JPH01224332A - Allylation of acetal - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a novel allylation method of acetal, and more specifically, the present invention relates to a novel allylation method of acetal, and more specifically, acetal and allyl halide are mixed with a lead compound, a tin compound, a bismuth compound, or a titanium compound. The present invention relates to a method for producing an allylated product by reacting one or more of them with a metal having a greater ionization tendency than those metals.

[Conventional technology and problems]

Up until now, acetal allylation methods include a method in which a metal allylating agent (for example, allyl silicon) is prepared in advance and then reacted with the acetal in the presence of a Lewis acid [Chemistry Letters (Chem, Lett, 1976, 941).
, Chem, Lett, 1978.575.
Tetrahedron Letters
Lett,).

1981, 37.3899.0ham, Lett.
1985°977, etc.] are known. However, all of these methods require complicated reaction operations and require the reaction to be carried out at low temperatures (for example, -78°C), so there are problems in implementing them on an industrial scale, and the yield is low. is not necessarily satisfactory. In addition, parvia (k), which reacts acetal and allyl halide in one step,
Allylation of acetals by a larbier-type reaction has not been known so far.

[Purpose of the invention]

The object of the present invention is to avoid the drawbacks of the above-mentioned conventional methods.

The object of the present invention is to provide an industrially advantageous method for producing an acetal allylated product in a high yield in one step using a safe and simple operation.

[Contents of the invention]

The present invention is based on the general formula [wherein R and R represent hydrogen or a chain or cyclic alkyl, alkenyl, alkynyl group, or aralkyl group, aryl group, or heterocyclic group, and may be the same or different; A ring may be formed from a carbon chain containing a carbon atom or a heteroatom.

Furthermore, these may have a substituent;

R is a chain or cyclic alkyl or alkenyl.

It represents an alkynyl group, an acyl group, an aralkyl group, an aryl group, or a heterocyclic group, which may be the same or different, and may form a ring with a carbon chain or a carbon chain containing a heteroatom tt. Furthermore, these may have a substituent. ] in a polar solvent, a lead compound,
In the presence of one or more of tin compounds, bismuth compounds, or titanium compounds and a compound having a higher ionization tendency than those metals, the general formula [wherein R-R is hydrogen, a chain or cyclic alkyl group, or an aralkyl group, Indicates an aryl group, a heterocyclic group,
They may be the same or different, and a carbon chain or a carbon chain containing a heteroatom may form a ring. Furthermore, they may have substituents; and X is chlorine, bromine or iodine. This is an acetal allylation method characterized by reacting with an allyl halide represented by Formula [wherein R1-R7 and R are the same as above. ] is obtained.

INDUSTRIAL APPLICABILITY The present invention is useful as a safe and simple allylation method for acetals obtained naturally or synthetically, and the resulting allylated products are useful as pharmaceuticals.

It is a compound that requires 1 iL as an intermediate for synthesizing agricultural chemicals and the like.

In the present invention, R and R represent hydrogen, a chain or cyclic alkyl, alkenyl, alkynyl group, an aralkyl group, an aryl group, or a #J bare ring group, and may be the same or different, and may be a carbon chain or A ring may be formed by a carbon chain containing a heteroatom. Furthermore, these may have a substituent. Further, R is a chain or cyclic alkyl.

Indicates an alkenyl, alkynyl group, an acyl group, an aralkyl group, an aryl group, or a heterocyclic group, which may be the same or different and form a ring with a carbon chain or a carbon chain containing a heteroatom. You can leave it there.

Furthermore, these may have a substituent.

Preferred chain alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, ter
Examples include straight chain or branched alkyl groups of C to C28 such as t-butyl, amyl, isoamyl, hexyl, octyl, decyl, and to3-decyl.

Preferred cyclic alkyl groups include C3 to C16 alicyclic groups such as cyclopropyl, cyclobutyl, cyclonityl, cyclohexyl, cyclooctyl, and cyclodecyl, and 1-methylcyclopropyl.

2.2-dimethylcyclopropyl, 3-methylcyclostyl, 1-methylcyclointhyl, 3-ethylcyclohentyl, 3-tert-butylcyclopentyl, 4-
Examples include 03 to C16 alicyclic groups having at least one C□ to C28 side chain, such as inpropylcyclohexyl and 4-tert-butylcyclohexyl.

Preferred linear alkenyl and alkynyl groups include tejavinyl, ethynyl, 1-proynyl, 2-methyl-1-proynyl, flobinyl, 3-butenyl, phthynyl, phthynyl, pentagenyl, pentynyl, hexenyl, hexynyl, and heptenyl.

Heptynyl, octenyl, octenyl. 9-decenyl,
Examples include 02-c28 linear or branched unsaturated hydrocarbon groups such as prenyl and geranyl. Preferred cyclic alkenyl groups include cyclobutenyl,
03 such as cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclooctagenyl, etc.
~C Engineering. Examples include alicyclic unsaturated hydrocarbon groups.

Specific examples of preferred acyl groups include formyl, acetyl, flopionyl, valeryl, and benzoyl.

Examples include toluoyl and furoyl groups.

Specific examples of preferred aralkyl groups include (endyl, 7enethyl, phenylbutyl, diphenylmethyl, triphenylmethyl, naphthylmethyl, naphthylethyl, etc.).

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-su7tyl and β-su7tyl.

Examples include anthranyl and pyrenyl groups.

Preferred heterocyclic groups include cyclic groups containing oxygen, nitrogen, sulfur atoms, etc. Specific examples thereof include tetrahydrofuryl, furyl, tetrahydro90♂ranyl, pyranyl, pyrrolyl, hyharidinyl, pyridyl, oxasilyl, and morpholinyl.

Tetrahuman 90thienyl, thienyl, thiadiazolyl,
Triazolyl, thiazolyl, triazolyl.

Examples include a tetrazolyl group.

In addition, when forming a ring with a carbon chain or a carbon chain containing a heteroatom (-(CH2)k-), k is 2 to 13 and -C
;Hetero atoms such as oxygen, nitrogen, and sulfur may be substituted for the H2 group.

Examples of substituents for R, R, or R include hydroxyl groups, seeded hydroxyl groups (excluding those with acetal bonds), acyloxy groups, halogens, and C1-C5 straight-chain or branched alkyl groups.

02-C6 straight chain or branched unsaturated hydrocarbon group, aralkyl group, amino group, amino group substituted with C-C5 straight chain or branched alkyl group, protected amine group,
Nitro group, protected thiol group.

A carboxyl group, a protected carboxyl group, a sulfonic acid group, a protected sulfonic acid group, and a cyanide group, and the number of substituents is one or more, and these may be the same or different. . Examples of protecting groups for hydroxyl groups include methyl, ethyl, propyl, isopropyl,
Lower alkyl groups such as butyl groups, or thio r-la double green (Theodora W, Green
6 Protective Groups in Organic Φ Synthesis by e)
ps in Organic Synt-hesis)
'' (A Weiley Interscience Publication'/vin; A Weiley Interscience Publication)
encePublication, 1981), all of the hydroxyl groups described in Chapter 2 can be mentioned. Specific examples of the acyloxy group include formyloxy, acetyloxy, propionyloxy, valeryloxy, benzoyloxy, toluoyloxy, and furoyloxy groups. Examples of chlorogens include fluorine, chlorine, bromine, and iodine. Examples of C0 to C5 straight chain or branched alkyl groups include methyl, ethyl, propyl, and isopropyl.

Examples include butyl, tart-butyl, amyl, and isoamyl groups. Examples of straight chain or branched unsaturated hydrocarbon groups of 02 to C6 include vinyl, ethynyl, zolobal, butenyl, hexenyl, and examples of 4-e, 7-ralkyl groups include benzyl, phenethyl, and phenylpropyl. , phenyl phther, diphenylmethyl group and the like. Examples of C1-C5 straight chain or branched alkyl groups substituted with amine groups include methyl, ethyl, propyl, and isopropyl.

Examples include butyl, tert-butyl, amyl, isoamyl groups, and the like. Examples of protecting groups for amino groups include the protecting groups for amine groups described in Chapter 7 of the same book. Methyl is a protective group for thiol groups.

Ethyl, propyl, isozolobyl, butyl, tart-
Examples include C-C5 alkyl groups such as butyl, amyl, and isoamyl groups, phenyl groups, benzyl groups, and phenethyl groups. Examples of carboxyl group-protecting groups include the carboxyl group-protecting groups described in Chapter 5 of the same book. As a protecting group for sulfonic acid group, methyl,
ethyl, propyl, isopropyl, butyl, tart
- Alkyl groups such as butyl, amyl, isoamyl groups, phenyl groups.

Aralkyl groups such as benzyl and phenethyl groups can be mentioned.

In the present invention, R and R represent water, a chain or cyclic alkyl group, an aralkyl group, an aryl group, or a heterocyclic group, which may be the same or different, and are carbon chains or carbon atoms containing heteroatoms. The chain may form a ring. Furthermore, these may have a substituent. Chain alkyl groups include methyl, ethyl, propyl, and isopropyl.

Examples include C1 to C50 groups such as 7'ti/l/, tert-butyl, amyl, and isoamyl groups. Examples of cyclic alkyl groups include cyclozolopyl and cyclobutyl.

C3 to C60 groups such as cyclopentyl and cyclohexyl can be mentioned. Aralkyl groups include benzyl, phenethyl groups, etc., and aryl groups include phenyl, phenyl, etc.
Examples of heterocyclic groups include .alpha.-naphthyl and .beta.-naphthyl groups, and examples of heterocyclic groups include furyl, pyranyl, pyrrolyl, 2'lysyl, and thienyl groups. In addition, when a ring is formed by a carbon chain or a carbon chain containing a heteroatom, C-(CH2)k-, l, k
is 2 to 13, and a hetero atom such as oxygen, nitrogen, or sulfur may be substituted for the 10H2- group. Examples of the substituent include the above-mentioned substituent groups.

In the present invention, the allyl halide represented by the general formula (It) may be used in an amount of 1 equivalent relative to the acetal represented by the general formula (1) when obtaining an allylated product, and 2 equivalents when obtaining a double allylated product. However, better results can be obtained when used in excess, and the preferred range of use is the general formula (I
) 1 to 4 equivalents to obtain an allylated product, 2 equivalents to obtain a double allylated product to the acetal represented by
~10 equivalents.

Next, the solvent used in the present invention is preferably an aprotic polar solvent, such as 1) ethers, 2) IJ sils, polyhaloalkanes, etc. Specific examples include tetrahydrofuran, :)oxane, 1,2-dimethoxyethane, acetonitrile, propionitrile, methylene chloride, and carbon tetrachloride.

These may be used alone or in mixtures. Moreover, water may be contained as necessary. Particularly preferred are ethers such as tetrahydrofuran and 1,2-dimethoxyethane, and the amount used is not particularly limited, but it is preferable that the amount is such that at least the raw material is completely dissolved. However, there is no particular problem since the reaction will proceed even if the amount is less than that, but from the viewpoint of operation, it is preferable to use a homogeneous solution.

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

It 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 lead iodide, lead nitrate, lead sulfate,
Lead persalt, lead borate.

Inorganic acid lead such as lead carbonate and lead phosphate, lead acetate, lead oxalate,
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 to be used, a wide variety of conventionally known compounds can be used as well as the ld lead compound.

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. A wide range of conventionally known bismuth compounds can be used. For example,
Hismuth halides such as bismuth chloride and bismuth iodide, and bismuth nitrate.

Bismuth oxide and the like are listed as examples that can be used. In addition, the titanium compound used in the present invention has a titanium valence of 0.
It may be trivalent, trivalent or tetravalent.

Moreover, these compounds may be in the form of hydrates. As the titanium compound used, a wide variety of conventionally known titanium compounds can be used. For example, titanium trichloride.

Titanium halides such as titanium tetrachloride and titanium tetrabromide, titanium sulfate, titanium sulfate, titanium oxysulfate, titanium oxide, titanium (It/) oxyacetylacetonate, tetraethyl titanate, tetrapropyl titanate,
Tetra-1so-propyl titanate, tetrabutyl titanate, titanocene dichloride, etc. may be used. These lead, tin, bismuth, or titanium compounds can be used alone or in combination of two or more. Particularly preferred are halides such as lead chloride, lead bromide, tin chloride, tin bromide, bismuth chloride, bismuth iodide, titanium tetrachloride, and titanium tetrabromide. The amount of these metal compounds used is based on the general formula (1) usually used as a starting material.
0.001 to 0 per equivalent of acetal expressed by
．． The amount is preferably 5 equivalents; if it is less than 0.001 equivalents, it will take a long time to complete the reaction, and if it is more than 0.5 equivalents, it will not be economical and side reactions will occur, resulting in a decrease in yield.

Metals that have a greater ionization tendency than lead, tin, bismuth, or titanium used in the present invention include aluminum, iron,
Nickel, cobalt, magnesium, or a mixture thereof can be used, and aluminum is particularly preferred. There are no particular restrictions on the shapes of these metals used.

It can be used in various shapes such as powder, plate, foil, lump, or needle. In addition, the amount used is preferably in the range of 0.7 to 3 equivalents per equivalent of acetal represented by general formula (1), and if it is less than 0.7 equivalents, the reaction progresses slowly or may not be completed. figure.

If the amount is 3 equivalents or more, it will not affect the progress of the reaction much, but it will not be economical.

Further, in the present invention, a catalytic amount of Lewis acid can be used to speed up the progress of one reaction. A wide range of conventional Lewis acids can be used (for example,
Examples include ferric chloride, aluminum chloride, aluminum bromide, and boron trifluoride.
) 0.001 to 1 amount of acetal expressed as
0.5 equivalent', preferably in the range of amount, 0.5 f
If the amount is more than i, side reactions such as acetal duplication occur.

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

Although the preferred range varies depending on the amount of tin, bismuth or titanium compound used, the bath medium, etc., the reaction is usually carried out at about 0 to 100°C, preferably at 0 to 50°C.

〔Example〕

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

Example 1 m f2) (3) In a round bottom flask, take 551n9 (0.15 mmol) of lead bromide, 135m9 (0.5 mmol) of aluminum bromide, and 135m9 (5 mmol) of finely cut aluminum foil, Tetrahibirofuran 1071A for this! , benzaldehyde dimethyl acetal (1) 760In9 (5 mmol)
, allyl bromide (2) 0.85 d (10 mmol) was added, and the mixture was stirred at 20° C. for 1 hour to carry out a reaction. After the reaction was completed, 5% salt M10+1/e was added to the reaction solution and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate, and condensed to obtain 760 m9 of an oily substance. This product was purified using a silica gel column to obtain 745 m9 of colorless liquid compound (3) (yield 92%).

Compound (3): 1H-NMR (CDC: 13) δ2
．． 25-2.60 (m e 2 He CH2':'
-C) + 115 (8* 3Ht CHs-O)
.

4.09 (t, J7Hz, IH, CH-0) 3
4.72-5.15 (m.

2H,CH2-G), 5.36-6.06 (m
-IH,CH=C).

7.17 (s, 5H, Ar).

Examples 2 to 4 Reactions were carried out under the conditions shown in Table 1 using tin bromide (■), bismuth chloride, and titanium gold tetrachloride in place of lead bromide in Regret Example 1, and compound (3) was prepared as shown in Table 1. It was obtained in the yield shown in .

Table 1 Examples Catalyst Aluminum Reaction time Yield 4 (mmol) (mmol) (hour)
(%)2 5nBr2(0,15) 5
3 723 BtG13(0,1
5) 5 8 90 Conditions not listed in Table 1 are the same as in Example 1.

In a round bottom flask, add 55 m9 (0.ts mmol) of lead bromide, 135 m (0.5 mmol) of aluminum bromide, and 135 m (5 mmol) of finely cut aluminum foil, and 10 m1 of tetrahydrofuran. p-Methoxybenzaldehyde dimethyl acetal (4) 91 om
9 (5 mmol), allyl bromide (2) 2.61 d (30
mmol) was added thereto, and the reaction was carried out by stirring at 20°C for 1 hour. After the reaction was completed, 5% hydrochloric acid IQmJi was added to the reaction solution and extracted with ethyl acetate. The extract was washed with saturated sodium bicarbonate solution and saturated saline.

After drying with anhydrous magnesium sulfate, 1! 750 m9 of oil was obtained. This product was purified using an all-silica gel column to obtain a colorless liquid compound (5
) was obtained in an amount of 725 m9 (yield: 72 g).

Compound +51: 1H-NMR (CDC13) δ 2
．． 26-2.32 (m, 2H, CH2C-C), 2
．． 34-2.40 (m-2H.

CH2G=C), 2.62-2.68 (m, I
H-OH), 3.77(S, 3He aH3-o
) -4-91(d d-J ~10-3m2, 2H
z= 2H, CH2=C), 4.95 (d d,
J ~16.9°1.5Hz, 2H, CH2=C)
, 5.64 (dtit, J=16.9°10.3
．． 7.0Hz, 2H,CH;C), 6.82(
d, J=8.8 Hz + 2 H−A r ) +
705 (d e J ~8-8 h*2
HtAr).

Examples 6 to 12 R5R' (III) 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.

Claims (3)

[Claims] (1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) [In the formula, R^1 and R^2 are hydrogen, chain or cyclic alkyl, alkenyl, alkynyl group, aralkyl group, aryl group, It represents a heterocyclic group, which may be the same or different, and may form a ring with a carbon chain or a carbon chain containing a heteroatom. Furthermore, these may have a substituent; R represents a chain or cyclic alkyl, alkenyl, alkynyl group, or acyl group, aralkyl group, aryl group, or heterocyclic group, and may be the same or different. or a carbon chain or a carbon chain containing a heteroatom may form a ring. Furthermore, these may have a substituent. ] in a polar solvent, a lead compound, a tin compound,
In the presence of one or more bismuth compounds or titanium compounds and a metal with a greater ionization tendency than those metals, the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) [In the formula, R^3 to R^7 represents 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 form a ring with a carbon chain or a carbon chain containing a heteroatom. Good too. Furthermore, they may have substituents; also, X is chlorine, bromine or iodine. An acetal allylation method characterized by reaction with an allyl halide represented by ]. (2) Metals that have a greater ionization tendency than lead, tin, bismuth, or titanium are aluminum, iron, nickel, cobalt,
The method for allylating an acetal according to claim 1, which is magnesium or a mixture thereof. (3) The acetal allylation method according to claim 1, in which a catalytic amount of Lewis acid is coexisting.