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Bull Soc Chim Belg 1992 - A Convenient Preparation of Pivalaldehyde-Some Remarks On The Bouveault Synthesis

This document describes a convenient method for preparing pivalaldehyde (2,2-dimethylpropanal) through the Bouveault synthesis. The key steps are: 1) Tert-butylmagnesium chloride is reacted with 100% excess dimethylformamide (DMF) at low temperature (-20°C) to form pivalaldehyde. 2) This produces pivalaldehyde in 71-75% yield with the only byproduct being 2,2,3,3-tetramethylbutane. 3) Fractional distillation provides pivalaldehyde of over 99.5% purity, demonstrating this procedure to be a useful and efficient synthetic route for this compound

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0% found this document useful (0 votes)
313 views3 pages

Bull Soc Chim Belg 1992 - A Convenient Preparation of Pivalaldehyde-Some Remarks On The Bouveault Synthesis

This document describes a convenient method for preparing pivalaldehyde (2,2-dimethylpropanal) through the Bouveault synthesis. The key steps are: 1) Tert-butylmagnesium chloride is reacted with 100% excess dimethylformamide (DMF) at low temperature (-20°C) to form pivalaldehyde. 2) This produces pivalaldehyde in 71-75% yield with the only byproduct being 2,2,3,3-tetramethylbutane. 3) Fractional distillation provides pivalaldehyde of over 99.5% purity, demonstrating this procedure to be a useful and efficient synthetic route for this compound

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janina_nazarska
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Bull. SOC.Chim.Belg.vol.

101 / no 9 / 1992

0037-9646 / 92 / $ 2.00
Q 1992 Comite van

+ 0.00

EUROPEAN SECTION

Beheer van h e tB u l l e t i n V.Z.W.

A CONVENIENT PREPARATION OF PIVALALDEHYDE : SOME REMARKS ON THE BOUVEAULT SYNTHESIS


Ryszard 6. Nazarski,* Maciej K. Tasz and Romuald Skowro6ski Department of Organic Chemistry, University ofxbdi, Narutowicza 68, 90-136Xodi, Poland
Received : 04/05/1992 -Accepted: 10/07/1992

ABSTRACT

A simple and versatile procedure of pivalaldehyde synthesis is described. The synthesis is based on the formylation of tert-butyl magnesium chloride with excess of DMF in low temperature and can be easily performed in bulk scale. The application of DMF for the formylation of tertiary Grignard compounds is briefly discussed in terms of steric effects.
INTRODUCTION

Pivalaldehyde (or 2,2-dimethylpropanal,1 ) i s a simple, small molecule of great practical


t s synthesis has been interest. Up to now, however, no useful laboratory procedure of i

reported. Aldehyde 1 used to be prepared by formylation of tert-butylmagnesium chloride ( 2 ) with methyl formate, ethyl formate,' N-methylf~rmanilide~ and N,N-dimethylformamide (DMF). ' a ' 4 Some other, generally less convenient methods were also applied. The use of DMF in the formylation of organometallic compounds (either Grignard or organolithium) w a s abandoned for a long time, probably due to the discouraging report of Bouveault,la which claimed a very poor yield of 1. Other attempts4 to apply DMF for the formylation of 2 were generally unsuccessful. Recently, some inviting papers5 appeared concerning the Bouveault synthesis of aldehydes, using N-formylalkylamines including DMF. 6 However, only one tertiary organolithium compound has been Since large amounts of title compound were required ,in our investigations on sterically crowded systems we decided to try to optimize the conditions of the Bouveault synthesis of 1 with DMF as formylating agent observing the recently published data. This work is to present the resulting useful, highly-efficient synthetic procedure.
RESULTS AND DISCUSSION

'

A major problem in the Bouveault synthesis of 1 is the remarkable difference in the

reaction of tertiary Grignard compounds comparing to the primary and secondary ones.la The importance of steric hindrance increases even more dramatically in the case of organolithium reagents, where its influence can be observed even for secondary compounds.' However, in preliminary experiments' we found that use of N-formylpiperidinel0 in the formylation of 2 leads to satisfactory (48%) yield of 1. It made us reexamine the more readily available dimethylformamide which should have even less steric requirements. In our modification of Bouveault procedure, we have used a 100% the formylation was carried out in lowered temperature.l ' b ! c of DMF and

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Total yield of aldehyde 1 is 71-75% (based on magnesium used and estimated from ' H n.m.r. spectrum of the crude reaction product). The only by-product w a s 2,2,3,3-tetramethylbutane
(3). This very volatile, inert compound usually forms to some e x t e n t ' '

during the preparation

of the reagent 2, and may be eliminated by spinning-band fractional distillation which in our case gives 1 of more than 99.5%purity (*H n.m.r. control).

DMF

> Me3C-CHO

2. H+
Me3C-MgC1
2

M e , $ C 1
A

Me3C-CMe

On the other hand, we have not found any traces of an alcohol side-product formed in the reaction. Thus, the possible reduction process6 does not take place during the preparation of
1. This is in agreement with a low-temperature aldehyde formation in the synthesls of some 13 unsymmetrical sec-alcohols using a specific formylating agent.

The addition of the first equivalent of DMF is a fairly exothermic process, accompanied with a temporary formation of a light-grey precipitate. The additlon of the second portion of
DMF does not evolve more heat; the final light-grey precipitate of the reaction complex forms

at this time. Generally, DMF in 100% excess formylates well the tert-butylmagnesium chloride 2, giving the target aldehyde 1 in relatively pure form and with high yield. To our knowledge this is the first example of successful aldehyde preparation starting from the tertiary Grignard compound. It seems possible that a formylating agent with small molecular size (as DMF) 1 s a good reagent for the Bouveault preparation of sterically crowded aldehydes. If it i s right, the failure of the attempted synthesis of 1 starting from 2 and DMF with hexamethylphosphoramide (HMPA) as a dipolar solvent (or c o ~ o l v e n t ) can ~ ~ be explained in terms of steric hindrance of the latter compound. [ W A molecules can solvate Grignard reagentseb and, especially for tertiary ones, the access of formylating agent is hindered].
EXPERIMENTAL

The ' H n.m.r. spectra were recorded on a Tesla BS 467 (60 MHz) spectrometer in carbon tetrachloride solutions with tetramethylsilane as an internal reference. The tert-butylmagnesium chloride solution [prepared according to a modified procedure l4 from 24.31 g (1.00mole) of magnesium and 104.6 g (1.13 mole) of tert-butyl chloride in 1100 ml of anhydrous ethyl ether under dry argon atmosphere] i s cooled to -20C (dry ice-acetone bath) and the solution of 73.09 g (1.00 mole) of anhydrous DMF in 1 0 0 ml of ether is added over a 35-min period at such rate that temperature of the reaction mixture does not exceed 1 5 ' C . (An exothermic process takes place; light-grey precipitate forms and disappears). A second portion of 73.09 g (1.00 mole) of DMF is then dropped quickly at -8OC; light-grey s stirring and precipitate forms. After additional 5 min, 0.5 g of hydroquinone 1 s left overnight at argon stream are stopped, the cooling bath is removed and the mixture i ambient temperature under argon atmosphere. The contents of the flask is then cooled in ice bath and acidified by addition of 4 mol/l hydrochloric acid until pH 1. The ether layer is separated and the aqueous solution is extracted with four 70-1111portions of peroxide-free ethyl ether. The organic phases are combined, dried (magnesium or calcium sulfate) and the drying agent is separated rapidly. The filtrate is concentrated very slowly (Vigrew) to a volume of about 110 ml. The residual liquid is then fractionated under argon through an efficient 30-cm Vigreux column. After about 16-g forerun the fraction ( c a . 10 g, bp 5 0 7 2 ' C ) containing about 75% of 1, ether, and traces s obtained. The main fraction (51.8 - 55.0 g of colourless liquid, 57 - 61% yield) is of 3 i

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collected (bp 72-74OC, n D " 1.37941, consistent of 2 [n.m.r. 6: 1.02 ( s , 9H), and 9.37 ( s , l H ) ] contaminated by 3 - 4% of 3; n.m.r. 6: 0.83 ( s ) . The product should be used as soon as possible; after 1-day standing at room temperature without air-oxygen protection about 6% of 1 is oxidized to 2,2-dimethylpropanoic acid, n.m.r. 6: 1.16 ( s ) . In refrigerator 1 solidifies and may be stored under argon without addition of stabilizer. REFERENCES ! '
( a ) L. Bouveault. C. R. Acad. Sci 1904, 138, 1108; ( b ) K. N. Campbell, J. Am. Chem. SOC. 1937, 59. 1980. 2. H. C. Brown, H. I. Schlesinger, and A. 8. Burg, J. Am. Chem. SOC. 1939, 61, 673. 3. E. E. Smlssman, R. H. Johnsen. A. W. Carlson, and B. F. Aycock, J . Am. Chem. SOC. 1956. 78, 3395. 4. ( a ) J. G. Sharefkin and A. Forschirm, Anal. Chem. 1963, 35, 1616; ( b ) J. Fauvarque, J. Ducom, and J. -F. Fauvarque, C. R. Acad. Sci. Ser. C 1972. 275, 511. 5. G. A. Olah, L. Ohannesian, and M. Arvanaghi, Chem. Rev. 1987, 87, 671. 6. ( a ) W. Amaratunga and J. M. J. FrBchet, Tetrahedron Lett. 1983, 24, 1143; ( b ) E. E. Aboujaoude, N. Collignon, and P. Savignac, Synthesis 1983, 634; (c) G. A. Olah, G. K. Surya Prakash, and M. Arvanaghi, Synthesis 1984, 228. 7. G. A. Olah, L. Ohannesian, and M. Arvanaghi, J . Org. Chem. 1984, 49, 3856. 8. E. A. Evans, J . Chem. SOC. 1956, 4691. 9. M. K. Tasz, Master Thesis, Institute of Chemistry, University of Ebdt, 1983. 10. ( a ) G. A. Olah, and M. Arvanaghi, Angew. Chem. I n t . Ed. Engl. 1981, 20, 878; ( b ) G. A. Olah, and M . Arvanaghi, Org. Synth. 1985, 64, 114. 11. ( a ) L. I. Smith and M. Bayliss, J . Org. Chem. 1941, 6, 437; ( b ) L. Brandsma 'Preparative Acetylenic Chemistry', Elsevier, Amsterdam, 1971, pp. 68-69, 81-82; (c) C. Hansson and B. Wickberg, J . Org. Chem. 1973, 38, 3074. 12. F. C. Whitmore, C. J. Stehman and J. M. Herndon, J . Am. Chem. SOC. 1933, 55, 3807. 13. D. L. Comins and W. Dernell, Tetrahedron Lett. 1991, 22, 1085. 14. F. C. Whitmore and D. E. Badertscher, J . Am. Chem. SOC. 1933, 55, 1559. 15. B. Varughese and J. T. Sommerfeld, J . Chem. Eng. Data 1989, 34, 25.

1.

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