JPH02240040A - Production of 3-keto-1-alcohol - Google Patents

Abstract

PURPOSE:To obtain the title compound in high yield by carrying out intramolecular or intermolecular aldol type reaction using only beta-ketocarboxylic acid ester having a carbonyl group or the above-mentioned beta-ketocarboxylic acid ester and carbonyl compound as raw materials in the presence of a Pd based catalyst. CONSTITUTION:beta-Ketocarboxylic acid allyl type or propagyl type ester [e.g. 1-(5-oxopentyl)-2-oxocyclopentancarboxylic acid allyl ester] having carbonyl group is subjected to intramolecular aldol type reaction in the presence of a palladium compound catalyst to provide the 3-keto-1-alcohol [e.g. spiro[5,5]decane-7-on-1-ol]. beta-Ketocarboxylic acid allyl type or propagyl type ester is subjected to intermolecular aldol type reaction with a carbonyl compound to provide the 3-keto-1-alcohol. The reaction proceeds without using any acid or base and side reaction with a functional group can be suppressed even when a raw material having the functional group is used.

Description

[Detailed explanation of the invention] (In industrial use field) The present invention is 3- for more details regarding the method of producing 3 -keto -1 -alcohol, aludol -type reaction using β -ketocarboxylate ester and palladium compound catalyst. Keto
The present invention relates to a method for producing 1-alcohol.

(Prior Art) Conventionally, a method for producing 3-keto-1-alcohol by subjecting a carbonyl compound to an aldol-type reaction in the presence of a transition metal compound such as titanium or zirconium has been known (Journal of American Chemical).
Society 1983, 105, P1664-166
5. Tetrahedron Letters. 1980. rainbow. P
3975-3978, etc.). However, this method was not economical because it required a stoichiometric amount of the metal compound. In response, an aldol-type reaction using rhodium compounds was developed. For example, trimethylsilyl enolate of an unsaturated ketone or an unsaturated getone is subjected to an aldol-type reaction with an aldehyde in the presence of a rhodium compound to produce a 3-keto-
1-A method for producing alcohol is known (Chemistry Letters, 1985. P187
5-1878. Journal of Organometallic Chemistry. 1988, 352. P223-238 etc.). According to this method, the reaction proceeds even with a catalytic amount of rhodium compound, so it is an economical method.

However, this method has the problem that the raw materials and catalysts are limited to those mentioned above, and the range of application is narrow.

(Problem to be Solved by the Invention a) As a result of intensive research to develop a new reaction different from these conventional techniques, the present inventors have found that either a β-ketocarboxylic acid ester having a carbonyl group is used alone as a raw material, or Alternatively, they discovered that 3-keto-1-alcohol can be obtained by using a combination of β-ketocarboxylic acid ester and a carbonyl compound and causing an intramolecular or intermolecular aldol-type reaction between them in the presence of a palladium compound catalyst. The present invention was completed based on the findings.

(Means for Solving the Problems) According to the present invention, as a first invention, a ryoryl-type or propargyl-type ester of a β-ketocarboxylic acid having a carbonyl group is converted into an intramolecular aldol-type ester in the presence of a palladium compound catalyst. A second invention provides a method for producing 3-keto-1-alcohol, which is characterized by reacting an allyl or propargyl ester of β-ke1 carboxylic acid with a carbonyl compound in the presence of a palladium compound catalyst. 3 characterized by causing an intermolecular aldol type reaction
- A method for producing keto-1-alcohol is provided.

In the present invention, when performing the first invention, that is, an intramolecular aldol type reaction, an allyl type or brobagyl type ester of β-ketocarboxylic acid having a carbonyl group is used as a raw material. Gagaru β-ketocarboxylic acid ester is represented by the following general formula (1) or (n).

R3 R. - C=0 circles may be chain-like or may form a ring in any combination. ) In formula (1), R1 is bonded to an alkyl group such as a methyl group, ethyl group, probyl group, or bentyl group, or R2 or R to form a cyclobencune ring, a cyclohexane ring,
It refers to an alkylene group forming a ring such as a cyclooctane ring or a cyclododecane ring, and examples include those in which an aromatic ring such as a benzene ring is bonded to these alkylene groups.

Examples of R2 include a hydrogen atom, an alkyl group similar to R+, and an alkylene group.

R3 is an alkylene group such as a methylene group, ethylene group, or bentylene group, or R1 or R! An example is an alkylene group similar to R, which is bonded with R to form a ring.

Examples of R4 include alkylene groups such as methylene group, ethylene group, propylene group, and bentylene group.

The above R and ~4 may have a functional group such as an alkoxycarbonyl group or a cyan group. Examples include the same alkylene groups as R2 or R31, and the same alkylene groups as R1 in General 2 (1) which form a ring by bonding with R2 or R31.

Examples of R8 include the same ones as R2 in general formula (1).

R and l are the same alkyl groups as R in general formula (1) or R
, l or Rt to form a ring and the same alkylene group as above R.

Examples of R4 include the same ones as R4 in general formula (1).

The above RIZ Rt*R3Z R4 has a functional group such as an alkoxycarbonyl group or a cyano group.

These compounds can be synthesized according to conventional methods. For example, taking 1-butanal-2-oxocyclobentanecarboxylic acid allyl ester, Dieckmann condensation of adipic acid diallyl ester yields 2-oxocyclopencunecarboxylic acid. After cyclization to allyl acid, 4-tetrahydropyranyloxybutyl iodo is reacted in the presence of potassium carbonate to introduce a 4-tetrahydrobyranyloxybutyl group into the 1-position of 2-oxocyclopentane,
It is then heated in acetic acid or hydrolyzed in alcohol using an acid catalyst to remove the tetrahydrobilanyl group and form a butanol group, which is then oxidized to a butanal group by a Swern oxidation method or a chromic acid oxidation method. Ru.

On the other hand, in the present invention, the second invention, that is, a carbonyl compound is used as a raw material. Such β-ketocarboxylic acid ester is represented by the following general formula (III>).

(In the formula, Rt, Rs, and Rq may be chain-like or may form a ring in any combination.) In the general formula (I[[), R7 is the same as Rl in the general formula (f) above. The above R bonded to a similar alkyl group, Rf or R9 to form a ring
, refers to alkylene groups similar to , and examples include those in which an aromatic ring such as a benzene ring is bonded to these alkylene groups. R cloud and R9 are hydrogen atoms or alkyl similar to R7,
An example is an alkylene group.

The above R7 to R9 may have a functional group such as an alkoxycarbonyl group or a cyan group.

These compounds may be synthesized by conventional methods; for example, 2-oxocyclopentanecarboxylic acid allyl ester can be synthesized by Dieckmann condensation of adivic acid diallyl ester.

Further, the carbonyl compound has a carbonyl group and is represented by the following general formula (IV).

(In the formula, RI1 is an alkyl group such as a methyl group, ethyl group, propyl group, pentyl group, etc., an alkenyl group such as a vinyl group, allyl group, methallyl group, crotyl group,
Alkynyl groups such as ethynyl group and provinyl group,
A phenyl group or a benzyl group? Examples include aromatic hydrocarbon residues such as ester groups, and groups containing functional groups such as ester groups and ketone groups. Examples of R■ include the same substituent as R+1 or a hydrogen atom. The amount of carbonyl compound used is 1 to 10 per mole of allylic or probagyl ester of β-ketocarboxylic acid.
mol, preferably 1 to 6 mol, more preferably 2 to 4 mol
It is selected as appropriate within the range of moles. In the present invention, a palladium compound catalyst is used in the reaction. Here, the palladium compound catalyst refers to a palladium compound itself or one consisting of a palladium compound and a ligand.

The palladium compound is a palladium salt or complex, and specific examples thereof include tetrakistriphenylphosphinepalladium, tris(dibenzylideneacetone)nipalladium(0), tris(tribenzylideneacetylacetone)tripalladium(0), Palladium acetate, palladium blobionate, palladium butyrate, palladium benzoate, palladium acetylacetonate, palladium nitrate, palladium sulfate, palladium chloride, etc.
Among them, zero-valent palladium compounds are prized. The ligand used is a monodentate or polydentate electron-donating compound having a Group I element of the periodic table, that is, nitrogen, phosphorus, arsenic, or antimony, as a coordination atom, such as pyridine, trimethylamine, etc. , α.
α'-Diviridyl, 1. Nitrogen-containing compounds such as lO-phenanthroline; triethylphosphine, triphenylphosphine, triphenylphosphite, triphenylthiophosphite, α. Examples include phosphorus-containing compounds such as β-ethylene di(diphenyl)phosphine; arsenic-containing compounds such as triethyl arsenic; and antimony-containing compounds such as tribrovir antimony. Among these, phosphorus-containing compounds are preferred in terms of reaction activity, selectivity, economic efficiency, etc.

Although such a ligand is not necessarily essential as a catalyst component, by using an appropriate amount, the stability of the catalyst can be greatly improved. The amount of the ligand used is not necessarily constant depending on the type, but is usually 50 mol or less, preferably 1 to 20 mol, per mol of palladium compound.

The amount of the catalyst to be used in the present invention is appropriately selected, but is usually 0.01 to 10 mol, preferably 0.1 to 10 mol, per 100 mol of the β-ketocarboxylic acid ester or β-ketocarboxylic ester having a carbonyl group as the raw material. It is used in an amount of 8 mol, more preferably 1 to 6 mol.

Although the palladium compound and the ligand may be reacted in advance, the catalyst is usually prepared by bringing each component into contact with each other in a reaction system.

The reaction of the invention is carried out in the presence of a catalyst.

Specific examples include nitriles such as acetonitrile, brobionitrile, and penzonitrile; amides such as dimethylformamide, dimethylacetamide, and N-methylpyrrolidone; and tetrahydrofuran, dioxane, dibutyl ether, and ethylene glycol dimethyl ether. Ethers; acetone,
Carbons such as methyl ethyl ketone; Esters such as ethyl acetate and ethyl propionate; Alcohols such as ethanol, propanol, and ethylene glycol; Frequent sulfoxides such as dimethyl sulfoxide; n-hexane, cyclohexane, benzene, toluene, xylene, etc. Examples include hydrocarbons such as, among others, nitriles and ethers. Moreover, water can also be made to coexist as appropriate.

These solvents are usually used in an amount of 1 to 500 times, preferably 5 to 100 times, the amount of the β-ketocarboxylic acid ester.

Although other reaction conditions can be selected as appropriate, the reaction temperature is usually 0 to 100°C, preferably 10 to 60°C, and the reaction time is usually 1 to 100 hours, preferably 1 to 50 hours.

After the reaction is completed, highly pure 3-keto-l-alcohol can be obtained by separating the target product from the reaction solution according to a conventional method. Separation and purification may be carried out according to conventional methods, such as column chromatography and vacuum distillation.

The 3-keto-1-alcohol obtained in this way is
-Ke1: Varies depending on the type of carboxylic acid ester. For example, when an intramolecular aldol type reaction is carried out using a β-ketocarboxylic acid ester represented by the above-mentioned formula (N), a 3-keto-1-alcohol represented by the following general formula (V) is obtained.

Further, when an intramolecular aldol type reaction is performed using a β-ketocarboxylic acid ester represented by the general formula (n), a 3-keto-1-alcohol represented by the following general formula (Vl) is obtained.

On the other hand, when an intermolecular aldol type reaction is carried out using a β-ketocarboxylic acid ester represented by the general formula (DI), a 3-keto-1-alcohol represented by the following general formula (■) is obtained.

(Each of the above, R l + RIZ Rt +
R3 + R3ZR4, R, ~9 and RI+4 are the same as described above. ) 3-keto-1- thus obtained
Alcohol is effective as a synthetic intermediate for fragrances, terbenes, physiologically active substances, and pharmaceuticals.

(Effects of the Invention) Thus, according to the present invention, 31-keto-1-alcohol can be obtained in high yield by carrying out an aldol-type reaction using raw materials and catalysts that have not been used in the prior art.

In particular, when performing an intramolecular aldol type reaction, the target product can be obtained with high selectivity and high yield, and target products with structures such as bicyclo type and spiro type can be easily synthesized.

Further, since the reaction proceeds without using an acid or a base, even when a raw material having a functional group is used, side reactions to the functional group can be suppressed.

(Example) The present invention will be described in more detail with reference to Examples below. In addition, parts and percentages in the examples are based on weight unless otherwise specified.

Example 1 Under a nitrogen atmosphere, acetonitrile f$t&0.0 containing 0.013 mmol of palladium acetate and 0.027 mmol of triphenylphosphine was prepared. 5ml to 1-(5
-Oxopentyl)-2-Oxopentanecarboxylic acid allyl ester Contains 2 to 4 mmol of acetonitrile? Drop into 0.3ml at night, 2
The mixture was stirred at 0°C for 5 hours.

After the reaction was completed, the mixture was extracted with methylene chloride and purified by silica gel chromatography to obtain subiro (5.5) decan-7-one-1-ol in a yield of 93%.

The erythro form/threo form ratio of this product was analyzed using gas chromatography and was found to be 1/1.

The physical property values are shown below.

Rf=0.61 and 0.51(ethyl ac
etate/hexane=1/1). less po
lar isomer:IR(neat)3500.1
730 cm-';”CNMR (CDCl:+)
δ18.8(t), 19.8(t), 21.0(t
). 27. Ht), 29.0(t). 32.8(t
), 38.5 (t), 51.8 (s) 71.0 (d
), 220(s); HR? IS(ET) for CI
OHl602(M″), calcd 168.1150
+found 168.1173. polar i
somer: IR(r+eat)3470. 172
0cm-': ”C NMR (CDCj2z)619
．． 2(t). 21.2(t), 24.4(t),
26.4(t), 31.6(2xt), 38.9(t
). 55.5 (s), 72.5 (dL 223.8
(s);' +IRMS(El)for C+oLaO
z(M”)+ calcd 168.115Q, Fo
und 168.1148. Example 2 Palladium acetate 0.024 mno+ and triphenylphosphine 0.024 mno+ under nitrogen atmosphere. 1 ml of an acetonitrile solution containing 0 5 mmol of 3-oxo-2-methyl-2-(3-formylbrobyl)butyric acid allyl ester 0
, 0.5 ml of acetonitrile solution containing 44 mmol
and stirred at 20° C. for 29 hours. After the reaction is complete,
When treated in the same manner as in Example 1, 2-acetyl-2-methylcyclopencun-1-ol was obtained with a yield of 82%.

The ratio of erythro form/threo form in this product was 1/5.

Example 3 An experiment was conducted in the same manner as in Example 1 except that the raw materials shown in Table 1 were used and the reaction temperature and reaction time were specified, and the product was obtained in the yield shown in Table 1. Ta.

However, the amounts of palladium acetate and triphenylphosphine used are 5 mo1% and 10 mo1%, respectively, based on the raw materials.
And so.

Example 4 Under a nitrogen atmosphere, 0.017 mmol of tetrakistriphenylphosphine palladium was added to two acetonitrile solutions containing 59 mmol of 1-(5-oxobentyl)-2-oxocyclopencune carboxylic acid allyl ester Q. The mixture was added and stirred at 20°C for 5 hours.

After the reaction was completed, the same treatment as in Example 1 resulted in spiro (
5;5) Decane-7-one-1-ol was obtained with a yield of 85%.

Example 5 In 1 mji of 98% aqueous solution of tetrahydrofuran, raw material β-ketocarboxylic acid ester l mmol hexanal 3 mnol, palladium acetate 0. 0 5 mm
1 and triphenylphosphine 0. 1 mmol was added and stirred at 20°C for a predetermined time. After the reaction was completed, the same treatment as in Example 1 was carried out, and 3-methyl-4-hydroxynonan-2-one was obtained in the yield shown in Table 2.

Table 2 Example 6 2-oxocyclobentanecarboxylic acid allyl ester 1 mmols hexanal 3 in 1 mβ acetonitrile
Add 0.05 mmol of palladium acetate and 1 mmol of triphenylphosphine Q, 20 °C.
The mixture was stirred for 2 hours. After the reaction was completed, the procedure was carried out as in Example 1, and 2-(1'-hydroxyhexyl)cyclobencun-1-one was obtained in a yield of 53%.

Furthermore, 2-(2'-bropenyl)cyclobencun-1-one was obtained as a by-product in a yield of 41%.

Example 7 2-Methylacetoacetic acid-1',1'-dimethylallyl ester 1. 0 8 mmol, hexanal 1. 6 nm
ol, tetrakistriphenylphosphine palladium 0
．． 0.27 mmol was added and stirred at 20°C for 2 hours. After the reaction was completed, the same treatment as in Example 1 was carried out.
Monomethyl-4-hydroxynonan-2-one was obtained with a yield of 50%.

Patent applicant: Zeon Corporation Procedural amendment (self-button) March 29, 1999

Claims (1)

[Scope of Claims] 1. A 3-keto-1-alcohol, which is characterized by subjecting an allyl or propargyl ester of a β-ketocarboxylic acid having a carbonyl group to an intramolecular aldol reaction in the presence of a palladium compound catalyst. Manufacturing method. 2. A method for producing 3-keto-1-alcohol, which comprises subjecting an allyl or propargyl ester of β-ketocarboxylic acid to an intermolecular aldol reaction with a carbonyl compound in the presence of a palladium compound catalyst.