JPH04103578A - Production of furan derivative - Google Patents

Abstract

PURPOSE:To obtain the title compound useful as a synthetic intermediate for medicines, agricultural chemicals, perfumes, etc., under a mild condition in high yield industrially and advantageously by reacting acetylene ketone with a specific compound in the presence of a palladium compound and an oxirane compound. CONSTITUTION:1 equivalent beta,gamma-acetylene ketone (e.g. 4-undecen-2-one) shown by formula I (R<1> to R<3> are H, alkyl, aryl or R<1> and R<2>, R<1> and R<3> or R<2> and R<3> are bonded to form alkylene) is made to react with 1-20 equivalent compound (e.g. allyl chloride) shown by formula R<4>X (R<4> is alkenyl; X is halogen) in the presence of a palladium compound shown by the formula PdX2 or PdX2L2 (L is nitrile compound, phosphine compound or phosphite compound) and an oxirane compound to give the objective compound shown by formula II.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a process for producing furan derivatives. Furan derivatives are useful as synthetic intermediates for medicines, agricultural chemicals, fragrances, and the like.

Problems to be Solved by the Prior Art and the Invention For example, the following production method is known as a production method for furan derivatives.

(I) A method is known in which a 14-dicarboxylic acid derivative is cyclized by dehydration by heating in an acetic acid medium for a long period of time under relatively high temperature conditions using a strong acid such as sulfuric acid as a catalyst [Nippon Kagaku Complete Edition "New Experimental Chemistry Course"] , Volume 14 (IV), 1888-18
95 pages (1973)].

In this method, the reaction conditions are too harsh, resulting in the formation of many resinous by-products and a low yield.

(2) A method is known in which T-bromo-β-alkoxyketone is thermally cyclized in a nonpolar solvent (Japanese Patent Laid-Open No. 51
-136663).

Although this method produces furan derivatives in good yield, it requires a long reaction time and requires a low temperature of -30°C or lower to synthesize the raw material T-bromo-β-alkoxyketone. However, this method is not suitable for industrial use.

(3) A method of synthesis using a palladium catalyst using acetylene alcohol and allyl halide as raw materials is known [tetrahedron (Tetra
-hedron) Volume 41, 3655-3661 (I
985)3.

In this method, in addition to the furan derivative (target product) having a substituent at the 3-position of the furan ring, a structurally similar furan derivative having no substituent at the 3-position is produced as a by-product, and the separation of the by-product is extremely difficult. It is very difficult.

There is a need for an industrially advantageous method for producing furan derivatives in good yield under mild conditions.

Means for Solving the Problems The present invention provides a method for solving the problems using the general formula (I): represents or R', l!: R2
, R' and R3 or R2 and R3 may be taken together to form an alkylene), and the general formula (■): R'X (n) (wherein, R4 is represents an alkenyl group, and X represents a halogen atom), and a compound represented by the general formula (■): P d X2 (I) (wherein,
): p dX, R2 (IV) (wherein, X has the same meaning as above and L represents a nitrile compound, a phosphine compound or a phosphite compound) and reacts in the presence of a palladium compound and an oxirane compound. The present invention relates to a method for producing a furan derivative represented by the general formula (■): (wherein R'SR'', R3 and R' have the same meanings as above).

The method of the present invention selectively produces furan derivatives under mild conditions, resulting in a high yield.

- The alkyl group of Funato (I) is an alkyl group having 1 to 12 carbon atoms, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl, decyl, dodecyl, and the like. The aryl group is an aryl group having 6 to 12 carbon atoms, and includes, for example, phenyl, trinopenaphthyl, and the like. Examples of alkylene include ethylene, trimethylene, tetramethylene, hexamethylene, methylethylene, phenylethylene, and 2-methyltetraethylene. - The raw material compound represented by Funato (I) is manufactured by Pure and Applied Chemistry, for example.
ry) 55.

1845-1852 (I983),
Examples include 4-undecyn-2-one, 7-decyn-5-one, 2-(I-butynyl)cyclohexanone, 5-phenyl-4-pentyn-2-one, and the like.

Examples of the alkenyl group of general formula (n) include allyl, methallyl, butenyl, and hexenyl. −Sailor (
Examples of the halogen atom in n), (III) and (rV) include a chlorine atom, a bromine atom, and an iodine atom.

Examples of the IJ compound of general formula (TV) include acetonyl, benzonitrile, etc., examples of the phosphine compound include triphenylphine, and examples of the phosphite compound include triethylphosphite.

Examples of the compound represented by -G formula (II) (compound ■) include allyl chloride, allyl bromide, methallyl chloride,
Methallyl bromide, 1-methyl-2-propenyl, 3-90
Examples include rho-1-, ff-n, 3-10-rho-3-methyl-1-butene, 3-chloro-1-hexene, and β, T-
1 for acetylene ketone. -100 equivalents, preferably 1-20 equivalents.

P d X 2 and P d phosphite) palladium, etc., in an amount of 0.001 to 0.2 equivalent, preferably 0.01 to 0.2 equivalent, relative to β, T-acetylene ketone.
1 equivalent is used.

Oxirane compounds are used to prevent damage to hydrogen halide generated during the reaction, such as ethylene oxide, propylene oxide, isobutylene oxide, cyclohexene oxide, cyclopentene oxide, etc. It is used in an amount of 2-100 equivalents, preferably 10-70 equivalents. The reaction is carried out in a suitable solvent at Cl-100°C, preferably 15-70°C.
It takes 5 minutes to 20 hours to complete.

Tetrahydrofuran, acetonitrile, diethyl ether, 12-dichloroethane, methylene chloride, etc. are used as a solvent, but if the oxirane compound used can be used as a solvent, there is no need to add a new solvent.

After the reaction is completed, the reaction mixture is concentrated and then isolated and purified. Isolation and purification is performed, for example, by methods such as distillation, silica gel column chromatography, and recrystallization.

Examples are shown below.

Example 1 500 mg of 4-undecyn-2-one was added to allyl chloride 2
．． After dissolving in 3 g and 10.8 g of isobutylene oxide, 39 μm of dichlorobis(acetonitrile)palladium was added thereto. The mixture was reacted at 25° C. for 3 hours, and then concentrated using an evaporator. The concentrated residue was purified by silica gel column chromatography [silica gel: Wako Gel C-100 (Wako Pure Chemical Industries, Ltd.)] to obtain 3-allyl 2-hexyl-5-methylfuran 434 (yield 70%) as a liquid substance. Ta.

The physicochemical properties of this compound are shown below.

H-NMR (CDCJ!,), δ value (ppm) 0
．． 88(3)1. t, J=6.1Hz).

1.17-1.40 (6H, m), 1.48-1.6
8 (2H, m), 2.21 (3H.

t, J=1.0Hz), 2.50(2)1. t, J=
7.5) 1z), 3.05(dt, J=6, 6.3.
0Hz), 4.96 (I)1. ddt, J=
3.1.10.0.3.0Hz).

5, 04 (IH, dat, J=3.1.16.9.
3.0Hz), 5.78(IN, q, Jl, 0
Hz), 5.89 (IH, ddt, J=10.0.
16.9.6.6Hz)IR(neat) (cm=
), 3080. 1640. 1580. 9
95. 907 High resolution mass spectrum (C,,) 12
．． 0) Calculated value: 206.1669, Actual value: 206.1580 Example 2-4 The same procedure as in Example 1 was carried out except that Compound (1) shown in Table 1 was used instead of allyl chloride in Example 1, and Furan derivatives (liquid substances) shown in Table 1 were produced.

Table 1 The physicochemical properties of the furan derivatives produced in each example are shown below.

Example 2) 1-NMR (CDCj!s), δ value (ppm)
0.88 (3H, t, J=6.1Hz>.

1.15-1.37(6)1. m), 1.43(,6
3 (2tl, m), 1゜66 (3) 1゜s>, 2
．． 18 (3H, s), 2.48 (2fl, t, J=7
,8)1z), 2.96(2B,s), 4.7(I
(Ift, m), 4.74 (I)t, m), 5.4
7(l)I, 5)IR(neat) (CID-')
, 3075.1660.890 High resolution mass spectrum (as C,,82,0) Calculated value: 220.182
5. Actual value: 220.1769 Example 3 +-NMR (CDfJ 3), δ value (ppm) 0.
88 (3H, t, J=6.1Hz) 1.18-1.42
(6H, m), 1.48-1.61 (2H, m),
1.69 (38゜), 2.2CI (3)1. s),
2.50 (I, 2) 1. t, J=7.5Hz>, 2
．． 55 (0.8H, t, J=7.5Hz), 2.
98 (I2H, m), 3.05 (0,8H.

br-d, J=6.0Hz), 5.48(2H, m>
, 5.77 (IH,s), (E/Z mixture; B:
Z=6:4 molar ratio) IR(neat) (am
-'), 3020.1580.970 High resolution mass spectrum (as C,,82,0) Calculated value: 220
．． 1825. Actual value: 220.1753 Example 4' H-NMR (C1]Cf, ), δ value (ppm)
0.87 (3H, t, J=6.8)1z).

1.21 (3H, d, J=7.2flz), 1.2
0-1.37 (6H, m), 1,461.71 (2
H, m), 1.54 (3H, s>, 2.18 (
3)1. s), 2.51 (2H, t, J=7.4H
z), 3.28 (IH, m), 4.96 (If
t, ddd, J=1.9, 1.9, 10.3Hz),
4.99 (ltl, ddd, J=1.9, 1.9, 1
7.2)1z), 5.79(IH,s), 5.
92 (IH, ddd, J=6.4, 10.3.17.2
Hz) IR(neat) (am-'), 3080.
1640. 1,580. 1262°917, 8
00 High resolution mass spectrum (as C15H240) Calculated value: 220.1825. Actual value: 220.1
772 Effects of the Invention Furan derivatives can be industrially advantageously produced in good yield under mild conditions by the method of the present invention.

Claims (1)

[Claims] General formula (I): ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R^1, R^2, and R^3 represent a hydrogen atom, an alkyl group, or an aryl group. or R^1 and R
^2, R^1 and R^3 or R^2 and R^3 may be taken together to form alkylene), β, γ
- Acetylene ketone and a compound represented by general formula (II): R^4X (II) (wherein R^4 represents an alkenyl group and X represents a halogen atom) are combined into general formula (III): PdX_2 ( III) (wherein, X has the same meaning as above) or the general formula (I
V): PdX_2L_2(IV) (wherein, X has the same meaning as above, and L represents a nitrile compound, a phosphine compound, or a phosphite compound) and reacting in the presence of a palladium compound and an oxirane compound. General formula (V) characterized by: ▲There are mathematical formulas, chemical formulas, tables, etc.▼(V) (In the formula, R^1, R^2, R^3 and R^4 have the same meanings as above) A method for producing a furan derivative represented by