The Bodroux-Tschitschibabin Aldehyde Synthesis
Lee Irvin Smith, Milward Bayliss
J. Org. Chem. 6, 437-442 (1941)
Bodroux1, who prepared triarylmethanes by action of Grignard reagents upon chloroform or bromoform, found that the yield was usually quite low and never better than 25%.
HCX3 + 3 RMgX -> R3CH + 3 MgX2
Hoping to improve the yields, he substituted ethylorthoformate for the haloform, but in this case no triaryl methanes resulted; only aldehydes were formed.
HC(OC2H5)3 + RMgX -> RCH(OC2H5)2 + MgXOC2H5
RCH(OC2H5)2 + H2O -H+-> RCHO + 2 C2H5OH
Tschitschibabin2, independently and at about the same time, discovered the same reaction. He discovered that if the orthoformic ester was first added to the ethereal solution of the Grignard reagent, and then most of the solvent removed by distillation, a point was reached at which a vigorous reaction ensued. Much heat was evolved and the reaction product was a viscous oil which gave the acetal on treatment with acidified water. The acetal could be obtained pure by fractionation and from it the aldehyde could be obtained. Tschitschibabin and Jelgasin3 discovered somewhat later that the reaction was not confined to one of the ethoxyl groups of the ester, although Bodroux4 found that replacement of the first ethoxyl group was a slow reaction and that yields (of benzaldehyde) were improved by refluxing the mixture after addition of the orthoformic ester.
Wood and Comley5 also found that poor yields of aldehydes were obtained unless, after adding the orthoformic ester, most of the ether was removed and the residue was heated.
Bert6 prepared an extensive series of aldehydes using chlorides of the type Ar(CH2)nCl, and a number of other investigators have prepared aldehydes by means of the orthoformate synthesis.
As the yields of aldehydes obtained by different investigators using this method have varied widely, it appeared that the reaction was greatly affected by relatively slight differences in procedure. In order to evaluate these, a study was undertaken which had as its object the determination of the optimum conditions for preparation of a simple aromatic aldehyde, benzaldehyde, and the application of these conditions to the preparation of a few other aromatic aldehydes. In general, the Grignard reagents (0.2 moles) were prepared in ether in the usual way. After formation of the reagent, enough ether was added to bring the total amount up to 4.5 moles per mole of halogen compound. The orthoformic ester was then mixed with an equal volume of ether and slowly added to the Grignard solution, after which the mixture was processed. Four variants in the conditions were examined:
1. the length of time the reagents were allowed to stand after mixing;
2. the duration of the period of refluxing, after the ether was removed;
3. the relative amount of orthoformic ester used;
4. the effect of the nature of the solvent.
In addition, the isolation and purification of the aldehyde itself was investigated.
Three experiments were made in which the time of standing was varied. After three hours, 10.7g (21.5%) of benzaldehyde bisulfite compound was obtained; after six and one-half hours, 37g (81%), and after fifteen hours, 40.2g (89.2%).
Using a fifteen-hour period of standing, the ether was then boiled off and the residue was heated on the steam-bath. After fifteen minutes of heating, the yield of bisulfite compound was 40.2g (89.2%) and after sixty minutes the yield was 34.5g (75.6%). These results showed that heating after removal of the ether offered no advantages and might even be disadvantageous if the time of heating were prolonged.
Using a fifteen hour period of standing, then removing the ether and heating the residue for fifteen minutes, the effect of varying the amount of orthoformic ester was determined. The results showed that there was a slight increase in the yield (89.2% to 95.0%) of benzaldehyde when a 100% excess of the halogen compound was used. However, this advantage is more than offset when the halogen compound is a costly one.
In determining the effect of the solvent, the Grignard reagent (0.2 moles) was prepared in the usual way, then dry toluene (50 mL) was added. The ether was distilled off and when the temperature reached 90°C, orthoformic ester (0.2 moles) was added. The reaction-mixture was decomposed by boiling for fifteen minutes with 5 N sulfuric acid and the aldehyde was then isolated. The results showed that this procedure is not advantageous, but rather the reverse. Thus, when the reaction product was decomposed immediately after mixing the reagents, the yield of aldehyde bisulfite compound was 29.6%; when the mixture was heated for fifteen hours,the yield was 65.8%.
Blank experiments showed that the yield of bisulfite compound from benzaldehyde was from 85-90%. Decomposition of the bisulfite compound with dilute sulfuric acid, followed by steam distillation, ether extraction of the distillate and fractionation of the aldehyde gave yields of aldehyde of about 80%. When the bisulfite compound was decomposed by dilute sodium hydroxide, the yield of aldehyde was only 55-60%. It thus appeared that the maximum yield of benzaldehyde, weighed as the bisulfite compound, was around 90% and that this high yield could be obtained by observing the following conditions:
1. The reaction-mixture should be allowed to stand for fifteen hours after mixing the reagents;
2. The ether should be removed and the residue heated for not longer than fifteen minutes on the steam-bath;
3. Equimolecular quantities of the Grignard reagent and orthoformic ester should be used.
Using these conditions, o-, m- and p-bromotoluenes were converted to the toluic aldehydes via the Grignard reagents in yields of 51.7, 56.2, and 50.4% respectively.
Experimental
The apparatus consisted of a 1-liter 3-necked flask, fitted with a dropping-funnel, mechanical stirrer, and condenser. All openings to the air were protected by calcium chloride guard tubes. Magnesium turnings, which had been washed with ether and dried in a desiccator, were placed in the flask, the apparatus was assembled and heated on the steam-bath while a current of dry air was passed through. After the flask had cooled, ether (10 mL) and a crystal of iodine were introduced. The halogen compound was mixed with an equal volume of ether and about 10 mL of this solution was dropped onto the magnesium. After the reaction started, enough ether was added to the solution of the halogen compound to bring the total up to 4.5 moles per mole of halogen compound. This solution was then added, with vigorous stirring, at the rate of about two drops per second. After the addition was complete, the mixture was refluxed and stirred for fifteen minutes longer. Then, with stirring, the orthoformic ester, dissolved in an equal volume of ether, was added at the rate of about two drops per second. No apparent reaction occurred. After the addition of the reagent was complete, the reaction-mixture was processed as described under the several headings above. The reaction-mixture was decomposed by addition of ice and 5N sulfuric acid and refluxed for a few minutes to decompose the acetal. If the ether had been distilled off, the cooled mixture was extracted with ether three times (50 mL each time); otherwise, the ether layer was merely separated. The combined ethereal solutions (volume about 150 mL) were shaken vigorously with saturated sodium bisulfite solution (50 mL) and filtered. The filtrate was shaken with fresh bisulfite solution and again filtered. The combined solids were washed with cold alcohol (50 mL), then with ether (50 mL), and spread in the air to dry. After fifteen minutes, the material was weighed.
References
[1] Bodroux, Compt. Rend., 138, 92 (1904)
[2] Tschitschibabin, J. Russ. Phys.-Chem. Soc., 36, 1284 (1903); Ber., 37, 186, 850 (1904)
[3] Tschitschibabin & Jelgasin, Ber., 47, 48, 1843 (1914)
[4] Bodroux, Compt. Rend., 138, 700 (1904)
[5] Wood & Comley, J. Soc. Chem. Ind., 42, 429T (1923)
[6] Bert, Compt. Rend., 186, 699 (1928)
