JPS6249356B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a cyclic 2-carbon compound consisting of (n+3) carbon atoms.
-alkyl-1-cycloalken-1-yl acetate or 2,(n+3)-dialkyl-1-
Cycloalken-1-yl acetates (1), or 2-alkyl-2-hydroxy-1-cycloalkanones or 2,(n+3)-dialkyl-
The present invention relates to a method for producing oxo fatty acid esters (3) by electrolytically oxidizing 2-hydroxy-1-cycloalkanones (2) and their esters in a protic mixed solvent such as methanol, ethanol, and acetic acid.
In detail, it is shown in formula (1) (R ¹ and R ² represent hydrogen, a linear or branched alkyl group or alkenyl group having 1 to 13 carbon atoms, such as methyl, ethyl, n-propyl, isopropenyl, n-pentyl, or n-hexyl. Also, n is 2~
Indicates 14 integers. 〓 indicates the cleavage position. ) 2-alkyl-1-cycloalken-1-yl acetate or 2,(n+3)-dialkyl-
A compound represented by 1-cycloalken-1-yl acetate or a compound represented by formula (2) (R ¹ and R ² represent hydrogen, a linear or branched alkyl group or alkenyl group having 1 to 13 carbon atoms, such as methyl, ethyl, n-propyl, isopropenyl, n-pentyl, or n-hexyl. X represents hydrogen and an ester group such as an acetyl group or a benzyl group. Also, n represents an integer from 2 to 14. 〓 represents the cleavage position.) 2-Alkyl-2-hydroxy-1-cycloalkanone or 2-alkyl-2-hydroxy-1-cycloalkanone , (n+3)-dialkyl-2
-Hydroxy-1-cycloalkanone and its ester compounds are supported in an electrolytic solvent made mainly of methanol, ethanol, or acetic acid, diluted with an appropriate organic solvent if necessary. Platinum,
By passing a current through a suitable electrode material such as carbon, nickel, or lead under a constant terminal voltage (approximately 10 to 30 V) without particularly regulating the oxidation potential, the general formula (3) can be obtained. Compounds represented by the oxocarboxylic acid esters shown (R ¹ , R ² , R ³ are hydrogen, methyl, ethyl, n-
propyl, isopropenyl, n-pentyl, n-
Indicates straight chain and branched alkyl groups and alkenyl groups having 1 to 13 carbon atoms such as hexyl. Moreover, n represents an integer of 2 to 14. ) This invention relates to a new method for producing chain-like ketoesters. The oxocarboxylic acid ester (3) according to the present invention is a useful compound that can be used as a fragrance base material and as a synthetic intermediate, particularly as a carbon chain extender for terpenes. Furthermore, hydroxycarboxylic acid esters and higher fatty acid esters that are easily derived from oxo fatty acid esters can be used as important synthetic intermediates in the production of various lactones and musk fragrances. The main method for producing compound (3) according to the present invention described in various literatures is to add 1-alkyl-1-cycloalkanol prepared with a cycloalkanone and Grignard reagent to chromic anhydride in acetic acid. oxidation method (L.Fieser and J.
Szmuszkovicz, J. Amer, Chem Soc., 70 ,
3352 (1948)) and the method of oxidizing 2-alkyl-1-cycloalkanol with chromic acid-sulfuric acid (J.
Schaeffer and A.Snoddy, Org.Synth., Coll.
Vol. 4, 19 (1963) is available. In addition, Japp-Klingemann
A method of synthesizing ketoesters by nitrosation with ethyl nitrite under alkaline conditions, followed by acid decomposition (I. Ugi, R. Huisge, and D.
Pawellek, Ann.Chem., 641, 63 (1961)) is known. Furthermore, a method for ozonolysis of cycloalkanone enol ethers, silyl enol ethers, and enol acetates (P.
Grieco, J. Noguez, and Y. Masaki,
Tetrahedron Lett., 4213 (1975), R.Clark and
C.Heathcock, J.Org.Chem., 41, 1396) and m
- Oxidation method with chlorperbenzoic acid (I.
Borowitz, G. Gonis, R. Kelsey, R. Rapp, and
G. Williams, J.Org.Chem., 31, 3020 (1966). In addition, as a special method, 2-alkylidene-1-cycloalkanone is oxidized with hydrogen peroxide under alkaline conditions (G.Guill anton, Bull.
Soc.Chim.Fr., 2871 (1969), J.Aandley, A.
Swigar, and R. Silrerstein, J.Org.Chew., 44,
2954 (1979)). However, all of these reactions require polluting reagents or expensive reactants, and are only applied in special cases, and none of these reactions have been established as general synthetic methods. few. Furthermore, it tends to lack the ability to selectively produce only a single product, which poses many problems as an industrial synthesis method. As a result of intensive research into the development of a new synthetic method to overcome these problems, the present inventors have established a novel and highly selective practical method for producing (3). . The present invention uses 2-alkylcycloalkanone as a starting material and heats it in acetic anhydride containing a small amount of P-toluenesulfonic acid.
- A method of electrolyzing alkyl-1-cycloalken-1-yl acetate (1) to oxidatively cleave the enolic olefin of (1) to lead to a ketoester (3), and a method of converting (1) into monoperphthalate. The 2-alkyl-2-hydroxy-1-cycloalkanone (2) obtained by epoxidation with acid and subsequent treatment with acetic acid is electrolytically oxidized to form a carbon-carbon bond at the α-position of the carbonyl group of (2). It is characterized by causing the oxidative cleavage of (3) and selectively synthesizing (3) as a single product. The present invention has solved the following synthetically difficult problems. In other words, the ring of the 2-alkyl-1-cycloalkanone starting material can be achieved by regioselectively introducing a carbonyl group into any position of the ketoester (3) and elongating the main chain of (3) to any desired length. This is possible by determining the size of In addition, it is possible to stereoselectively introduce a substituent and an optically active carbon into any position of (3).
-Alkyl-1-cycloalkanone can be selected. Furthermore, as mentioned above, the compound (3) containing an unsaturated bond in the molecule, which is difficult to synthesize by the conventional method using an oxidizing agent, can be easily produced by the present invention. Here, we will describe a research example related to the conversion of a cyclic compound into a chain carbonyl compound using an electrolytic reaction related to the present invention, and briefly explain how the present inventors came to discover the present invention. Regarding the electrolytic oxidation of cyclic compounds to lead to chain carbonyl compounds, there have been a few reports on 1,2-glycols (pinacols), but there have been few studies on enolic olefins. few. It has been reported that 1,2-glycols produce corresponding dicarbonyl compounds (R. Michielli and P. Elring, J. Am. Chem. Soc.,
91, 6863 (1969); T. Shono, Y. Matsumara,
T. Hashimoto, K. Hibino, H. Hamaguchi, and
T.Aoki, J.Am.Chem.Soc., 97, 2546 (1975))
However, satisfactory results have not been obtained in terms of yield and selectivity, and it has not been possible to replace the conventional chemical method using metaperiodic acid. Then, instead of 1,2-glycol,
It was found that good results were obtained by the cleavage reaction of 1-methoxy-2-phenylthiocycloalkane by electrolytic oxidation (S. Torii, T. Inokuchi,
and N.Takahasi, J.Drg.Chem., 43, 5020
(1978)). However, the oxidative cleavage reaction of 2-hydroxy-1-cycloalkanones remained unexamined. Regarding the electrolytic oxidation reaction of enolic olefins, it has been described that in the case of enol acetate, 2-hydroxy-1-cycloalkanone or 2-cycloalken-1-one and a mixture thereof are produced ( T.
Shono, Y. Matsumura, and Y. Nakagawa, J.
Am.Chem.Soc., 96, 3532 (1974)), but no double bond cleavage reaction of enol acetate was discovered. Examples of cleavage of enolic olefins by electrolytic reactions have been investigated only in the special case of methyl enol ethers such as 1-methoxy-1-cyclohexene, methyl, and 2-methoxy-1-cyclopentene-1-carboxylate. It has been reported that the corresponding acetal esters and diesters are produced (T. Shono, Y.
Matsumura, H. Hamaguchi, T. Imanishi, and
K.Yoshida, Bull.Chem.Soc.Japan, 51.2179
(1978); S. Torii, H. Tanaka, T. Fukuoka,
and S.Hirai, Bull.Cham.Soc.Japan, 46, 2534
(1973)). Another unique reaction, although the product yield and selectivity are low, is the oxidative cleavage reaction of the adduct of cyclohexanone with sodium sulfite (M. Oyama and M. Ohno, Tefrahedron.
Lett., 5201 (1966)). The production mechanism of each of the lactones of 3-hydroxyhexanoic acid and 4-hydroxyhexanoic acid obtained here is different from the production mechanism of the ketoesters obtained by the present invention. The conditions for producing the oxo fatty acid ester which is the compound (3) of the present invention are detailed below. 2-alkyl-1-cycloalkene, the starting material according to the present invention
1-yl acetate (1) and 2-alkyl-2-
Hydroxy-1-cycloalkanone (2) is a compound that can be easily synthesized from readily available 2-alkyl-1-cycloalkanones, and the compound used in the present invention includes hydrogen as R ¹ and R ² . , methyl, ethyl, n-propyl, isopropyl, isopropenyl, n-butyl, isobutyl, n-pentyl, isoamyl, n-hexyl, isohexyl, n-octyl, n-nonyl, n-decyl, n
- Refers to undecyl, n-dodecyl, etc. Compound
In (2), X represents hydrogen, an acetyl group, a benzoyl group, etc., and n representing the ring size includes 2 to 14. That is, for the enol acetate type compound represented by general formula (1), 2-pentyl-1
-Cyclopenten-1-yl acetate, 2-pentyl-1-cyclohexen-1-yl acetate, 2-methyl-1-cyclohexen-1-yl acetate, 2,6-dimethyl-1-cyclohexen-1-yl acetate, 2 -isopropyl-
5-Methyl-1-cyclohexen-1-yl acetate, 2-isopropenyl-5-methyl-1-
Cyclohexen-1-yl acetate, 2-pentyl-1-cyclohepten-1-yl acetate, 2-methyl-1-cyclododecen-1-yl acetate, 2-methyl-1-cyclotridecen-1-yl acetate, 2- Examples include methyl-1-cyclopentadecen-1-yl acetate. On the other hand, 2-alkyl- represented by general formula (2)
For compounds consisting of 2-hydroxy-1-cycloalkanone and its ester, 2-acetoxy-2-pentyl-1-cyclopentanone, 2-hydroxy-2-pentyl-1-cyclohexanone, 2-acetoxy- 2-methyl-1-cyclohexanone, 2-hydroxy-2,6-dimethyl-
1-cyclohexanone, 2-hydroxy-2-isopropyl-5-methyl-1-cyclohexanone, 2-hydroxy-2-isopropenyl-5-
Methyl-1-cyclohexanone, 2-hydroxy-2-pentyl-1-cycloheptanone, 2-hydroxy-2-methyl-1-cyclododecanone,
Examples include compounds such as 2-hydroxy-1-cyclododecanone and 2-hydroxy-2-methylcyclopentadecanone. These 2-alkyl-
1-Cycloalken-1-yl acetate (1) or 2-alkyl-2hydroxy 1-cycloalkanone (2) or its ester is added to methanol or a mixed solvent of ethanol and acetic acid, if necessary, with ethyl acetate or ether. , tetrahydrofuran, n-hexane, n-pentane, or other solvent to prepare an electrolytic solution, and add a neutral salt such as lithium perchlorate or tetraethylammonium tosylate as a supporting electrolyte to this.
Keto ester ( 3) is an innovative method for selectively generating. The supporting electrolyte used in the electrolytic reaction of the present invention is mainly metal salts such as lithium perchlorate, sodium perchlorate, tetraethylammonium tosylate, tetraethylammonium perchlorate, and tetrabutylammonium tetrafluoroborate, or Tetraammonium salts are used. The amount of these supporting electrolytes to be used is 0.01 to 10 kg per mole of the raw material compound at a concentration of 5 to 20% V/V, preferably 0.1 to 1 kg. Further, as a cosolvent, tertiary butanol, isopropyl alcohol, and isobutyl alcohol are usually used in an amount of 3 to 15% by weight, preferably 2 to 5% by weight, based on methanol or ethanol and acetic acid. Furthermore, if necessary, methyl acetate, ethyl acetate, propyl acetate, ether, tetrahydrofuran, dimethoxyethane, dimethylformamide, n-pentane,
A suitable amount of a low boiling point solvent such as n-hexane, petroleum ether or benzene can be used. The amount used is 0.1 to 21 moles of raw material compound.
It is in the range of 20, preferably 0.5 to 5. In the electrolytic oxidation reaction according to the present invention, ordinary electrodes for electrolysis are used, and among these, it is preferable to use platinum and carbon electrodes. The temperature during the electrolytic reaction is usually in the range of 0 to 70°C, preferably 1 to 35°C. As a method for the electrolytic reaction, a normal current regulation method, a potential regulation method, or a method of performing electrolysis while keeping the terminal voltage constant can be adopted. In either case, the current density is usually 1 to 100 mA/cm ² , preferably 2 to 100 mA/cm 2 .
The electrolytic reaction is carried out by keeping it within the range of 30mA/ ^cm2 ,
The ketoester (3) can be obtained in high yield by applying an electric current of 4 to 20 F/mol. The product can be purified to obtain a pure substance by either distillation, chromatography, or recrystallization. Next, the method of the present invention will be specifically explained using examples. [Example 1] An electrolytic cell is used in which a platinum plate electrode (1.5 x 2 cm ^{2 ) is attached to a 100 ml H-tube reactor in which the anode and cathode cells are separated by a glass diaphragm as shown in FIG. 1} (see attached sheet). Add 20ml of a mixed solution of methanol and acetic acid 10:1 to the anode tank, 16ml to the cathode tank, and 0.5g of lithium perchlorate as a supporting salt to the anode tank, and add 0.5g of lithium perchlorate to the cathode tank as a supporting salt.
Weigh out 0.2g of each. Furthermore, 2-
Add 160 mg (0.76 mmol) of pentyl-1-cyclohexen-1-yl acetate and set the terminal voltage to 20 V.
The electrolytic reaction is carried out at a current value of 3.0 to 12.0 mA/cm ² . When a current of 6.7 F/mol is applied at a reaction temperature of 2 to 3°C, the reaction is stopped, most of the methanol solvent is distilled off under reduced pressure, and the residue is extracted with ether. The extract is washed with brine, and the organic tank is dried over anhydrous sodium sulfate and concentrated to obtain 120 mg of crude product. When this product was developed on a silica gel column with a mixed solvent of hexane-ether 10:1, 117 mg (72%) of methyl 6-oxoundecanoate was obtained. The physical constants and spectral data of this product are as follows. boiling point,
133-135℃/19Torr; Infrared absorption spectrum:
1738, 1710, 1340, 1199, 1171cm ^-1 ; Nuclear magnetic absorption spectrum: δ0.91 (t, 3.J=6H ₃ , CH ₃ ), 1.05
~1.79 (m, 10, CH ₂ ), 2.10 ~ 2.45 (m, 6,
COCH ₂ ), 3.61 (S, 3, OCH ₃ ) ppm. Analytical values: C, 67.46; H, 10.54%. Calcd _{for C12H22O3} : C, 67.26; H, 10.35 _% . [Examples 2 to 5] Examples were carried out in the same manner as in Example 1, except that the electrolyte, the current density, the amount of electricity, and the reaction temperature were changed as shown in Table 1. The results are shown in Table 1. [Example 6] Weighed 19 ml of methanol, 0.5 g of lithium perchlorate, and 2-acetoxy-2-methyl-1-cyclohexanone (85 mg, 0.5 mmol) into the anode chamber of the same electrolytic reaction tank as in Example 1, Weigh 16 ml of methanol and 0.2 g of lithium perchlorine into the cathode chamber.
When the terminal voltage is set to 20V, the current value is 5.3 to 11.3mA/
The electrolytic reaction is carried out at cm ² , and a current of 5.0 F/mol is applied while maintaining the reaction temperature at 20 to 25°C. After the reaction is completed, most of the methanol in the anode chamber is recovered by distillation under reduced pressure, and the residue is extracted with ether. The extract is washed with brine, and the organic layer is dried over anhydrous sodium sulfate and concentrated. When the crude product is purified with a silica gel column, methyl 6-oxohepetanoate is obtained.
65 mg (82%) was obtained. The physical constants and spectral data of this product are as follows. boiling point:
110-112℃/19Torr; Infrared absorption spectrum:
1735 (C=0), 1710 (C=0), 1440, 13720,
1202, 1172cm ^-1 ; Nuclear magnetic absorption spectrum: δ1.35
~1.70 (m, 4, CH ₂ ), 2.00 ~ 2.55 (m, 4,
COCH ₂ ), 2.08 (s, 3, COCH ₃ ), 3.61 (s,
3, OCH ₃ ) ppm, analysis value: C, 60.83; H, 8.93
Calculated value as % C ₈ H ₁₄ O ₃ : C, 60.74; H, 8.92
%. [Examples 7 to 14] The same procedure as in Example 6 was carried out except that the electrolyte substance, current density, quantity of electricity, and reaction temperature were changed as shown in Table 2. The results are shown in Table 2.

【table】

【table】 [Brief explanation of the drawing]

FIG. 1 is a diagram showing an example of a reactor used in the method of the present invention. 1...Thermometer, 2...Platinum electrode, 3...Stirrer bar, 4...Gas outlet.

Claims (1)

[Scope of Claims] 1. A 1-cycloalkene-1-cycloalkene having a 5- to 17-membered ring represented by formula (1) in a solvent mainly containing an organic solvent.
yl acetates, or 5 represented by formula (2)
~17-membered 2-hydroxy-1-cycloalkanones or their esters are electrolytically oxidized to produce carbon-
A method for producing an oxo fatty acid ester represented by formula (3), which comprises cleaving a carbon bond. (R ¹ and R ² represent hydrogen or a linear or branched alkyl group or alkenyl group having 1 to 13 carbon atoms, and n represents an integer of 2 to 14.) (R ¹ and R ² represent hydrogen or a linear or branched alkyl group or alkenyl group having 1 to 13 carbon atoms, X represents hydrogen or an ester residue, and n
represents an integer from 2 to 14. ) (R ¹ , R ² , R ³ represent hydrogen or a linear or branched alkyl group or alkenyl group having 1 to 13 carbon atoms, and n represents an integer of 2 to 14.) 2 of formula (1) If the compound is 2-alkyl-1-cycloalken-1-yl acetate or 2,(n+
3)-Dialkyl-1-cycloalken-1-yl acetate (n represents an integer of 2 to 14). 3 The compound of formula (2) is a 2-alkyl-2-hydroxy-1-cycloalkanone or 2,(n+
3)-Dialkyl-2-hydroxy-1-cycloalkanone (n is an integer of 2 to 14). 4 As a solvent, a mixed solvent consisting of an aliphatic alcohol having 1 to 6 carbon atoms and a fatty acid having 1 to 6 carbon atoms, and if necessary, lower fatty acid esters or a low boiling point solvent such as ether, benzene, hexane, etc. The method according to claim 1, which uses a mixed solvent prepared by adding. 5. The method according to claim 1, wherein the electrode is made of platinum, carbon, nickel, lead, stainless steel, or an electrode that can be substituted for these. 6 Electrolytic reaction in the range of 0 to 70°C, preferably 0 to 70°C
A method according to claim 1, which is carried out at a temperature of 35°C. 7 As the supporting electrolyte, an alkali metal salt can be used, but preferably lithium perchlorate,
Sodium perchlorate, potassium perchlorate, etc. are preferred, and ammonium salts include amines in which the nitrogen atom is substituted with a linear, branched, or cyclic alkyl group having 1 to 6 carbon atoms, or aromatic compounds such as pyridine and aniline. Ammonium salts containing group amines, etc.
Perchloric acid, tetrafluoroboric acid, sulfuric acid as counterions,
2. A method according to claim 1, in which anionic moieties such as nitric acid are preferred and any one or mixture of these supporting electrolytes is used. 8 Preferable 0.5 to 100 mA/ for selectively producing oxo fatty acid ester (3) which is an electrolysis product
Current density in the range of ^cm2 , 2-20 Faraday/mol
and 2-alkyl-1-cycloalken-1-yl acetates (1), or 2
-Alkyl-2-hydroxy-1-cycloalkanone (2) The electrolyte is carried out in an amount of supporting electrolyte in the range of 1 to 20 moles per mole of the compound (2). Method.