TRANSCODING PROPENYLBENZENES
The Baeyer Condensation is a very old. It was developed in the late 1800s by Adolf Von Baeyer whose early experiments involved phenol and formaldehyde
to form phenol-formaldehyde resins (which later led to the discovery of Bakelite) and the condensation between ketones and aldehydes (think
Baeyer-Villiger) with aryl compounds, which would eventually be applied to the synthesis of DDT (DichloroDiphenylTrichloroethane; notorious banned
pesticide) and Bisphenol A (4,4'-dihydroxy-2,2-diphenylpropane; used for epoxy glue).
Using this method, followed by catalytic cleavage, a variety of propenylbenzenes can be synthesized.
Two aromatic molecules, substituted or no, in the presence of an acid or base catalyst, condense with an aldehyde or ketone to form a diarylalkane.
DDT is formed through the condensation of chlorobenzene and chloral; Bisphenol A, through the condesation of phenol and acetone. And, if
propionaldehyde were condensed with anisole, using a catalytic amount of acid or base (like simple H2SO4 or NaOH), 1,1-(dimethoxyphenyl)propane would
result.
Diarylalkanes can easily be cleaved with either acids or bases (again, simple ones like H2SO4 or NaOH) into two molecules: one that is an aromatic and
one that is a 1-arylalkene. For those that are confused, this means that propenylbenzenes can be formed in two steps. Two substituted or unsubstituted
benzene molecules react with one propionaldehyde molecule to form one intermediate, 1,1-diphenylpropane (and water). This can then be cleaved (or
“cracked”) to form one of the aforementioned benzene molcules and one molecule of the desired propenylbenzene. To be clear, isosafrole is a
propenylbenzene.
Anisole is a very common aryl compound used in this type of reaction. For those that have doubts that benzodioxole (methylenedioxybenzene) can
substitute it, see US 2560173.
Following is a very good example of the above reaction taken from US 4026951:
EXAMPLE 1
a. Condensation
A mixture of 432 g (4 mols) of anisole and 4 g. of concentrated H3PO4 was heated to 150 C in a reaction vessel equipped with a stirrer, metering unit
and descending condenser. After the afore mentioned temperature has been reached, 58 g (1 mol) of propionaldehyde were added through the metering unit
over a period of 1.5 hours and, at the same time, the water of reaction formed distilled off. On completion of the addition, the upper phase of the
reaction mixture was decanted from the phosphoric acid precipitated and the excess anisole removed from the reaction mixture by distillation, leaving
251.8 of condensation product consisting of pp'-, o,p'- and o,o'-1,1-dimethoxy diphenyl propane. The yield amounted to 98.4%, based on the
propionaldehyde used.
b. Splitting
For splitting, 100 g of 1,1-dimethoxy diphenyl propane from the condensation stage (a) were heated to 200 C in a distillation apparatus fitted with a
Claisen attachment, followed by the addition of 0.5 g of concentrated phosphoric acid. The products formed during the splitting reaction distilled off
over a period of 15 minutes at about 5 to 30 Torr. According to analysis by gas chromotography, the distillate (95.5 g) contained 32.7 g of unsplit
1,1-dimethoxy diphenyl propane, 24.1 g of trans-p-anethole, 9.1 g of trans-o and cis-p-anethole and 1.2 g of p-propyl anisole, corresponding to a
yield of 91.4% of anetholes, based on reacted condensate. Pure trans-p-anethole was obtained from the product of splitting by fractional
distillation: b.p. 110 C/10 Torr.
Other very good examples of this reaction, with only slight experimental modifications (mostly related to the catalyst used), can be found in US
1798813, 2591651, 4071564, 4154769; GB 905994A; & CA 660173A .
Lets consider the drawbacks to the above reaction.
1. Uses propionaldehyde, which has a low boiling point, is volatile, has a suffocating smell and is not OTC.
2. Forms water as a by-product, which must be removed somehow.
How to avoid all this? Well, one need only review the contents of CA 708652A; GB 963294A; and as mentioned above, US 4026951.
EXAMPLE 2
A mixture of 324 g (3 mols) of anisole and 4 g of concentrated H3PO4 was heated to 150 C in a 500 ml capacity reaction vessel equipped with a
thermometer, stirrer and dropping funnel. After the above-mentioned temperature had been reached, 64 g (0.432 mol) of o-anethole
(2-methoxy-propen-1-yl benzene) were introduced into the thoroughly stirred anisole/phosphoric acid mixture over a period of 1 hour, followed by
stirring for 1 hour at the same temperature. The excess anisole was then distilled off at 50 C/5 Torr, leaving 110 g of a condensation product
consisting predominantly of the o,p'-isomers of 1,1-dimethoxy diphenyl propane. The yield was substantially quantitative.
For splitting, the condensate was heated to 200 C in the presence of the phosphoric acid left in the condensate. The products of splitting formed,
anisole, and the o-p-anetholes, distill off over a period of 10 minutes at 10 Torr.
Distillation of 55 g of 1,1-dimethoxy diphenyl propane gave 17.8 g of distillate which contained 14% of trans-p-anethole according to analysis by gas
chromotography. 24.2 g of condensate were recovered.
The Example illustrates that o-anethole can be converted by the process according to the invention into trans-p-anethole.
A higher yield could likely have been obtained had a better acid or base catalyst been used, but more on this in a minute. For now, what is important
is that the desired p-anethole was obtained from undesired o-anethole by reacting it with anisole using the method already described. It appears then
that anethole, or, as some of the other patents listed above indicate, isoeugenol, could be used as a precursor to isosafrole by condensing it with
benzodioxole (via NaOH or KOH catalyst, which will surely not effect the methylenedioxy bridge) and then be cleaved and distilled in the same pot by
adding vacuum and increasing the temperature.
Another good example of the p-anethole condensation (this time with phenol) is taken from:
Arylalkylation of Phenols and Naphthols with Derivatives of styrene
Ng. Ph. Buu-Hoi, Henri Le. Bihan, Fernand Binon, Pierre Maleyran
J. Org. Chem., 1952, 17 [8], pp 1122–1127
It is likely TsOH (formed by reaction of H2SO4 and toluene) is acting as the catalyst and not H2SO4.
EXPERIMENTAL
Condensation of anethole with phenol. To a warm mixture of 94 g. of phenol and 10 g. of sulfuric acid, a solution of 74 g. of redistilled anethole in
100 ml. of toluene was added in small portions. The mixture was refluxed for two hours, washed after cooling with an aqueous solution of sodium
carbonate, then with water, and dried over sodium sulfate. After evaporation of the solvent, the residue was vacuum-fractionated, giving 72 g. (60%
yield) of crude (a-anisyl-n-propyl)phenol (II) boiling at 200-240/13 mm; after redistillation, the product formed a pale yellow, viscous oil, b.p.
212-217/13 mm.
Supportive information on this reaction can be found in the following reference:
Synthesis of Substituted 1,1-Diarylethanes
D. S. Hoffenberg, E. M. Smolin, K. Matsuda
J. Chem. Eng. Data, 1964, 9 (1), pp 104–106
In it, "Anisole" and "Resorcinol di-Me-Ether" (1,3-dimethoxybenzene ?) are condensed with paraldehyde to form the expected ring substituted
1,1-diarylethanes in low yield (40% & 36%, respectively) using 65% aqueous H2SO4 as an acid catalyst (water appears to inhibit this reaction).
I call this process “transcoding” – as in, transcoding anethole to isosafrole. Why transcoding? One transcodes video formats such as, for
example, .avi or .wmv to .mpeg or .vob – but they are all the same video, just with different containers. By the same token, anethole to isosafrole
are both propenylbenzenes, but with different ring substituents, and the process of converting one to the other could be construed as transcoding.
Some may question whether the cleavage reaction will prefer the formation of isosafrole over the original anethole starting material. The answer may
lie in US 3359317 (with support from US 3311660 & 4374272).
The authors of the patent provide a means to synthesize alkenyl-anilnes which do not involve splitting bis-aminophenyl-alkanes. In their own words:
It has now been found that alkenyl-anilines may be obtained readily and in good yields by heating hydroxy-phenyl-amino-phenyl-alkanes over
alkaline catalysts and distilling off the alkenyl-anilines as and when they are formed, phenol being obtained as the other fission product.
The hydroxyphenyl-aminophenyl-alkanes are readily obtainable in good yields by the addition of aromatic amines on to alkenyl-phenols in the presence
of acidic or basic catalysts according to the process of copending application Ser. No. 295,203 and now U.S. Patent No. 3,311,660.
Having regard to this process of production, the splitting of the hydroxyphenyl-aminophenyl-alkanes into alkenyl-anilines and phenols is
surprising. It was to have been expected that the splitting would lead to the reformation of the original starting materials. In point of fact, the
hydroxyphenyl-aminophenyl-alkanes can also be readily decomposed again into alkenyl-phenols and anilines by bringing them to decomposition
temperatures over acidic catalysts. On the other hand, by a purely thermal splitting, a mixture of alkenyl-phenols, alkenyl-anilines, phenols and
anilines results.
So there it is. A means to transcode anethole or isoeugenol to isosafrole. Benzodioxole would be required to carry out this synthesis, but it is
reported to be simple to produce via a reaction between catechol, DCM, NaOH and DMSO.
For some who find appeal in forming allylpyrocatechol from eugenol, it may be possible to produce propenylpyrocatechol through this reaction by
replacing benzodioxole with catechol.
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[Edited on 13-4-2010 by Sulfuro]
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