JPS5867648A - Preparation of substituted dienecarboxylic ester - Google Patents

Abstract

PURPOSE:To obtain the titled compound, useful as an intermediate for perfumes, etc., and having the E-configuration of the double bond between the 3- and 4- positions, only by treating a lower alkyl ester of chrysanthemum-monocarboxylic acid with a sulfonic acid, e.g. p-toluenesulfonic acid. CONSTITUTION:A lower alkylester of chrysanthemum-monocarboxylic acid expressed by formulaI(R' is lower alkyl), optionally any one of the trans- and cis- isomers or a mixture thereof, is treated with a sulfonic acid, e.g. benzenesulfonic acid or an alkylsulfonic acid, to cleave the bond between the 2- and 3-positions of the three-membered ring selectively and give the aimed substituted dienecarboxylic acid, e.g. ethyl (E)-5-methyl-2-(1-methyl-ethenyl)-3-hexenoate, expressed by formula II (R is a group of formula III or IV).

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is represented by the general formula (I). ) represents a group represented by ] Regarding the method for producing the substituted diene carboxylic acid ester shown in the following, more specifically, in the general formula (1), R' has the same meaning as above. The present invention relates to a method for producing a substituted dienecarboxylic acid ester represented by the general formula (2), which comprises treating a lower alkyl ester of a dilute acid represented by the above formula (2) with a sulfonic acid.

The dienecarboxylic acid ester obtained by the present invention is an important compound as an intermediate in the organic synthetic chemical industry such as pharmaceuticals, agricultural chemicals, and fragrances.

Conventionally, the following method has been known as a method for producing substituted diene carboxylic acid esters represented by the general formula (2).

For example, a method for obtaining substituted dienecarposi acid ethyl ester by heating dilute acid ethyl ester to a temperature of 1r500°C has been reported (Tetrahedron
Letters, 8795 (1965)), and according to the description in this document, the product is 8 of the above general formula (x).
．． The configuration of the double bond at the 4-position is EQ. However, according to the studies of the present inventors, the product obtained by this method is type 2, and is not the substituted dienecarboxylic acid varnish or chloride of the type E device, which is the object of the present invention.

Also, a method for obtaining an alkyl ester of a substituted dienecarboxylic acid by dehydrating and ring-opening an alkyl ester of trans-2,2-dimethyl-3-(1-hydroxy-2-methylpropyl)cyclopropane 1-carboxylic acid. (Special Publication No. 41-19056, Agr, Bio,
flhem,.

2g, 456 (1964), Tetrahedro
n Letters.

2441 (1976)), but in this case, the raw material must be synthesized from trans-caronic acid or isobutyric acid chloride through a complex multistep process, which is not satisfactory for industrial implementation. I can't say it's a method.

Furthermore, although the method differs from the method of the present invention in that a carboxylic acid is used as a raw material, it has been reported that a dienecarboxylic acid is obtained by heating a trans-dilute acid together with pyridine hydrochloride to 210C (J, Chem. 8oo,
Perkin Trans, I, 196r197?
)) According to this, the main components are neutral olefins and lactones.

The yield of the substituted dienecarboxylic acid is extremely low, and it cannot be used as the intermediate of the present invention.

Under these circumstances, the inventors of the present invention have conducted extensive studies on the method for producing the substituted dienecarboxylic acid ester represented by the general formula (I).
By treating the lower alkyl ester of dilute acid with sulfonic acids, selective cleavage of the 2.8-position of the three-membered ring occurs.

The configuration of the double bond at the 8 and 4 positions represented by the general formula (Ri) is E
It was discovered that a substituted diene carboxylic acid ester of the type can be obtained in good yield, and the present invention was completed after various studies were carried out.

The substituted diene carboxylic acid ester represented by the general formula (I) obtained by the method of the present invention can be converted into a d-substituted diene alcohol represented by the formula (m), (w) Yachimata, which is useful as a fragrance by a reduction reaction, or a d-substituted diene alcohol represented by the formula (w) Yachimata. It can lead to the substituted alcohol represented by B8, ie, tetrahydrolavangelol, and is extremely important as an intermediate thereof.

Next, one method of the present invention will be explained in detail.

In carrying out the present invention, the lower alkyl ester of the dilute acid represented by general formula (x), which is a raw material, may be either trans form, cis form, or a mixture thereof.

In addition, as sulfonic acids, aryl or alkyl sulfonic acids such as para-toluenesulfonic acid, benzenesulfonic acid, naphthalenesulfonic acid, methanesulfonic acid, etc. are used, and the amount used is usually determined by the primary chrysanthemum acid ester of the raw material. The amount ranges from 1/100 to 1 mole, preferably from 1/10 to 172 mole.

Although one solvent is not essential in the method of the invention.

In order to allow the reaction to proceed more smoothly, it is preferable to use a solvent that does not essentially inhibit the two-component reaction. Examples of such solvents include halogenated hydrocarbons such as chloroform and dichloroethane, aromatic hydrocarbons such as benzene and toluene, saturated hydrocarbons such as hexane and heptane, and mixed solvents thereof.

The reaction temperature is usually in the range of 80°C to 150°C or the boiling point of the solvent used, preferably in the range of 70°C to 150°C. Also, the reaction time varies depending on the reaction conditions, but
The objective is sufficiently achieved in 10 minutes to 60 hours, and the progress of the reaction can be confirmed by gas chromatography or thin layer chromatography.

Although the reaction can be carried out either under reduced pressure or under increased pressure, the purpose can be easily achieved even under normal pressure.

Furthermore, when carrying out the present invention, it can be carried out in either a batch format or a continuous format. Alternatively, either method of intermittent input can be adopted.

After removing the sulfonic acids used from the reaction solution in which the reaction has been completed as described above by extraction, filtration, washing, etc.
By concentrating the reaction solution.

The desired substituted diene carboxylic acid ester is obtained.

This product can be further purified by means such as distillation and chromatography, if necessary.

Next, the method of the present invention will be explained in more detail with reference to Examples.

Example 1 2.2-dimethyl-3-(2-methyl-1-propenyl)-cyclopropane-1-carboxylic acid ethyl ester (
cis/trans=85/65)20. Of toluene 4
00-, and to this add para-toluenesulfonic acid 5. (l
F was added and the mixture was reacted at 110°C for 6 hours. The reaction solution was washed with water and concentrated to obtain a residue of 15.2f. This is then distilled (b
, p5o~75°C/1.5+wt#) to obtain a pale yellow oil of 12.8f as a distillate. According to its gas chromatograph, this product consists of two main components, the ratio of which is 49.4% for compound (1) and 50.6% for compound (2).
Met.

Next, 10 g of this distillate was rectified (theoretical plate number = 80 plates, reflux ratio: 5o, /i) to give a boiling point of 98 to 100°C/11
Fraction of wmHf4. Of (containing compound (1): 9
+s, +s%) and a fraction 4.1 f with a boiling point of 71 to 78°C/l·2■Hp (content of compound (2): 95.6%)
was obtained separately.

These compounds are identified as compound (1) from the following spectral data.
): (E)-5-methyl-2-(l-methyl-ethynyl)-
Ethyl 8-hexenoate compound (2): (E)-5-methyl-2-(1-methyl-ethylidene)
It was confirmed that it was ethyl -8-hexenoate.

Compound (mu)? “ Infrared absorption spectrum (Na (1t, liquid buifram method)
tar-” 1740, 1650, 90 ONMR
Spectrum ((3DCL@, TM8..200MBz) δ (ppm) 5.54 (B-8, H-4, m) a -8
? (II-9a, s, fl)4.15rH-1
0, q, Jl (1, It = 6, BHz) 8 # 60 (H-fl, d, J*, Hatake = 6.8H
z) 2.86 (H-5, m) 1.76 (H-8,!) 1, 26 (Ii-11, t, J so, tt =
+6,g)lz) 1.0O(H-6,d, Ja, @= 6.13Hz) The configuration of H-8tH-4 was determined by the 60MHz NMR spectrum (
Jll, 4=15,7H21 revealed that it was type 4E.

Compound (2) 9 Infrared absorption spectrum (Na (7t, liquid film method) n
[11) B5.1650, 1680.97ONMRx vector ((] DnZ@ * TMS e 60 MH
1) δppm 6.2 (H-8, d, Jm, *a
=1'1Hz)5.45(H-4,q,Js,aw17
Hz.

Ja, a-7Hz) 4.26 (H-10,q, -Jse, tx=7Hz)2
．． 2 (H-5, m) 1.8 (H-8, H-9, s) i, 5ru-11, t, Jte, 11==78Z)o
,95('H-6.d,Js,a=6Efz)ill
-8,8-4 configuration is Jl, 4=1.7' Hz
Therefore, it was found to be type E.

Example 2 2.2-Dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic acid ethyl ester (cis/trans=!I 6/85'4.1 f to toluene 10-
was added, and 2.1 g of 2-naphthalenesulfonic acid was added thereto, followed by reaction at 110°C for 6 hours. After the completion of the reaction Example 1
After the same post-treatment, concentration and distillation, the boiling point is 60-71.
℃/1.0 mBf fraction 1.96F was obtained.

This one is from that gas chromatograph.

Said compound C1) 4.8%, compound (2) 81.4%.

The composition is 14.8% raw material.

Reference Example 1 Lithium aluminum hydride 2. under nitrogen gas atmosphere.
611 was added to dry ether 10G-, and while stirring at -20°C, a solution of (E)-5-methyl-2-(l-methyl-ethenyl)-8-hexenoic acid ethyl ester 17.91 dissolved in dry erthyl 100- was gradually added dropwise. After the addition was completed, the mixture was stirred at -20°C for 1 hour, and then the reaction solution was gradually added to ice water under a nitrogen atmosphere to deactivate the lithium aluminum hydride, and then acidified with dilute hydrochloric acid. After separating the ether layer, the aqueous layer was extracted with ether, and the ether layers were combined and concentrated to obtain 14.4f of pale yellow oil. Next, this was distilled to give an S point of 75 to 776/6■Hf
A fraction of 12.9f was obtained as an oil.

The distillate is based on the spectrum data below.

(E)-5-methyl-2-(l-metheruethenyl)-
It was confirmed that it was 8-hecan-1-ol.

Infrared absorption spectrum (NaCA, 6-body film)-'
8860.8080.1e14G, 980°W 0O NMR spec) J! / (CC1a', 7M8.20
6M11g)arppm”) 5.54(B-3,
dd, Js, 4=15.1Hz, J, s=*6. l
Hz) 6, 28 ('fT-46aa, JL4shi15.
lHz, Ha, B=8.31Bz) 4.87 (H-8s, s) 4.78 (TT-88, l) 8.68 (H-1, m)? ! , 8B (H-2, m) g, g8 ('H-rs, m) 1.77 (H-10, 8) 1.72 (■-9, s) 0.99. (H-6, d, Jl, @== 6.8Hz
) The configuration of fl-B, H-4 is J m, a = 15.1
Hz, it was found that it was type E.

Reference example 2 Lithium aluminum hydride 6.6 in nitrogen gas atmosphere
11 was suspended in dry ether 200+d, and a mixed solution of 8.02N dry ethanol and 60-d dry ether was gradually added dropwise at 0°C. After the dropwise addition was completed, the solution was stirred at 0°C for 1 hour, cooled to -20°C, and (E), -6
-Methyl-2-(l-methyl-ethylidene)-8,-hexenoic acid, 6.6 ethyl ester 24.9 I dissolved in 75 I of dry ether was gradually added dropwise. After the dropwise addition was completed, the mixture was stirred at -20°C for 7 hours, and then post-treated in the same manner as in Reference Example 1. The organic layer was separated, and the aqueous layer was extracted with ether.

The organic layers' were combined and concentrated to leave a pale yellow oil as a residue.
．． 51/ was obtained. This is distilled and S point is 2℃/2w
Fraction ILIt of HjF ~78°C/1 mm Hl was obtained as an oil. This product was confirmed to be (1)-3-methyl-2-(l-methyl-ethylidene)-8-hecan-l-ol from the following spectrum data.

Infrared absorption spectrum (Na01.Liquid film) 51″
'8450.188! , 1160.10S! ONM
R spectrum (CC, 7M8.eoMHz) δ
(ppm'j 6.211 (kJ-Jl, d,
Jl, 4 = = 16Hz) 5.65' (B-4, dd, J Karasu, 4 = 161 (z
, Ja, 1s=6.5Hz) 4.17rH-1,s) 2.67(El-9,S) 2.8. (H-5, m) 1.88 (H-8, s) 1.80 (Low 8.3) 1.6 (H-6, d, Js, e=7tTz) Reference example 8 For creating a nitrogen gas atmosphere 5 ibaradium-carbon 1. at room temperature. δ
f was suspended in 100% dry ethanol. This is then added with (E)-5-methyl-2-(l-methyl-ethynyl)
-8-hexenoic acid ethyl ester to,oy was added, and the system was vigorously stirred at room temperature for 7 hours while maintaining a hydrogen atmosphere. The reaction was stopped when approximately 5.2 tons of hydrogen gas was absorbed, and the catalyst was removed and concentrated to produce a pale yellow oil of 17.5 #
I got it. This was then distilled to a boiling point of 69-71℃15
Fraction 16.8f of swH1 was obtained as an oil. This product was confirmed to be 2-isoprobyl-6-methyl-hexanoic acid ethyl ester from the spectrum data below.

Crystal 3 NMR spectrum (Cnta, TM8.60M, Htomi) arppm) 4.05 (H-9,q, Js, xo=
'1z)2.1~0.7(■-2,8,4,5,?.

m) 1,25 (H-10,t, J e,to = yH
z) 0.85 (H-@, B-B, d, Jul, @=Jma, @Yo5,5Hz) Qn Then, the ester was prepared in the same manner as Reference H1.

Reduction using 1.95 f of lithium aluminum hydride and 210 f of dry ether gave a pale yellow oil of 18.1
I got g. This was then distilled to give an oil, boiling point 72-bf. From the spectrum data below, this product is 2-isopropyl-5-methyl-hexane-
1-It’s definitely all! 1 was given.

Infrared absorption spectrum (Na(]t, liquid film)'
8880.1460,1880,1865゜0π 05O NMR SHE'y) JL/ (cct4. TM8
．． 60MBz) δ (ppm) 8.48 (M-1, d
)8.07()1-9. br) 2.1~0.6 (H-2,B, 4.5,7゜m) 0.87 ([-6,8,d, Js, .=Jy, 5=4
Hz) Procedural amendment (!l c) November 1933 Yu O Commissioner of the Patent Office 487 Haruki Tono 1, Indication of the case Showa! ;'6 Patent order No. r660”7!;;No. 2,
Name of the invention 1 Flexible diene h/Lit of diene ester; Aff1
3. Relationship with the case of the person making the amendment Patent applicant address 5-15 Kitahama, Higashi-ku, Osaka Name (
209) Sumitomo Chemical Co., Ltd. Representative Sat
Mr. Takeshi 4, Agent address: 5-15 Kitahama, Higashi-ku, Osaka ■Kantake Kobatake Hasashi 1j Iso fp oral procedure amendment (voluntary) November 20, 1980 Haruki Miyajimada, Commissioner of the Patent Office 1 , Indication of the case 1986 Patent Application No. 166075 2 Name of the invention Process for producing substituted diene carboxylic acid ester 3 Relationship with the person making the amendment Patent applicant Address 5-1 Kitahama, Higashi-ku, Osaka Akiji name (209
) Sumitomo Chemical Co., Ltd. 5, Detailed explanation of the invention in the specification subject to amendment 6 Contents of amendment (1) November 20, 1988 Procedural amendment with fi (
Engraved specification) III, page 4, between lines 2 and 8 2.
2-dimethyl-3-(2-methyl-1-propenyl)-
Cyclopropane-1-carboxylic acid ethyl ester (cis/trans concentration 99/1) i! , 1 to 6P. ! -Dichloroethane 47JP was added thereto, concentrated sulfuric acid 0.81 F was added thereto, and the mixture was reacted at 70°C for 1 hour. The reaction solution was washed with water and then concentrated to obtain a residue of 2.8F. 9 This was then distilled (bP5
0-75° C./1.5 mHg) L, a pale yellow oil of 1.9 F was obtained as a distillate.

This product was found to contain the above compound (L
) 52. t, %, compound ■22.3%, raw material 115.
The composition was 7%.

2.2-dimethyl-3-(2-methyl-1-flobenyl)-cyclopropane-1-carboxylic acid ethyl ester (cis/tran X!*9/1) 2 Jt to 1.2-dichloroethane 47.5 F was added, and trifluoromethanesulfonic acid 0.19 F was added thereto and reacted at %21'C for 26 hours. The reaction solution was poured with water and concentrated to obtain a residue of 2.4F. This was then steamed [(bp62-76℃/1.6
MHg') L, 2.2 tons of pale yellow oil was obtained as a distillate. The gas chromatograph showed that the compound σ) was 58.5%.

-A D procedural amendment (voluntary) August 30, 1980 1. Indication of the case 1982 Patent Application No. 166075 2. Name of the invention Process for producing substituted diene carboxylic acid esters 3. Person making the amendment Related Patent Applicant Address 5-1 Kitahama, Higashi-ku, Osaka City Name of Asahi (209
) Representative Hijikata of Sumitomo Chemical Co., Ltd.
Take 4, Agent Address: 5-1 Akiji, 5-1, Kitahama, Higashi-ku, Osaka, 6, Detailed explanation of the invention in the specification subject to amendment 6, Contents of amendment (1) Procedural amendment dated November 20, 1981 (Engraving specification) Page 6, IJ, line 5, ``Trans J is corrected to [Trmnl, J.

(2) The formula (indentation) on page 6 of the same is corrected as follows.

" Goods, ” Insert the following into .

“Example 5 (IR)-2,2 dimethyl-3-(2-methyl-1-
propenyl)-cyclopropane-1-carboxylic acid ethyl ester (cis/trans 119/81)10. Of dichloroethane 190. of was added, and to this was added 1.8-methanesulfonic acid, and the mixture was reacted at 70°C for 2 hours. After washing the reaction solution with water, it was concentrated and distilled under reduced pressure to reduce the boiling point to 62~
A distillate of 9.12 F was obtained at 74° C./1.5 WHf. The above compound (
The composition was 1) 40.2%, the above compound + 2) 89.0%, and raw materials (0.5% cis, 14.8% trans).

This distillate, 8.95 F, was then rectified to a boiling point of 99 to 1
Optically active compound (1) 2.9 f was obtained as a fraction of Ol'C/1.6 MHf.

2O,S; -6-methyl-2-(8-den)-6-methyl-2-( l-methylethynyl)-
Ethyl 8-hexenoate, that is, the optically active compound (L
)'''ts.'' (4) In the 9th line of page 18 of the procedural amendment (written specification) dated May 20, 1980, the phrase ``atmosphereization'' was replaced with ``atmosphere''. correct.

(5) Add and insert the following in the same No. 2 OA.

“Reference example 4 Place platinum oxide in a flask that has been replaced with nitrogen gas. 0.069 and 8 ml of ethanol were charged.

After replacing the mixture with hydrogen gas, the mixture was vigorously stirred at room temperature under the same atmosphere. After 80 minutes, a solution of the optically active compound (110,5f obtained in Example 5) dissolved in ethanol 2TId was added dropwise to the same flask, and the mixture was vigorously stirred at room temperature until absorption of hydrogen gas stopped. After removing it, it is concentrated under reduced pressure and distilled using a Kugelrohr, with a boiling point of 66~
75℃/unit-Hfmer Hf0.44F was obtained. This one has an optical rotation α. +9.27 (neat) of ethyl d-g-isopropyl-6-methyl-heloxanoate, the NMR spectrum was consistent with that of Reference Example 8.

By hydrolyzing a part of the compound to produce the corresponding carboxylic acid, the following optically active alcohol and diastereomeric ester were synthesized, and the optical isomer ratio of the carboxylic acid was analyzed by gas chromatography. Ta.

Reference Example 5 0.2 t of lithium aluminum hydride and 8 d of dried ethyl ether were added to a flask which had been replaced with va gas, and after cooling to -80°C and stirring, the d-2-isopropyl-6 obtained in Reference Example 4 was added. -Methyl-ethyl hexanoate 0.42F
and a solution of 2d of dry ethyl ether was added dropwise. -80~
After stirring at −10° C. for 8 hours, ethyl acetate was added to inactivate the reaction solution, which was then pressurized into ice water. After washing with dilute hydrochloric acid, dilute alkali, and water, sodium sulfate was added to dry. After concentration, it is distilled using a Kugelrohr, and the boiling point is 180-1'86.
A distillate with a temperature of 0.82 fcD at a temperature of 0.82 fc/2QawHr was obtained.

The optical rotation of this object is α20-)-12,89@(nea
t) From the following data, it was confirmed that it was d-tetrahydrolavangelol.

47.0 (d, C-2) 87.2 (based on c-B or 4) 28.5 (d, C-3) 28.0 (d, C-5) 25.5 (E, C- 4 or 8) 22.8 ((1, C-6 or 7 or 9 or 10) 22.
5(q,s)19.8(Q,
# ) 19.8 (q,
# ) Hl (9Q MHz, CDC6
,) δ (PPm) + 8.55 (bm, H-4) around 1.7 (bm, H-5, H-8, H-2) 1.62 (b@, 0
H) 1.25 (bln, H-8, 8-4) 0.89 (d, H-6, 7, 9, to)" or more

Claims (1)

[Claims] First'! The general formula % is characterized in that lower alkyl esters of 11 acids are treated with sulfonic acids. ) represents a group represented by ] A method for producing a substituted diene carboxylic acid ester.