JPS6233220B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to 4,6,8-trimethyldecan-2-one represented by the following formula. 4,6,8-trimethyldecan-2-one provided by the present invention is a 2,4,
It is useful as a synthetic intermediate for 6,8-tetramethyldecanoic acid octadecyl ester. 2, 4,
6,8-Tetramethyldecanoic acid octadecyl ester has a low freezing point and viscosity, and high chemical stability, so it can be used in highly acidic or alkaline cosmetics such as rinse liquids, cold liquids, and oil shampoos, as well as higher fatty acid metal salts. It is ideal for formulating products such as soap. Furthermore, such esters are characterized by high spreadability, and by blending them, creams with good spreadability can be made. 4,6,8-trimethyldecane-2- of the present invention
ion can be prepared by the following steps (1) to (7). (1) A step of reacting 1-halo-2-butene with mesityl oxide and/or isomesityl oxide in the presence of an alkali condensing agent. The reaction product of this step is usually represented by the following formula (3)
-isopropenyl-5-hepten-2-one and 3-isopropylidene represented by the formula ()-
It is a mixture of 5-hepten-2-one. [In the above formula, X is a halogen atom such as chlorine or bromine, and the dotted line indicates that a double bond exists at either of the positions indicated by this.] The above reaction is a reaction between ketones and organic halogens. This can be carried out by a known method of producing a substituted ketone by reacting a compound with a compound in the presence of an alkali condensing agent. The alkaline condensing agent is preferably sodium amide, potassium amide, lithium amide, sodium hydroxide, potassium hydroxide, sodium alcoholate, or potassium alcoholate, and is preferably about equimolar to about 10 times the molar amount relative to 1-halo-2-butene. is used in an equimolar to 4-fold molar amount. (2) A desired step of isomerizing the unsaturated ketone of formula () above to an unsaturated ketone of formula (). This step is performed as necessary. expression() and expression()
The unsaturated ketones of formula (2) can be separated by precision distillation, and the isomerization reaction may be applied to the separated unsaturated ketones of formula (), but if a mixture of both is subjected to the isomerization reaction, The unsaturated ketone of formula (), which has a lower boiling point than the unsaturated ketone of formula (), can be efficiently recovered in high purity by distilling it afterwards or by distilling a mixture of the two under isomerization reaction conditions. It's advantageous. The isomerization reaction is carried out by converting the unsaturated ketone of formula () into an acidic catalyst such as oxalic acid, adipic acid, or phenols, or by using 1,8-diazabicyclo-[5,4,0]
-Undecene-7,1,5-diazabicyclo-
This can be carried out by heating in the presence of an organic amine catalyst such as [4,3,0]-nonene-5, triethylamine, hexamethylenetetramine, etc., or by treatment with an aqueous or alcoholic solution of an alkali metal compound. can. (3) It is represented by the following formula () of the unsaturated ketone of formula (). A step of rearrangement to 4,6-dimethyl-3,7-octadien-2-one. This rearrangement reaction is carried out by converting the ketone of formula () under an inert gas atmosphere at a temperature of 150 to 250℃, preferably 170 to 200℃.
This can be done by heating to ℃. Ketones of formula () usually have cis/trans isomers of about (10 to
20)/(90-80), and since it is difficult to separate the two by distillation, they are subjected to the reaction in the form of a mixture. However, since the cis form is difficult to rearrange to the ketone of formula () due to the 1,3-diaxial effect, the cis form may be isomerized to the trans form, if necessary. (4) A step of hydrogenating 4,6-dimethyl-3,7-octadien-2-one of formula () to obtain an unsaturated ketone of formula () below. This hydrogenation saturates carbon-carbon unsaturated bonds, and can be carried out by a method known per se that is suitable for that purpose. The reaction is generally carried out in the presence of a conventional hydrogenation catalyst such as palladium, platinum, Raney nickel, Raney cobalt, or silica alumina, in a solvent such as a hydrocarbon, alcohol, ether, ketone, ester, or carboxylic acid, at room temperature to 150 °C. It is carried out at ℃. The reaction pressure may be either normal pressure or increased pressure. (5) The saturated ketone of formula () is propargyl bromide,
A step of preparing an acetylenic alcohol represented by the following formula () by reacting with a propargyl halide such as propargyl chloride. The above reaction can be carried out in a dry solvent such as diethyl ether or tetrahydrofuran in the presence of metallic magnesium or metallic aluminum in an amount equal to or greater than the mole of the compound of formula (). Preference is given to reaction in an inert atmosphere. (6) A step of preparing an unsaturated ketone of the following formula () by hydrating and dehydrating the obtained acetylenic alcohol of the formula (). For example, J.Am.Chem.Soc., 60 , 718
(1938), ie, by dehydrating and hydrating the acetylenic alcohol of formula () using sulfuric acid in the presence of an acidic catalyst such as mercuric sulfate in an alcoholic aqueous solution. The dehydration reaction and the hydration reaction may thus be carried out simultaneously or separately. (7) A step of hydrogenating the unsaturated ketone of formula () to 4,6,8-trimethyldecane-2-one. This reaction is 4,6-dimethyl-
It can be carried out in a manner analogous to that already described for the hydrogenation of 3,7-octadien-2-one. 4,6,8-trimethyldecane-2- of the present invention
On subjected this to a cyanohydrination reaction, dehydrated and solvolyzed the product in the presence of an acid, and hydrogenated the resulting unsaturated carboxylic acid of formula () or its ester to form a compound of formula (). 2,
It can be derived from 4,6,8-tetramethyldecanoic acid or its ester. [The dotted line in formula () indicates that a double bond exists at either of the positions indicated by this, and in the formula, R indicates a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms.] In the method described above, the cyanohydrination reaction of 4,6,8-trimethyldecan-2-one can be carried out by a method generally employed in the synthesis of cyanohydrins by the addition reaction of cyanide to a carbonyl compound. The reaction product is therefore a cyanohydrin of the following formula () corresponding to the starting ketone. Applicable cyanides include hydrogen cyanide, cyanides of alkali metals such as sodium and potassium, cyanides of alkaline earth metals such as magnesium, calcium, strontium and barium, and ammonium cyanide, with water-soluble cyanides being particularly preferred. . Potassium cyanide or sodium cyanide are most preferably used in terms of availability or handling. These metal cyanides may be generated in situ in the reaction system. The reaction can be carried out, for example, by the following method. 1 Using a method called the Ultee method, anhydrous hydrogen cyanide is applied to the ketone when it is cold. A trace amount of alkali cyanide is added to accelerate the reaction and increase the yield. Note that the reaction at cold time has the meaning of suppressing the reverse decomposition of cyanohydrin. This method has the advantage that cyanohydrin can be easily isolated and purified. 2 This is a method called the Urech method, in which a ketone is dissolved in an aqueous solution of cyanide, and then an inorganic acid such as sulfuric acid or hydrochloric acid is added. In this case as well, it is preferable to carry out the reaction in the cold. 3 Sodium bisulfite adduct method. This is a method in which cyanide is reacted with a sodium bisulfite adduct of a ketone. Since the reaction is carried out in alkaline conditions, no hydrogen cyanide is generated and there is little danger. 4 Method using ion exchange resin. This method involves reacting a ketone with hydrogen cyanide using a sulfonic acid-based ion exchange resin as a catalyst, and the yield is high. The product of the cyanohydrination reaction can be separated and purified from the reaction mixture, but the product in the reaction mixture can be directly dehydrated and solvolyzed in the presence of an acid to form an unsaturated carboxylic acid of formula () or It is advantageous to convert it into its ester. The acid that acts as a dehydrating agent and a catalyst for solvolysis is suitably a strong inorganic acid such as sulfuric acid, hydrochloric acid, or phosphoric acid, and is usually used in an amount of about equimolar to about 3 times the molar amount of the cyanohydrination reaction product. It will be done. Dehydration and solvolysis reactions can be carried out by heating, but in consideration of controlling the reaction rate and selectivity of the reaction, the initial stage of the reaction is carried out at a relatively low temperature of room temperature to 100°C, followed by heating at a temperature of 100 to 200°C. Preferably, it is carried out at a relatively high temperature. It is assumed that dehydration and solvolysis proceed simultaneously. If this reaction is carried out in an aqueous system, an unsaturated carboxylic acid in which R in formula () is a hydrogen atom will be obtained as a reaction product, and if carried out in the presence of alcohol, a corresponding alcohol ester of the unsaturated carboxylic acid will be obtained. . The alcohol can be a primary, secondary and tertiary alcohol having 1 to 20 carbon atoms, such as methanol, ethanol, propanol, butanol, octanol, cetyl alcohol, octadecyl alcohol. The unsaturated carboxylic acid obtained in the above reaction is esterified into an unsaturated carboxylic ester, and the obtained unsaturated carboxylic ester is converted into another type of unsaturated carboxylic acid by re-esterification or transesterification after hydrolysis. It can also be converted to esters. The resulting unsaturated carboxylic acid of formula () or its ester is then hydrogenated to give 2,4,6,8-tetramethyldecanoic acid of formula () or its ester. This reaction can be carried out in a manner similar to that already described for the hydrogenation of 4,6-dimethyl-3,7-octadien-2-one of formula (). The product can be obtained by esterification, hydrolysis followed by esterification or transesterification, as described for the unsaturated carboxylic acid of formula () or its ester.
It can be derived into octadecyl ester. Next, the present invention will be specifically explained with reference to Examples. Example 1 (1) Production of 3-isopropenyl-5-hepten-2-one. 900 g of 1-chloro-2-butene and 1960 g of mesityl oxide were mixed in a 55% by weight aqueous solution of 600 g of sodium hydroxide in the presence of 20 g of trimethylstearylammonium chloride at room temperature for 2 hours.
The reaction was carried out at ℃ for 1 hour. The reaction solution was poured into water and extracted with ether. The extract layer was washed with water, dried, and then the solvent was distilled off under reduced pressure. According to gas chromatography analysis, the residue was 3-isopropenyl-5.
-Hepten-2-one/3-isopropylidene-
It contained a 5/55 mixture of 5-hepten-2-one. This residue is crudely distilled to a boiling point of 72 to 100℃/
973 g of the above mixture was obtained as a 25 mmHg fraction. By precision distilling the fraction, 3-isopropenyl-5-hepten-2-one has a boiling point of 83-85℃/
As a fraction of 25 mmHg, 3-isopropylidene-
5-hepten-2-one with a boiling point of 85-90℃/25mmH
It could be obtained as a fraction of g. Next, 3-isopropylidene-5-heptene-2- containing 21% 3-isopropenyl-5-hepten-2-one
1,8-diazabicyclo-[5,4,0]-7-undecene 6.2 as an isomerization catalyst
g was charged into a distillation column and distilled under isomerization conditions while maintaining the bottom temperature at 108-112°C, the top temperature at 89-90°C, and the degree of vacuum at 27 mmHg to obtain 3-isopropenyl-5- with a purity of 98.8%. 591 g of hepten-2-one was obtained. The structure of the compound was confirmed by the following method. Infrared absorption spectrum (neat) 1685, 1612, 1350, 1185, 970 (cm ^-1 ) Nuclear magnetic resonance spectrum (δ ⁱⁿ _ppn ^CCl4 ) 1.49, 1.60, 1.68 (each s9H, CH ₃ -) 1.92 (s, 3H,

[Formula]) 2.77 (s, 2H, -CH ₂
--) ca.5.19 (broad s, 2H, --CH=
CH-) Infrared absorption spectrum (neat) 1715, 1642, 1340, 1379, 1355, 1160, 970,
900 (cm ^-1 ) Nuclear magnetic resonance spectrum (δ ⁱⁿ _ppn ^CCl4 ) 1.49 (s, 6H, CH ₃ -) 1.89 (s, 3H

[Formula]) ca.1.90~2.40 (m, 2H, -CH ₂ -) 2.96 (t, 1H

[Formula] J=7Hz) 4.71 (s, 2H〓C=CH ₂ ) ca.5.14, 5.18 (m, 2H, -CH=CH-) Note that 3-isopropenyl-5-heptene-2-
The cis- and trans structures in ON were confirmed by carbon-13 nuclear magnetic resonance spectroscopy (ppm; in CDCl ₃ ).

[Formula] -17.4 -207.3 -126.3 -114.2 -127.9 -142.2 ― 27.8 ― 19.6 ― 61.1 ― 31.6

[Formula] - 12.2 -207.3 -124.9 -114.2 -127.2 -142.2 - 26.0 -19.6 - 61.1 - 31.6 (2) 4,6-dimethyl-3,7-octadiene-
Production of 2-one 400 g of 3-isopropenyl-5-hepten-2-one obtained in (1) above was kept at an oil bath temperature of 200±2℃ and an internal temperature of 188 to 192℃ under a nitrogen atmosphere.11 A rearrangement reaction was carried out by heating for a certain period of time. The reaction solution was subjected to precision distillation as it was, and as a fraction with a boiling point of 60°C/5.0 mmHg or less, the raw material cis/trans mixed 3-isopropenyl-5-hepten-2-one and a part of the product Δ ³ -cis, 247 g of a mixture of 4,6-dimethyl-3,7-octadien-2-one was recovered;
137.6 g of Δ ³ -trans,4,6-dimethyl-3,7-octadien-2-one (purity 94%) was obtained as a fraction with a boiling point of 57±1° C./4.0 mmHg. The structure of this product was confirmed by the following method. Infrared absorption spectrum (neat) 1688, 1615, 1359, 1351, 1213, 1165 (cm ^-1 ) Nuclear magnetic resonance spectrum (δ ⁱⁿ _ppn ^CCl4 ) 0.88, 1.94 (s, 3H, CH ³ -) 2.00, 2.03 (s, 6H, CH ₃ ―,

【formula】) ca.2.00~2.40 (m.3H,

【formula】) 4.80 (d, 1H

[Formula] J=10Hz) 4.83 (d, 1H,

[Formula] J=17Hz) 5.56 (ddd, 1H,

[Formula] J=10Hz, 17Hz, 7Hz) 5.90 (s, 1H,

[Formula]) Carbon-13 nuclear magnetic resonance spectrum (ppm;
inCDCl ₃ ) ―113.6 ―125.6 ―143.7 ―198.7 ― 36.2 ― 20.3 ― 49.0 ― 19.7 ―156.8 ― 32.2 (3) Production of 4,6 dimethyloctan-2-one 4,6 obtained by method (2) above -dimethyl-
Dissolve 75 g of 3,7-octadien-2-one in 300 ml of n-hexane, and add 3 g of 2% palladium-carbon.
Using this as a catalyst, hydrogenation reaction was carried out at a reaction temperature of 50° C. under a hydrogen pressure not exceeding 10 Kg/cm ² . After the reaction, the catalyst was separated and the mother liquor was concentrated under reduced pressure to obtain 74.6 g of a colorless liquid, which was distilled under reduced pressure to a boiling point of 89-90.
72.1 g of 4,6-dimethyloctan-2-one was obtained as a fraction at °C/21 mmHg. The structure of this product was confirmed by the following method. Infrared absorption spectrum (neat) 1718, 1461, 1377, 1360, 1168 (cm ^-1 ) Nuclear magnetic resonance spectrum (δ ⁱⁿ _ppn ^CCl4 ) 0.72, 0.76, 0.78, 0.84 (s, 9H, CH ₃ -) ca.0.80~ 1.40 (m, 6H,

【formula】) 1.97 (s, 3H,

【formula】) ca.1.80~2.35 (m, 2H,

[Formula]) (4) 4,6,8-trimethyldecane-1-yne-
Production of 4-ol: 11 g of metallic magnesium in 150 ml of dry ether
70.0 g of 4,6-dimethyloctan-2-one obtained in (3) above and propargyl bromide were added to a mixture of mercuric chloride and 0.7 g under a nitrogen gas atmosphere.
A solution of 53.6 g of the mixture dissolved in 350 ml of ether was added dropwise under reflux to carry out the reaction. After the addition, the mixture was refluxed for an additional hour, and then the reaction mixture was poured into an acetic acid aqueous solution, extracted with ether, washed with water, and dried. After removing the solvent from the extract layer under reduced pressure, the boiling point was 68.
75.8 g of 4,6,8-trimethyldecane-1-yn-4-ol was obtained as a fraction at ~69°C/0.2 mmHg. The structure of this product was confirmed by the following method. Infrared absorption spectrum 3440, 3300, 2120, 1463, 1378, 1148, 635
(cm ^-1 ) Nuclear magnetic resonance spectrum (δ ⁱⁿ _ppn ^CCl4 ) ca.0.76, 0.83, 0.88, 0.94 (m, 9H, CH ³
--) 1.17 (s, 3H, CH ³ --) ca.1.00~1.80 (m, 8H,

[Formula] ca.1.84, 1.90 (m, 2H, -CH ² -) 2.21, 2.24 (s, 2H, -OH, -C≡CH) (5) 4,6,8-trimethyl-3-decene-2 ―
90 ml of 30% aqueous methanol, 1 g of mercury sulfate and 0.6 g of sulfuric acid were mixed in a 300 ml three-necked flask, and 4,6,8-trimethyldecane-1 obtained in (4) above was added to the mixture under reflux. -in-4-all 58.8g
20 ml of 30% aqueous methanol solution was added dropwise. After dropping, the reaction was carried out under reflux for 24 hours, and gas chromatography (PEG20M, 150℃) analysis confirmed that the raw materials had disappeared and two new peaks appeared at positions with short retention times, and then the reaction was terminated. did. After neutralizing the reaction solution with sodium hydrogen carbonate, methanol was distilled off under reduced pressure, and the residue was extracted with ether, washed with water, and dried. The solution was removed from the ether layer, and the residue was vacuum distilled to obtain 49.6 g of 4,6,8-trimethyl-3- as a fraction with a boiling point of 130-137°C/22 mmHg.
I got Desen-2-on. The structure of this substance was confirmed by mass spectrometry and infrared absorption spectroscopy (neat; 1680,
1612, 1462, 1378, 1215, 1165 cm ^-1 ) and nuclear magnetic resonance spectra. (6) Production of 4,6,8-trimethyldecan-2-one 4,6,8-trimethyl-3-decene-2 obtained by the method (5) above by the same method as in 3 above.
Hydrogenate 45 g of -on using 2% palladium on carbon, and use the same treatment to reduce the boiling point to 74-76℃/0.3mm
43.6 g of 4,6,8-trimethyldecane-2-one was obtained as a Hg fraction. The structure of this substance was confirmed by mass spectrometry [m/e=198, 133, 130,
165, 151, 140], the Mclafferty conversion peak [M] ⁺ -58 = 140, which is unique to ketones, and the infrared absorption spectrum (neat; 1716, 1462,
1378, 1360, 1165 cm ^-1 ) and nuclear magnetic resonance spectra. (7) Production of methyl 2,4,6,8-tetramethyldecanoate 40g of 4,6,8-trimethyldecane-2-one obtained in (6) above was mixed with 11.7g of potassium cyanide in water.
After adding to the solution dissolved in 50 ml, the reaction temperature was increased to 20 ml.
66 g of 30% sulfuric acid was added dropwise while keeping the temperature below °C. Next, potassium carbonate was added to neutralize the mixture, and when the neutralization point was reached, 5 g of potassium carbonate was further added to salt out the product, followed by ether extraction. Ether was distilled off from the extract layer to recover 41.3 g of crude cyanohydrin, which was added little by little to 32 g of concentrated sulfuric acid. At this time, since a considerable amount of heat was generated, the reaction was carried out in a water bath and the temperature was maintained at 60 to 70°C. Next, the reaction temperature was raised to about 150°C to continue the dehydration and hydrolysis reaction, and after further cooling, methanol 100°C was added.
ml was added and the reaction was carried out under reflux for 3 hours. After neutralizing the reaction mixture with sodium hydrogen carbonate, methanol was distilled off under reduced pressure, poured into water, and extracted with ether. Distill the extract layer to boiling point 88-95℃/0.3mm
34.2 g of a mixture of methyl 2-methylene-4,6,8-trimethyldecanoate and methyl 2,4,6,8-tetramethyl-2-decenoate as a Hg fraction.
I got it. The mixture was hydrogenated in the same manner as in (3) above to obtain 33.6 g of methyl 2,4,6,8-tetramethyldecanoate as a fraction with a boiling point of 87-90°C/0.3 mmHg. The structure of this product was confirmed by infrared absorption spectrum, mass spectrometry, and nuclear magnetic resonance spectrum. (8) Production of octadecyl 2,4,6,8-tetramethyldecanoate A mixture of 3 g of methyl 2,4,6,8-tetramethyldecanoate obtained in (7) above and 5 g of octadecyl alcohol The mixture was heated under reflux in 30 ml of toluene in the presence of 0.1 g of potassium oxide, and the transesterification reaction was carried out while constantly distilling off methanol by-produced outside the reaction system. The reaction mixture was poured into water and extracted with ether. The solvent was distilled off from the extracted layer under reduced pressure. The residue was purified by silica gel column chromatography (benzene:hexane = 1:1) to obtain a colorless liquid.
2.3g was obtained. This item is standard 2, 4, 6, 8
- Confirmed by complete agreement of infrared absorption spectrum, mass spectrometry, and nuclear magnetic resonance spectrum with tetramethyldecanoic acid octadecyl ester.

Claims (1)

[Claims] 1 4,6,8-trimethyldecane-2-one.