IL29604A - The preparation of 3-isothiazolones and 3-hydroxyisothiazoles - Google Patents

Description

The preparation of and ROHM HAAS NT This invention is concerned with a novel process for the preparation of substituted and hydroxyisothiazoles which have biocidal activity as disclosed in copending Applications filed on even date More this invention is concerned with a process for the preparation of compounds of the formula wherein Y is of to 6 carbon aralkyl of up to 10 carbon halogen or substituted in which each group contains up to carbon of 2 8 carbon or a bamoyl group having the structure in which R and are or R is halogen or substituted carbalkoxyalkyl of the structure viLerein is alkyl or an aryl group of the formula wherein is nitro or and n is a number from 0 to As regards the various containing substituents these are typically propyl or It should be noted that Formula I is a chemically correct designation for all of the compounds prepared by the novel process constituting this due to their tautomeric the following formula is somewhat more accurate those situations where Y represents that those represented by Formula II are referred to generically as referred to at times as whereas all the other compounds I are more properly termed ferred to at times as Of the latter term may in part be utilized to any of the compounds within the scope of Formula In accordance with the the isothiazolones are by the of a which be by the formula wherein X and Z are hydrogen or and Y is as Typical agents include sulfuryl sulfuryl and the Chlorine and sulfuryl chloride are the preferred halogenating is prefera ly carried out using at least Cyclization J mole equivalents of halogenating or to be more specific t providing an excess of halogenating the isothiazolone may be halogenated at the 4 positions of Formula here mole of halogenating agent are halogenation take For 7 mole equivalents of halogenating agent are Preparation of having the 4 5 position substituted with different halogens is achieved by the halogenation of an isothiazolone already halogenated at one of the two positions in For if a is then such can be obtained by bromination of a or the chlorination of a starting isothiazolone of prepared by the of a as described Procedures tions therein for what might be termed would be evident to one skilled in the is not critical to the reaction that the will proceed at Generally and it will be carried out in the range of to best The reaction out in an inert such as ethyl Isothiazolonium salts can be formed along with the during the cyclization process when Y in Formula III is of 1 to 13 carbon atoms aralkyl of up to 10 carbon Such salts have the ing structures desired or an acid scavenger can be porated in the reaction medium so as to avoid isothiazolonium salt Typical scavengers which might so utilised would include for pyridine and It should be noted at this point that the isothiazolonium salts can also transformed or neutralized to free isothiazolones by being contacted with water or weak The which are to form the isothiazolones are known and may bo in several an alpha or beta or uted or acrylic acid is reacted with thiol acetic Upon completion of the the product is so as to obtain a propionic which in oxidised to the disulfide This n teriai is then converted to a and in treated with ammonia or substituted ammonia such as alkyl The cyclization process is ted by the following EXAMPLE 1 Preparation of and In a one flask equipped with a mechanical and dropping funnel there was mixed of ethylene dichloride and of This mixture was stirred at and of sulfuryl chloride was added dropwise over 2 On completion of the the reaction slurry was allowed to warm to and stirred overnight to assure The reaction slurry was then and the precipitate was digested in 1 0 of hot The aqueous solution was filtered to remove some insoluble material and then cooled in ice to yield after filtration and drying of isothiazole as a tan crystalline The aqueous filtrate was then continuously extracted with the ether extract was dried over magnesium sulfate and evaporated to leave of which crystallized upon cooling to a white crystalline from 2 Preparation of To an ethylene dichloride slurry of there was added at over hour of After the reaction slurry was allowed to to and stirred overnight to assure ether extraction from The ethylenedichloride upon evaporation to approximately yielded an additxonal quantity of less pure Complete evaporation of the ethylene dichloride filtrate gave of oily residue which upon sublimation at gave of Preparation of was slurried in of ethylene dichloride and a solution of of sulfuryl chloride in 25 of ethylene dichloride was added dropwise at e over one The slurry was stirred overnight to svxe completion of the reaction and then filtered to give of gray The product was crystallized from ethyl acetate to give a of EXAMPLE 4 Preparation of In ΟΟ of ethylene dichloride there was slurried of pionamide at Nitrogen was bubbled through the slurry to remove the hydrogen chloride to be formed in the and 243 of sulfuryl chloride was added dropwise over two The was then allowed to warm to and stirred overnight to assure complete After this solution to leave a yellow oil residue which was crystallized from to give of coloured Preparation of and o The was slurried in 200 of ethylene A solution of of sulfuryl chloride in of ethylene dich oride was added slowly at After addition the slurry was allowed to stir overnight to assure complete Filtration then gave mixture of solid isothiazolonium which were heated in 100 of and filtered to after 0 122 Subsequent cooling of the aqueous solution in ice yielded of solid EXAMPLE 6 Preparation of To a solution of 100 of ethyl acetate and of prepared in accordance with Example there was added at a solution of 8 of bromine in of ethyl After addition the red reaction solution was allowed to warm to room and after 1 the solvent was removed under reduced pressure to leave 7 of dark Treatment of this solid with water after 14 from EXAMPLE 7 Preparation of 4 To an ethyl acetate solution of of prepared in accordance with Example there was added of sulfuryl chloride over 20 minutes at A white tate formed at After stirring for 2 the reaction mixture mixture was allowed to warm to room The filtered from a small amount of solid and the solvent was removed under reduced In this there was obtained of gummy which by treatment with water and drying gave of after crystallization from insufficientOCRQuality

Claims (1)

10 CLAIM IS Λ for a of Formula I or wherein of up to carbon halogen or substituted in which group contains up to or a carbamoyl group of tho halogen or substituted of tho is and is a is aa group of formula wherein is nitro or and n is a from 0 to halogen or sai process cotaprisins a by with halogenatlng said being of tho 11 wherein X Z o and Y defined Λ process according to i wherein Y is of up to carbon halogen or substituted in which oach group contains up to carbo carbamoyl group as defined in Claim A process according to Claim 1 wherein is A process according to Claim 1 wherein the ating is present to tho extent of at least A process according to Claim wherein the ating agent is present to tho extent of at 5 A process according to Claim wherein the resultant therefrom is subsequently halogenated with a different halogen than that in preparing said A process according to Claim wherein tho agent is present to the extent of at least 7 A process according to any one of tho preceding clai Wherein tho cyclizntion reaction is carried out i on ine A process according to any one of tho preceding tho agent in tho cyclization reaction sulfuryl or A according to any ono of tho v tho cyclizatioa oarrlod out presence of on A process to 1 carriod out hereinbefore described with reference to of Λ by a aooordins to of For the A plicants insufficientOCRQuality