Preparation of 3,3-dimethylbutyraldehyde by oxidation of 3,3-dimethylbutanol

Abstract: This invention provides a method for preparing 3,3-dimethylbutyraldehyde comprising the step of contacting 3,3-dimethylbutanol with an oxidizing metal oxide for a time and at a temperature sufficient for said metal oxide to oxidize 3,3-dimethylbutanol to form said 3,3-dimethylbutyraldehyde. The method of this invention provides a commercially practicable means of preparing 3,3-dimethylbutyraldehyde.

Description: BACKGROUND OF THE INVENTION Field of the Invention This invention relates to a method for preparing 3,3-dimethylbutyraldehyde by oxidation of 3,3-dimethylbutanol, whereby dimethylbutanol is oxidized with a metal oxide as in claim 1. Related Background Art Several methods are known for the preparation of 3,3-dimethylbutyraldehyde by oxidation of 3,3-dimethylbutanol. In EP 0391652 and EP 0374952, 3,3-dimethylbutyraldehyde is produced by oxidation of 3,3-dimethylbutanol with oxalyl chloride, dimethyl sulfoxide, and triethylamine in a dichloromethane solution. This procedure is the well known Swern oxidation, which produces extremely malodorous dimethyl sulfide as a byproduct. Use of this procedure on a commercial scale requires costly and inefficient measures to prevent release of objectionable quantities of dimethyl sulfide. This is a major disadvantage. A similar procedure is reported in Cheung, C.K. et al., Journal of Organic Chemistry, Vol. 54, p. 570 (1989). This reference describes mixing 3,3-dimethylbutanol, dimethyl sulfoxide, trifluoroacetic acid, pyridine, and dicyclohexylcarbodiimide in benzene to produce 3,3-dimethylbutyraldehyde. The major disadvantage of this procedure is that, like the Swern oxidation, it produces dimethyl sulfide as a byproduct. Another disadvantage of the procedure is that isolation of the product requires removal of the byproduct dicyclohexylurea and distillation to purify the product. Oxidation of 3,3-dimethylbutanol has also been carried out using pyridinium chlorochromate, as described in Wiberg, K.B., et al., Journal of the American Chemical Society, Vol. 103, p. 4473 (1981). This method has the disadvantage of using an extremely toxic chromium salt which must be completely removed from the product. In addition, use of this method necessitates expensive disposal of chromium-containing waste streams from the reaction. In Gulkova, D. and Kraus, M., Collect. Czech. Chem. Commun., Vol. 57, pp. 2215-2226 (1992), the catalytic dehydrogenation of 3,3-dimethylbutanol to 3,3-dimethylbutyraldehyde is described. ZnO-Cr 2 O 3 catalysts are indicated to have satisfactory activity and selectivity. It is also possible to oxidize 3,3-dimethylbutanol with a catalytic amount of PdCl 2 (CH 3 CN) 2 , together with triphenylphosphine and 2-bromomesitylene in N,N-dimethylformamide and water. Einhorn, J., et al., Journal of Organic Chemistry, Vol. 61, p. 2918 (1996). This procedure, however, requires a relatively expensive catalyst. General methods are known for the oxidation of alcohols to aldehydes with either copper(II) oxide or 2,2,6,6-tetramethyl-1-piperidinyloxy, free radical. The vapor-phase oxidation of alcohols by copper(II) oxide is described in Sheikh, M.Y., et al., Tetrahedron Letters, 1972, p. 257. Although oxidation of a number of primary alcohols to the corresponding aldehydes is described, none of these alcohols has a branched carbon skeleton as does 3,3-dimethylbutanol. No suggestion is made that the procedure is applicable to oxidation of such compounds. Oxidation of primary and benzylic alcohols by hypochlorite in solution, catalyzed by 4-methoxy-2,2,6,6-tetramethyl-1-piperidinyloxy, free radical is described in Anelli, P.L., et al., Journal of Organic Chemistry, Vol. 52, p. 2559 (1987); Anelli, P.L., et al., Organic Synthesis, Vol. 69, p. 212 (1990). These references also mention use of 2,2,6,6-tetramethyl-1-piperidinyloxy, free radical, but do not suggest that either of these oxidizing agents is suitable for oxidation of 3,3-dimethylbutanol. Oxidation of alcohols with N-chlorosuccinimide, catalyzed by 2,2,6,6-tetramethyl-1-piperidinyloxy, free radical is reported in Einhorn, J., et al., Journal of Organic Chemistry, Vol. 61, p. 7452 (1996). No suggestion is made that this procedure is applicable to oxidation of 3,3-dimethylbutanol. 3,3-Dimethylbutyraldehyde is an intermediate that is useful in the preparation of the sweetener N-[N-(3,3-dimethylbutyl)-L-α-aspartyl]-L-phenylalanine disclosed in U.S. Patent No. 5,480,668 and U.S. Patent No. 5,510,508. Accordingly, a method for preparing that intermediate which is both economical and specific is highly desired. SUMMARY OF THE INVENTION This invention is directed to a method for preparing 3,3-dimethylbutyraldehyde comprising the step of contacting 3,3-dimethylbutanol with an oxidizing metal oxide for a time and at a temperature sufficient for said metal oxide to react with and thereby oxidize said 3,3-dimethylbutanol to form 3,3-dimethylbutyraldehyde, said metal oxide being selected from the group consisting of copper (II) oxide, vanadium pentoxide, manganese dioxide, nickel (IV) oxide and ruthenium dioxide. The method of this invention provides a commercially practicable means of preparing 3,3-dimethylbutyraldehyde. DETAILED DESCRIPTION OF THE INVENTION In accordance with an embodiment of this invention, oxidation of 3,3-dimethylbutanol to 3,3-dimethylbutyraldehyde is carried out by passing vaporized starting material in an inert carrier gas over an oxidizing metal oxides as defined herein above. The mixture of carrier gas and starting material is typically passed through a metal column packed with the oxidizing metal oxide. The flow rate, reaction temperature, residence time, column length and diameter, concentration of starting material, and column packing material, are interdependent and may be readily determined by one of ordinary skill in the art without undue experimentation. The reaction temperature is generally set to ensure oxidation while substantially precluding over-oxidation. Suitable reaction temperatures for this method are typically in the range from 250°C to 350°C. Preferably, the reaction is carried out at 300°C. Generally, a carrier gas is employed to facilitate transport of the 3,3-dimethylbutanol over an oxidizing metal oxide. It is believed that yield may be optimized by setting the flow rate in conjunction with a selected reaction temperature that does not result in over-oxidation to achieve maximal oxidation of the alcohol to the aldehyde and minimal formation of acid. Suitable carrier gases for the reaction include nitrogen, argon, helium, neon and xenon. The preferred carrier gases are nitrogen and helium, and the most preferred carrier gas is nitrogen. Preferably, the oxygen content in the carrier gas is minimized to avoid over-oxidation. The reaction is conducted at a temperature and for a time sufficient to provide the desired 3,3-dimethylbutyraldehyde. Suitable reaction times will vary depending on the conditions, and are typically in the range from 2 minutes to 8 hours. Preferable reaction times are from 2 minutes to 3 hours, most preferably from 2 minutes to 30 minutes. Oxidizing metal oxide compound suitable for use in this reaction include copper(II) oxide, vanadium pentoxide, manganese dioxide, nickel(IV) oxide, and ruthenium dioxide. Preferred metal oxides are copper(II) oxide and manganese dioxide. The most preferred metal oxide is copper(II) oxide. After reaction, it may be possible to regenerate the spent metal oxide by exposure to oxygen at an elevated temperature, e.g., 500°C. Isolation of the product from this reaction is particularly simple and efficient. The oxidized product, formed in the vapor phase, may be merely condensed from the carrier gas by cooling to form a liquid product of high purity. The 3,3-dimethylbutyraldehyde produced by the oxidation method of this invention is useful as an intermediate in the preparation of the sweetener N-[N-(3,3-dimethylbutyl)-L-α-aspartyl-L-phenylalanine. The example which follows is intended as an illustration of certain preferred embodiments of the invention and no limitation of the invention is implied. EXAMPLE Oxidation of 3,3-Dimethylbutanol by Copper(II) Oxide Vapors of 3,3-Dimethylbutanol were passed along with a flow of nitrogen gas at 30 ml/min. through a stainless steel column [1,83m x 6.35mm (6'x1/4")] packed with copper oxide wire worm (available from Aldrich Chemical Co., Milwaukee, WI) and plugged at each end with glass wool in a gas chromatograph. The injector and detector temperatures were set at 200°C. When the column temperature was set at 250°C a mixture of 70% 3,3-dimethylbutyraldehyde was obtained and 30% of the starting alcohol along with a negligible amount of acid. At a column temperature of 300°C, almost complete oxidation of the alcohol occurred, but 30% of acid was formed along with the 3,3-dimethylbutyraldehyde. The formation of 3,3-dimethylbutyraldehyde was confirmed by capillary GC analysis.

Claims: A method for preparing 3,3-dimethylbutyraldehyde comprising the step of contacting 3,3-dimethylbutanol with an oxidizing metal oxide for a time and at a temperature sufficient for said metal oxide to react with and thereby oxidize said 3,3-dimethylbutanol to form 3,3-dimethylbutyraldehyde, said metal oxide being selected from the group consisting of copper (II) oxide, vanadium pentoxide, manganese dioxide, nickel (IV) oxide and ruthenium dioxide. A method for preparing 3,3-dimethylbutyraldehyde according to claim 1, wherein said 3,3-dimethylbutanol is in a vapor phase. The method of claim 1 or 2, wherein the oxidizing metal oxide is copper(II) oxide. The method of claim 3, wherein the temperature is from 250°C to 350°C. The method of claim 4, wherein the vapor phase comprises 3,3-dimethylbutanol and a carrier gas. The method of claim 5, wherein the carrier gas is selected from the group consisting of nitrogen, argon, helium, neon and xenon. The method of claim 6, wherein said time is from 2 minutes to 8 hours.

Inventors: AGER DAVID J, KATRIZKY ALAN R, PRAKASH INDRA, AGER, DAVID J., KATRIZKY, ALAN R., PRAKASH, INDRA
Applicants: NUTRASWEET CO, THE NUTRASWEET COMPANY
Application year: 1998
Main classification: C07C45
IPC codes: C07C45