JPH04288035A - Production of alpha,beta-unsaturated ketone - Google Patents

Abstract

PURPOSE:To produce an alpha,beta-unsaturated ketone useful as an intermediate for pharmaceuticals, agricultural chemicals, perfumes, etc., in an industrialy advantageous manner in high yield at a low cost under mild and neutral condition. CONSTITUTION:The objective compound of formula II can be produced at a low cost by reacting a compound of formula I (R<1> and R<2> are H, alkyl or aryl; R<1> and R<2> may together form an alkylene bond; R<3> is alkyl or aryl; R<4> is alkyl) in the presence of 0.001-0.2 equivalent (preferably 0.01-0.1 equivalent) (based on the compound of formula I) of a compound of formula MAuX4 (M is alkali metal; X is halogen) or formula AuX3 in 2-100 equivalent (preferably 10-50 equivalent) (based on the compound of formula I) of a hydrated solvent at 0-100 deg.C (preferably 30-80 deg.C). The solvent is preferably an alcohol such as methanol, ethanol, 2-propanol, 1-butanol and t-butanol and the water-content of the solvent is preferably 1-20%.

Description

Description: [0001] The present invention relates to a method for producing α,β-unsaturated ketones useful as synthetic intermediates for pharmaceuticals, agricultural chemicals, fragrances, and the like. [Prior art] Using propargyl alcohol as a raw material, α
, as a method for producing β-unsaturated ketones, 1,1,3
A method of rearranging triphenyl-2-propyn-1-ol to 1,3,3-triphenyl-2-propen-1-one under acidic sulfuric acid is known (Chemistry Dictionary, Vol. 8).
Volume, 832 pages, Kyoritsu Shuppan, 1962). This method is
As sulfuric acid is used as the acid, severe acidic conditions are required, and the only applicable substrates are those with aryl substitution, so the scope of application is narrow. SUMMARY OF THE INVENTION An object of the present invention is to provide an industrially advantageous method for producing α,β-unsaturated ketones in a high yield under mild and neutral conditions. [Means for Solving the Problems] The present invention provides the general formula (I) (
In the formula, R1 and R2 represent a hydrogen atom, an alkyl group or an aryl group, or R1 and R2 may be taken together to form an alkylene bond. R3 represents an alkyl group or an aryl group, R4 represents an alkyl group),
General formula (II) MAuX4 (II) (wherein M represents an alkali metal and X represents a halogen atom) or general formula (III) AuX3 (III) (
The reaction is carried out in a water-containing solvent in the presence of a gold compound represented by the formula (IV) (wherein, R1, R2 and R3 are as defined above). Provided is a method for producing an α,β-unsaturated ketone represented by The present invention will be explained in detail below. General formula (
In I), the alkyl group is an alkyl group having 1 to 12 carbon atoms, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl, decyl, dodecyl, etc., and the aryl group is an alkyl group having 6 to 12 carbon atoms. Examples of the aryl group include phenyl, tolyl, xylyl, and naphthyl, and examples of the alkylene group include ethylene, trimethylene, tetramethylene, pentamethylene, phenylethylene, and 2-methyltetramethylene. In the general formula (II), examples of the alkali metal include lithium, sodium, potassium, etc., and examples of the halogen atom include chlorine, bromine, iodine, etc. As the propargyl alkyl ether represented by the general formula (I), for example, 4-methoxy-2-
Nonine, 7-methoxy-5-dodecine, 3-methoxy-
1-phenyl-1-pentyne, 3-methoxy-1-phenyl-1-octyne, 2-methoxy-2-methyl-3-
Decyne, 4-methoxy-4-methyl-5-dodecyne, 1
-Methoxy-2-octyne, 1-methoxy-2-dodecine, 1-methoxy-1-(1-propynyl)cyclohexane, 1-methoxy-1-(1-octynyl)cyclohexane, etc., and general synthesis methods thereof. For example,
[Synthesis of Acetylens, Allens and Cumulens
Allenes, Allenes and Cumule
nes), L. Brandsma (L. Brandsma)
), H. D. Verkr (H.D. Verkr)
uijsse) co-author, pp. 231-234, El Sephire Scientific Publishing Co., Ltd. (El
sevier Scientific Publish
ing Company), 1981]. Examples of the compound represented by the general formula (II) include lithium chloroaurate, sodium chloroaurate, potassium chloroaurate, sodium bromaurate, sodium iodoaurate, etc. ) Examples of the compound represented by gold chloride, gold bromide, gold iodide, etc.
equivalents, preferably 0.01-0.1 equivalents. These compounds may be used in the form of hydrates. Any solvent can be used as long as it is highly compatible with water, but alcohols such as methanol, ethanol, 2-propanol, 1-butanol, and t-butanol are preferred. These solvents are used in an amount of 2 to 100 equivalents based on propargyl alkyl ether,
Preferably, it is used in the range of 10-50 equivalents. or,
These solvents are used mixed with water during the reaction, and the water content at that time is preferably 1-20%. The reaction is carried out at 0-100°C, preferably 30-80°C, and is completed in 1-20 hours. After the reaction is completed, the target product is isolated and purified. Isolation and purification is carried out by conventional methods such as silica gel chromatography and distillation. EXAMPLES The physical and chemical properties of the compounds obtained in the examples were measured using the following equipment. (a) Measured using NMR Varian XL-200 (200MHz). Tetramethylsilane was used as an internal standard. (b) IR Measured using JASCO IR-810 manufactured by JASCO Corporation. The sample was sandwiched between rock salt plates without dilution.
Prepared in the form of a thin film. Example 1 770 mg (5 mmol) of 4-methoxy-2-nonine was dissolved in a mixture of 10 ml of methanol and 1 ml of water. To this was added 100 mg of sodium chloraurate dihydrate (0
．． After adding 25 mmol), the mixture was heated under reflux for 2 hours. After the resulting reaction mixture was cooled to room temperature, methanol was distilled off using an evaporator. The residue was dissolved in diethyl ether (30 ml) and diluted with saturated brine for 25 minutes.
% aqueous ammonia (30 ml). The obtained diethyl ether solution was dried using anhydrous sodium sulfate, filtered, and then concentrated. The concentrated residue was subjected to silica gel column chromatography [Silica gel: Silica gel 60 [manufactured by Nacalai Tesque Co., Ltd.]]
By purification, trans-3-nonen-2-one (525 mg, yield 75%) was obtained as a liquid substance. The physicochemical properties of this compound are shown below. 1H-NMR (CDCl3) δ (ppm): 0
．． 89 (3H, t, J=6.8Hz), 1.2
4-1.55 (6H, m), 2.22 (2H,
ddt, J=1.6, 6.2, 6.2Hz),
2.23 (3H, s), 6.02 (1H, d
t, J=16.0, 1.6Hz), 6.83 (1
H, dt, J = 16.0, 7.0Hz) 00
13] IR (neat) cm-1: 3050,
3000, 1698, 1675, 1624, 1
360, 1254, 980] Elemental analysis (
(as C9H16O): Example 2-5 In Example 1, the propargyl alkyl ether shown in Table 1 was used instead of 4-methoxy-2-nonine, and the reaction was carried out for the reaction time shown in Table 1. Except for this, the same procedure as in Example 1 was carried out to obtain α,β-unsaturated ketones (liquid substances) shown in Table 1. [0016]
Table 1


Propargyl Example Alkyl Ace Reaction Time Product
Yield Tel (amount used: mg) (
time) (obtained amount: mg)
(%) 2 7-methoxy-5-
2 trans-6-dodecene 7
9 Dodecine
-5-on
(784)
(575) 3 3-methoxy-1- 10 trans-1-phenyl 21 phenyl-1-
Pentyne-3-penten-1-one (870)
(168) 4
2-methoxy-2-10
2-methyl-2-decene- 70
Methyl-3-dodecine 4-
On (728)
(470)
5 1-methoxy-(1-10
1-Cyclohexylidene-30
propynyl) cyclohe 2-
Propanone xane (760)
(207)
The physical and chemical properties of the compounds obtained in each example are shown below. Compound 1H-NMR of Example 2 (CDCl3) δ (ppm): 0
．． 90 (3H, t, J=6.7Hz), 0.9
3 (2H, t, J=7.2Hz), 1.29-1
．． 67 (10H, m), 2.23 (2H, d
dt, J = 1.6, 7.3, 7.3Hz),
2.53 (2H, t, J = 7.5Hz), 6.
10 (1H, dt, J = 16.0, 1.6H
z), 6.83 (1H, dt, J = 1 6.
0, 7.3Hz)0019]IR (neat)
cm-1: 3050, 1699, 1676, 1
631, 1378, 1192, 983 0020
] Elemental analysis (as C12H22O): 1H-NMR of the compound of Example 3 (CDCl3) δ (ppm): 1
．． 16 (3H, t, J=7.2Hz), 2.3
6 (2H, ddq, J = 1.6, 6.2, 7
．． 2Hz), 6.87 (1H, dt, J = 1
6.0, 1.6Hz), 7.12 (1H, dt
, J = 16.0, 6.2Hz), 7.50 (
3H, m), 7.95 (2H, m) 0022
]IR (neat) cm-1: 3050, 16
71, 1648, 1621, 1283, 121
5, 990, 972, 691 [0023] Elemental analysis (as C11H12O): [0024] Compound 1H-NMR of Example 4 (CDCl3) δ (ppm): 0
．． 88 (3H, t, J=6.7Hz), 1.2
2-1.71 (8H, m), 1.89 (3H,
d, J=2.0Hz), 2.14 (3H, d,
J = 2.0Hz), 2.40 (2H, t,
J=7.4Hz), 6.08 (1H, septi
, J=2.0Hz)0025]IR (neat)
cm-1: 1689, 1622, 1378,
1132, 730 0026] Elemental analysis (as C11H20O): [0
Compound 1H-NMR of Example 5 (CDCl3) δ (ppm): 1
．． 52-1.75 (6H, m), 2.12 (2
H, m), 2.13 (3H, s), 2.81
(2H, br-t, J=6.0Hz), 6.02
(1H, s) IR (neat) c
m-1: 3000, 1687, 1620, 11
73, 960 0029 Elemental analysis (as C9H14O): 00
Example 6-8 In Example 1, propargyl alkyl ether and gold chloride shown in Table 2 were used in place of 4-methoxy-2-nonine and sodium chloraurate, and the reaction time was as shown in Table 2. The same procedure as in Example 1 was carried out except for the reaction.
An α,β-unsaturated ketone (liquid substance) shown in Table 2 was obtained. [0031]
Table 2


Propargyl Examples Alkyl ether Reaction time Products
Yield Tel (amount used: mg) (
time) (obtained amount: mg)
(%) 6 4-methoxy-2-
2 trans-6-dodecene 7
6 Nonin
-2-on
(462)
(319) 7 7-methoxy-5- 2 trans-6-
dodecene 77 dodecene
-5
-on (470)
(336)
8 2-methoxy-2-10
2-methyl-2-decene- 72
Methyl-3-dodecine
4-on (437)
(290)
[0032] According to the method of the present invention, α,β-unsaturated ketones can be industrially advantageously produced in good yield under mild and neutral conditions. The method of the invention has a wider range of applications than known methods.

Claims (1)

[Claims] Claim 1: General formula (I) (wherein R1 and R2 represent a hydrogen atom, an alkyl group, or an aryl group, or R1 and R2 may be taken together to form an alkylene bond. R3 represents an alkyl group or an aryl group, and R4 represents an alkyl group), the propargyl alkyl ether represented by the general formula (II) MAu
(II) (wherein M represents an alkali metal and X represents a halogen atom) or general formula (III) AuX3 (III) (
The reaction is carried out in a water-containing solvent in the presence of a gold compound represented by the formula (IV) (wherein, R1, R2 and R3 are as defined above). A method for producing an α,β-unsaturated ketone represented by