METHYLENATION
A Convenient, High-Yielding Method for the Methylation of Catechols
Bashall,A;Collins,J
Tetrahedron Letters
Vol.16(40) 1975, pp.3489-3490
DOI: 10.1016/S0040-4039(00)91391-1
http://tinyurl.com/26w83vo
Abstract
The methylenedioxy group occurs in many natural products and, in addition, has been
suggested s a protectingg roup for catechols. However, synthetically, the methylenation of catechols has never been easy and high yields difficult to obtain. Bonthrone and Cornforth have shown that if the reaction is carried out using dichloromethane in a dipolar, aprotic solvent such as dimethylsulphoxide coupled with the slow addition of a mixture of solid sodium hydroxide and the catechol, good yields of the methylenated catechol may be obtained. Several substituted catechols have been methylenated in high yield using dichloromethane in dimethylformamide or dimethylsulphoxide in the presence of a bronse, cupric oxide or nickel oxide catalyst.
The Synthesis of 3,4-dihydroxy-2-methoxybenzaldehyde : The use of Methylenedioxy as a Protecting Group
Bick,I;Russell,R
Aust. J. Chem.
Vol.22(7) 1969 pp.1563-1568
DOI: 10.1071/CH9691563
http://www.publish.csiro.au/paper/CH9691563.htm
Abstract
The substance 3,4-dihydroxy-2-methoxybenzaldehyde (X) is not easily accessible and has not hitherto been prepared, although the isomeric compound 2,3-dihydroxy-4-methoxybenzaldehyde (XII) has been wrongly described under the above name.1 Since formylation of 1-methoxy-2,3-methylenedioxybenzenew as reported2,3 to produce in good yield 2-methoxy-3,4-methylenedioxybenzaldehyde (II), a possible route to the desired substance was available provided the methylenedioxy group in the latter could be hydrolysed satisfactorily without affecting the methoxyl. We have therefore examined the recorded methods for inserting and removing a methylene ether group: hitherto the formation of 1,3-benzodioxoles has been a sealed-tube reaction which gives low yields and has not been an attractive preparative procedure, but with recent improvements4 and with modifications in the method for their hydrolysis, we have found that this group could be used with advantage for blocking a catechol group even in the presence of a methoxyl.
High Selectivity in the Oxidation of Mandelic Acid Derivatives and in O-Methylation of Protocatechualdehyde: New Processes for Synthesis of Vanillin, iso-Vanillin, and Heliotropin
Bjorsvik,HansRene;Liguori,Lucia;Minisci,Francesco
Org. Proc. Res. Dev.
Vol.4(6) 2000 pp.534–543
DOI: 10.1021/op0000529
http://pubs.acs.org/doi/abs/10.1021/op0000529
Abstract
New synthetic procedures for vanillin, iso-vanillin, heliotropin, and protocatechualdehyde starting from catechol are described. The utilisation of statistical experimental design and multivariate modelling and the mechanistic interpretation of the acid and base catalysis in the condensation of catechol derivatives with glyoxylic acid and in the regiocontrolled methylation of protocatechualdehyde and of the Cu(II) salt catalysis in the oxidative decarboxylation of mandelic acid derivatives have allowed the development of new highly selective processes.
The Methylenation of Catechols
Bonthrone,W;Cornforth,J
J. Chem. Soc. C.
1969 pp.1202-1204
DOI: 10.1039/J39690001202
http://www.rsc.org/publishing/journals/J3/article.asp?doi=J39690001202
Abstract
High yields in the methylenation of catechols by methylene chloride are obtained by using a polar aprotic solvent for reaction and maintaining low concentrations of the catechol dianion.
A Re-Examination of the Methylenation Reaction
Cabiddu,Maria;Cadoni,Enzo;DeMontis,Stefania;Fattuoni,Claudia;Melis,Stefana;Usai,Michele
Tetrahedron
Vol.59(24) 2003 pp.4383-4387
DOI: 10.1016/S0040-4020(03)00619-7
http://tinyurl.com/28swkqm
Abstract
A re-examination of the methylenation reaction of 1-hydroxy-2-mercapto-, 1,2-dihydroxy- and 1,2-dimercapto-substituted benzenes by bromochloromethane with cesium carbonate shows that these substrates give mixtures of five- and ten-membered benzocondensed heterocyclic compounds and in some cases even dibenzodioxines.
The Preparation of Methylenedioxy-Methoxybenzaldehydes
Campbell,Kenneth;Hopper,Paul;Campbell,Barbara
J. Org. Chem.
Vol.16(11) 1951 pp.1736–1741
DOI: 10.1021/jo50005a011
http://pubs.acs.org/doi/abs/10.1021/jo50005a011
Abstract
Since many pharmacologically active natural products contain several methoxy and/or methylenedioxy groups attached to one aromatic nucleus, it would be of interest to determine the pharmacological effect of such groups in various type of synthetic drugs. Alles (1) has shown, for example, that the polymethoxy and methylenedioxy phenylaminoethanols have an antifibirllatory action not shown by their unsubstituted analogs. Comparatively few such series have been made, however, because the necessary starting materials are very difficult to obtain.
The Methylenation of Several Allylbenzene-1,2-diol Derivatives in Aprotic Polar Solvents
Fujita,Harushige;Yamashita,Masataro
Bull. Chem. Soc. Japan.
Vol.46(11) 1973 pp.3553-3554
ONLINE ISSN: 1348-0634
http://tinyurl.com/2c8cs48
Abstract
The aprotic polar solvents, such as DMF (N,N-dimethylformamide) and DMSO (dimethyl sulfoxide), accelerated very effectively the methylenation of 1,2-dihydroxy-4- (I), 1,2-dihydroxy-3,4-dimethoxy-5- (II), and 1,2-dihydroxy-3-methoxy-5-allylbenzene (III) in the presence of bronze and cupric oxide as catalysts.
Methylenation of Allyl Substituted Catechols with Methylene Dichloride
Fujita,Harushige;Yamashita,Masataro
J. Synth. Org. Chem (Japan)
Vol.31(11) 1973 pp.932-934
ONLINE ISSN: 1883-6526
http://tinyurl.com/2e9nved (Not uploaded here, get it from the link)
Abstract
Methylenation of 1, 2-dihydroxy-3-, 1, 2-dihydroxy-4-, 1, 2-dihydroxy-3, 4-dimethoxy-5- and 1, 2-dihydroxy-3-methoxy-5-allylbenzenes with methylene dichloride in DMF or DMSO was found to be accelerated more effectively by nickelous oxide than metallic nickel and nickelic oxide, as catalyst. DMF and DMSO gave better results than other solvents.
* In Japanese mainly.
Methylenation of Catechols
Fujita,Harushige;Yamashita,Masataro
J. Synth. Org. Chem (Japan)
Vol.32(6) 1974 pp.467-470
ONLINE ISSN: 1883-6526
http://tinyurl.com/23yshj4 (Not uploaded here, get it from the link)
Abstract
Effects based upon kinds of methylenating agent, solvent and base used, were remarkably observed in methylenation of catechol (1a), pyrogallol (1b), 1, 2-dihydroxy-3-methoxy-(1c) and 1, 2-dihydroxy-4, 5-dimethoxybenzenes (1d), 2, 3-dihydroxy-4-methoxy-(1e), 3, 4-dihydroxy-(1f) and 3, 4-dihydroxy-5-methoxybenzaldehydes (1g) and 3, 4-dihydroxy-5-bromobenzaldehyde (1h), on this heterogeneous reaction system. In addition to these effects, however, there was remarkable fluctuation in yields dependent on reaction operation, but itwas elucidated that the methylenedioxy derivatives were obtained in good yields from inexpensive methylene dichloride and the above aromatic compounds in a short period, when concentrations of (1a1h) have been regulated below 1 M in the reaction system according to a procedure devised by the present authors.
* In Japanese mainly.
Synergist Synthesis, Synthesis of Methylene-C14-Dioxyphenyl Compounds: Radioactive Safrole, Dihydrosafrole, Myristicin, Piperonyl Butoxide and Diastereoisomers of Sulfoxide
Kuwatsuka,Shozo;Casida,J
J. Agric. Food Chem.
Vol.13(6) 1965 pp.528–533
DOI: 10.1021/jf60142a012
http://pubs.acs.org/doi/abs/10.1021/jf60142a012
Abstract
Methylene-C14 iodide, prepared by reduction of iodoform-C14 was made to react with the appropriate catechol to yield the following methylene-C14-dioxyphenyl compounds with a specific activity of 1 .O millicurie per millimole: safrole, dihydrosafrole, myristicin, sulfoxide synergist { 1,2-methylenedioxy-4-[2-(octylsulfinyl)propylbenzene 1, and piperonyl butoxide {a-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propyltoluene}. Yields from iodoform-C14 were 31 to 55% on a 0.5- to 0.8-mmole scale except with piperonyl butoxide, where the yield appeared to be related to the specific activity of the eththylene-14-iodide used. The octylthio, octylsulfhyl, and octylsulfonyl analogs of sulfoxide synergist, substituted on the 1-, 2-, or 3-position of the propyl group, were prepared in nonradioactive form for comparative purposes. Sulfoxide synergist and the 1-octylsulfinyl analog were resolved by chromatography into the enantiomorphs of the diastereoisomers about the sulfoxide grouping and the asymmetric carbon of the propyl grouping. The potency as synergists for the insecticidal activity of carbaryl (1-naphthyl methylcarbamate) and pyrethrum with houseflies (Musca dornestica L.) was compared for all the nonradioactive methylenedioxyphenyl compounds prepared.
The Synthesis of [Methylenedioxy-14C]Paroxetine BRL 29060A
Lawrie,K;Rustidge,D
J. Labeled Cmpds & RadioPharm
Vol.33(8.) 1993 pp.777-781
10.1002/jlcr.2580330814
http://www3.interscience.wiley.com/journal/112731657/abstract
Abstract
Paroxetine (1), BRL 29060A, a potent antidepressant, has been prepared radiolabelled with carbon-14 in the methylenedioxy group in 5 steps and 20.9% overall yield from [14C]dibromomethane. Two altenative preparations of 3,4-[methylenedioxy-14C]phenol (2) are also described.
Cupric Oxide as an Efficient Catalyst in Methylenation of Catechols
Tomita,Masao;Aoyagi,Yoshiaki
Chem. Pharm. Bull.
Vol.16(3) 1968 pp.523-526
ONLINE ISSN: 1347-5223
http://tinyurl.com/27uxlmo
Abstract
Methylenation of catechols with methylene halides was found to be catalyzed more effectively by cupric oxide in dimethylformamide.
A Convenient, High-Yielding Method for the Methylation of Catechols
Bashall,A;Collins,J
Tetrahedron Letters
Vol.16(40) 1975, pp.3489-3490
DOI: 10.1016/S0040-4039(00)91391-1
http://tinyurl.com/26w83vo
Abstract
The methylenedioxy group occurs in many natural products and, in addition, has been
suggested s a protectingg roup for catechols. However, synthetically, the methylenation of catechols has never been easy and high yields difficult to obtain. Bonthrone and Cornforth have shown that if the reaction is carried out using dichloromethane in a dipolar, aprotic solvent such as dimethylsulphoxide coupled with the slow addition of a mixture of solid sodium hydroxide and the catechol, good yields of the methylenated catechol may be obtained. Several substituted catechols have been methylenated in high yield using dichloromethane in dimethylformamide or dimethylsulphoxide in the presence of a bronse, cupric oxide or nickel oxide catalyst.
The Synthesis of 3,4-dihydroxy-2-methoxybenzaldehyde : The use of Methylenedioxy as a Protecting Group
Bick,I;Russell,R
Aust. J. Chem.
Vol.22(7) 1969 pp.1563-1568
DOI: 10.1071/CH9691563
http://www.publish.csiro.au/paper/CH9691563.htm
Abstract
The substance 3,4-dihydroxy-2-methoxybenzaldehyde (X) is not easily accessible and has not hitherto been prepared, although the isomeric compound 2,3-dihydroxy-4-methoxybenzaldehyde (XII) has been wrongly described under the above name.1 Since formylation of 1-methoxy-2,3-methylenedioxybenzenew as reported2,3 to produce in good yield 2-methoxy-3,4-methylenedioxybenzaldehyde (II), a possible route to the desired substance was available provided the methylenedioxy group in the latter could be hydrolysed satisfactorily without affecting the methoxyl. We have therefore examined the recorded methods for inserting and removing a methylene ether group: hitherto the formation of 1,3-benzodioxoles has been a sealed-tube reaction which gives low yields and has not been an attractive preparative procedure, but with recent improvements4 and with modifications in the method for their hydrolysis, we have found that this group could be used with advantage for blocking a catechol group even in the presence of a methoxyl.
High Selectivity in the Oxidation of Mandelic Acid Derivatives and in O-Methylation of Protocatechualdehyde: New Processes for Synthesis of Vanillin, iso-Vanillin, and Heliotropin
Bjorsvik,HansRene;Liguori,Lucia;Minisci,Francesco
Org. Proc. Res. Dev.
Vol.4(6) 2000 pp.534–543
DOI: 10.1021/op0000529
http://pubs.acs.org/doi/abs/10.1021/op0000529
Abstract
New synthetic procedures for vanillin, iso-vanillin, heliotropin, and protocatechualdehyde starting from catechol are described. The utilisation of statistical experimental design and multivariate modelling and the mechanistic interpretation of the acid and base catalysis in the condensation of catechol derivatives with glyoxylic acid and in the regiocontrolled methylation of protocatechualdehyde and of the Cu(II) salt catalysis in the oxidative decarboxylation of mandelic acid derivatives have allowed the development of new highly selective processes.
The Methylenation of Catechols
Bonthrone,W;Cornforth,J
J. Chem. Soc. C.
1969 pp.1202-1204
DOI: 10.1039/J39690001202
http://www.rsc.org/publishing/journals/J3/article.asp?doi=J39690001202
Abstract
High yields in the methylenation of catechols by methylene chloride are obtained by using a polar aprotic solvent for reaction and maintaining low concentrations of the catechol dianion.
A Re-Examination of the Methylenation Reaction
Cabiddu,Maria;Cadoni,Enzo;DeMontis,Stefania;Fattuoni,Claudia;Melis,Stefana;Usai,Michele
Tetrahedron
Vol.59(24) 2003 pp.4383-4387
DOI: 10.1016/S0040-4020(03)00619-7
http://tinyurl.com/28swkqm
Abstract
A re-examination of the methylenation reaction of 1-hydroxy-2-mercapto-, 1,2-dihydroxy- and 1,2-dimercapto-substituted benzenes by bromochloromethane with cesium carbonate shows that these substrates give mixtures of five- and ten-membered benzocondensed heterocyclic compounds and in some cases even dibenzodioxines.
The Preparation of Methylenedioxy-Methoxybenzaldehydes
Campbell,Kenneth;Hopper,Paul;Campbell,Barbara
J. Org. Chem.
Vol.16(11) 1951 pp.1736–1741
DOI: 10.1021/jo50005a011
http://pubs.acs.org/doi/abs/10.1021/jo50005a011
Abstract
Since many pharmacologically active natural products contain several methoxy and/or methylenedioxy groups attached to one aromatic nucleus, it would be of interest to determine the pharmacological effect of such groups in various type of synthetic drugs. Alles (1) has shown, for example, that the polymethoxy and methylenedioxy phenylaminoethanols have an antifibirllatory action not shown by their unsubstituted analogs. Comparatively few such series have been made, however, because the necessary starting materials are very difficult to obtain.
The Methylenation of Several Allylbenzene-1,2-diol Derivatives in Aprotic Polar Solvents
Fujita,Harushige;Yamashita,Masataro
Bull. Chem. Soc. Japan.
Vol.46(11) 1973 pp.3553-3554
ONLINE ISSN: 1348-0634
http://tinyurl.com/2c8cs48
Abstract
The aprotic polar solvents, such as DMF (N,N-dimethylformamide) and DMSO (dimethyl sulfoxide), accelerated very effectively the methylenation of 1,2-dihydroxy-4- (I), 1,2-dihydroxy-3,4-dimethoxy-5- (II), and 1,2-dihydroxy-3-methoxy-5-allylbenzene (III) in the presence of bronze and cupric oxide as catalysts.
Methylenation of Allyl Substituted Catechols with Methylene Dichloride
Fujita,Harushige;Yamashita,Masataro
J. Synth. Org. Chem (Japan)
Vol.31(11) 1973 pp.932-934
ONLINE ISSN: 1883-6526
http://tinyurl.com/2e9nved (Not uploaded here, get it from the link)
Abstract
Methylenation of 1, 2-dihydroxy-3-, 1, 2-dihydroxy-4-, 1, 2-dihydroxy-3, 4-dimethoxy-5- and 1, 2-dihydroxy-3-methoxy-5-allylbenzenes with methylene dichloride in DMF or DMSO was found to be accelerated more effectively by nickelous oxide than metallic nickel and nickelic oxide, as catalyst. DMF and DMSO gave better results than other solvents.
* In Japanese mainly.
Methylenation of Catechols
Fujita,Harushige;Yamashita,Masataro
J. Synth. Org. Chem (Japan)
Vol.32(6) 1974 pp.467-470
ONLINE ISSN: 1883-6526
http://tinyurl.com/23yshj4 (Not uploaded here, get it from the link)
Abstract
Effects based upon kinds of methylenating agent, solvent and base used, were remarkably observed in methylenation of catechol (1a), pyrogallol (1b), 1, 2-dihydroxy-3-methoxy-(1c) and 1, 2-dihydroxy-4, 5-dimethoxybenzenes (1d), 2, 3-dihydroxy-4-methoxy-(1e), 3, 4-dihydroxy-(1f) and 3, 4-dihydroxy-5-methoxybenzaldehydes (1g) and 3, 4-dihydroxy-5-bromobenzaldehyde (1h), on this heterogeneous reaction system. In addition to these effects, however, there was remarkable fluctuation in yields dependent on reaction operation, but itwas elucidated that the methylenedioxy derivatives were obtained in good yields from inexpensive methylene dichloride and the above aromatic compounds in a short period, when concentrations of (1a1h) have been regulated below 1 M in the reaction system according to a procedure devised by the present authors.
* In Japanese mainly.
Synergist Synthesis, Synthesis of Methylene-C14-Dioxyphenyl Compounds: Radioactive Safrole, Dihydrosafrole, Myristicin, Piperonyl Butoxide and Diastereoisomers of Sulfoxide
Kuwatsuka,Shozo;Casida,J
J. Agric. Food Chem.
Vol.13(6) 1965 pp.528–533
DOI: 10.1021/jf60142a012
http://pubs.acs.org/doi/abs/10.1021/jf60142a012
Abstract
Methylene-C14 iodide, prepared by reduction of iodoform-C14 was made to react with the appropriate catechol to yield the following methylene-C14-dioxyphenyl compounds with a specific activity of 1 .O millicurie per millimole: safrole, dihydrosafrole, myristicin, sulfoxide synergist { 1,2-methylenedioxy-4-[2-(octylsulfinyl)propylbenzene 1, and piperonyl butoxide {a-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propyltoluene}. Yields from iodoform-C14 were 31 to 55% on a 0.5- to 0.8-mmole scale except with piperonyl butoxide, where the yield appeared to be related to the specific activity of the eththylene-14-iodide used. The octylthio, octylsulfhyl, and octylsulfonyl analogs of sulfoxide synergist, substituted on the 1-, 2-, or 3-position of the propyl group, were prepared in nonradioactive form for comparative purposes. Sulfoxide synergist and the 1-octylsulfinyl analog were resolved by chromatography into the enantiomorphs of the diastereoisomers about the sulfoxide grouping and the asymmetric carbon of the propyl grouping. The potency as synergists for the insecticidal activity of carbaryl (1-naphthyl methylcarbamate) and pyrethrum with houseflies (Musca dornestica L.) was compared for all the nonradioactive methylenedioxyphenyl compounds prepared.
The Synthesis of [Methylenedioxy-14C]Paroxetine BRL 29060A
Lawrie,K;Rustidge,D
J. Labeled Cmpds & RadioPharm
Vol.33(8.) 1993 pp.777-781
10.1002/jlcr.2580330814
http://www3.interscience.wiley.com/journal/112731657/abstract
Abstract
Paroxetine (1), BRL 29060A, a potent antidepressant, has been prepared radiolabelled with carbon-14 in the methylenedioxy group in 5 steps and 20.9% overall yield from [14C]dibromomethane. Two altenative preparations of 3,4-[methylenedioxy-14C]phenol (2) are also described.
Cupric Oxide as an Efficient Catalyst in Methylenation of Catechols
Tomita,Masao;Aoyagi,Yoshiaki
Chem. Pharm. Bull.
Vol.16(3) 1968 pp.523-526
ONLINE ISSN: 1347-5223
http://tinyurl.com/27uxlmo
Abstract
Methylenation of catechols with methylene halides was found to be catalyzed more effectively by cupric oxide in dimethylformamide.
Bashall.Collins.A.Convenient.High.Yielding.Method.for.the.Methylenation.of.Catechols.pdf