphic and polymorphic forms, in all proportions.
  • the amorphic, isomorphic and polymorphic forms can be prepared and/or separated and/or purified according to general methods, which are known per se by a person ordinary skilled in the art.
  • Alkyl refers to straight chain, branched or cyclic carbon chain, or any combination thereof.
  • Representative examples of alkyl include methyl, ethyl, propyl, 1-methylethyl, butyl, 1- methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3- methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2- dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1- dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-tri
  • the alkyl is at the end of a composite substituent, as, for example, in alkylcycloalkyl
  • the part of the composite substituent at the start for example the cycloalkyl
  • other radicals for example alkenyl, alkynyl, hydroxyl, halogen, carbonyl, carbonyloxy and the like, are at the end.
  • alkenyl used either alone or in compound words includes straight-chain or branched Ci to C24 alkenes, preferably Ci to C15 alkenes, more preferably Ci to C10 alkenes, most preferably Ci to Ce alkenes.
  • alkenyl include ethenyl, 1- propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1 -methyl- 1-propenyl, 2-methyl-l-propenyl, l-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3- pentenyl, 4-pentenyl, 1 -methyl- 1-butenyl, 2-methyl- 1-butenyl, 3 -methyl- 1-butenyl, 1-methyl-
  • Alkenyl also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl.
  • alkynyl examples include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2- butynyl, 3-butynyl, l-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1- methyl-2-butynyl, lmethyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-l-butynyl, 1,1-dimethyl-
  • alkoxy used either alone or in compound words included Ci to C24 alkoxy, preferably Ci to C15 alkoxy, more preferably Ci to C10 alkoxy.
  • alkoxy include methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy,
  • alkylthio includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, propylthio, 1-methylethylthio, butylthio, 1-methylpropylthio, 2- methylpropylthio, 1,1-dimethylethylthio, pentylthio, 1-methylbutylthio, 2-methylbutylthio, 3- methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexylthio, 1,1- dimethylpropylthio, 1,2-dimethylpropylthio, 1-methylpentylthio, 2-methylpentylthio, 3- methylpentylthio, 4-methylpentylthio, 1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3- dimethylbutylthio, 2,2-dimethylbutylthio, 2,
  • halogen either alone or in compound words such as “haloalkyl”, includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as “haloalkyl”, said alkyl may be partially or fully substituted with halogen atoms which may be the same or different.
  • haloalkyl examples include chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1- bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2- fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, l,l-dichloro-2,2,2-trifluoroethyl, and l,l,l-trifluoroprop-2-yl. This definition also applies to haloalkyl as
  • haloalkoxy means straight-chain or branched alkoxy groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above.
  • Non-limiting examples of haloalkoxy include chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1- bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2- chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2- trichloroethoxy, pentafluoroethoxy and l,l
  • haloalkylthio means straight-chain or branched alkylthio groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above.
  • Non-limiting examples of haloalkylthio include chloromethylthio, bromomethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethy lthio , chlorofluoromethy lthio , dichlorofluoromethy lthio , chlorodifluoromethylthio, 1-chloroethylthio, 1-bromoethy lthio, 1- fluoroethy lthio, 2- fluoroethy lthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2-chloro-2- fluoroethy lthio, 2- chloro
  • aryl as used herein is a group that contains any carbon-based aromatic group including, but not limited to, benzene, naphthalene, phenyl, biphenyl, anthracene, and the like.
  • the aryl group can be substituted or unsubstituted.
  • the aryl group can be a single ring structure or comprise multiple ring structures that are either fused ring structures or attached via one or more bridging groups such as a carbon-carbon bond.
  • carrier or “carbocyclic” or “carbocyclyl” include “aromatic carbocyclic ring system” and “nonaromatic carbocylic ring system” or polycyclic or bicyclic (spiro, fused, bridged, nonfused) ring compounds in which the ring may be aromatic or non-aromatic (where aromatic indicates that the Hueckel rule is satisfied and non-aromatic indicates that the Hueckel rule is not statisfied).
  • Non limiting examples of non-aromatic carbocyclic ring system are cyclopropyl, cyclobutyl, cyclopentyl, norbornyl and the like.
  • Non limiting examples of aromatic carbocyclic ring system are phenyl, napthalene and the like.
  • hetero in connection with rings refers to a ring in which at least one ring atom is not carbon and which can contain 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that each ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs.
  • non-aromatic heterocycle means three- to fifteen-membered, preferably three- to twelve-membered, saturated or partially unsaturated heterocycles containing one to four heteroatoms from the group of oxygen, nitrogen and sulphur: mono, bi- or tricyclic heterocycles which contain, in addition to carbon ring members, one to three nitrogen atoms and/or one oxygen or sulphur atom or one or two oxygen and/or sulphur atoms; if the ring contains more than one oxygen atom, they are not directly adjacent; for example (but not limited to) oxiranyl, oxetanyl, aziridinyl, azetidinyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl, 3-tetrahydrothienyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-isoxazolidinyl, 4- isoxazolidinyl, 5-
  • heteroaryl as used herein is a group that contains fused or unfused three to fifteen membered, preferably three to tweleve membered, more preferably 5 or 6 membered; monocyclic or polycyclic unsaturated ring system, containing heteroatoms selected from the group of oxygen, nitrogen, sulphur, phosphorous, boron etc.
  • Non-limiting examples of 5 membered heteroaryl groups include 2-furyl; 3-furyl; 2-thienyl; 3-thienyl; 2-pyrrolyl; 3-pyrrolyl; 3-isoxazolyl; 4-isoxazolyl; 5-isoxazolyl; 3-isothiazolyl; 4- isothiazolyl; 5-isothiazolyl; 3-pyrazolyl; 4-pyrazolyl; 5-pyrazolyl; 2-oxazolyl; 4-oxazolyl; 5- oxazolyl; 2-thiazolyl; 4-thiazolyl; 5-thiazolyl; 2-imidazolyl; 4-imidazolyl; l,2,4-oxadiazol-3- yl; l,2,4-oxadiazol-5-yl; l,2,4-thiadiazol-3-yl; l,2,4-thiadiazol-5-yl; l,2,4-triazol-3-yl; 1,3,4- oxadiazol-2-yl
  • Non-limiting examples of 6 membered heteroaryl groups include 2-pyridinyl; 3-pyridinyl; 4- pyridinyl; 3-pyridazinyl; 4-pyridazinyl; 2-pyrimidinyl; 4-pyrimidinyl; 5-pyrimidinyl; 2- pyrazinyl; l,3,5-triazin-2-yl; l,2,4-triazin-3-yl; l,2,4,5-tetrazin-3-yl and the like.
  • Non-limiting examples of benzofused 5-membered heteroaryl include indol-l-yl; indol-2-yl; indol-3-yl; indol-4-yl; indol-5-yl; indol-6-yl; indol-7-yl; benzimidazol-l-yl; benzimidazol-2- yl; benzimidazol-4-yl; benzimidazol-5-yl; indazol-l-yl; indazol-3-yl; indazol-4-yl; indazol-5- yl; indazol-6-yl; indazol-7-yl; indazol-2-yl; l-benzofuran-2-yl; l-benzofuran-3-yl; 1- benzofuran-4-yl; l-benzofuran-5-yl; 1-benzofuran- 6-yl; l-benzofur
  • Non-limiting examples of benzofused 6-membered heteroaryl include quinolin-2-yl; quinolin-3-yl; quinolin-4-yl; quinolin-5-yl; quinolin-6-yl; quinolin-7-yl; quinolin-8-yl; isoquinolin-l-yl; isoquinolin-3-yl; isoquinolin-4-yl; isoquinolin-5-yl; isoquinolin-6-yl; isoquinolin-7-yl; isoquinolin-8-yl and the like.
  • Non-limiting examples of fused 6-5-membered heteroaryl include Indolizinyl; pyrazolo[l,5- a]pyridinyl; imidazo[l,2-a]pyridinyl; pyrrolo[l,2-a]pyrimidinyl; pyrazolo[l,5-a]pyrimidinyl; imidazo[l,2-a]pyrimidinyl; pyrrolo[l,2-a]pyrazinyl; pyrazolo[l,5-a]pyrazinyl; imidazo[l,2- a]pyrazinyl and the like.
  • the present invention is directed to an improved process for the preparation of bromo- formimine compound of Formula (I)or salt thereof,
  • X and X 1 is bromine
  • R is selected from the group consisting of CN, OH, COR 1 , and OCOCH3;
  • R 1 is selected from the group consisting of hydrogen, halogen, OR y , CN, NO2, SH, NH 2 , NH(Ci-C 6 -alkyl), N(Ci-C 6 -alkyl) 2 , NH-S0 2 -R x , Ci-C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 - C 6 -alkynyl, Ci- C 6 -alkoxy, Ci-C 6 -haloalkoxy, Ci-C 6 -alkylthio, Ci-C 6 -haloalkylthio a saturated or partially unsaturated three- to ten-membered carbocycle or heterocycle, five- or six-membered heteroaryl and aryl, wherein R x and R y are selected from the group consisting of hydrogen, Ci-C 6 -alkyl, Ci-C 6 -haloalkyl, and aryl;
  • X 3 and X 2 are independently selected from hydrogen, C0 2 R', and C(0)NR 2 R 3 ;
  • R 2 and R 3 are selected from the group consisting of hydrogen, halogen, SH, Ci-C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, Ci-C 6 -alkoxy, Ci-C 6 -haloalkoxy, Ci-C 6 -alkylthio, Ci-C 6 -haloalkylthio a saturated or partially unsaturated three - to ten-membered carbocycle or heterocycle, five- or six-membered heteroaryl and aryl;
  • the step (a) comprising reacting the compound of Formula (II)or salt thereof with bromine in a suitable solvent at a suitable pH, wherein suitable solvent is a polar solvent and suitable pH is in the range of about 8 to 14.
  • the bromination reaction is carried out at temperature of about 5 °C to 35 °C.
  • the amount of bromine used is in the range of about 0.25 to 3 mole equivalents, based on the formimine compound or salt thereof, preferably the amount of bromine is in the range of about 0.25 to 2.0 mole equivalents.
  • the step (b) comprises recycling ofbromine anion by means of addition of a suitableoxidizing agent, wherein the oxidizing agent is selected from the group comprising of fluorine; chlorine; hydrogen peroxide; nitric acid or nitrate compounds; sulfuric acid; peroxydisulfuric acid; peroxy mono sulfuric acid; chlorite, chlorate, perchlorate and other analogus of halogen compounds; hypochlorite and other hypohalite compounds such as sodium hypochlorite; hexavalent chromium compounds such as chromic and dichromic acids, chromium trioxide, pyridinium chlorochromate, chromate/dichromate compounds; permanganate compounds such as potassium permanganate; sodium perborate; nitrous oxide, nitrogen dioxide, dinitrogen tetroxide; potassium nitrate; sodium bismuthate and mixture thereof.
  • a suitableoxidizing agent is selected from the group comprising of fluorine; chlorine; hydrogen peroxide; nitric
  • reaction mixture is carried out at temperature of about 5 °C to 35 °C.
  • the step (c) optionally comprises the isolation of bromo-formimine compound of Formula (I)or salt thereof, wherein the isolation may be carried out by any conventional method, such as by filtration or solvent extraction.
  • Suitable solvent is selected from the group comprising of, water, alcohol or chlorinated solventsor a mixture thereof, wherein alcohol is selected from tert-amyl alcohol, benzyl alcohol, 1,4-butanediol, 1,2,4-butanetriol, n-butanol, 2-butanol, tert-butyl alcohol, denatured alcohol, di(propylene glycol) methyl ether, diethylene glycol, ethanol, ethylene glycol, 2- ethylhexanol, furfuryl alcohol, methanol, 2-(2-methoxyethoxy)ethanol, 2-methyl- 1 -butanol, 2-methyl- 1-pentanol, neopentyl alcohol, 2-pentanol, 1,3 propanediol, n-proponol, and propylene glycol; chlorinated solvent is selected from carbon tetrachloride, dichloromethane, chloroform, methylchloride, chloroethane,
  • the solvent is a polar solvent such as water.
  • Other solvents that can also be employed in the present invention is selected from the group comprising of,bromoform, carbon tetrabromide, ethylene dibromide, toluene, xylene, benzotrifluorideor a mixture thereof. pH of the reaction mixture may be maintained by means of addition of a suitable base, wherein the base is selected from organic base or inorganic base.
  • Organic base is selected from the group comprising of, but not limited to, alkyl ammonium hydroxide such as tetramethyl ammonium hydroxide, tetraethyl ammonium hydroxide, tetrapropyl ammonium hydroxide, tetrabutyl ammonium hydroxide, trimethyl-2-hydroxyethyl ammonium hydroxide (choline), triethyl-2-hydroxy ethyl ammonium hydroxide, ethyltrimethyl ammonium hydroxide; alkyl amine such as trimethylamine, triethylamine, tributylamine, tripentylamine, monoethanolamine, diethylamine; pyridine, 4- dimethylaminopyridine, 2,4-lutidine, 2,6-lutidine, collidine, alpha-picoline, beta-picoline, gamma.-picoline, quinoline, isoquinoline, aniline, diemthylaniline, N, N-d
  • Inorganic base is selected from the group comprising of, but not limited to, alkali or alkaline earth metal hydroxides, carbonates, bicarbonates, bisulfates, acetate, methoxide, ethoxide, phosphate, sulfite, sulfate preferably selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium bisulfate, potassium bisulfate, sodium acetate, potassium acetate, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, trisodium phosphate, tripotassium phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen sulfide, sodium sulfate, and mixtures thereof.
  • alkali or alkaline earth metal hydroxides carbonates, bicarbonates, bisulfates, acetate, methoxide, ethoxide, phosphate, sul
  • the base is selected from triethylamine, pyridine, potassium hydroxide, sodium hydroxide, and sodium carbonate.
  • bromo-formimine compound of Formula (I) or salt thereof obtained according to the present invention process is more than 99 %, when measured by HPLC.
  • Bromo-formimine compound of Formula (I) prepared by the process of the present invention includes, but are not limited to,dimethylcarbonohydrazonicdibromide (la), hydroxycarbonimidicdibromide (lb), and methoxycarbonimidicdibromide (Ic).

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  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
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Abstract

The present invention discloses an improved process for the preparation of bromo-formimine compounds. More particularly, the present invention discloses an improved process for the preparation of bromo-formimine compounds, wherein bromine anion is recycled by using a suitable oxidizing agent.

Description

TITLE OF THE INVENTION: PROCESS FOR PREPARATION OF BROMO FORMIMINE COMPOUNDS
FIELD OF THE INVENTION:
The present invention relates to a process for the preparation of hromo-formimine compounds or salt thereof. More particularly, the present invention relates to an improved process for the preparation of bromo-formimine compounds or salt thereof, wherein bromine anion is recycledby using a suitable oxidizing agent.
BACKGROUND OF THE INVENTION:
Bromo-formimine compounds are a commercially important class of organic compounds. Bromo-formimines are useful as intermediates in the synthesis of a wide variety of organic compounds, such as microbicides, agricultural pesticides and pharmaceutical agents.
Bromo-formimine bactericide are suitable for use in a variety of industries, such as, but not limited to, cooling towers; air washers; mineral slurries; pulp and paper processing fluids; paper coatings; swimming pools; spas; adhesives; caulks; mastics; sealants; agriculture adjuvant preservation; construction products; cosmetics and toiletries; shampoos; disinfectants and antiseptics; Formulated industrial and consumer products; soaps; laundry rinse waters; leather and leather products; wood, including lumber, timber, fiberboard, plywood, and wood composites; plastics; lubricants; hydraulic fluids; medical devices; metalworking fluids; emulsions and dispersions; paints, including marine paints; varnishes, including marine varnishes; latexes; odor control fluids; coatings, including marine coatings; petroleum processing fluids; fuel; oil field fluids; photographic chemicals; printing fluids; sanitizers; detergents; textiles, such as fibers; and textile products, such as clothes and carpets.
General process for the preparation of formimine compounds are disclosed in U.S. Patent No. 4,879,314 and U.S. Patent No. 6,207,863. Presently known methods for preparing bromo-formimine generate significant levels of effluent as by-products such as sodium bromide and hydrogen bromide, which impacts on product yield as well as cost.
Therefore, there is a need to develop an effective process for the preparation of formimine compounds or salt thereof, wherein by-products can be recycled to reduce effluent and improvement in the yield without impacting the purity of formimine compounds or salt thereof.
SUMMARY OF THE INVENTION:
The present invention provides an improvedprocess for the preparation of hromo-formimine compound of Formula (I)or salt thereof,
Formula (I)
wherein,
X and X1 is bromine;
R is selected from the group consisting of CN, OH, COR1, and OCOCH3;
R1 is selected from the group consisting of hydrogen, halogen, ORy, CN, NO2, SH, NH2, NH(Ci-C6-alkyl), N(Ci-C6-alkyl)2, NH-S02-Rx, Ci-C6-alkyl, C2-C6-alkenyl, C2- C6-alkynyl, Ci- C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, Ci-C6-haloalkylthio a saturated or partially unsaturated three- to ten-membered carbocycle or heterocycle, five- or six-membered heteroaryl and aryl, wherein Rx and Ry are selected from the group consisting of hydrogen, Ci-C6-alkyl, Ci-C6-haloalkyl, and aryl;
wherein, the process comprising the steps of:
a) reacting a formimine compound of Formula (II) or salt thereofwith bromine in a suitable solvent at a suitable pH,
Formula (II) wherein:
X3 and X2 are independently selected from hydrogen, CO2R1, and C(0)NR2R3; R2 and R3 are selected from the group consisting of hydrogen, halogen, SH, Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, Ci-C6-haloalkylthio a saturated or partially unsaturated three - to ten-membered carbocycle or heterocycle, five- or six-membered heteroaryl and aryl;
b) recycling of bromine anion by addition of a suitableoxidizing agent,
c) optionally, isolating the compound of Formula (I)or salt thereof.
The purity of bromo-formimine compound of Formula (I)or salt thereofobtained according to the present invention processis more than 99 %, when measured by HPLC.
DETAILED DESCRIPTION OF THE INVENTION:
DEFINITIONS:
The foregoing definitions provided herein for the terminologies used in the present disclosure are for illustrative purpose only and in no manner limit the scope of the present invention disclosed in the present disclosure.
As used herein, the terms "comprises", "comprising", "includes", "including",“consisting” or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such process or method.
Further, unless expressly stated to the contrary, "or" refers to an inclusive“or” and not to an exclusive“or”. For example, a condition A“or” B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B is true (or present).
Also, the indefinite articles "a" and "an" preceding an element or component of the present invention are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore "a" or "an" should be read to include one or at least one, and the singular word form of the element or component also includes the plural unless the number is obviously meant to be singular.
Alkyl, alkenyl, alkynyl, carbocycle, heterocycle, aryl and heteroaryl groups, as defined herein, are optionally substituted (e.g., "substituted" or "unsubstituted" alkyl, "substituted" or "unsubstituted" alkenyl, "substituted" or "unsubstituted" alkynyl, "substituted" or "unsubstituted" carbocyclyl, "substituted" or "unsubstituted" heterocyclyl, "substituted" or "unsubstituted" aryl or "substituted" or "unsubstituted" heteroaryl group). In general, the term "substituted", whether preceded by the term "optionally" or not, means that at least one hydrogen present on a group (e.g., a carbon or nitrogen atom etc.) is replaced with a permissible substituent, e.g., a substituent which upon substitution results in a stable compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction under normal conditions (temperature, pressure, air etc.). Unless otherwise indicated, a "substituted" group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position.
Any of the compounds according to the invention can exist in one or more optical, geometric or chiral isomer forms depending on the number of asymmetric centres in the compound. The invention thus relates equally to all the optical isomers and to their racemic or scalemic mixtures (the term "scalemic" denotes a mixture of enantiomers in different proportions), and to the mixtures of all the possible stereoisomers, in all proportions. The diastereomers and/or the optical isomers can be separated according to the methods which are known per se by a person ordinary skilled in the art.
Any of the compounds according to the invention can also exist in one or more geometric isomer forms depending on the number of double bonds in the compound. The invention thus relates equally to all geometric isomers and to all possible mixtures, in all proportions. The geometric isomers can be separated according to general methods, which are known per se by a person ordinary skilled in the art. Any of the compounds according to the invention, can also exist in one or more amorphic or isomorphic or polymorphic forms, depending on their preparation, purification storage and various other influencing factors. The invention thus relates all the possible amorphic, isomorphic and polymorphic forms, in all proportions. The amorphic, isomorphic and polymorphic forms can be prepared and/or separated and/or purified according to general methods, which are known per se by a person ordinary skilled in the art.
“Alkyl” refers to straight chain, branched or cyclic carbon chain, or any combination thereof. Representative examples of alkyl include methyl, ethyl, propyl, 1-methylethyl, butyl, 1- methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3- methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2- dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1- dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1- ethyl-l-methylpropyl and l-ethyl-2-methylpropyl or the different isomers. If the alkyl is at the end of a composite substituent, as, for example, in alkylcycloalkyl, the part of the composite substituent at the start, for example the cycloalkyl, may be mono- or polysubstituted identically or differently and independently by alkyl. The same also applies to composite substituents in which other radicals, for example alkenyl, alkynyl, hydroxyl, halogen, carbonyl, carbonyloxy and the like, are at the end.
The term "alkenyl", used either alone or in compound words includes straight-chain or branched Ci to C24 alkenes, preferably Ci to C15 alkenes, more preferably Ci to C10 alkenes, most preferably Ci to Ce alkenes. Representative examples of alkenyl include ethenyl, 1- propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1 -methyl- 1-propenyl, 2-methyl-l-propenyl, l-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3- pentenyl, 4-pentenyl, 1 -methyl- 1-butenyl, 2-methyl- 1-butenyl, 3 -methyl- 1-butenyl, 1-methyl-
2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, l-methyl-3-butenyl, 2-methyl-3-butenyl,
3-methyl-3-butenyl, l,l-dimethyl-2-propenyl, 1,2-dimethyl- 1-propenyl, l,2-dimethyl-2 - propenyl, 1 -ethyl- 1-propenyl, l-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4- hexenyl, 5-hexenyl, 1 -methyl- 1-pentenyl, 2-methyl- 1-pentenyl, 3 -methyl- 1-pentenyl, 4- methyl- 1-pentenyl, l-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4- methyl-2-pentenyl, l-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4- methyl-3-pentenyl, l-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4- methyl-4-pentenyl, l,l-dimethyl-2-butenyl, l,l-dimethyl-3-butenyl, 1,2-dimethyl-l-butenyl,
1.2-dimethyl-2-butenyl, l,2-dimethyl-3-butenyl, 1,3-dimethyl-l-butenyl, l,3-dimethyl-2- butenyl, 1,3 -dimethyl-3 -butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-l-butenyl, 2,3- dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-lbutenyl, 3,3-dimethyl-2-butenyl,
1 -ethyl- 1 -butenyl, l-ethyl-2-butenyl, l-ethyl-3 -butenyl, 2-ethyl- 1-butenyl, 2-ethyl-2-butenyl,
2-ethyl-3-butenyl, l,l,2-trimethyl-2-propenyl, l-ethyl-l-methyl-2-propenyl, l-ethyl-2-methyl-l- propenyl and l-ethyl-2-methyl-2-propenyl and the different isomers. "Alkenyl" also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl.
Representative examples of alkynyl include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2- butynyl, 3-butynyl, l-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1- methyl-2-butynyl, lmethyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-l-butynyl, 1,1-dimethyl-
2-propynyl, 1 -ethyl -2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1- methyl-2-pentynyl, l-methyl-3-pentynyl, l-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2- methyl-4-pentynyl, 3-methyl-l-pentynyl, 3-methyl-4-pentynyl, 4-methyl-l-pentynyl, 4- methyl-2-pentynyl, l,l-dimethyl-2-butynyl, l,l-dimethyl-3-butynyl, l,2-dimethyl-3-butynyl,
2.2-dimethyl-3-butynyl, 3,3-dimethyl-l-butynyl, l-ethyl-2-butynyl, lethyl-3-butynyl, 2-ethyl-
3-butynyl and l-ethyl-l-methyl-2-propynyl and the different isomers.
The term“alkoxy” used either alone or in compound words included Ci to C24 alkoxy, preferably Ci to C15 alkoxy, more preferably Ci to C10 alkoxy. Examples of alkoxy include methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy,
1.1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2- dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 1- methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy,
1.2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3- dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2- trimethylpropoxy, 1 -ethyl- 1-methylpropoxy and l-ethyl-2-methylpropoxy and the different isomers. This definition also applies to alkoxy as a part of a composite substituent, for example haloalkoxy, alkynylalkoxy, etc., unless specifically defined elsewhere.
The term “alkylthio” includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, propylthio, 1-methylethylthio, butylthio, 1-methylpropylthio, 2- methylpropylthio, 1,1-dimethylethylthio, pentylthio, 1-methylbutylthio, 2-methylbutylthio, 3- methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexylthio, 1,1- dimethylpropylthio, 1,2-dimethylpropylthio, 1-methylpentylthio, 2-methylpentylthio, 3- methylpentylthio, 4-methylpentylthio, 1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3- dimethylbutylthio, 2,2-dimethylbutylthio, 2,3-dimethylbutylthio, 3,3-dimethylbutylthio, 1- ethylbutylthio, 2-ethylbutylthio, 1,1,2-trimethylpropylthio, 1,2,2-trimethylpropylthio, 1-ethyl- 1-methylpropylthio and l-ethyl-2-methylpropylthio and the different isomers.
The term "halogen", either alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. Further, when used in compound words such as "haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1- bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2- fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, l,l-dichloro-2,2,2-trifluoroethyl, and l,l,l-trifluoroprop-2-yl. This definition also applies to haloalkyl as a part of a composite substituent, for example haloalkylaminoalkyl etc., unless specifically defined elsewhere.
The term "haloalkoxy" means straight-chain or branched alkoxy groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above. Non-limiting examples of haloalkoxy include chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1- bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2- chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2- trichloroethoxy, pentafluoroethoxy and l,l,l-trifluoroprop-2-oxy. This definition also applies to haloalkoxy as a part of a composite substituent, for example haloalkoxyalkyl etc., unless specifically defined elsewhere.
The term "haloalkylthio" means straight-chain or branched alkylthio groups where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as specified above. Non-limiting examples of haloalkylthio include chloromethylthio, bromomethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethy lthio , chlorofluoromethy lthio , dichlorofluoromethy lthio , chlorodifluoromethylthio, 1-chloroethylthio, 1-bromoethy lthio, 1- fluoroethy lthio, 2- fluoroethy lthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2-chloro-2- fluoroethy lthio, 2- chloro-2,2-difluoroethylthio, 2,2-dichloro-2-fluoroethylthio, 2,2,2-trichloroethylthio, pentafluoroethy lthio and l,l,l-trifluoroprop-2-ylthio. This definition also applies to haloalkylthio as a part of a composite substituent, for example haloalkylthioalkyl etc., unless specifically defined elsewhere.
The term "aryl" as used herein is a group that contains any carbon-based aromatic group including, but not limited to, benzene, naphthalene, phenyl, biphenyl, anthracene, and the like. The aryl group can be substituted or unsubstituted. In addition, the aryl group can be a single ring structure or comprise multiple ring structures that are either fused ring structures or attached via one or more bridging groups such as a carbon-carbon bond.
The terms "carbocycle" or "carbocyclic" or "carbocyclyl" include "aromatic carbocyclic ring system" and "nonaromatic carbocylic ring system" or polycyclic or bicyclic (spiro, fused, bridged, nonfused) ring compounds in which the ring may be aromatic or non-aromatic (where aromatic indicates that the Hueckel rule is satisfied and non-aromatic indicates that the Hueckel rule is not statisfied).
Non limiting examples of non-aromatic carbocyclic ring system are cyclopropyl, cyclobutyl, cyclopentyl, norbornyl and the like. Non limiting examples of aromatic carbocyclic ring system are phenyl, napthalene and the like.
The term "hetero" in connection with rings refers to a ring in which at least one ring atom is not carbon and which can contain 1 to 4 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that each ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs.
The terms "heterocycle" or "heterocyclic" or "heterocyclyl" include "aromatic heterocycle or heteroaryl ring system" and "nonaromatic heterocycle ring system" or polycyclic or bicyclic (spiro, fused, bridged, nonfused) ring compounds in which the ring may be aromatic or non aromatic, wherein the heterocycle ring contains at least one heteroatom selected from N, O, S(0)o-2, and or C ring member of the heterocycle may be replaced by C(=0), C(=S), C(=CR*R*) and C=NR*, * indicates integers (where aromatic heterocycle or heteroaryl ring indicates that the Hueckel rule is satisfied).
The term "non-aromatic heterocycle" means three- to fifteen-membered, preferably three- to twelve-membered, saturated or partially unsaturated heterocycles containing one to four heteroatoms from the group of oxygen, nitrogen and sulphur: mono, bi- or tricyclic heterocycles which contain, in addition to carbon ring members, one to three nitrogen atoms and/or one oxygen or sulphur atom or one or two oxygen and/or sulphur atoms; if the ring contains more than one oxygen atom, they are not directly adjacent; for example (but not limited to) oxiranyl, oxetanyl, aziridinyl, azetidinyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl, 3-tetrahydrothienyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-isoxazolidinyl, 4- isoxazolidinyl, 5-isoxazolidinyl, 3-isothiazolidinyl, 4-isothiazolidinyl, 5-isothiazolidinyl, 3- pyrazolidinyl, 4-pyrazolidinyl, 5-pyrazolidinyl, 2-oxazolidinyl, 4-oxazolidinyl, 5- oxazolidinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 2-imidazolidinyl, 4- imidazolidinyl, l,2,4-oxadiazolidin-3-yl, l,2,4-oxadiazolidin-5-yl, l,2,4-thiadiazolidin-3-yl,
1.2.4-thiadiazolidin-5-yl, l,2,4-triazolidin-3-yl, l,3,4-oxadiazolidin-2-yl, 1,3,4-thiadiazolidin-
2-yl, l,3,4-triazolidin-2-yl, 2,3-dihydrofur-2-yl, 2,3-dihydrofur-3-yl, 2,4-dihydrofur-2-yl, 2,4- dihydrofur-3-yl, 2,3-dihydrothien-2-yl, 2,3-dihydrothien-3-yl, 2,4-dihydrothien-2-yl, 2,4- dihydrothien-3-yl, 2-pyrrolin-2-yl, 2-pyrrolin-3-yl, 3-pyrrolin-2-yl, 3-pyrrolin-3-yl, 2- isoxazolin-3-yl, 3-isoxazolin-3-yl, 4-isoxazolin-3-yl, 2-isoxazolin-4-yl, 3-isoxazolin-4-yl, 4- isoxazolin-4-yl, 2-isoxazolin-5-yl, 3-isoxazolin-5-yl, 4-isoxazolin-5-yl, 2-isothiazolin-3-yl, 3- isothiazolin-3-yl, 4-isothiazolin-3-yl, 2-isothiazolin-4-yl, 3-isothiazolin-4-yl, 4-isothiazolin-4- yl, 2-isothiazolin-5-yl, 3-isothiazolin-5-yl, 4-isothiazolin-5-yl, 2,3-dihydropyrazol-l-yl, 2,3- dihydropyrazol-2-yl, 2,3-dihydropyrazol-3-yl, 2,3-dihydropyrazol-4-yl, 2,3-dihydropyrazol- 5-yl, 3,4-dihydropyrazol-l-yl, 3,4-dihydropyrazol-3-yl, 3,4-dihydropyrazol-4-yl, 3,4- dihydropyrazol-5-yl, 4,5-dihydropyrazol-l-yl, 4,5-dihydropyrazol-3-yl, 4,5-dihydropyrazol-4- yl, 4,5-dihydropyrazol-5-yl, 2,3-dihydrooxazol-2-yl, 2,3-dihydrooxazol-3-yl, 2,3- dihydrooxazol-4-yl, 2,3-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4-dihydrooxazol-3-yl,
3.4-dihydrooxazol-4-yl, 3,4-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4-dihydrooxazol-
3-yl, 3,4-dihydrooxazol-4-yl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, l,3-dioxan-5-yl, 2- tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, 3-hexahydropyridazinyl, 4- hexahydropyridazinyl, 2-hexahydropyrimidinyl, 4-hexahydropyrimidinyl, 5- hexahydropyrimidinyl, 2-piperazinyl, l,3,5-hexahydrotriazin-2-yl, l,2,4-hexahydrotriazin-3- yl, morpholinyl, thiomorpholinyl, and cycloserines. This definition also applies to heterocyclyl as a part of a composite substituent, for example heterocyclyloalkyl etc., unless specifically defined elsewhere.
The term "heteroaryl" as used herein is a group that contains fused or unfused three to fifteen membered, preferably three to tweleve membered, more preferably 5 or 6 membered; monocyclic or polycyclic unsaturated ring system, containing heteroatoms selected from the group of oxygen, nitrogen, sulphur, phosphorous, boron etc.
Non-limiting examples of 5 membered heteroaryl groups include 2-furyl; 3-furyl; 2-thienyl; 3-thienyl; 2-pyrrolyl; 3-pyrrolyl; 3-isoxazolyl; 4-isoxazolyl; 5-isoxazolyl; 3-isothiazolyl; 4- isothiazolyl; 5-isothiazolyl; 3-pyrazolyl; 4-pyrazolyl; 5-pyrazolyl; 2-oxazolyl; 4-oxazolyl; 5- oxazolyl; 2-thiazolyl; 4-thiazolyl; 5-thiazolyl; 2-imidazolyl; 4-imidazolyl; l,2,4-oxadiazol-3- yl; l,2,4-oxadiazol-5-yl; l,2,4-thiadiazol-3-yl; l,2,4-thiadiazol-5-yl; l,2,4-triazol-3-yl; 1,3,4- oxadiazol-2-yl; l,3,4-thiadiazol-2-yl and l,3,4-triazol-2-yl; 1-pyrrolyl; 1-pyrazolyl; 1,2,4- triazol-1- yl; 1-imidazolyl; 1,2,3-triazol-l-yl; 1,3,4-triazol-l-yl and the like.
Non-limiting examples of 6 membered heteroaryl groups include 2-pyridinyl; 3-pyridinyl; 4- pyridinyl; 3-pyridazinyl; 4-pyridazinyl; 2-pyrimidinyl; 4-pyrimidinyl; 5-pyrimidinyl; 2- pyrazinyl; l,3,5-triazin-2-yl; l,2,4-triazin-3-yl; l,2,4,5-tetrazin-3-yl and the like.
Non-limiting examples of benzofused 5-membered heteroaryl include indol-l-yl; indol-2-yl; indol-3-yl; indol-4-yl; indol-5-yl; indol-6-yl; indol-7-yl; benzimidazol-l-yl; benzimidazol-2- yl; benzimidazol-4-yl; benzimidazol-5-yl; indazol-l-yl; indazol-3-yl; indazol-4-yl; indazol-5- yl; indazol-6-yl; indazol-7-yl; indazol-2-yl; l-benzofuran-2-yl; l-benzofuran-3-yl; 1- benzofuran-4-yl; l-benzofuran-5-yl; 1-benzofuran- 6-yl; l-benzofuran-7-yl; 1-benzothiophen- 2-yl; l-benzothiophen-3-yl; l-benzothiophen-4-yl; 1- benzothiophen-5-yl; l-benzothiophen-6- yl; l-benzothiophen-7-yl; l,3-benzothiazol-2-yl; 1,3- benzothiazol-4-yl; l,3-benzothiazol-5-yl; l,3-benzothiazol-6-yl; l,3-benzothiazol-7-yl; l,3-benzoxazol-2-yl; l,3-benzoxazol-4-yl; 1,3- benzoxazol-5-yl; l,3-benzoxazol-6-yl; l,3-benzoxazol-7-yl and the liked.
Non-limiting examples of benzofused 6-membered heteroaryl include quinolin-2-yl; quinolin-3-yl; quinolin-4-yl; quinolin-5-yl; quinolin-6-yl; quinolin-7-yl; quinolin-8-yl; isoquinolin-l-yl; isoquinolin-3-yl; isoquinolin-4-yl; isoquinolin-5-yl; isoquinolin-6-yl; isoquinolin-7-yl; isoquinolin-8-yl and the like. Non-limiting examples of fused 6-5-membered heteroaryl include Indolizinyl; pyrazolo[l,5- a]pyridinyl; imidazo[l,2-a]pyridinyl; pyrrolo[l,2-a]pyrimidinyl; pyrazolo[l,5-a]pyrimidinyl; imidazo[l,2-a]pyrimidinyl; pyrrolo[l,2-a]pyrazinyl; pyrazolo[l,5-a]pyrazinyl; imidazo[l,2- a]pyrazinyl and the like.
When a group contains a substituent which can be hydrogen, then, when this substituent is taken as hydrogen, it is recognized that said group is being un-substituted.
All amounts are percent by weight (“% wt”), unless otherwise noted. All ranges are inclusive. As used throughout the specification, the following abbreviations are applied: g=gram;and °C=Centigrade.
The specification herein and the various features and advantageous details thereof are explained with reference to the non-limiting examples in the description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the specification herein may be practiced and to further enable those of skilled in the art to practice the specification herein. Accordingly, the examples should not be construed as limiting the scope of the specification herein.
Any discussion of documents, acts, materials, devices, articles and the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application.
The numerical values mentioned in the description and the foregoing claims though might form a critical part of the present invention of the present disclosure, any deviation from such numerical values shall still fall within the scope of the present disclosure if that deviation follows the same scientific principle as that of the present invention disclosed in the present disclosure.
The present invention is directed to an improved process for the preparation of bromo- formimine compound of Formula (I)or salt thereof,
Formula (I)
wherein,
X and X1 is bromine;
R is selected from the group consisting of CN, OH, COR1, and OCOCH3;
R1 is selected from the group consisting of hydrogen, halogen, ORy, CN, NO2, SH, NH2, NH(Ci-C6-alkyl), N(Ci-C6-alkyl)2, NH-S02-Rx, Ci-C6-alkyl, C2-C6-alkenyl, C2- C6-alkynyl, Ci- C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, Ci-C6-haloalkylthio a saturated or partially unsaturated three- to ten-membered carbocycle or heterocycle, five- or six-membered heteroaryl and aryl, wherein Rx and Ry are selected from the group consisting of hydrogen, Ci-C6-alkyl, Ci-C6-haloalkyl, and aryl;
wherein, the process comprising the steps of:
a) reacting a formimine compound of Formula (II) or salt thereof with bromine in a suitable solvent at a suitable pH,
Formula (II)
wherein:
X3 and X2 are independently selected from hydrogen, C02R', and C(0)NR2R3; R2 and R3 are selected from the group consisting of hydrogen, halogen, SH, Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, Ci-C6-haloalkylthio a saturated or partially unsaturated three - to ten-membered carbocycle or heterocycle, five- or six-membered heteroaryl and aryl;
b) recycling of bromine anion by addition of a suitable oxidizing agent,
c) optionally, isolating the compound of Formula (I)or salt thereof.
The step (a) comprising reacting the compound of Formula (II)or salt thereof with bromine in a suitable solvent at a suitable pH, wherein suitable solvent is a polar solvent and suitable pH is in the range of about 8 to 14. The bromination reaction is carried out at temperature of about 5 °C to 35 °C. The amount of bromine used is in the range of about 0.25 to 3 mole equivalents, based on the formimine compound or salt thereof, preferably the amount of bromine is in the range of about 0.25 to 2.0 mole equivalents.
The step (b) comprises recycling ofbromine anion by means of addition of a suitableoxidizing agent, wherein the oxidizing agent is selected from the group comprising of fluorine; chlorine; hydrogen peroxide; nitric acid or nitrate compounds; sulfuric acid; peroxydisulfuric acid; peroxy mono sulfuric acid; chlorite, chlorate, perchlorate and other analogus of halogen compounds; hypochlorite and other hypohalite compounds such as sodium hypochlorite; hexavalent chromium compounds such as chromic and dichromic acids, chromium trioxide, pyridinium chlorochromate, chromate/dichromate compounds; permanganate compounds such as potassium permanganate; sodium perborate; nitrous oxide, nitrogen dioxide, dinitrogen tetroxide; potassium nitrate; sodium bismuthate and mixture thereof.
The addition of a suitable oxidizing agentin the reaction mixture is carried out at temperature of about 5 °C to 35 °C.
The step (c) optionally comprises the isolation of bromo-formimine compound of Formula (I)or salt thereof, wherein the isolation may be carried out by any conventional method, such as by filtration or solvent extraction.
Suitable solvent is selected from the group comprising of, water, alcohol or chlorinated solventsor a mixture thereof, wherein alcohol is selected from tert-amyl alcohol, benzyl alcohol, 1,4-butanediol, 1,2,4-butanetriol, n-butanol, 2-butanol, tert-butyl alcohol, denatured alcohol, di(propylene glycol) methyl ether, diethylene glycol, ethanol, ethylene glycol, 2- ethylhexanol, furfuryl alcohol, methanol, 2-(2-methoxyethoxy)ethanol, 2-methyl- 1 -butanol, 2-methyl- 1-pentanol, neopentyl alcohol, 2-pentanol, 1,3 propanediol, n-proponol, and propylene glycol; chlorinated solvent is selected from carbon tetrachloride, dichloromethane, chloroform, methylchloride, chloroethane, hexachloroethane, pentachloroethane, 1, 1,1,2- tetrachloroethane, 1,1,2,2-tetrachloroethane, 1,1,2-trichloroethane, 1,1,1-trichloroethane, 1,2- dichloroethane, 1,1-dichloroethane, chloroethane, tetrachloroethene, trichloroethylene, 1,2- dichloroethene, and 1,1-dichloroethene. It is preferred that the solvent is a polar solvent such as water. Other solvents that can also be employed in the present invention is selected from the group comprising of,bromoform, carbon tetrabromide, ethylene dibromide, toluene, xylene, benzotrifluorideor a mixture thereof. pH of the reaction mixture may be maintained by means of addition of a suitable base, wherein the base is selected from organic base or inorganic base.
Organic base is selected from the group comprising of, but not limited to, alkyl ammonium hydroxide such as tetramethyl ammonium hydroxide, tetraethyl ammonium hydroxide, tetrapropyl ammonium hydroxide, tetrabutyl ammonium hydroxide, trimethyl-2-hydroxyethyl ammonium hydroxide (choline), triethyl-2-hydroxy ethyl ammonium hydroxide, ethyltrimethyl ammonium hydroxide; alkyl amine such as trimethylamine, triethylamine, tributylamine, tripentylamine, monoethanolamine, diethylamine; pyridine, 4- dimethylaminopyridine, 2,4-lutidine, 2,6-lutidine, collidine, alpha-picoline, beta-picoline, gamma.-picoline, quinoline, isoquinoline, aniline, diemthylaniline, N, N-dimethylaniline, diethylaniline, benzidine, acetanilide, toluidine, and mixtures thereof.
Inorganic base is selected from the group comprising of, but not limited to, alkali or alkaline earth metal hydroxides, carbonates, bicarbonates, bisulfates, acetate, methoxide, ethoxide, phosphate, sulfite, sulfate preferably selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium bisulfate, potassium bisulfate, sodium acetate, potassium acetate, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, trisodium phosphate, tripotassium phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen sulfide, sodium sulfate, and mixtures thereof.
Preferably, the base is selected from triethylamine, pyridine, potassium hydroxide, sodium hydroxide, and sodium carbonate.
The purity of bromo-formimine compound of Formula (I) or salt thereof obtained according to the present invention process is more than 99 %, when measured by HPLC. Bromo-formimine compound of Formula (I) prepared by the process of the present invention includes, but are not limited to,dimethylcarbonohydrazonicdibromide (la), hydroxycarbonimidicdibromide (lb), and methoxycarbonimidicdibromide (Ic).
Formula (la) Formula (lb) Formula (Ic) The bromo-formimine compounds of Formula (I)or salt thereof produced according to the process of present invention can be subsequently converted to microbicides, agricultural pesticides or pharmaceutical agents.
The following examples are presented to illustrate further aspects of the present invention, but are not intended to limit the scope of the invention in any aspect.
Examples:
Example l:Synthesis of dimethylcarbonohydrazonic dibromide by using methyl-2- (dimethylhydrazinylidene)ethanoate
To a solution of 25% sodium hydroxide (36g), methyl-2- (dimethylhydrazinylidene)ethanoate(lOg) was added at 25-30°C. The reaction mixture was heated at 65-70°C for 2 h. Water (50 g) and isobutyl acetate (50 g) were added to the reaction mixture and heated to 50-55°C, followed by addition of 50% sulphuric acid (30 g) to the reaction mixture. After completion of the reaction, the reaction mixture was cooledto 25-30 °C. The organic and aqueous layer were separated to obtain 2- (dimethylhydrazinylidene)ethanoic acid (7.15 g).
Yield: 80%.
To a solution of water (20 g) and liquid bromine (9.86 g) in a reactor, a solution of 2- (dimethylhydrazinylidene)ethanoic acid (7.15 g) in 10% sodium hydroxide (50 g) was added.Chlorine gas (4.4 g) was purged into the reaction mixture at 25-30 °C for 2 h. After the completion of the reaction, isobutyl acetate (35 g) was added to the reaction mixture. The organic and aqueous layers were separated to obtain dimethylcarbonohydrazonic dibromide. Yield: 88%
Example 2: Synthesis of hydroxycarbonimidic dibromide by using methyl 2- (hydroxyimino)ethanoate
To a solution of 25% sodium hydroxide (28 g), methyl-2-(hydroxyimino)ethanoate (10 g) was added at 25-30 °C. The reaction mixture was heated at 65-70 °C for 2 h. Water (50 g) and isobutyl acetate (50 g) were added to the reaction mixture and heated to 50-55 °C, followed by addition of 50% sulphuric acid (28 g) to the reaction mixture. After the completion of the reaction, the reaction mixture was cooled to 25-30 °C. The organic and aqueous layer were separated to obtain 2-(hydroxyimino)ethanoic acid (6.5 g).
Yield: 80%.
To a solution of water (20 g) and liquid bromine (11.6 g) in a reactor, a solution of 2- (hydroxyimino)ethanoic acid (6.5 g) in 10% sodium hydroxide (40 g) wasadded. Chlorine gas (5.18 g) was purged into the reaction mixture at 25-30 °Cfor 2 h. After the completion of the reaction, isobutyl acetate (25 g) was added to the reaction mixture. The organic and aqueous layers were separated to obtain hydroxycarbonimidic dibromide.
Yield: 88%
Example 3: Synthesis of hydroxycarbonimidic dibromide by using 2- (hydroxyimino)propanedioic acid
To a solution of water (20 g) and liquid bromine (12.0 g) in a reactor, a solution of 2- (hydroxyimino)propanedioic acid (10 g) in 10% sodium hydroxide (48 g) was added. Chlorine gas (5.33 g) was purged into the reaction mixture at 10-15 °C for 30 min, and reacted for 2 h. After completion of the reaction, isobutyl acetate (25 g) was added to the reaction mixture. The organic and aqueous layers were separated to obtain hydroxycarbonimidic dibromide. Yield: 70%
Example 4: Synthesis of methoxycarbonimidic dibromide by using 2 (methoxyimino)ethanoic acid
To a solution of water (20 g) and liquid bromine (15.0 g) in a reactor, a solution of 2- (methoxyimino) ethanoic acid (10 g) in 10% sodium hydroxide (40 g) was added. Chlorine gas (6.9 g) was purged into the reaction mixture at 10-15 °C for 30 min, and reacted for 2 h. After completion of the reaction, ethyl acetate (35 g) was added to the reaction mixture. The organic and aqueous layers were separated to obtain hydroxycarbonimidic dibromide.
Yield: 77%

Claims

Claims:
1. An improved process for the preparation of bromo-formimine compound of Formula
(I),
Formula (I)
wherein,
X and X1 is bromine;
R is selected from the group consisting of CN, OH, COR1, and OCOCHsiR1 is selected from the group consisting of hydrogen, halogen, ORy, CN, NO2, SH, NH2, NH(Ci-C6-alkyl), N(Ci-C6-alkyl)2, NH-S02-Rx, Ci-C6-alkyl, C2-C6-alkenyl, C2-C6- alkynyl, Ci- C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, Ci-C6-haloalkylthio a saturated or partially unsaturated three- to ten-membered carbocycle or heterocycle, five- or six-membered heteroaryl and aryl, wherein Rx and Ryare selected from the group consisting of hydrogen, Ci-C6-alkyl, Ci-C6-haloalkyl, and aryl; wherein, the process comprising the steps of:
a) reacting a formimine compound of Formula (II) with bromine in a suitable solvent at a suitable pH,
Formula (II)
wherein:
X3 and X2 are independently selected from hydrogen, C02R', and C(0)NR2R3; R2 and R3 are selected from the group consisting of hydrogen, halogen, SH, Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, Ci-C6-alkylthio, Ci-C6-haloalkylthio a saturated or partially unsaturated three - to ten-membered carbocycle or heterocycle, five- or six-membered heteroaryl and aryl;
b) recycling of bromine anion by addition of a suitable oxidizing agent, c) optionally, isolating the compound of Formula (I).
2. The process according to claim 1, wherein the oxidizing agent is selected from the group comprising of fluorine, chlorine, hydrogen peroxide, nitric acid, sulfuric acid, peroxydisulfuric acid, peroxy mono sulfuric acid, chlorite, chlorate, perchlorate, hypochlorite, sodium hypochlorite, chromium trioxide, pyridiniumchlorochromate, potassium permanganate, sodium perborate, nitrous oxide, nitrogen dioxide, dinitrogen tetroxide, potassium nitrate, sodium bismuthate or a mixture thereof.
3. The process according to claim 1, wherein the solvent is a polar solvent.
4. The process according to claim 1, wherein the solvent is selected from the group comprising of water, alcohol, chlorinated solvent or a mixture thereof.
5. The process according to claim 4, wherein the solvent is water.
6. The process according to claim 1, wherein the amount of the bromine is in the range of 0.25 to 3 mole equivalents, based on the formimine compound of Formula (II).
7. The process according to claim 1, wherein the base is selected from organic or inorganic base.
8. The process according to claim 1, wherein the pH of the reaction is maintained in the range of 8 to 14.
9. The process according to claim 1, wherein the compound of Formula(I)can be subsequently converted to microbicides, agricultural pesticides or pharmaceutical agents.
EP20742881.4A 2019-05-24 2020-05-23 Process for preparation of bromo formimine compounds Pending EP3976578A1 (en)

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