JPH0463866B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing 2,3-dimethylpentanal by Grignard reaction. 2,3-Dimethylpentanal is a compound useful as an intermediate in the production of mebutamate, which is used as a medicine such as a hypotensive agent and a sleep-inducing agent. Conventionally, various methods have been proposed for producing 2,3-dimethylpentanal. For example, British Patent No. 1015911 and US Patent No. 3359324 disclose that dicrotylpropional obtained by aldol condensation of propionaldehyde and crotyl alcohol is decrotylated in the liquid phase in the presence of a mineral acid or a Lewis acid. Alcoholized, 1
-Bropenyl crotyl ether was obtained, and this product was subjected to Claisen rearrangement reaction in the gas phase to form 2,3-dimethyl-4-pentenal, which was then hydrogenated to form 2,3-dimethyl-4-pentenal.
- A method for producing dimethylpentanal is described. This method uses a large amount of crotyl alcohol, which is highly toxic and difficult to handle in terms of safety and hygiene, and requires multiple steps with poor yields, such as aldol condensation and Claisen rearrangement reaction at high temperatures. Furthermore, expensive precious metal catalysts are required. Furthermore, in Japanese Patent Application Laid-open No. 127407/1983, 3-methyl-2-pentene, carbon monoxide and hydrogen are
A process is described for preparing 2,3-dimethylpentanal by reaction in the presence of a rhodium complex compound at 150 DEG C. and 200-400 bar. This method has drawbacks such as the need to use an expensive rhodium complex catalyst and the use of oxo gas, which is dangerous to handle. French Patent No. 1377141 discloses that 1-methoxy-2,3-
A method has been proposed in which dimethyl-2-petanol is produced and subsequently hydrolyzed using hydrochloric acid to produce 2,3-dimethylbentanal. In this method, it is necessary to produce the raw material methyl-sec-butyl-ketone from an acetylene compound, which is difficult to obtain industrially. Furthermore, in JP-A-54-125613, methyl secondary butyl ketone and methyl chloroacetate are reacted under an alkali catalyst, and 2,3-epoxy-
Methyl 3,4-dimethylhexanoate was obtained, and this product was converted into 2,3-epoxy-
A method has been proposed for producing 2,3-dimethylpentanal by the so-called Dalzen reaction, in which 3,4-dimethylhexanoic acid is decomposed with p-toluenesulfonic acid. This method has relatively short steps among various methods and is considered to be an economical method, but the raw material methyl secondary butyl ketone is difficult to obtain, and the rearrangement reaction step of chrysidiester to aldehyde compound is difficult to obtain. It has the disadvantage of poor performance. In view of the current situation, the present inventors have prepared a 2,3-dimethylpentanal compound by a simple operation.
The present invention was achieved as a result of intensive research into economical industrial production methods in order to obtain high yield and high purity. That is, the present invention provides formula [1] 2-methylpentanal represented by the general formula [2] CH ₃ MgX' [2] (In the formula, X' represents a chlorine, bromine, or iodine atom.)
A Grignard reagent represented by the general formula [3] CuX ² [3] (wherein X ² represents a chlorine, bromine, or iodine atom.)
The present invention relates to a method for producing 2,3-dimethylpentanal, which is characterized in that the reaction is carried out in the presence of a cuprous halide compound represented by: Generally, when 2-methylpentenal represented by formula [1] and the Grignard reagent represented by formula [2] are simply reacted, the 1,2 addition reaction proceeds preferentially, and the main product is the 1,2 -dimethyl-2-penten-1-ol. The present inventors have discovered a novel fact that the presence of a cuprous halide compound promotes the 1,4 addition reaction in the above reaction, allowing 2,3-dimethylpentanal to be obtained in good yield. be. The 2-methylpentanal compound of the present invention can be easily produced by aldol condensation of propionaldehyde in the presence of caustic potash and simultaneous dehydration. Grignard reagents can also be easily produced by known methods. The cuprous halide compounds used in the present invention include cuprous chloride, cuprous bromide, and cuprous iodide. The reaction of the present invention is preferably carried out in an atmosphere of an inert gas such as nitrogen or helium, in a known solvent commonly used in Grignard reactions such as ether, tetrahydrofuran, toluene, etc., at a temperature ranging from -20°C to room temperature. In order to carry out the method of the present invention smoothly, for example, an ether solution of a methylmagnesium halide compound prepared by a known method is added to cuprous halide in ether at -15°C to room temperature, preferably at -10°C. ～−
Slowly drip under a helium stream at 15℃,
Stir, then cool to -20°C, and add the ether of 2-methylpentenal to the solution from -20°C to -18°C.
Add slowly and stir at ℃. After stirring for an additional hour, the mixture was heated to room temperature and stirred overnight. After the reaction is completed, hydrolysis is performed with a saturated ammonium chloride solution and then with a 3% aqueous hydrochloric acid solution while cooling in an ice bath. This is carried out by separating the organic layer, expelling the solvent, and then purifying it by a known method such as distillation. Further, the molar ratio of cuprous halide to Grignard reagent is suitably in the range of 0.005 to 3.0, and more preferably in the range of 0.5 to 2.0 to obtain good results. Further, the molar ratio of Grignard reagent to 2-methyl-pentenal is suitably in the range of 1.0 to 5.0, but more preferably in the range of 1.2 to 3.0 to obtain good results. As described above, the present invention uses readily available and inexpensive raw materials, does not require special reaction conditions, and can easily separate and purify the target product, etc.
This is an industrially advantageous method for producing 2,3-dimethylbentanal with numerous advantages. Next, the present invention will be explained in more detail with reference to Examples. Example 1 In a flask equipped with a stirrer, thermometer, dropping funnel and helium inlet, 1500 ml of well-dried ether and 49.5 g (0.26 mol) of cuprous iodide were added.
was added and stirred under a helium stream. To this, 200 ml of an ether solution of 43.2 g (0.26 mol) of methylmagnesium iodide, which had been prepared previously, was added.
The mixture was added and stirred at −10° C. to −15° C. over 40 minutes under a helium stream. After adding, cool to -20℃,
75 ml of an ether solution containing 9.8 g (0.1 mol) of 2-methylpentenal was added and stirred at a temperature between -20°C and -18°C over 2.5 hours. After the addition, the mixture was stirred at −20° C. for 1 hour, returned to room temperature, and stirred overnight. The mixture was then hydrolyzed with 150 ml of saturated ammonium chloride solution followed by 150 ml of 3% hydrochloric acid while cooling in an ice bath. Separate the organic layer, extract the aqueous layer with ether, combine the organic layers,
Wash with saturated sodium chloride solution, add sodium sulfate, dry, and distill. First, excess ether is recovered, and then 2,3-dimethylpentanal (colorless transparent liquid) is recovered as a fraction with a boiling point of 138-139℃/760mmHg ) was obtained. The yield was 6.4 g, and the yield was 55.8%. NMR and IR spectra confirmed that it was the desired product. Examples 2 to 4 Experiments were conducted using the same method as in Example 1, with varying amounts of cuprous iodide. The results are shown in Table 1.

[Table] Examples 5 to 8 Experiments were conducted in the same manner as in Example 1, using cuprous bromide instead of cuprous iodide and varying the amount added. The results are shown in Table 2.

[Table] Examples 9 to 12 Experiments were conducted in the same manner as in Example 1, using cuprous chloride instead of cuprous iodide and varying the amount added. The results are shown in Table 3.

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Claims (1)

[Claims] 1 Formula [] 2-methylpentenal represented by the general formula [2] CH ₃ MgX' [2] (wherein X' represents a chlorine, bromine, or iodine atom)
A Grignard reagent represented by the general formula [3] CuX ² [3] (wherein X ² represents a chlorine, bromine, or iodine atom)
1. A method for producing 2,3-dimethylpentanal, which comprises reacting in the presence of a cuprous halide compound represented by: