MXPA00000415A - Method for preparing 3,3-dimethylbutyraldehyde - Google Patents

Abstract

A method is disclosed for preparing 3,3-dimethylbutyraldehyde by using silica gel to isomerize 3, 3-dimethyl-1,2-epoxybutane, which in turn may be prepared by oxidation of dimethylbutene. Also disclosed is a method for oxidizing dimethylbutene with dimethyldioxirane to form 3,3-dimethyl-1, 2-epoxybutane. The methods provide an economical means of preparing 3,3-dimethylbutyraldehyde.

Description

METHOD FOR PREPARING 3,3-PIMETILBUTIRALDEHIDO BACKGROUND OF THE INVENTION FIELD OF THE INVENTION This invention relates to a method for preparing 3,3-dimethylbutyraldehyde very economically by regioselective isomerization of vaporized 1,2-epoxy-3,3-dimethylbutane in the presence of silica gel. The invention also relates to a method for preparing 1,2-epoxy-3,3-dimethylbutane from 3,3-dimethylbutene by oxidation with dimethyldioxirane.

BACKGROUND OF THE RELATED ART The rearrangement of epoxides in carbonyl compounds has been known for a long time. See, for example, Smith, J. G. Synthesis, 629 (1984). For example, epoxies have been converted to aldehydes in a regiospecific manner through the use of lithium perchlorate in dimethyl ether (LPDE). Sudha, R., and others, J. Org. Chem. 61, 1877 (1996). However, this reference published that the acyclic terminal olefin epoxides, such as 1,2-epoxyhexane did not react in the LPDE medium.

Another example is provided in Lemini, C, and others, Synth. Commun. 25, 2695 (1995) showing the transformation of arylmonosubstituted oxiranes and 2-aryl, 2-methyl disubstituted to aldehydes using silica gel as a reagent in a solution under very light conditions. The Patent of E.U.A. No. 2,660,609 refers to the shading of alkylene oxides such as ethylene oxide, 1,2-propylene oxide or 1,2-butylene oxide for aldehyde in the vapor phase using silica gel or fuller earth in fluidized form. However, these references do not describe or suggest the regiospecific somerization of 3,3-dimethylbutyraldehyde with silica gel. In addition, the latter reference also describes the formation of ketones and alcohols together with the aldehydes in the isomerization of 1,2-epoxyalkanes with silica. The rearrangement produces different products (aldehydes, ketones or alcohols) depending on the reactants, reaction conditions and substituents (review in the isomerization of epoxides to aldehydes: JG, Synthesis 1984, 637; Rickborn, B. in Comprehensive Organic Synthesis, ed. BM Trost, I. Fleming and G. Pattenden, Pergamon, Oxford, 1991, vol.3, p.733-775). In this way, the behavior of the tert-butyl group is not predictable for straight or branched chain alkanes. For example, the rearrangement of 1,2-epoxyalkanes (House, H., J. Amer. Chem. Soc. 1955, 77, 5083, wherein R is alkyl group) with boron trifluoride etherate produces only aldehyde and non-ketone, whereas when R is a tert-butyl group, a mixture of products or the starting material is recovered (unpublished results). Only basic ketone, pinacolone, is formed with LiBr basic alumina (unpublished results). The effect of alkyl groups on the rearrangement of 1,2-epoxyalkanes using LiBr-HMPA can also be observed in Rickborn and Gerkin (Rickbom, B. and Gerkin, RM, J. Am. Chem. Soc. 1971, 93, 1693) . Therefore, the effective conditions for n-alkyl or certain branched chain alkyl groups are not necessarily effective for the tert-butyl group. 3,3-dimethylbutyraldehyde is a useful intermediate in the preparation of the sweetener N- [N- (3,3-dimethylbutyl) -L-a-aspartyl] -L-phenylalanine described in the Patent of E.Ü.A. No. 5,480,668 and in the U.S. Patent. No. 5,510,508. Also, a method for preparing said intermediate that is both economic and specific is desired.

BRIEF DESCRIPTION OF THE INVENTION This invention relates to a method for preparing 3,3-dimethylbutyraldehyde comprising the step of isomerizing vaporized 3,3-dimethyl-1,2-epoxybutane in the presence of silica gel. The invention also relates to the method described above further comprising the step of oxidizing 3,3-dimethylbutene to form 3,3-dimethyl-1,2-epoxybutane before the isomerization step. Another embodiment of the invention relates to a method for preparing 3,3-dimethyl-1,2-epoxybutane by treating 3,3-dimethylbutene with dimethyldioxirane.

The method of the invention allows the preparation of 3,3-dimethylbutyraldehyde in a reproducible and highly economical manner so that the use of the aldehyde in the preparation of a sweetener derived from aspartame can be practiced commercially.

DETAILED DESCRIPTION OF THE INVENTION The method of the invention provides a means for the regiospecific isomerization of vaporized 3,3-dimethyl-1,2-epoxybutane to form 3,3-dimethylbutyraldehyde by the use of silica gel. Some examples of silica gels include Merck silica gels, grade 60, grade 7754, grade 10180 and grade 10184 available from Aldrich Chemical Co., Milwaukee, Wisconsin. Typically, silica gels have a mesh size of about 70 to about 230. The preparation of 3,3-dimethylbutyraldehyde comprises the mixture of 3,3-dimethyl-1,2-epoxybutane with silica gel over a period of time and at a pressure and temperature sufficient to form 3,3-dimethylbutyraldehyde in the vapor phase. Generally, the reaction temperature is between 200 ° C and 400 ° C and the reaction pressure, which will be dependent on the upper space of the reaction vessel, is normally high, for example, around 35.15 kg / cm2 at 59.75 kg / cm2, preferably around 45.69 to 52.72 kg / cm2. The reaction time is usually maintained between 2 and about 72 hours.

The reaction is generally carried out by mixing 1,2-epoxy-3,3-dimethylbutane with silica gel in a reaction vessel. Useful reaction vessels are known to those skilled in the art and can be of different sizes depending on the production needs. Generally the weight ratio of silica gel to 3,3-dimethyl-1,2-epoxybutane will be in the range of about 10: 1 to about 1: 1, preferably about 5: 1 to about 3: 1. Normally the reaction mixture will be flushed with an inert gas, such as argon, followed by heating and stirring at the temperature and pressure desired to vaporize the 1,2-epoxy-3,3-dimethylbutane. In a preferred embodiment of the invention, the method includes the step of preparing 3,3-dimethyl-1,2-epoxybutane by oxidation of dimethylbutene before the isomerization step. This two-step synthesis is illustrated below.

Isomerization -CH2CHO Siice Oxidant Gel The oxidation step is normally achieved by exposing 3,3-dimethylbutene to an oxidizing agent. Preferred oxidizing agents include dimethyldioxirane, oxygen, peroxide, NaOCI and percents. Exemplary percents include without limiting perbenzoic acid, metachlorobenzoic acid, monoperoxyphthalic acid, trifluoroperacetic acid, magnesium monoperoxyphthalate, peracetic acid. Other oxidizing reagents include peroxides such as, for example, hydrogen peroxide, t-butylhydroperoxide and dibenzoylperoxide. A particularly preferred oxidizing agent is dimethyldioxirane. Generally, the oxidizing agent is present in an amount of between 1.0 to about 1.05 percent by molar weight of dimethylbutene. Typically, the oxidation step begins at a temperature between -5 ° C and about 0 ° C and at atmospheric pressure and is conducted at about 22-25 ° C with a reaction time of about 24 hours. Another embodiment of the invention comprises a method for forming 3,3-dimethyl-1,2-epoxybutane through oxidation of 3,3-dimethylbutene with dimethyldioxirane. Oxidation of 3,3-dimethylbutene with dimethyldioxirane can preferably be achieved through the in situ generation of dimethyldioxirane by the reaction of acetone with "Oxone" (potassium peroxymonosulfate available from Du Pont de Nemours &Company, Wilmington, Delaware) . In such a case the Oxone and acetone are generally mixed in a molar ratio of from about 1: 5 to about 1: 9 in combination with 3,3-dimethylbutene. The following examples are presented as an illustration of certain preferred embodiments of the invention, and are not intended to be limited for any reason.

EXAMPLE 1 Synthesis of 1,2-epoxy-3,3-dimethylbutane Acetone Oxona ac.

A solution of potassium monopersulfate (Oxona, 4.08 g, 16.1 mmol) and EDTA (ca. 200 mg) dissolved in distilled water (100 mL) was added to a two-phase 0.60 M KH2P? 4 / Na2HP? 4 buffer solution. (200 mL, pH 7.5), CH2Cl2 (300 mL), acetone (8.3 mL, 0.113 mol), 18-crown-6 (1, 4.7, 10.13, 16-hexaoxacyclooctadene) which was used as a phase transfer catalyst, (2.5 g, 9.46 mmoles), and 3,3-dimethylbutene (1.29 mL, 0.84 g, 10 mmoles) . All solutions were maintained at 0 ° C before their addition; The resulting mixture was stirred at 0 ° C for one hour, then allowed to warm to room temperature, and stirred for 22 hours. After this time, the reaction mixture was transferred in a dividing funnel, and the organic layer was separated. The aqueous phase was extracted three times with CH2Cl2 (150 mL each). The combined CH2Cl2 solutions were dried over MgSO 4, filtered, concentrated by distillation to a small volume (50 to 65 mL), analyzed and quantified by gas chromatography (GC).

Yield of 75 to 77.1% (751.5 to 772.7 mg, 7.50 to 7.71 mmoles). 1 H NMR (CDCl 3): 0.86 (9H t-Bu), 2.55 (2H, CH 2), 2.66 (1H, CH); 13 C-NMR (CDCl 3): 24.7, 29.743.2, 59.2.

EXAMPLE 2 Repositioning epoxide using silica as a catalyst In a cold Parr reactor, 1,2-epoxy-3,3-dimethylbutane was placed (10 g, 99.8 mmol). The reactor was placed in a dry ice bath and 40 g of silica was added slowly. The reactor was closed and flushed at 3.51 kg / cm2 twice with argon. Then it warmed up and stirred carefully. As the temperature increased, the pressure in the reactor also increased. The maximum pressure was calculated at 51.67 kg / cm2 and the optimum temperature between 200 to 400 ° C. At a temperature of 300 to 310 ° C, the pressure reached 49.21 kg / cm2-49.91 kg / cm2 and the reactor was kept under these conditions during the remaining reaction time. Different reaction times were investigated: 1 day and 3 days. The conversion was analyzed by GC. To achieve this, at the desired time, the stirring was stopped and the reactor was placed on dry ice until the pressure dropped to 0.70 kg / cm2 - 3.51 kg / cm2. The gas valve was opened and the pressure released (no 3,3-dimethylbutyraldehyde was detected in this gas). Aliquots of silica were taken, suspended in methanol, and the methanol extract was analyzed by GC. After one day, under these conditions, a conversion of 71% was observed. When the reaction time was 3 days instead of one, the percent conversion of the redisposition increased to an average of 94% (84.4, 91.5, 100, 100%).

The formation of 3,3-dimethylbutyraldehyde was further confirmed by converting it to the 2,4-dinitrophenyl hydrazine derivative. The spectroscopic analysis of the fusion point and the Nuclear Magnetic Resonance (NMR) coincided with the one described in the literature (Puterbaugh, WH and Newman, MS, J. Am. Chem. Soc., 79, 3469 (1957) Other variations and modifications of the invention will be apparent to those skilled in the art.The invention should not be limited except as to what is intended. set forth in the following claims.

Claims (14)

NOVELTY OF THE INVENTION CLAIMS

1. A method for preparing 3,3-dimethylbutyraldehyde comprising the step of isomerizing vaporized 3,3-dimethyl-1,2-epoxybutane in the presence of silica gel at an effective temperature and pressure to form said 3,3-dimethylbutyraldehyde.

2. A method according to claim 1, further characterized in that said silica gel is a silica gel grade 60.

3. A method according to claim 2, further characterized in that said silica gel has a size of mesh in the scale of about 70 to about 230.

4. A method according to claim 1, further characterized in that said isomerization step is carried out at a temperature of about 200 ° C to about 400 ° C.

5. A method according to claim 4, further characterized in that the isomerization step is carried out at a pressure of about 35.15 kg / cm2 to about 59.75 kg / cm2.

6. A method according to claim 1, further characterized in that said step of shading is carried out for a time of about 2 to about 72 hours.

7. - A method for preparing 3,3-dimethylbutyraldehyde comprising the steps of: (a) oxidizing dimethylbutene to form 3,3-dimethyl-1,2-epoxybutane; and (b) vaporizing and isomerizing said 3,3-dimethyl-1,2-epoxybutane in the presence of silica gel at an effective temperature and pressure to form said 3,3-dimethylbutyraldehyde.

8. A method according to claim 7, further characterized in that said oxidation step is carried out in the presence of oxygen, peroxide, dimethyldioxirane, NaOCI or a peracid.

9. A method according to claim 7, further characterized in that said isomerization step is carried out at a temperature of about 200 ° C to about 400 ° C.

10. A method according to claim 9, further characterized in that the isomerization step is carried out at a pressure of about 35.15 kg / cm2 to about 59.75 kg / cm2.

11. A method according to claim 10, further characterized in that said step of shading is performed for a time of about 2 hours to about 72 hours.

12. A method according to claim 8, further characterized in that said oxidation step is initiated at a temperature of about -5 ° C to about 0 ° C and is carried out at a temperature in the range of 22 ° C to about 25 ° C.

13. - A method according to claim 12, further characterized in that said oxidation step is carried out for 24 hours.

14. A method according to claim 12, further characterized in that said oxidation step is performed for about 24 hours.