Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
  • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
  • C07D277/62—Benzothiazoles
  • C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
• • 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
  • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
  • A01N57/10—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-oxygen bonds or phosphorus-to-sulfur bonds
  • A01N57/16—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-oxygen bonds or phosphorus-to-sulfur bonds containing heterocyclic radicals

Definitions

• Typical salts are alkali metal salts, for example sodium or, preferably, potassium. salts and amine salts for example triethylamine or diethanolamine or. preferably, dimethylamine salts.
• Typical esters are C, alkyl esters for example methyl, isopropyl or, preferably, ethyl esters. Benazolin and its esters and salts was originally described in British Pat. Specification No. 862,226. The
• the 4-chloro-2- hydroxybenzothiazole is contaminated with significant amounts of unacceptable by-products that have to be removed, generally at a later stage in the overall process for making benazolin or its esters or salts. This involves an extra purification step which is clearly timeconsuming and costly and which it would be desirable to avoid. Further, the formation of these unwanted byproducts represent a waste of starting material.
• the purpose of the invention has therefore been to devise a method of making 4-chloro-2- hydroxybenzothiazole in a higher degree of purity and in better yield and/or shorter reaction time than has been obtainable previously on a commercial scale as an intermediate in the preparation of benazolin and its esters and salts.
• a process for preparing 4-chloro-2-hydroxybenzothiazole comprises diazotising 2-amino-4-chlorbenzothiazole hydrolhalide and hydrolysing the product, the diazotisation being carried out in the presence of a halogenated aliphatic hydrocarbon in which the major products of the diazotisation reaction are soluble to the extent of at least 10% w/v at 20C.
• the major product of the diazotisation reaction are 2-halo-4-chlorobenzothiazoles.
• the major product is 2-bromo-4- chlorobenzothiazole.
• 2,4-Dichlorobenzothiazole is also usually formed.
• halogenated aliphatic hydrocarbons for use in the invention are chlorinated hydrocarbons, for example ethylene dichloride which is particularly preferred, methylene chloride, chloroform, carbon tetrachloride, tetrachlorethane, trichloroethylene, perchloroethylene, 1,2-dichloropropane and 1,1 ,1- trichloroethane.
• Other halogenated hydrocarbons include bromine-containing hydrocarbons, for example ethylene dibromide. It is preferred that the solvent is one which has a boiling point of between 4090C, preferably 6090C.
• the diazotising reaction is preferably carried out at a temperature below 30C. e.g. at 2025C., usually in hydrochloric acid having a concentration greater than lN, preferably between 5.5 and 6.5N.
• the reaction is also preferably carried out in the presence of acetic acid.
• the quantity of organic solvent is not critical but is preferably at least 20% by volume of the total reaction mixture, for example 2560% by volume.
• the diazotisation reaction is generally continued for at least 2 but often less than 7 or even 5 hours. It is generally continued until there is substantially no solid material left suspended in the aqueous phase.
• the organic phase is then separated and is preferably evaporated to dryness before being hydrolysed.
• the hydrolysis may be carried out by reacting with a mineral acid, for ex- :ample concentrated hydrochloric acid, preferably in the presence of a water miscible solvent, for example methanol, ethanol or industrial methylated spirits.
• hydrolysis is suitably carried out at a temperature of 50-l50C. and preferably under reflux.
• the product can be isolated by conventional means and then, if desired, converted to benazolin; for example by the method described in British Pat. Specification No. 966,496.
• the method described in this specification comprises condensing the 4-chloro-2- hydroxybenzothiazole with a compound selected from ACH B or R OCH CN wherein A is a halogen atom, B is carboxyl group or the salt, ester, amide or nitrile thereof and R is an alkanesulphonyl or arylsulphonyl group, in the presence of an alkaline condensing agent to give a compound of formula I and if necessary converting B to give a desired group selected from carboxyl or the salts or esters thereof, such as those described above.
• the use of the halo genated aliphatic hydrocarbons as solvents in the invention has a further important advantage.
• the 2-amino-4-chlorobenzothiazole hydrohalide may be made by cyclising N-2-chlorophenylthiourea in the same organic solvent system as that used for the subsequent diazotisation reaction with the result that the 2-amino-4-ch]orobenzothiazole hydrohalide can be produced and reacted in the same organic solvent system without any necessity for isolating it before the diazotisation step.
• the overall yield and the overall time required for carrying out the production of benazolin from N-2- chlorophenylthiourea is improved still further.
• Preferred conditions for cyclising the N-2- chlorophenylthiourea to make 2-amino-4- chlorobenzothiazole hydrohalide comprise reacting the thiourea with a source of chlorine or bromine atoms in a halogenated aliphatic hydrocarbon solvent, such as those discussed above.
• the preferred source of chlorine atoms is sulphuryl chloride while the preferred source of bromine atoms is bromine.
• the reaction temperature is preferably 30 to 100C.
• the invention is illustrated in the following Examples in which percentages are by weight. The yields are of pure substance, so that the apparent yields (of impure material) are slightly higher than shown.
• Example 1 was repeated replacing the ethylene dichloride with in turn equivalent volumes of chloroform (Example 4); tetrachloroethylene (Example 5); 1,1,1- trichloroethane (Example 6); 1,2-dichloropropane (Example 7); ethylene dibromide (Example 8); and double the equivalent volume of carbon tetrachloride (Example 9).
• the 4-chloro-2-hydroxybenzothiazole obtained in each of these examples had a purity in the range 93 to 95% and gave yields of, respectively 73%, 66%, 65%, 72%, 61% and 71%. Higher yields may be obtained by conducting the diazotisation for a longer period.
• Aqueous sodium hydroxide (2.5N; 440 ml.) was added and refluxing continued for one-half hour. The solution was then cooled and acidified to pH 1 to 2 with hydrochloric acid. The resulting product was filtered off, washed with water and dried to give benazolin, m.p. l858C.
• Example 1 COMPARATIVE EXAMPLE Example 1 was repeated except that benzene was used instead of ethylene dichloride, the sodium nitrite addition took 5 hours instead of 2 and the stirring was continued for 16 hours instead of 2 hours.
• the 4- chloro-2-hydroxybenzothiazole was obtained in 77% yield and was only 87% pure and was contaminated inter alia with 8.3% of 4-chloro-2-phenylbenzothiazole which was difficult to separate at this stage.
• the product was converted into benazolin as described in Example 1 1 it was necessary to remove this impurity by carrying out an extraction with methylene chloride after the hydrolysis with sodium hydroxide.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Life Sciences & Earth Sciences (AREA)
• Agronomy & Crop Science (AREA)
• Pest Control & Pesticides (AREA)
• Plant Pathology (AREA)
• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Dentistry (AREA)
• General Health & Medical Sciences (AREA)
• Wood Science & Technology (AREA)
• Zoology (AREA)
• Environmental Sciences (AREA)
• Thiazole And Isothizaole Compounds (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (1)

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Cited By (2)

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• 1972
  • 1972-12-01 GB GB5568472A patent/GB1397089A/en not_active Expired
• 1973
  • 1973-11-20 NL NL7315862A patent/NL7315862A/xx not_active Application Discontinuation
  • 1973-11-21 IE IE2116/73A patent/IE39320B1/xx unknown
  • 1973-11-22 ZA ZA738920A patent/ZA738920B/xx unknown
  • 1973-11-23 US US418733A patent/US3888871A/en not_active Expired - Lifetime
  • 1973-11-23 IL IL43690A patent/IL43690A/en unknown
  • 1973-11-27 CS CS8171A patent/CS175468B2/cs unknown
  • 1973-11-27 BE BE138215A patent/BE807856A/fr unknown
  • 1973-11-28 AT AT997673A patent/AT331240B/de not_active IP Right Cessation
  • 1973-11-28 AU AU63005/73A patent/AU473940B2/en not_active Expired
  • 1973-11-29 PL PL1973166924A patent/PL89548B1/pl unknown
  • 1973-11-29 FR FR7342591A patent/FR2208907B1/fr not_active Expired
  • 1973-11-29 CA CA186,985A patent/CA1023749A/fr not_active Expired
  • 1973-11-29 IT IT7353972A patent/IT1000168B/it active
  • 1973-11-30 NO NO4587/73A patent/NO140102C/no unknown
  • 1973-11-30 SE SE7316243A patent/SE415098B/xx unknown
  • 1973-11-30 CH CH1687473A patent/CH587259A5/xx not_active IP Right Cessation
  • 1973-11-30 LU LU68895A patent/LU68895A1/xx unknown
  • 1973-11-30 FI FI3690/73A patent/FI56004C/fi active
  • 1973-11-30 ES ES420999A patent/ES420999A1/es not_active Expired
  • 1973-12-01 JP JP48134828A patent/JPS5824437B2/ja not_active Expired
  • 1973-12-03 DE DE2360202A patent/DE2360202C2/de not_active Expired

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