The Preparation of Methylenedioxy-methoxybenzaldehydes
Kenneth N. Cambell, Paul F. Hopper and Barbara K. Campbell
Abstract
Since many pharmacologically active natural products contain several and/or methylenedioxy groups attached to one aromatic nucleas it would be of interest to determine the pharmacological effect of such groups in various types of synthetic drugs. Alles(1) has shown, for example, that the polymethoxy and methylenedioxy phenylaminoethanols have an antifibrillatory 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
Harushige Fujita and Masataro Yamashita
Bulletin of the Chemical Society of Japan
Vol. 46 (1973) No. 11 pp.3553-3554
DOIi:10.1246/bcsj.46.3553
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.
Cupric Oxide as an Efficient Catalyst in Methylenation of Catechols
Masao Tomita and Yoshiaki Aoyagi
CHEMICAL & PHARMACEUTICAL BULLETIN
Vol. 16(3) 1968 pp.523-526
Abstract
Methylenation of catechols with methylene halides was found to be catalyzed more effectively by cupric oxide in dimethylformamide.
The Synthesis of [methylenedioxy-14C]Paroxetine BRL 29060A
K W M Lawrie and D C Rustidge
Journal of Labelled Compounds and Radiopharmaceuticals
Vol.33(
1993 pp.777-781
Abstract
Paroxetine (l), 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.
Synergist Synthesis, Synthesis of Methylene-C14-Dioxyphenyl Compounds: Radioactive Safrole, Dihydrosafrole, Myristicin, Piperonyl Butoxide and Diastereoisomers of Sulfoxide
Shozo Kuwatsuka, J. E. Casida
J. Agric. Food Chem.
1965, 13(6), pp 528–533
DOI: 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)propyl]benzene 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 methylene-C14 iodide used. The octylthio, octylsulfinyl, 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 Methylenation of Catechols
W. Bonthrone and J. W. Cornforth
J. Chem. Soc. C
1969, 1202-1204
DOI: 10.1039/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.
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
Hans-Rene Bjørsvik, Lucia Liguori, and Francesco Minisci
Organic Process Research & Development
2000, 4, pp.534-543
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 Synthesis of 3,4-Dihydroxy-2-MethoxyBenzaldehyde: The use of Methylenedioxy as a Protecting Group
I. R. C. Bick and R. A. Russel
Australian Journal of Chemistry
22(7) 1563 - 1568
DOI:10.1071/CH9691563
Abstract
The substance 3,4-dihydroxy-2-methoxybenzaldehyde 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. Since formylation of 1-methoxy-2,3-methylenedioxybenzenew as reported to produce in good yield 2-methoxy-3,4-methylenedioxybenzaldehyde, 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 improvements 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.
Nuclear Oxidation in Flavones and Related Compounds: Part XXIV. Synthesis of Myristicin and Elemicin
K. Visweswara Rao, T. R. Seshadri FASC and T. R. Thiruvengadam
Proceedings Mathematical Sciences
Volume 30, Number 3 / September, 1949
DOI: 10.1007/BF03049176
Summary
Employing the two stage process of ortho-oxidation eugenol is converted into 5-hydroxy eugenol. Methylation of this yield elemicin and methylenation myristicin. This constitutes the most convenient synthesis of these naturally occurring compounds and is highly significant from the point of view of biogenesis.
The 2-aminotetralin system as a structural base for new dopamine- and melatonin-receptor agents
(1994), Doctoral Thesis,
Copinga, Swier
http://irs.ub.rug.nl/ppn/294304037
The research described in this thesis is divided into two parts. Part I (chapters 1-3) deals with the development of a novel 2-aminotetralin as a mixed dopamine Dl/D2-receptor agonist, whereas part I1 (chapters 4-6) concerns the development of 2-amidotetralins as nonindolic melatonin-receptor agents.
Chapter 2:...
2.3.2 5,6-Methylenedioxy-2-[N-n-PROPYL-N-(Thienyl)Ethylamino]-Tetralin (at page 12/23)
Key intermediate in the synthesis of 5,6-methylenedioxy-2-N-n-propyl-N-2-(2-thienyl)ethylaminoltetralin (5,6-OCH20-PTAT, 20) was 5,6-methylenedioxy-2-tetralone (50). This tetralone 50 was synthesized from 2-hydroxy-3-methoxybenzaldehyde (26) via a-diazoketone 49, as described previously by Nichols and coworkers [63]. As outlined in Scheme 2.6, the fust step of this synthetic pathway involved the demethylation of 2-hydroxy-3-methoxybenzaldehyde (26) by the use of 48% hydrobromic acid in glacial acetic acid in accordance with the method of Pauly and colleagues [80,81]. The 37% yield of this reaction was lower than the previously described yields [81,82]. The next step, the conversion of 2,3-dihydroxybenzaldehyde (44) to 2,3-methylenedioxybenzaldehyde (45), was accomplished by the method of Tomita and Aoyagi [83]. The methylenation, involving two sequential, aliphatic nucleophilic substitutions [84], was carried out using dibromomethane as methylenating agent (instead of diiodomethane [82]) in the presence of potassium carbonate as ionizing base, copper(I1) oxide as catalyst, and dimethylfomamide as solvent [85-871.]
Kenneth N. Cambell, Paul F. Hopper and Barbara K. Campbell
Abstract
Since many pharmacologically active natural products contain several and/or methylenedioxy groups attached to one aromatic nucleas it would be of interest to determine the pharmacological effect of such groups in various types of synthetic drugs. Alles(1) has shown, for example, that the polymethoxy and methylenedioxy phenylaminoethanols have an antifibrillatory 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
Harushige Fujita and Masataro Yamashita
Bulletin of the Chemical Society of Japan
Vol. 46 (1973) No. 11 pp.3553-3554
DOIi:10.1246/bcsj.46.3553
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.
Cupric Oxide as an Efficient Catalyst in Methylenation of Catechols
Masao Tomita and Yoshiaki Aoyagi
CHEMICAL & PHARMACEUTICAL BULLETIN
Vol. 16(3) 1968 pp.523-526
Abstract
Methylenation of catechols with methylene halides was found to be catalyzed more effectively by cupric oxide in dimethylformamide.
The Synthesis of [methylenedioxy-14C]Paroxetine BRL 29060A
K W M Lawrie and D C Rustidge
Journal of Labelled Compounds and Radiopharmaceuticals
Vol.33(
1993 pp.777-781Abstract
Paroxetine (l), 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.
Synergist Synthesis, Synthesis of Methylene-C14-Dioxyphenyl Compounds: Radioactive Safrole, Dihydrosafrole, Myristicin, Piperonyl Butoxide and Diastereoisomers of Sulfoxide
Shozo Kuwatsuka, J. E. Casida
J. Agric. Food Chem.
1965, 13(6), pp 528–533
DOI: 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)propyl]benzene 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 methylene-C14 iodide used. The octylthio, octylsulfinyl, 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 Methylenation of Catechols
W. Bonthrone and J. W. Cornforth
J. Chem. Soc. C
1969, 1202-1204
DOI: 10.1039/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.
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
Hans-Rene Bjørsvik, Lucia Liguori, and Francesco Minisci
Organic Process Research & Development
2000, 4, pp.534-543
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 Synthesis of 3,4-Dihydroxy-2-MethoxyBenzaldehyde: The use of Methylenedioxy as a Protecting Group
I. R. C. Bick and R. A. Russel
Australian Journal of Chemistry
22(7) 1563 - 1568
DOI:10.1071/CH9691563
Abstract
The substance 3,4-dihydroxy-2-methoxybenzaldehyde 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. Since formylation of 1-methoxy-2,3-methylenedioxybenzenew as reported to produce in good yield 2-methoxy-3,4-methylenedioxybenzaldehyde, 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 improvements 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.
Nuclear Oxidation in Flavones and Related Compounds: Part XXIV. Synthesis of Myristicin and Elemicin
K. Visweswara Rao, T. R. Seshadri FASC and T. R. Thiruvengadam
Proceedings Mathematical Sciences
Volume 30, Number 3 / September, 1949
DOI: 10.1007/BF03049176
Summary
Employing the two stage process of ortho-oxidation eugenol is converted into 5-hydroxy eugenol. Methylation of this yield elemicin and methylenation myristicin. This constitutes the most convenient synthesis of these naturally occurring compounds and is highly significant from the point of view of biogenesis.
The 2-aminotetralin system as a structural base for new dopamine- and melatonin-receptor agents
(1994), Doctoral Thesis,
Copinga, Swier
http://irs.ub.rug.nl/ppn/294304037
The research described in this thesis is divided into two parts. Part I (chapters 1-3) deals with the development of a novel 2-aminotetralin as a mixed dopamine Dl/D2-receptor agonist, whereas part I1 (chapters 4-6) concerns the development of 2-amidotetralins as nonindolic melatonin-receptor agents.
Chapter 2:...
2.3.2 5,6-Methylenedioxy-2-[N-n-PROPYL-N-(Thienyl)Ethylamino]-Tetralin (at page 12/23)
Key intermediate in the synthesis of 5,6-methylenedioxy-2-N-n-propyl-N-2-(2-thienyl)ethylaminoltetralin (5,6-OCH20-PTAT, 20) was 5,6-methylenedioxy-2-tetralone (50). This tetralone 50 was synthesized from 2-hydroxy-3-methoxybenzaldehyde (26) via a-diazoketone 49, as described previously by Nichols and coworkers [63]. As outlined in Scheme 2.6, the fust step of this synthetic pathway involved the demethylation of 2-hydroxy-3-methoxybenzaldehyde (26) by the use of 48% hydrobromic acid in glacial acetic acid in accordance with the method of Pauly and colleagues [80,81]. The 37% yield of this reaction was lower than the previously described yields [81,82]. The next step, the conversion of 2,3-dihydroxybenzaldehyde (44) to 2,3-methylenedioxybenzaldehyde (45), was accomplished by the method of Tomita and Aoyagi [83]. The methylenation, involving two sequential, aliphatic nucleophilic substitutions [84], was carried out using dibromomethane as methylenating agent (instead of diiodomethane [82]) in the presence of potassium carbonate as ionizing base, copper(I1) oxide as catalyst, and dimethylfomamide as solvent [85-871.]
Campbell.Hopper.Campbell.The.Preparation.of.Methylenedioxy.MethoxyBenzaldehydes.pdf