CA1068288A - 2-lower alkyl-2,3-dihydro-5-benzofuranyl esters of lower alkyl sulfonic acids - Google Patents
2-lower alkyl-2,3-dihydro-5-benzofuranyl esters of lower alkyl sulfonic acidsInfo
- Publication number
- CA1068288A CA1068288A CA234,108A CA234108A CA1068288A CA 1068288 A CA1068288 A CA 1068288A CA 234108 A CA234108 A CA 234108A CA 1068288 A CA1068288 A CA 1068288A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 to carbon atoms of the hetero ring
- C07D307/83—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
Abstract
ABSTRACT
Compounds of the formula I
Compounds of the formula I
Description
~)tj 8i~8 ~3
- 2 Case: 1938 The present invention relates to a chemical process for preparing comFounds of the general formula:
~7S2 l~C~2tl R~
~in which Rl and R2 may be the same or different and each is selected from hydrogen or an alkyl group (notably an alkyl group containing 1 to 6 carbon atoms, e.g. methyl, ethyl or propyl . .
groups) or Rl and R2 together form an alkylene chain te.g. one !
1~ containing 2 to 5 carbon atoms); M is an alkyl group; R4, R5 and R6 may be the same or different and each is selected from hydlogen, an alkyl (e.g. lower alkyl) or an al~oxy te.g. lower alkoxy) group .. . .
or a halogen aton; and ~ is an alkyl group (e.g. l~er alkyl, notably methyl, ethyl or propyl) 7. These compounds find use as , .
herbicides.
The tern lower is used herein with respect to alkyl and alkoxy groups to denote that these group`s contain from 1 to 6 c~rbon atoms.
AccordIngly, the present invention provides a process for repar m g a co pcund of formula I which co~prises reacting a '.tr ~
compound of ~ormula:
j:
~ - 2 -!~ . . : .
--`` 1068Z8l3 _ 3 _ ~SOzO ~\~ o ~ -.
5Cwherein ~ - ~ have the values above and ~ O and ~ 1 may be the same or different and each is selected from a lower alkyl group ~: or ~ O and ~ 1 together with the nitrogen atom form a heterocyclic .
ing~7 with a mixture of a stron~ acid as hereinafter defined and a compound of the foImula HOM wherein M has the values given above.
10The invention is of especial application in the production of . compounds of formula I wherein ~ and ~ a~e both lcwer aIkyl groups (notably methyl or ethyl groups) and R4 - ~ are hydrogen, is a methyl and M is lower alkyl, notably methyl, ethyl, propyl or isopropyl. The preferred starting material of formula II has ~ O and ~ 1 together with the nitroj~en atom forming a heterocyclic ring selected from piperidino, pyrrolidino, and notably rpholino.
The term strong a d d as used herein is to denote a mineTal acîd or an organic aid; which does not take part in delete~ious side roactions during the pIocess, apart from ~ 20 foTzing a salt witlh the amine ~ 0 ~ 1 released durLng t'he ,3~ ~ ~ pTocess; and ~hich preferably dissociates ~n water to giYo at least 1 gran equiYalent of H per gr~m mol of acid. Thus, suitable strong acids~or pTesent use lnclude hydroc~loric, sulphuric and phosphoric ~, ~
.~ 25 ~
~7S2 l~C~2tl R~
~in which Rl and R2 may be the same or different and each is selected from hydrogen or an alkyl group (notably an alkyl group containing 1 to 6 carbon atoms, e.g. methyl, ethyl or propyl . .
groups) or Rl and R2 together form an alkylene chain te.g. one !
1~ containing 2 to 5 carbon atoms); M is an alkyl group; R4, R5 and R6 may be the same or different and each is selected from hydlogen, an alkyl (e.g. lower alkyl) or an al~oxy te.g. lower alkoxy) group .. . .
or a halogen aton; and ~ is an alkyl group (e.g. l~er alkyl, notably methyl, ethyl or propyl) 7. These compounds find use as , .
herbicides.
The tern lower is used herein with respect to alkyl and alkoxy groups to denote that these group`s contain from 1 to 6 c~rbon atoms.
AccordIngly, the present invention provides a process for repar m g a co pcund of formula I which co~prises reacting a '.tr ~
compound of ~ormula:
j:
~ - 2 -!~ . . : .
--`` 1068Z8l3 _ 3 _ ~SOzO ~\~ o ~ -.
5Cwherein ~ - ~ have the values above and ~ O and ~ 1 may be the same or different and each is selected from a lower alkyl group ~: or ~ O and ~ 1 together with the nitrogen atom form a heterocyclic .
ing~7 with a mixture of a stron~ acid as hereinafter defined and a compound of the foImula HOM wherein M has the values given above.
10The invention is of especial application in the production of . compounds of formula I wherein ~ and ~ a~e both lcwer aIkyl groups (notably methyl or ethyl groups) and R4 - ~ are hydrogen, is a methyl and M is lower alkyl, notably methyl, ethyl, propyl or isopropyl. The preferred starting material of formula II has ~ O and ~ 1 together with the nitroj~en atom forming a heterocyclic ring selected from piperidino, pyrrolidino, and notably rpholino.
The term strong a d d as used herein is to denote a mineTal acîd or an organic aid; which does not take part in delete~ious side roactions during the pIocess, apart from ~ 20 foTzing a salt witlh the amine ~ 0 ~ 1 released durLng t'he ,3~ ~ ~ pTocess; and ~hich preferably dissociates ~n water to giYo at least 1 gran equiYalent of H per gr~m mol of acid. Thus, suitable strong acids~or pTesent use lnclude hydroc~loric, sulphuric and phosphoric ~, ~
.~ 25 ~
3 --`-` 1068288 acids, but do not include nitric acid which may oxidise the reagents and/or products. The strong acid may be used in the form of an aqueous solution thereof or in an anhydrous foTm. The strong mineral acid for present use is preferably hydrochloric acid which desirably provides not less than 20 parts by weight of HCl per 80 parts of water in the reaction mixture.
The compound HOM is, as indicated in the preferred compounds which it is desired to produce, preferably an alkanol, notably methanol, ethanol, propanol or iso-propanol.
The process of the invention is carried out in a liquid medium which may be merely an excess of the alkanol reagent. However, the process is conveniently carried out by adding a solution of the ~- compound of form~la II ~e.g. in a non-polar organic solvent, notably ben2ene, xylene, toluene or hexane) to an agitated n~cture of the strong acid and alkanol so as to form a two phase reaction nixbure. The addition ~ay tak~ place in one or more stages or may be on a co~tinuous basis where the process is operated continuously.
The reaction may be carried out at elevated temperatures, although it is preferred to use temperatures below 40 & .
We ha~e found that the relative proportions of strong acid, -~ alkanol, and compound of formula II af~ct the yield and quallty of the product. We prefer to employ more than 1.5 lar proportions of kanol and more than 1.2 molar eq~ivalent proportions of strong acid per molar proportion of co~pound of formula II. Whilst the process may be carried out under substantially anhydrous 1, , `
,.,, ij,~,.
~. .
, , . , ~ ~ , ,'. , .. -. ~ , : ` , :
. , 10~8288 . . ~
conditions, as when H2S04 is used as the strong acid, water may be preferred with some strong acids, e.g. when HCl is present. In this case we prefer to use more than 0.35 parts by weight of HCl per part of water in the reaction mixture.
It is preferred to agitate the reaction mixture and it will be appreciated that all weights and proportions are in respect of the total reaction mIxture not just the organic or aqueous phase.
Apart from the reagents and solvents, the reaction mixture may contain minor amounts of other non-deleterious materials.
; 10 Thus, the compound of formula II need not be in pure form but F" may be used in the form of the reaction product from an earlier process step as autlined below.
The compound of formula I may be recovered from the reaction mix*ure by allowing the mixture to separate into organic and aqueous phases, remoring the organic layer and recovering the product therefrom, e.g. by distillation (to remove excess alkanol and solvent when present), washing with a mild alkali te~g. an ' alkali-metal, notably sodium, carbonate) and further distillation, ~3 preferably under reduced pressure, to remove final amounts of ~; 20 solYent. The isolated product may then be purified by convenSional techniques.
Asi indicated above, the compound of fonmula II may be used in the fo m of the reaction mIxture in which it is produced. The ' ~ preferred method for producing the compound is by the reaction of a compound of ~oTmula:
. .
~068288 III: H0 ~ " R2 R5 ~ o \ N / ~ 0 R6 Rll S with a compound of formula ~ S02Hal where Hal is halogen, preferably in the presence of an acid acceptor to remove the H-Hal as it is formed. Suitable acid acceptors include tertiary amines, notably trialkylamines, e.g. trimethylamine or triethylamine;
arcmatic tertiary amines, e.g. dimethylaniline; and pyridine and ` 10 its hGmologues.
Whilst the reà~ents may be used in substantially the stoichiometric amounts, we prefer to use a small excess, e.g.
up to 20~ lar excess, of the compound ~ S02Hal based on the compound of formula III and an excess, e.g. 10 to 50% molar r` 15 excess, of acid acceptor based on the amount of H-Hal ~hich would ~ theoretically be liberated.
,t., The reaction mar be-carr~d out merely by mixing together the ~ S02Hal and ccnqx~snd of fonmula III simLltane~usly or sequentially and in one or more stages. Desirably the reaction temperature is less than loo&, preferably within the range 30 to 80 & . However, to aid uniform reaction we preer to carry out the reaction in an organic solvent as reaction medium or in an excess of the acid aceeptor. Suitable solvents include ` noo-polar organic solYents~ e.g. benzene, toluene, xylene, or hexane.
When the reaction is substantially complete, as evidenced by analysis of a sample sho~nng little or no remaining compound of formula III, the product compound of formula II ~ay be recovered using conventional techniques. Ho~ever, we prefer not to isolate the product but merely to extract the halogen salt of the acid acceptor from the reaction mixture by water - extraction and separate off the organic layer containing the compound of formLla II for use in preparing the compound of formula I.
The compound of formula III may be prepared in a number of ways, but it is preferably prepared by reacting a suitably substituted benzoquinone with an enamine of formula Rl~ C=CHNRloRll.
Thus, where R4, R5 and R6 are all hydrogen the compound of formDIa III may be prepared by reacting para-benzoquinone with an appropriate ena~ine, e.g. ~CH3)2=CH-N~ O. Preferably the reacti~n is carried out in an organic solYent, e.g. benzene, toluene or hexane, under ref~ux. The reaction product of fo~m~la III may be recovered from the reaction mixture using A
~ conventicnal techniques, e.g. filtration foll~ed by washing and .
~1 i~
,~
~t ,'~
'' ' `'' ' ' ' ".'' ; ' '' ''' ' ' '., '' ' ", ~ , .' : . ' ' ' `. ' ' ` ` ' .
the product then reslurried in the organic solvent to be used in the preparation of the compound of form~la II, although this need not be done and the reaction mixture may be used directly.
The enamine to be used in the production of the compound of formula III is conveniently prepared by the reaction of the appropriate amine H- ~ o ~ l with the appropriate aldehyde ~ ~ CHCHO in a suitable solvent, e.g. benzene, toluene or hexane.
The reaction is pre~erably carried out under reflux and driven to completion by removal of water from the system, e.g. by removing the water layer obtained by condensing the solvent/water - azeotrope which distills of. The enamine product may be recovered from the reaction mixture and purified for use in the production of the compound of formula III using conventional techniques.
A particularly preferred process for preparing the ccn~xmnd of formula III comprises reacting the enamine and the appropriate benzoqui ne in the p~esence of the aldehyde ~ ~ CHCH0, the enamdne preferably being present in an excess over the benzoquinone.
~ The presence of the~aldehyde may be achieved either by adding the - aldehyde to the reaction mixtu~e as a separate reagent; or byha~ing atdPhyde present in the enamine used, e.g. by using excess aldehyde during the preparation of the enanine.
Thus, from another aspect the present invention provides a process for preparing a ccmpound of formula .
"
~ 25 ?i ~ ~
~ .
i :
1~)68Z88 ~ g RS~CC~R~H
, R6 ~.
~ e n Rl- R2~R4~ R5--R6- R7 and M have the values -; given above 7 which comprises Stage (a) reacting benzoquinone with an enamine of fonmula:
. .
RlR2C=cH-NRlORll ' 1~ R2, Rlo and Rll have the values given above 7 in the . presence of a compound of fonmula RlR2CHCHO, the enamine of ','A
. formula rv preferably being present at substantially all times ,~
.~ during the reaction in more than the stoichiometric amount . ., f~ requ~red to react with the benzoquinone; whereby there is produced a cocpound of formula III;
Stage tb) reacting this ~ th a co~pound of forwul8 ~ S02Hal to give a compound of fosmula II-; and Stage- tc) reacting this with a m~xture of a stsong acid as herein-defined and a cc~lx~und of ~ ~ .
~ -25 ~ 1068Z88 formula HOM ~where M has the values given above), wh~reby there is produced a compound of formula I.
The presence of the requisite amount of enamine in the reaction mixture for Stage (a) of the above process can be achieved by, for example, adding the benzoquinone to a reaction mixture containing the desired amount of enamine or by adding the benzoquinone and enamine in the desired proportions to a continuously operated process. Preferably the enamine is employed in an overall small excess, e.g. up to 10~, notably from 1 to 4~ molar excess, although it will be appreciated that - higher excesses may be used if desired. The addition is prefè~bly carried out wQth agitation and the reaction is desirably carried out at a temperature of rom 20 to 60 & , notably at 40 to 50 & , although lower or higher temperatures may be used, e.g. up to - 15 the refl K temperature of the reaction mixture. Where reaction is carried out at below the reflux temperature o the reaction mixture, it may be desired to heat the mixture to 100-120C in the final .
- stages to assist completion of reaction.
As indicated above, the reaction is carried out in the -~ 20 presence of a compound RlR2CHCHO. This is desirably one in which and ~ are the same as in the enamine used, e.g. Rl and R2 ` are both methyl groups, in which case the aldehyde is isobuty-:,, '.''! raldehyde- Desirably the al~'ehyde is present as,a 10 to 200 molar percent based on the en3mine used. The aldehyde may be added as a separate ingredient or as a solvent for one of the other reagents, " ~ '`. :
. . .
- , , . . . .. .. , : ., . , . .; .,. ., . . -, , . . , . :, , ~ :, : . . .
. - ... .. . . .. ... . .
:. ~ . . .i .~ - , , . : , e.g. for the enamine.
Stage (a) is usually carried out in a liquid medium. Suitable liquid media for present use include aromatic hydrocarbons, e.g.
benzene, toluene or xylene; aliphatic hydrocarbons, e.~. cyclohexane or petroleums ethers; halogenated hydrocarbons and aliphatic ketones, e.g. acetone or methyl ethyl ketone. It is however preferred that the li~uid medium be one in which the compound of formula III and water are only slightly soluble or miscible and the aromatic hrdrocarbons are exemplary of such liquids, - 10 The reagents for use in Stage ta) are known materi~ls and may be prepared by known processes. However, ~e have found it `- particularly advantageous if the enamine of formula I~ is prepared
The compound HOM is, as indicated in the preferred compounds which it is desired to produce, preferably an alkanol, notably methanol, ethanol, propanol or iso-propanol.
The process of the invention is carried out in a liquid medium which may be merely an excess of the alkanol reagent. However, the process is conveniently carried out by adding a solution of the ~- compound of form~la II ~e.g. in a non-polar organic solvent, notably ben2ene, xylene, toluene or hexane) to an agitated n~cture of the strong acid and alkanol so as to form a two phase reaction nixbure. The addition ~ay tak~ place in one or more stages or may be on a co~tinuous basis where the process is operated continuously.
The reaction may be carried out at elevated temperatures, although it is preferred to use temperatures below 40 & .
We ha~e found that the relative proportions of strong acid, -~ alkanol, and compound of formula II af~ct the yield and quallty of the product. We prefer to employ more than 1.5 lar proportions of kanol and more than 1.2 molar eq~ivalent proportions of strong acid per molar proportion of co~pound of formula II. Whilst the process may be carried out under substantially anhydrous 1, , `
,.,, ij,~,.
~. .
, , . , ~ ~ , ,'. , .. -. ~ , : ` , :
. , 10~8288 . . ~
conditions, as when H2S04 is used as the strong acid, water may be preferred with some strong acids, e.g. when HCl is present. In this case we prefer to use more than 0.35 parts by weight of HCl per part of water in the reaction mixture.
It is preferred to agitate the reaction mixture and it will be appreciated that all weights and proportions are in respect of the total reaction mIxture not just the organic or aqueous phase.
Apart from the reagents and solvents, the reaction mixture may contain minor amounts of other non-deleterious materials.
; 10 Thus, the compound of formula II need not be in pure form but F" may be used in the form of the reaction product from an earlier process step as autlined below.
The compound of formula I may be recovered from the reaction mix*ure by allowing the mixture to separate into organic and aqueous phases, remoring the organic layer and recovering the product therefrom, e.g. by distillation (to remove excess alkanol and solvent when present), washing with a mild alkali te~g. an ' alkali-metal, notably sodium, carbonate) and further distillation, ~3 preferably under reduced pressure, to remove final amounts of ~; 20 solYent. The isolated product may then be purified by convenSional techniques.
Asi indicated above, the compound of fonmula II may be used in the fo m of the reaction mIxture in which it is produced. The ' ~ preferred method for producing the compound is by the reaction of a compound of ~oTmula:
. .
~068288 III: H0 ~ " R2 R5 ~ o \ N / ~ 0 R6 Rll S with a compound of formula ~ S02Hal where Hal is halogen, preferably in the presence of an acid acceptor to remove the H-Hal as it is formed. Suitable acid acceptors include tertiary amines, notably trialkylamines, e.g. trimethylamine or triethylamine;
arcmatic tertiary amines, e.g. dimethylaniline; and pyridine and ` 10 its hGmologues.
Whilst the reà~ents may be used in substantially the stoichiometric amounts, we prefer to use a small excess, e.g.
up to 20~ lar excess, of the compound ~ S02Hal based on the compound of formula III and an excess, e.g. 10 to 50% molar r` 15 excess, of acid acceptor based on the amount of H-Hal ~hich would ~ theoretically be liberated.
,t., The reaction mar be-carr~d out merely by mixing together the ~ S02Hal and ccnqx~snd of fonmula III simLltane~usly or sequentially and in one or more stages. Desirably the reaction temperature is less than loo&, preferably within the range 30 to 80 & . However, to aid uniform reaction we preer to carry out the reaction in an organic solvent as reaction medium or in an excess of the acid aceeptor. Suitable solvents include ` noo-polar organic solYents~ e.g. benzene, toluene, xylene, or hexane.
When the reaction is substantially complete, as evidenced by analysis of a sample sho~nng little or no remaining compound of formula III, the product compound of formula II ~ay be recovered using conventional techniques. Ho~ever, we prefer not to isolate the product but merely to extract the halogen salt of the acid acceptor from the reaction mixture by water - extraction and separate off the organic layer containing the compound of formLla II for use in preparing the compound of formula I.
The compound of formula III may be prepared in a number of ways, but it is preferably prepared by reacting a suitably substituted benzoquinone with an enamine of formula Rl~ C=CHNRloRll.
Thus, where R4, R5 and R6 are all hydrogen the compound of formDIa III may be prepared by reacting para-benzoquinone with an appropriate ena~ine, e.g. ~CH3)2=CH-N~ O. Preferably the reacti~n is carried out in an organic solYent, e.g. benzene, toluene or hexane, under ref~ux. The reaction product of fo~m~la III may be recovered from the reaction mixture using A
~ conventicnal techniques, e.g. filtration foll~ed by washing and .
~1 i~
,~
~t ,'~
'' ' `'' ' ' ' ".'' ; ' '' ''' ' ' '., '' ' ", ~ , .' : . ' ' ' `. ' ' ` ` ' .
the product then reslurried in the organic solvent to be used in the preparation of the compound of form~la II, although this need not be done and the reaction mixture may be used directly.
The enamine to be used in the production of the compound of formula III is conveniently prepared by the reaction of the appropriate amine H- ~ o ~ l with the appropriate aldehyde ~ ~ CHCHO in a suitable solvent, e.g. benzene, toluene or hexane.
The reaction is pre~erably carried out under reflux and driven to completion by removal of water from the system, e.g. by removing the water layer obtained by condensing the solvent/water - azeotrope which distills of. The enamine product may be recovered from the reaction mixture and purified for use in the production of the compound of formula III using conventional techniques.
A particularly preferred process for preparing the ccn~xmnd of formula III comprises reacting the enamine and the appropriate benzoqui ne in the p~esence of the aldehyde ~ ~ CHCH0, the enamdne preferably being present in an excess over the benzoquinone.
~ The presence of the~aldehyde may be achieved either by adding the - aldehyde to the reaction mixtu~e as a separate reagent; or byha~ing atdPhyde present in the enamine used, e.g. by using excess aldehyde during the preparation of the enanine.
Thus, from another aspect the present invention provides a process for preparing a ccmpound of formula .
"
~ 25 ?i ~ ~
~ .
i :
1~)68Z88 ~ g RS~CC~R~H
, R6 ~.
~ e n Rl- R2~R4~ R5--R6- R7 and M have the values -; given above 7 which comprises Stage (a) reacting benzoquinone with an enamine of fonmula:
. .
RlR2C=cH-NRlORll ' 1~ R2, Rlo and Rll have the values given above 7 in the . presence of a compound of fonmula RlR2CHCHO, the enamine of ','A
. formula rv preferably being present at substantially all times ,~
.~ during the reaction in more than the stoichiometric amount . ., f~ requ~red to react with the benzoquinone; whereby there is produced a cocpound of formula III;
Stage tb) reacting this ~ th a co~pound of forwul8 ~ S02Hal to give a compound of fosmula II-; and Stage- tc) reacting this with a m~xture of a stsong acid as herein-defined and a cc~lx~und of ~ ~ .
~ -25 ~ 1068Z88 formula HOM ~where M has the values given above), wh~reby there is produced a compound of formula I.
The presence of the requisite amount of enamine in the reaction mixture for Stage (a) of the above process can be achieved by, for example, adding the benzoquinone to a reaction mixture containing the desired amount of enamine or by adding the benzoquinone and enamine in the desired proportions to a continuously operated process. Preferably the enamine is employed in an overall small excess, e.g. up to 10~, notably from 1 to 4~ molar excess, although it will be appreciated that - higher excesses may be used if desired. The addition is prefè~bly carried out wQth agitation and the reaction is desirably carried out at a temperature of rom 20 to 60 & , notably at 40 to 50 & , although lower or higher temperatures may be used, e.g. up to - 15 the refl K temperature of the reaction mixture. Where reaction is carried out at below the reflux temperature o the reaction mixture, it may be desired to heat the mixture to 100-120C in the final .
- stages to assist completion of reaction.
As indicated above, the reaction is carried out in the -~ 20 presence of a compound RlR2CHCHO. This is desirably one in which and ~ are the same as in the enamine used, e.g. Rl and R2 ` are both methyl groups, in which case the aldehyde is isobuty-:,, '.''! raldehyde- Desirably the al~'ehyde is present as,a 10 to 200 molar percent based on the en3mine used. The aldehyde may be added as a separate ingredient or as a solvent for one of the other reagents, " ~ '`. :
. . .
- , , . . . .. .. , : ., . , . .; .,. ., . . -, , . . , . :, , ~ :, : . . .
. - ... .. . . .. ... . .
:. ~ . . .i .~ - , , . : , e.g. for the enamine.
Stage (a) is usually carried out in a liquid medium. Suitable liquid media for present use include aromatic hydrocarbons, e.g.
benzene, toluene or xylene; aliphatic hydrocarbons, e.~. cyclohexane or petroleums ethers; halogenated hydrocarbons and aliphatic ketones, e.g. acetone or methyl ethyl ketone. It is however preferred that the li~uid medium be one in which the compound of formula III and water are only slightly soluble or miscible and the aromatic hrdrocarbons are exemplary of such liquids, - 10 The reagents for use in Stage ta) are known materi~ls and may be prepared by known processes. However, ~e have found it `- particularly advantageous if the enamine of formula I~ is prepared
4,- by the reaction of a compound of formula H- ~ ~ l with an excess j of a compound of formula ~ R2CHCH0 in the presence of a solvent !,,415 and the reaction mixture is used as such in the process of the .~
invention since in this manner the presence of the compound of ~,foTmula RlR2CHCHO, notably isobutyraldehyde, is ensured during ~;`the process of the invention.
~The reaction n~rture fron Stage ta) contains the compound of ,~20 formula III or a d~rivative thereof. The compound o ormu1a III
may be recovered fram the reaction mixture using conventional techniques, e.g, by filtration followed by washing and the product then reslurried in the organic solvent to be used in the `~preparation of the compound of formula I, although this need not be done and the reaction mixtu~e may be used directly in Stage Cb).
... ..
, ~ A . . . . , ~ .
~ 1068288 In Stage tb) of the process the compound of formula III is treated as described above to convert the hydroxy grou~ in the S-position to a RqS020- group; and in Stage (c) of the process the group in the 2-positlon is hydrolysed and alkoxylated by treatment with a mixture of a strong acid and an alkanol as described abo~e.
From the above, it will be seen that the production o the compound of formula I may be summarised as:
Stage l RlR2CHCHO
' 10 ~0~1 .
Stage 2 ~ R2C- ' ~ 0 ~ 1 1~ a benzoquinone ¦ 2 Stage 3 H0 ~ Cl _ R2 l 25 ~ ~C - H
: lR7S02Hal + acid acceptor 30 Stage 4 ~ Rl R7S2~ C~2 ~ ¦ Rlo ~strong acid ~`alkanol ~'~ 40 ~4 ~i 45 ~ ~ ~ H
.~ .
, I .
~ ) b ~ i `' ' .' ' ' . " . .. ' ,. "' ' ' :. '' "''' ' .' ' .,' . ," '' ' ' ' The above process stages may be carried out as distinct and separat~ steps but as indicated above, readily lend themselves to sequential operation in that reaction products fro~ one stage may be used directly in a later stage. Furthe~more, it is
invention since in this manner the presence of the compound of ~,foTmula RlR2CHCHO, notably isobutyraldehyde, is ensured during ~;`the process of the invention.
~The reaction n~rture fron Stage ta) contains the compound of ,~20 formula III or a d~rivative thereof. The compound o ormu1a III
may be recovered fram the reaction mixture using conventional techniques, e.g, by filtration followed by washing and the product then reslurried in the organic solvent to be used in the `~preparation of the compound of formula I, although this need not be done and the reaction mixtu~e may be used directly in Stage Cb).
... ..
, ~ A . . . . , ~ .
~ 1068288 In Stage tb) of the process the compound of formula III is treated as described above to convert the hydroxy grou~ in the S-position to a RqS020- group; and in Stage (c) of the process the group in the 2-positlon is hydrolysed and alkoxylated by treatment with a mixture of a strong acid and an alkanol as described abo~e.
From the above, it will be seen that the production o the compound of formula I may be summarised as:
Stage l RlR2CHCHO
' 10 ~0~1 .
Stage 2 ~ R2C- ' ~ 0 ~ 1 1~ a benzoquinone ¦ 2 Stage 3 H0 ~ Cl _ R2 l 25 ~ ~C - H
: lR7S02Hal + acid acceptor 30 Stage 4 ~ Rl R7S2~ C~2 ~ ¦ Rlo ~strong acid ~`alkanol ~'~ 40 ~4 ~i 45 ~ ~ ~ H
.~ .
, I .
~ ) b ~ i `' ' .' ' ' . " . .. ' ,. "' ' ' :. '' "''' ' .' ' .,' . ," '' ' ' ' The above process stages may be carried out as distinct and separat~ steps but as indicated above, readily lend themselves to sequential operation in that reaction products fro~ one stage may be used directly in a later stage. Furthe~more, it is
5. possible to recover excess reagents and solvents for re-use.
Thus, acid acceptor may be recovered rom the aqueous phase from stage 3 by treatment of the halogen salt with alkali ~e.g.
~- NaC~9 and subsequent distillation; the organic phase of the . reaction n~cture rom stage 4 may be fractionally distilled to recover alkanol and solvent, and the aqu~eous phases may be : distilled to recover alkanol and, possibly, acid, the residue then being treated with alkali to liberate the amine ~ oRll and the acid acceptor which may have been carried over in the organic phase from stage 3 to stage 4 and this residue .`~ 15 fractionally distilled to recover amine for use in stage 1 and acid acceptor for.use in stages 3.
- The process of the invention will now be illustrated by the ~a following Example, in which all parts and percentages are given " by weight unless stated otherwise:
-.~ 20 ~xa~ple 1 Sta~e 1 - Preparation o enamine To a stirred mixture of 332 parts of isobutyraldehyde with . 867.5 par~s of toluene was added 200.5 parts of morpholine. The temperature rose from 20C.to 41C. The mixture was re n uxed with 25 continuous separation and removal of the aqueous phase from the , ,d, 13 -~. .
, .
~, :
,1 , . . .. , . . . - .. . ~ . .
- 1~68288 returning solvent stream. To complete the water remo~al, the final stages were carried out with a fractionation column. The total time at reflux was 4.8 hours. The excess isobutyraldehyde was removed from the product by distillation.
;,5 Sta~e 2 - Prepar~tion of 2,3-dihydro-3,3-dimethyl-5-hydroxy-2-morpholinobenzofuran The solution of enamine in toluene produced in Stage 1 ~as added to 238.2 parts of technical benzoquinone in 226 parts of toluene over a period ~f 1.2 hours. The temperature was maintained at 35-4 & throughout the additions by heating or cooling as required. I~hien the heat of reaction was no longer observed, the reaction mixture was raised to the boiling point and ~aintained , at reflux for 0.5 hours. After cooling to 25C the insoluble product was ~iltered off, and washed with 670 parts of *oluene.
The solvent-wet filtered solid was reslurried in 1083 parts ; of toluene for stage 3.
Stage 3 - PreParation of 2,3-dihydro-3,3-dimethyl-2-morpholino-: benzofuran-5-~1 methanesulphonate The slurry fron stage 2 was heated to 40C with adequate mechanical agitation~ ~ethane sulphonyl chloride t258 parts) and t~iethylamine (228 parts) were added simultaneously but separately to the reaction mixture, which was maintained at 40-46C,with j external cooling, o~er a period of 0.35 hours. A further 23 parts of triethylamine were added, foll~ed by 585 parts o~ water.
The two-phase reaction n~cture was then heated to 50-55 & and .,, ^ ~ 14 -:
,,, ;~ A. .
- _ ,, ~
.. . .
.~ ' .
Thus, acid acceptor may be recovered rom the aqueous phase from stage 3 by treatment of the halogen salt with alkali ~e.g.
~- NaC~9 and subsequent distillation; the organic phase of the . reaction n~cture rom stage 4 may be fractionally distilled to recover alkanol and solvent, and the aqu~eous phases may be : distilled to recover alkanol and, possibly, acid, the residue then being treated with alkali to liberate the amine ~ oRll and the acid acceptor which may have been carried over in the organic phase from stage 3 to stage 4 and this residue .`~ 15 fractionally distilled to recover amine for use in stage 1 and acid acceptor for.use in stages 3.
- The process of the invention will now be illustrated by the ~a following Example, in which all parts and percentages are given " by weight unless stated otherwise:
-.~ 20 ~xa~ple 1 Sta~e 1 - Preparation o enamine To a stirred mixture of 332 parts of isobutyraldehyde with . 867.5 par~s of toluene was added 200.5 parts of morpholine. The temperature rose from 20C.to 41C. The mixture was re n uxed with 25 continuous separation and removal of the aqueous phase from the , ,d, 13 -~. .
, .
~, :
,1 , . . .. , . . . - .. . ~ . .
- 1~68288 returning solvent stream. To complete the water remo~al, the final stages were carried out with a fractionation column. The total time at reflux was 4.8 hours. The excess isobutyraldehyde was removed from the product by distillation.
;,5 Sta~e 2 - Prepar~tion of 2,3-dihydro-3,3-dimethyl-5-hydroxy-2-morpholinobenzofuran The solution of enamine in toluene produced in Stage 1 ~as added to 238.2 parts of technical benzoquinone in 226 parts of toluene over a period ~f 1.2 hours. The temperature was maintained at 35-4 & throughout the additions by heating or cooling as required. I~hien the heat of reaction was no longer observed, the reaction mixture was raised to the boiling point and ~aintained , at reflux for 0.5 hours. After cooling to 25C the insoluble product was ~iltered off, and washed with 670 parts of *oluene.
The solvent-wet filtered solid was reslurried in 1083 parts ; of toluene for stage 3.
Stage 3 - PreParation of 2,3-dihydro-3,3-dimethyl-2-morpholino-: benzofuran-5-~1 methanesulphonate The slurry fron stage 2 was heated to 40C with adequate mechanical agitation~ ~ethane sulphonyl chloride t258 parts) and t~iethylamine (228 parts) were added simultaneously but separately to the reaction mixture, which was maintained at 40-46C,with j external cooling, o~er a period of 0.35 hours. A further 23 parts of triethylamine were added, foll~ed by 585 parts o~ water.
The two-phase reaction n~cture was then heated to 50-55 & and .,, ^ ~ 14 -:
,,, ;~ A. .
- _ ,, ~
.. . .
.~ ' .
6,8288 period of 0.6 hours. After agitating for a further 0.5 hours 66 parts of water and a further 3.5 parts of triethylamane were added. The two-phase reaction mixture w~s then heated to 60-65 & and allowed to settle. After separation of the lower S layer of triethylamine hydrochloride solution, the upper solvent layer was allowed to evaporate to constant weight. Crude yield, 80.2 parts, purity by G.L.C. 98~, equivalent to 98.2 mole ~ yi~ld.
Hydrolysis/alkoxylation stage 65.4 parts of 2,3-dihydro-3,3-d~methyl-2-m~,rph~linobenzofuran-;~ 10 5-yl methane sulphonate prepared as above were dissolved in 150 parts of c~o~,mercial mix~ed xylenes. To this solution were added 24 parts of methyl alcohol, 13 parts of water, and 47.8 parts o~ 36~ W/w hydrochloric acid. The temperature rose to 28C.
The two-phase reaction mixture was agitated for 16 hours at ambient temperature and, after settling, the lower aqueous layer was r~emoved.
, The upper solvent-layer was evaporated to constant weight to give 53.3 parts of 2,3-dihydro-3,3-dimethyl-2-methoxy-benzofuu~ln-~r 5-yl methane-sulphonate of 95~ purity by G-L-C- analysis, e~uivalent to 94.8 mole % yield on 2J3-dihydro-3,3-dimethyl-2-morpholinobenzofuran-5-yl methanesulphonate.
yl ~, -~ 25 .~
~ - 17 -, - ~
1 , .~ .
10~132~3 ~llowed to settle. After separation of the lower layer of triethylamine nydrochloride solution, the upper solvent layer was passed to stage 4.
Sta~e 4 - Preparation of 2,3-dihydro-3,3-dimethyl-2-ethox~-S benzofuran-5-yl methane sulphonate To the solution ~rom stage 3 were added 350 parts of ethyl alcohol, 43 parts of water, and 655 parts of 30~ w/w hydrochloric acid. The temperature rose to 47 & . The two-phase reaction mixture was agitated for 16 hours with cooling to 20 & and, after settling, the lower aqueous layer was re ved.
.. . .
The upper solYent layer was distilled to remove the bulk of the unreacted ethyl alcohol, and washed with soldium carbonate solution t~ remove traces of hydrochloric acid. The solution ~; was then distilled to remove the remaining toluene leaving 564 parts of product of 98~ purity by GLC analysis, equivalent to 87.53 yield on technical benzoquinone.
,.;
,~
.
:
- : . ....
1068~88 Example 2 _ eparation of 2,3-dihydro-3,3-dimethyl-2-metho~Yy-benzofuran-5-yl methane sulphonate 2,3-Dihydro-3,3-dimethyl-5-hydroxy-2-morphol mobenzofuran (62.3 parts~ 98.0~ pure produced as in Example 1) was slurried in 180 parts o~ commercial mlxed xylenes. Methane sulphonyl chloride (31.25 parts) and triethylamine (27.6 parts) t~ere added simultaneously but separately to the reaction mixture, which tyas maintained at 40-45 & with external cooling, over a .~
~' ,~
:,~
,.
, .
, ., ~: . . . - :. . -; - ~ . .
.. . . .. . . .
,~ ' , ~ - . '. .~- -.: :, :: ~ . . . .
Hydrolysis/alkoxylation stage 65.4 parts of 2,3-dihydro-3,3-d~methyl-2-m~,rph~linobenzofuran-;~ 10 5-yl methane sulphonate prepared as above were dissolved in 150 parts of c~o~,mercial mix~ed xylenes. To this solution were added 24 parts of methyl alcohol, 13 parts of water, and 47.8 parts o~ 36~ W/w hydrochloric acid. The temperature rose to 28C.
The two-phase reaction mixture was agitated for 16 hours at ambient temperature and, after settling, the lower aqueous layer was r~emoved.
, The upper solvent-layer was evaporated to constant weight to give 53.3 parts of 2,3-dihydro-3,3-dimethyl-2-methoxy-benzofuu~ln-~r 5-yl methane-sulphonate of 95~ purity by G-L-C- analysis, e~uivalent to 94.8 mole % yield on 2J3-dihydro-3,3-dimethyl-2-morpholinobenzofuran-5-yl methanesulphonate.
yl ~, -~ 25 .~
~ - 17 -, - ~
1 , .~ .
10~132~3 ~llowed to settle. After separation of the lower layer of triethylamine nydrochloride solution, the upper solvent layer was passed to stage 4.
Sta~e 4 - Preparation of 2,3-dihydro-3,3-dimethyl-2-ethox~-S benzofuran-5-yl methane sulphonate To the solution ~rom stage 3 were added 350 parts of ethyl alcohol, 43 parts of water, and 655 parts of 30~ w/w hydrochloric acid. The temperature rose to 47 & . The two-phase reaction mixture was agitated for 16 hours with cooling to 20 & and, after settling, the lower aqueous layer was re ved.
.. . .
The upper solYent layer was distilled to remove the bulk of the unreacted ethyl alcohol, and washed with soldium carbonate solution t~ remove traces of hydrochloric acid. The solution ~; was then distilled to remove the remaining toluene leaving 564 parts of product of 98~ purity by GLC analysis, equivalent to 87.53 yield on technical benzoquinone.
,.;
,~
.
:
- : . ....
1068~88 Example 2 _ eparation of 2,3-dihydro-3,3-dimethyl-2-metho~Yy-benzofuran-5-yl methane sulphonate 2,3-Dihydro-3,3-dimethyl-5-hydroxy-2-morphol mobenzofuran (62.3 parts~ 98.0~ pure produced as in Example 1) was slurried in 180 parts o~ commercial mlxed xylenes. Methane sulphonyl chloride (31.25 parts) and triethylamine (27.6 parts) t~ere added simultaneously but separately to the reaction mixture, which tyas maintained at 40-45 & with external cooling, over a .~
~' ,~
:,~
,.
, .
, ., ~: . . . - :. . -; - ~ . .
.. . . .. . . .
,~ ' , ~ - . '. .~- -.: :, :: ~ . . . .
Claims (14)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for preparing a compound of the formula:
I [in which R1 and R2 may be the same or different and each is selected from the group consisting of hydrogen, an alkyl group containing from 1 to 6 carbon atoms and, together, an alkylene chain containing 2 to 5 carbon atoms; M is an alkyl group containing from 1 to 6 carbon atoms; R4, R5 and R6 may be the same or different and each is selected from the group consisting of hydrogen, an alkyl or alkoxy group containing from 1 to 6 carbon atoms and a halogen atom; and R7 is an alkyl group containing from 1 to 6 carbon atoms] which comprises reacting in a single stage a compound of the formula:
II [wherein R1-R7 have the values above and R10 and R11 may be the same or different and each is selected from the group consisting of an alkyl group containing from 1 to 6 carbon atoms and, together with the nitrogen atom, both forming a heterocyclic ring] with a mixture of an acid which dissociates in water to give at least one gram equivalent of H+ per gram mol of acid and a compound of the formula HOM wherein M has the values given above.
I [in which R1 and R2 may be the same or different and each is selected from the group consisting of hydrogen, an alkyl group containing from 1 to 6 carbon atoms and, together, an alkylene chain containing 2 to 5 carbon atoms; M is an alkyl group containing from 1 to 6 carbon atoms; R4, R5 and R6 may be the same or different and each is selected from the group consisting of hydrogen, an alkyl or alkoxy group containing from 1 to 6 carbon atoms and a halogen atom; and R7 is an alkyl group containing from 1 to 6 carbon atoms] which comprises reacting in a single stage a compound of the formula:
II [wherein R1-R7 have the values above and R10 and R11 may be the same or different and each is selected from the group consisting of an alkyl group containing from 1 to 6 carbon atoms and, together with the nitrogen atom, both forming a heterocyclic ring] with a mixture of an acid which dissociates in water to give at least one gram equivalent of H+ per gram mol of acid and a compound of the formula HOM wherein M has the values given above.
2. A process as claimed in claim 1 wherein the acid is selected from the group consisting of sulphuric, hydrochloric and phosphoric acids.
3. A process as claimed in claim 1 wherein more than 1.5 molar proportions of HOM are used per molar proportion of the compound of formula II.
4. A process as claimed in claim 1 wherein more than 1.2 molar proportions of acid are used per molar proportion of the compound of formula II.
5. A process as claimed in Claim 1 wherein the acid used is hydrochloric acid and more than 0.35 parts by weight of HCl are used per part by weight of water in the reaction mixture.
6. A process as claimed in claim 1 wherein the compound of formula II has been prepared by the reaction of a compound of formula III
with a compound of formula R7SO2Hal where Hal is halogen.
with a compound of formula R7SO2Hal where Hal is halogen.
7. A process as claimed in claim 6 wherein the reaction mixture containing the compound of formula II is used in the process of claim 1 without isolation of the compound of formula II therefrom.
8. A process as claimed in claim 6 wherein the compound of formula III has been prepared by the reaction of a suitably substituted benzoquinone with an enamine of formula R1R2C=CHNR10R11.
9. A process as claimed in claim 8 wherein the benzoquinone and the enamine are reacted in the presence of a compound of formula R1R2CHCHO.
10. A process for preparing a compound of the formula:
I [in which R1 and R2 may be the same or different and each is selected from the group consisting of hydrogen, an alkyl group containing from 1 to 6 carbon atoms and, together, an alkylene chain containing 2 to 5 carbon atoms; M is an alkyl group containing from 1 to 6 carbon atoms; R4, R5 and R6 nay be the same or different and each is selected from the group consisting of hydrogen, an alkyl or alkoxy group containing from 1 to 6 carbon atoms and a halogen atom; and R7 is an alkyl group containing from 1 to 6 carbon atams] which comprises:
Stage (a) reacting a benzoquinone with an enamine of formula:
R1R2C = CHNR10R11 IV
[wherein R1, R2, R10 and R11 have the values given above] in the presence of a compound of formula R1R2CHCHO, whereby there is produced a compound of formula III Stage (b) reacting a compound of formula III with a compound of formula R7SO2Hal to give a compound of formula II and Stage (c) reacting the compound of formula II in a single stage with a mixture of an acid and an alkanol HOM (where M has the values) given above), whereby there is produced a compound of formula I.
I [in which R1 and R2 may be the same or different and each is selected from the group consisting of hydrogen, an alkyl group containing from 1 to 6 carbon atoms and, together, an alkylene chain containing 2 to 5 carbon atoms; M is an alkyl group containing from 1 to 6 carbon atoms; R4, R5 and R6 nay be the same or different and each is selected from the group consisting of hydrogen, an alkyl or alkoxy group containing from 1 to 6 carbon atoms and a halogen atom; and R7 is an alkyl group containing from 1 to 6 carbon atams] which comprises:
Stage (a) reacting a benzoquinone with an enamine of formula:
R1R2C = CHNR10R11 IV
[wherein R1, R2, R10 and R11 have the values given above] in the presence of a compound of formula R1R2CHCHO, whereby there is produced a compound of formula III Stage (b) reacting a compound of formula III with a compound of formula R7SO2Hal to give a compound of formula II and Stage (c) reacting the compound of formula II in a single stage with a mixture of an acid and an alkanol HOM (where M has the values) given above), whereby there is produced a compound of formula I.
11. A process as claimed in claim 10 wherein the enamine has been prepared by the reaction of a compound of formula HNR10R11 with a compound of formula R1R2CHCHO.
12. A process as claimed in claim 1 wherein the groups R1 and R2 are both the same And each is selected fron an alkyl group; the groups R4, R5 and R6 are all hydrogen; the R7SO2 group is a group CH3SO2-;
the group M is a methyl, ethyl or propyl group; and the group -NR10R11 is selected from morpholino, piperidino and pyrrolidino.
the group M is a methyl, ethyl or propyl group; and the group -NR10R11 is selected from morpholino, piperidino and pyrrolidino.
13. A process as claimed in claim 1 wherein the compound of formula I is 2,3-dihydro-3,3-dimethyl-2-ethoxy-benzofuran-5-yl methane sulphonate.
14. A process for preparing a compound of the formula which comprises reacting p-benzoquinone with from 1 to 4% molar overall excess of the enamine in the presence of from 10 to 200 molar % of isobutyraldehyde (based on the enamine) in an aromatic hydrocarbon medium; reacting the reaction product with CH3SO2C1 in the presence of an acid acceptor; and reacting the reaction product in a single stage with a mixture of ethyl alcohol and a mineral acid selected from sulphuric acid, hydrochloric acid or phosphoric acid.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB33686/75A GB1522142A (en) | 1974-09-05 | 1974-09-05 | Process for the production of 2,3-dihydrobenzofurans |
| GB38814/74A GB1522141A (en) | 1974-09-05 | 1974-09-05 | 2,3-dihydrobenzofuran derivatives and a process for their preparation |
| GB3881874 | 1974-09-05 | ||
| GB3881574 | 1974-09-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1068288A true CA1068288A (en) | 1979-12-18 |
Family
ID=27448926
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA234,105A Expired CA1066702A (en) | 1974-09-05 | 1975-08-21 | Process for preparing benzofuran derivatives |
| CA234,108A Expired CA1068288A (en) | 1974-09-05 | 1975-08-21 | 2-lower alkyl-2,3-dihydro-5-benzofuranyl esters of lower alkyl sulfonic acids |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA234,105A Expired CA1066702A (en) | 1974-09-05 | 1975-08-21 | Process for preparing benzofuran derivatives |
Country Status (9)
| Country | Link |
|---|---|
| JP (2) | JPS5154547A (en) |
| AU (2) | AU497714B2 (en) |
| BE (2) | BE832937A (en) |
| CA (2) | CA1066702A (en) |
| CH (2) | CH608797A5 (en) |
| DE (2) | DE2537891A1 (en) |
| FR (2) | FR2296629A1 (en) |
| GB (2) | GB1522141A (en) |
| NL (2) | NL7510048A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3329126A1 (en) * | 1983-08-11 | 1985-02-28 | Bayer Ag, 5090 Leverkusen | NEW BENZO-CONDENSED, TETRACHLORATED, HETEROCYCLIC COMPOUNDS AND A METHOD FOR THEIR PRODUCTION |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3412109A (en) * | 1964-09-25 | 1968-11-19 | Upjohn Co | Process for 2-alkoxy-2, 3-dihydro 5-benzofuranols |
-
1974
- 1974-09-05 GB GB38814/74A patent/GB1522141A/en not_active Expired
- 1974-09-05 GB GB33686/75A patent/GB1522142A/en not_active Expired
-
1975
- 1975-08-20 AU AU84143/75A patent/AU497714B2/en not_active Expired
- 1975-08-20 AU AU84138/75A patent/AU497993B2/en not_active Expired
- 1975-08-21 CA CA234,105A patent/CA1066702A/en not_active Expired
- 1975-08-21 CA CA234,108A patent/CA1068288A/en not_active Expired
- 1975-08-26 DE DE19752537891 patent/DE2537891A1/en active Pending
- 1975-08-26 NL NL7510048A patent/NL7510048A/en not_active Application Discontinuation
- 1975-08-26 DE DE19752537913 patent/DE2537913A1/en active Pending
- 1975-08-29 NL NL7510228A patent/NL7510228A/en not_active Application Discontinuation
- 1975-08-29 BE BE159631A patent/BE832937A/en unknown
- 1975-08-29 BE BE159632A patent/BE832938A/en unknown
- 1975-09-03 JP JP50106109A patent/JPS5154547A/en active Pending
- 1975-09-04 CH CH7511485A patent/CH608797A5/en not_active IP Right Cessation
- 1975-09-04 FR FR7527164A patent/FR2296629A1/en active Granted
- 1975-09-04 CH CH1148675A patent/CH610587A5/en not_active IP Right Cessation
- 1975-09-04 FR FR7527165A patent/FR2283898A1/en active Granted
- 1975-09-05 JP JP50107156A patent/JPS5154548A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DE2537913A1 (en) | 1976-03-18 |
| FR2283898A1 (en) | 1976-04-02 |
| JPS5154547A (en) | 1976-05-13 |
| GB1522141A (en) | 1978-08-23 |
| FR2283898B1 (en) | 1978-10-20 |
| CH610587A5 (en) | 1979-04-30 |
| GB1522142A (en) | 1978-08-23 |
| BE832937A (en) | 1976-03-01 |
| JPS5154548A (en) | 1976-05-13 |
| FR2296629B1 (en) | 1980-04-11 |
| AU497714B2 (en) | 1979-01-04 |
| AU497993B2 (en) | 1979-02-01 |
| CH608797A5 (en) | 1979-01-31 |
| CA1066702A (en) | 1979-11-20 |
| AU8414375A (en) | 1977-02-24 |
| BE832938A (en) | 1976-03-01 |
| DE2537891A1 (en) | 1976-03-18 |
| NL7510048A (en) | 1976-03-09 |
| AU8413875A (en) | 1977-02-24 |
| NL7510228A (en) | 1976-03-09 |
| FR2296629A1 (en) | 1976-07-30 |
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