JPH01224338A - Method for allylating esters - Google Patents

Abstract

PURPOSE:To carry allylation in safe and simple operation, by reacting esters with an allyl halide in the presence of one or more of lead compounds, tin compounds or Bi compounds and a metal having a greater ionization tendency than that of the above-mentiond metals in a polar solvent. CONSTITUTION:Esters expressed by formula I (R<1> is H, alkyl, alkenyl, alkynyl, aralkyl, aryl, etc.; R is alkyl, alkenyl, aryl, heterocyclic ring, etc.; R<1> and R together form a ring) (e.g., a compound expressed by formula II) are reacted with an allyl halide expressed by formula III (R<2>-R<6> are H, alkyl, aryl, etc.; X is Cl, Br or I) (e.g., a compound expressed by formula IV) in the presence of one or more of lead compounds, tin compounds or bismuth compounds (e.g., lead bromide, tin chloride or tin bromide) and a metal having a greater ionization tendency than that of the above-mentioned metals (e.g., Al, Fe, Ni, Co or Mg, and especially preferably Al) in a polar solvent, such as tetrahydrofuran, to afford the aimed compounds expressed by formula V (e.g., a compound expressed by formula VI).

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a novel allylation method for esters, and more specifically, esters and allyl halides are mixed into lead compounds, tin compounds, or bismuth compounds. By reacting one or more metals in the presence of a metal with a greater tendency to ionize than those metals.

The present invention relates to a method for producing allylated products of esters.

[Conventional technology and problems]

Until now, various metals (for example, lithium, zinc 5 magnesium, boron,
There have been many reports on reactions using allylation of esters (bismuth, silicon, tin, lead, etc.), but there are relatively few reports on the allylation of esters;
Op Organic Chemistry (J, Org,
Chem,)+1963.28.3269. ), method using zinc [Journal of Organic Chemistry (J, Org, Chem,), 1976,
41.550. ) and a method using cerium and mercuric chloride [Journal of Organic Chemistry (J.

Org, Chem, ), 1984.49.3904
．． ) etc. are only known. However, the method using magnesium requires the reaction to be carried out under strictly controlled conditions and is not satisfactory in terms of yield.

Since the filtration method using zinc or cerium and mercuric chloride uses a large amount of zinc or mercury, it poses a pollution problem when carried out on an industrial scale, and is not necessarily satisfactory in terms of yield.

[Purpose of the invention]

An object of the present invention is to provide an industrially advantageous method for producing allylated products of esters in a high yield through safe and simple operations.

[Contents of the invention]

The present invention is based on the general formula % (1) [wherein R1 is hydrogen or a chain or cyclic alkyl,
It represents alkenyl, alkynyl group, aralkyl group, aryl group, heterocyclic group, acyl group, and alkoxycarbonyl group, which may have a substituent. Further, R represents a chain or cyclic alkyl, alkenyl, alkynyl group, aralkyl group, aryl group, or heterocyclic group,
Furthermore, these may have a substituent. R and R may be the same or different, and may be embedded with a carbon chain or a carbon chain containing a heteroatom.An ester represented by ◎] is added to a lead compound in a polar solvent.

In the presence of one or more tin compounds or bismuth compounds and a metal that has a greater ionization tendency than those metals, the compound of the general formula [wherein R and R are hydrogen, a chain or cyclic alkyl group, an aralkyl group, an aryl group, Indicates a heterocyclic group,
They may be the same or different, and may be filled with a carbon chain or a carbon chain containing a heteroatom. Furthermore, they may have substituent groups; and X is chlorine, bromine or iodine. This is a method for the allylation of esters, characterized by the reaction with allyl halides represented by the formula (I), in which one reaction raw material is the esters represented by the general formula (I) and the allyl halide represented by the general formula (II). , general formula [wherein R-R are the same as above. ] The allylated product is obtained.

The present invention is useful as a safe and simple allylation method for various esters, and the resulting allylated products are important compounds as intermediates for synthesizing pharmaceuticals, agricultural chemicals, and the like.

In the present invention, R1 represents hydrogen, a linear or cyclic alkyl, alkenyl, alkynyl group, aralkyl group, aryl group, heterocyclic group, acyl group, or alkoxycarbonyl group, which may have a substituent. Further, R represents a chain or cyclic alkyl, alkenyl, alkynyl group, aralkyl group, aryl group, or heterocyclic group.

Furthermore, these may have a substituent. R1 and R may be the same or different, and may form a ring with a carbon chain or a carbon chain containing a heteroatom.

Preferred chain alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, ter
Examples include C1 to C28 straight chain or branched alkyl groups such as t-butyl, amyl, isoamyl, hexyl, octyl, decyl, and to9decyl.

Preferred cyclic alkyl groups include cyclopropyl and cyclogutyl. Cyclo refers to C3 to C□6 alicyclic groups such as ethyl, cyclohexyl, cyclooctyl, cyclodecyl, and 1-methylcyclopropyl.

2.2-dimethylcyclopropyl, 3-methylcyclobutyl, 1-methylcyclobutyl, 3-ethylcycloR
cyclopentyl, 3-tart-butylcyclopentyl, 4
-inpropylcyclohexyl, 4-tert-
Examples include 03 to C□6 alicyclic groups having at least one C1 to C28 side chain, such as butylcyclohexyl.

Preferred linear alkenyl and alkynyl groups include hahynyl, ethynyl, 1-propenyl, 2-methyl-1-propenyl, flovinyl, 3-butenyl, butynyl, lentenyl, pentagenyl, thintynyl, hexentynyl, hexynyl, Heptenyl.

Heptenyl. Octenyl, octenyl. 9-decenyl,
Examples include 02 to C28 straight chain or branched unsaturated hydrocarbon groups such as prenyl and geranyl. Preferred cyclic alkenyl groups include cyclobutenyl,
Cyclo is nthenyl, cyclohexenyl.

A 03 to C16 alicyclic unsaturated hydrocarbon group such as cycloheptenyl, cyclooctenyl, cyclooctagenyl, etc. can be used.

Specific examples of preferred aralkyl groups include benzyl, phenethyl, phenylbutyl, diphenylmethyl, triphenylmethyl, su7thylmethyl, and naphthylethyl groups.

A preferred aryl group is a phenyl group or a polynuclear aromatic hydrocarbon group, and specific examples of the polynuclear aromatic hydrocarbon group are α-naphthyl and β-naphthyl.

Can you name anthranyl, male-renyl groups, etc.?

Preferred heterocyclic groups include cyclic groups containing gold such as oxygen, nitrogen, and sulfur atoms; specific examples thereof include tetrahydrofuryl, furyl, tetrahydropyranyl, pyranyl, pyrrolyl, and rilenyl. Pyridyl, oxacylyl, morpholinyl.

Tetrahydrothienyl, thienyl, thiadiazolyl, triazolyl, thiazolyl, triazolyl.

Examples include tetrazolyl groups.

A specific example of a preferred acyl group is formyl.

Acetyl, flopionyl, nocleryl, benzoyl.

Examples include toluoyl and furoyl groups.

Preferred alkoxycarbonyl groups include alkoxycarbonyl groups having the same groups as R mentioned above.

In addition, when a carbon chain or a carbon chain containing a heteroatom is formed on a ring (-(OH2)k-, k is 2 to 13 and -0H2
A heteroatom such as oxygen, nitrogen, or sulfur may be substituted for the - group. Specific examples include various lactones.

Examples of the substituent for R1 or H include hydroxyl group and halogen (excluding allyl bond).

C□-C5 straight chain or branched alkyl group, C2-C
6 straight chain or branched unsaturated hydrocarbon group, alkoxycarbonyl group, aralkyl group, amino group, amino group substituted with C1-C5 straight chain or branched alkyl group, protected amino group, nitro group , thiol group, protected thiol group, sulfonic acid group.

It is a protected sulfonic acid group or cyan group, and the number of substituents is one or more, and these may be the same or different. Examples of halogen include fluorine, chlorine, bromine, and iodine. C□-C5 straight chain or branched alkyl groups include methyl, ethyl, propyl, inpropyl, butyl, tert-butyl,
Examples include amyl and isoamyl groups. Examples of C2-C6 straight chain or branched unsaturated hydrocarbon groups include vinyl,
Ethynyl, furo is nil, futhynyl, hexe-A4 etc. t-
.

Examples of alkoxycarbonyl groups include methoxycarbonyl, ethoxycarbonyl, pendyloxycarbonyl groups, etc. Examples of aralkyl groups include benzyl, phenethyl,
Examples include phenylpropyl, phenylbutyl, diphenylmethyl groups, and the like. 01- substituted with amine group
Examples of C5 linear or branched alkyl groups include methyl and ethyl.

Examples include propyl, isopropyl, butyl, tart-butyl, amyl, isoamyl groups, and the like. As a protecting group for the amine group, Theodora D'Avlier-Gree (T
Protective Groups in Org Synthesis by Heodora W. Greene
anic 5yn-1hesis)'' (A Weary Interscience Published EF 7; A
Weiley-IntersciencePubli
cation, 1981), Chapter 7, for protecting amine groups. Protecting groups for thiol groups include methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, and amyl.

Examples include C□-C5 alkyl groups such as isoamyl group, phenyl group, benzyl group, and phenethyl group.

Methyl is the protecting group for the sulfonic acid group.

ethyl, propyl, isopropyl, butyl, tart
-Alkyl groups such as butyl, amyl, isoamyl groups, etc.

Examples include phenyl group, benzyl group, 7enethyl group, and the like.

In the present invention, R-R represents hydrogen, a chain or cyclic alkyl group, an aralkyl group, an aralkyl group, or a heterocyclic group, and may be the same or different, and may be a carbon chain or a heteroatom. A ring may be formed by a carbon chain containing

Furthermore, these may have a substituent. Chain alkyl groups include methyl, ethyl, propyl, and isopropyl.

Mention may be made of C1-C5 groups such as butyl, tart-butyl, amyl and isoamyl groups. Examples of the cyclic alkyl group include 03 to C6 groups such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Aralkyl groups include benzyl, phenethyl, etc., aryl groups include phenyl, α-naphthyl, β-naphthyl, etc., and heterocyclic groups include furyl and pyranyl.

Examples include pyrrolyl, pyridyl, and thienyl groups.

In addition, when forming a ring with a carbon chain or a carbon chain containing a heteroatom (-(GHz)k-), k is 2 to 13 and a heteroatom such as oxygen, nitrogen, or sulfur is substituted for the 10H2- group. It may enter. Further, as the substituent, the above-mentioned substituents can be mentioned.

In the present invention, the allyl halide represented by the general formula (I[) may be used in an amount of 2 equivalents per alkoxycarbonyl group of the ester represented by the general formula (1), but it is preferable to use an excess amount. Based on the results obtained, the preferred range of use is 2 to 6 equivalents per alkoxycarbonyl group of the ester represented by general formula (I).

Next, the solvent used in the present invention is preferably an aprotic polar solvent, such as ethers, polyhaloalkanes, etc., specifically, tetrahydrone.

Dioxane, 1,2-dimethoxyethane, methylene chloride, carbon tetrachloride, etc. are mentioned, and these may be used alone or in a mixture. Particularly preferred are ethers such as tetrahydrofuran and 1,2-dimethoxyethane, and although there are no particular restrictions on the amount of ether used, it is preferable that the amount is such that at least the raw material is completely dissolved. However, even if it is less than that, the reaction will still proceed, so there is no problem in terms of operation.

Preferably, a homogeneous solution is used.

The lead compound used in the present invention has a lead valence of 0.

They may be divalent or tetravalent, and these compounds may be in the form of hydrates. As the lead compound used, a wide variety of conventionally known lead compounds can be used. For example, lead chloride,
Lead halides such as lead bromide and iodide salts, lead nitrate, lead sulfate,
Lead perchlorate, lead borate.

Inorganic acid lead such as lead carbonate and lead phosphate, lead acetate, lead shelaate,
Fatty acid lead such as lead stearate can be used. In the tin compound used in the present invention, the tin valence may be zero, divalent or tetravalent, and these compounds may be in the form of a hydrate. As the tin compound used, a wide variety of conventionally known compounds can be used as well as lead compounds.

In the bismuth compounds used in the present invention, the valence of bismuth may be zero or trivalent, and these compounds may be in the form of hydrates. As the bismuth compound used, a wide variety of conventionally known bismuth compounds can be used. for example,
Bismuth halides such as bismuth chloride and bismuth iodide, and bismuth nitrate.

Bismuth oxide and the like are listed as examples that can be used. These lead, tin, or bismuth compounds can be used alone or in a mixture of two or more. Particularly preferred are lead chloride, lead bromide, tin chloride, and tin bromide.

These are halides such as bismuth chloride and bismuth iodide. The amount of these metal compounds to be used is preferably 1 to 0.5 equivalents of O,OO per equivalent of the ester represented by the general formula (1) used as a starting material;
If the amount is less than 1 equivalent, it will take a long time to complete the reaction, and if it is more than 0.5 equivalent, it will not be economical and side reactions will occur, reducing the yield. Aluminum is a metal that has a greater tendency to ionize than bismuth.

Examples include iron, nickel, cobalt, magnesium, or a mixture thereof, with aluminum being particularly preferred. There are no particular restrictions on the shape of these metals used, and they can be in the form of powder or plate.

It can be used in various shapes such as foil, block, or needle. In addition, the amount used should be 1.3 equivalents per one alkoxycarbonyl group of the ester IWJ represented by the general formula (I), but better results can be obtained by using it in a slightly overstated manner. The preferred range of use is 1.3 to 5 equivalents per alkoxycarbonyl group of the ester represented by general formula (1).

In this method, the presence of the above-mentioned solvent and catalyst is essential, and the object of the present invention cannot be achieved if any of them is absent.

The reaction temperature in the present invention is based on the raw material and lead.

The preferred range varies depending on the amount of tin or bismuth compound used, the solvent, etc., but is usually about 0 to 100°C.

Preferably it is carried out at 0 to 50°C.

〔Example〕

The present invention will be explained in more detail with reference to Examples below.

Example 1 In a round bottom flask, take 185 mmol of lead bromide (0.5 mmol) and finely cut aluminum (<270 m9C10 mmol), and add IQrnl of tetrahydrofuran.

Add 811m9 (5 mmol) of ester (1) and allyl bromide (211,31d (15 mmol),
The reaction was carried out by stirring at ℃ for 1.5 hours. After the reaction is complete.

10 ml of 5% salt was added to the reaction solution, and the mixture was extracted with n-hexane/ether (1:1) solution. The extract was washed with saturated aqueous sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate, and then condensed to 1M to obtain 1.19% of an oil. By purifying this product using a silica gel column, a colorless liquid product (3) was obtained as c+c+om9(
A yield of 98 cm) was obtained.

Compound (3): “H-NMR (CD(δ3)δ1.
78 (s, IH, OH), 2. ．． 16 (d, J
-7,0Hz, 4H, CH2C=C).

2.68 (s, 2 H, CHzAr), 4.78
~6.21 (m.

6H,0H-OH2), 7.11 (s, 5H,
Ar).

Examples 2-4 Lead chloride and tin bromide were used instead of lead bromide in Example 1.

A reaction was carried out using bismuth chloride under the conditions shown in Table 1, and compound (3) was obtained in the yield shown in Table 1.

Example Catalyst Aluminum Reaction time Yield 2
PbC12(0,5) 10 3
963 5nBr2(0,5) 10
3 70 Conditions not listed in Table 1 are:
Same as Example 1.

Example 5 In a round bottom flask, take 185 m9 (0.5 mmol) of lead bromide and <4 osm9 (1 s mmol) of finely cut aluminum, add 10 rnl of tetrahydrofuran, 418541 n9 (5 mmol) of lactone, and bromide. Allyl (2
)1.95m/(2Z5 mmol) and 2
The reaction was performed by stirring for a while. After the reaction is complete, add 5 to 1 reaction solution.
%HCl 10rILl? In addition, to n-reisan/ether (
1:1) solution. The extract was washed with saturated aqueous sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate, and condensed to give 990 mp of an oily substance. This product was purified using a silica gel column to obtain 892 m9 of colorless liquid compound (5) (yield 74%).

Compound (5): IH-NMR (CDC13) δ
0.66-1.86 (m, 17H, OH3, 0H2)
, 2.22(d, J=7.0Hzt 4H,0H
2C-C), 22-60C, 2H, OH).

3.50 (m, IH, CH-0), 4.82~6
．． 22 (m, 6H.

0H-OH2).

Examples 6-12 (1) (If)
Qll) The reaction was carried out under the same conditions as in Example 1 except as shown in Table 2, and the products listed in Table 2 were obtained in high yield and high selectivity.

*4 30 mmol of aluminum Historically used.

Claims (2)

[Claims] (1) General formula R^1-COOR (I) [wherein R^1 is hydrogen, linear or cyclic alkyl, alkenyl, alkynyl group, aralkyl group, aryl group, heterocyclic group, acyl group, alkoxycarbonyl represents a group, which may have a substituent; also, R
represents a chain or cyclic alkyl, alkenyl, alkynyl group, aralkyl group, aryl group, or heterocyclic group, which may have a substituent; R^1 and R may be the same or different; Alternatively, a carbon chain or a carbon chain containing a heteroatom may form a ring. ] in a polar solvent in the presence of one or more of lead compounds, tin compounds, or bismuth compounds and a metal with a greater ionization tendency than those metals. (II) [In the formula, R^2 to R^6 represent hydrogen, a chain or cyclic alkyl group, an aralkyl group, an aryl group, or a heterocyclic group, which may be the same or different, and have a carbon chain Alternatively, a ring may be formed from a carbon chain containing a heteroatom. Furthermore, these may have a substituent. Moreover, X is chlorine, bromine or iodine. A method for allylating esters, which is characterized by reacting with an allyl halide represented by ]. (2) The method for allylating esters according to claim 1, wherein the metal having a greater ionization tendency than lead, tin, or bismuth is any one of aluminum, iron, nickel, cobalt, and magnesium, or a mixture thereof.