JPS5951529B2 - Method for promoting base-catalyzed organic ion reactions - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for promoting a base-catalyzed organic ion reaction, and more particularly to a method for promoting a base-catalyzed organic ion reaction, and more particularly, the present invention relates to a method for promoting a base-catalyzed organic ion reaction, and more particularly to a method for promoting a base-catalyzed organic ion reaction, in which a basic alkali metal compound (excluding an organometallic compound having a carbon-metallic bond) is used in an organic liquid. Carpene reaction, ylide reaction or ring-closing reaction resulting from the elimination of mono-hydrogenide that is contacted with the reaction, substitution reaction of the active hydrogen of an active hydrogen compound with 25 organic groups, conversion of the active hydrogen compound to an activated unsaturated compound. When performing an organic ion reaction selected from the group consisting of an addition reaction, an addition reaction of an acetylene compound to a carbonyl compound, a self- or heterogeneous condensation reaction of a carbonyl compound, and a rearrangement reaction via a carbonyl compound, the formula壬A-0 → (A represents a straight chain or branched alkylene group having 2 to 4 carbon atoms) The structural unit represented by A-0 → (A represents a linear or branched alkylene group having 2 to 4 carbon atoms) is combined with an average of 6 structural units without forming a cyclic polyether structure. The present invention relates to a method of industrially advantageously advancing an organic ion reaction by allowing a polyoxyalkylene compound having at least 1 or more polyoxyalkylene compounds to be present in the reaction system.

When conducting an organic ion reaction contacted by a basic alkali metal compound (excluding organometallic compounds having a carbon-metal bond) in an organic liquid, the metal compound has low solubility in the reaction medium. It is often experienced that the reaction rate is extremely slow due to the low activity of the anion to be generated from the metal compound.The following is a method to improve this point and smoothly conduct the reaction in an organic liquid. The following methods are known.

The first method utilizes the high solubility of metal compounds in aprotic polar solvents such as dimethylformamide, acetamide, dimethylsulfoxide, hexamethylphosphoramide, and the like. It is well known that metal compounds are solvated in these aprotic polar solvents and exhibit high solubility and high reactivity. However, when this method is viewed from an industrial point of view, it also has the following drawbacks, and there are limits to the reactions that can be applied. 1) These polar solvents do not necessarily have sufficient thermal and chemical stability.

2) The solvent itself is corrosive, and there are restrictions on the material of the reactor.

3) Since the solvent is soluble in water, it is difficult to separate (recover) the metal compound (starting material and metal compound produced by the reaction) in the reaction mixture.

4 Nanki reaction products may be chemically unstable in these polar solvents.

5) Solvents are generally quite expensive and difficult to recover.

The second method is a revolutionary method that has developed rapidly over the past few years, and uses crowns as a catalyst.
A cyclic polyether named CrOwnether is used. Crown ethers primarily react with alkali metal salts to capture the corresponding metal cations, forming so-called naked anions.
iOn)〃 is generated. Therefore, in the coexistence of crown ether, the solubility of metal compounds in various organic liquids is improved, and anions are significantly activated, and reactions of organic ions contacted by anions are significantly promoted. This effect of crown ether is extremely attractive from an industrial perspective, and the amount of crown ether used can be a so-called catalytic amount.
No particular difficulty is expected in separating (recovering) the various products from the reaction mixture. However, crown ethers are extremely expensive due to the complexity of the synthesis method, and this is a major reason why this method has not been put into practical use, despite its wide applicability. ing. The present inventors have demonstrated that carbene reactions, ylide reactions, or ring-closing reactions due to the elimination of hydrogen halides contacted by basic alkali metal compounds (excluding organometallic compounds having carbon-metallic bonds) in organic liquids. , substitution reaction of active hydrogen of an active hydrogen compound with an organic group, addition reaction of an active hydrogen compound to an activated unsaturated compound,
Addition reaction of acetylene compounds to carbonyl compounds,
The present invention was achieved as a result of various studies aimed at effectively promoting organic ion reactions selected from the group consisting of self- or interspecies condensation reactions of carbonyl compounds and rearrangement reactions via carbonyl compounds in an economical manner. . That is, according to the present invention, when carrying out the above organic ion reaction contacted by a basic alkali metal compound (excluding organometallic compounds having a carbon-metal bond) in an organic liquid, the formula A structural unit (hereinafter referred to as an oxyalkylene unit) represented by A1O (where A represents a linear or branched alkylene group having a carbon network number of 2 to 4) is used to form a cyclic polyether. An average of 6 pieces without forming a structure? By making the above polyoxyalkylene compound present in the reaction system, the organic ion reaction can be significantly promoted. Hereinafter, a polyoxyalkylene compound that does not have a cyclic polyether structure will be simply referred to as a polyoxyalkylene compound. Furthermore, the term "organic liquid" as used herein refers to organic compounds and mixtures thereof that are liquid under reaction conditions, and is not necessarily synonymous with organic solvent. At the start of the reaction, the main component of the organic liquid may be the organic compound (organic reactant) itself used as a reactant,
It may be a mixture of an organic compound (organic solvent) used as a solvent and an organic reactant. Details including specific examples of the polyoxyalkylene compounds used in the present invention will be described later, but these polyoxyalkylene compounds are generally much cheaper and easier to obtain (or produce) than crown ethers. It is hot and has an effect that is almost comparable to that of crown ether.

Therefore, by using the method of the present invention, the above-mentioned organic ion reaction can be carried out industrially much more advantageously than when crown ether is used as a catalyst. In addition, polyoxyalkylene compounds generally have high thermal and chemical stability, and therefore the types of reactions to which the method of the present invention can be applied and the reaction conditions that can be adopted include using conventional aprotic polar solvents. It is much wider than the case,
Furthermore, restrictions regarding operating conditions when separating reaction products and the like from the reaction mixture are significantly relaxed. Furthermore, the use of the polyoxyalkylene compound according to the present invention is advantageous since the polyoxyalkylene compound acts as a kind of high-boiling solvent when products etc. are separated by distillation from the reaction mixture. - It also has the advantage of improving the distillation yield of all (0vera11). Furthermore, since polyoxyalkylene compounds are generally non-toxic and microbially degradable (BiOdegr&DBble), application of the method of the present invention will not result in deterioration of the working environment and natural environment. In the present invention, it is most important that the polyoxyalkylene compound used has an average of 6 or more oxyalkylene units, thereby providing the above-mentioned reaction promoting effect (catalytic effect).

Conventionally, if diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, tetraethene glycol dimethyl ether, diethylene glycol diethyl ether, diethylenoglycol dibutyl ether, etc. were used as a solvent, the Grignard reaction could be carried out more smoothly due to the solvating power of the metal compound. For example, sodium phenoxide is dissolved to some extent in these solvents, and the following formula n{4H9Ce+NaOC. H
, → n{, H9OC6H, +NaCl It is known that the reaction proceeds smoothly, but these are methods that use the above-mentioned ethers as a solvent, and are in the same category as the first method described above. However, there has been no report found that using a catalytic amount of these polyoxyalkyl V glycol ethers produces an effect of promoting the organic ion reaction that is the object of the present invention.

When a polyoxyalkylene compound is present in a reaction system according to the present invention, a polyoxyalkylene compound that is substantially soluble and chemically stable under the reaction conditions is generally charged to the reaction system. However, it is preferable to use a polyoxyalkylene compound as a precursor in the reaction system to provide a polyoxyalkylene compound that satisfies the above requirements (substantially soluble and chemically stable under the reaction conditions). It can also be prepared in

For example, when a polyoxyalkylene compound having an alcoholic hydroxyl group is added to a reaction system for producing ethers by reacting alcohols and organic halides in the presence of a base, the polyoxyalkylene compound has an alcoholic hydroxyl group.・Although it is etherified by reacting with a halogenide, the etherified polyoxyalkylene compound produced is no longer chemically stable in this reaction system. As the oxyalkylene compound, a polyoxyalkylene compound having an alcoholic hydroxyl group may be added, or an etherified product thereof may be added (in the former case, an ether of the added polyoxyalkylene compound having an alcoholic hydroxyl group) may be added. (However, this does not pose a major problem because the amount of polyoxyalkylene compound added is a catalytic amount, which is sufficient as described below.) Typical polyoxyalkylene compounds that can be used in the present invention are (I) polyalky V glycols;
() Aliphatic alcohols having about 30 or less carbon atoms, aliphatic hydrocarbon-substituted or unsubstituted phenols, aliphatic carbo/acids, aliphatic amines, aliphatic amides, or phosphoric acid monoesters, etc. A polyaddition reaction product obtained by reacting 6 mol or more of alkylene oxide having 2 to 4 carbon atoms per 1 mol, () a chemical modification such as esterification or etherification of the hydroxyl group of the above 00 reaction product. These are compounds in which one or both of the hydroxyl groups at both terminals of (y-alkylene glycols) have been chemically modified, such as esterification or etherification.

Many of these polyoxyalkylene compounds have the following general formula ([), (), (), (), (V), (), (),
and (l). These general formulas (1), (), (), (IV)
, (V), (Vl), () and (), A represents a straight or branched alkylene group having 2 to 4 carbon atoms,
Preferably -CH,CH,--CH,CH(CH,)-
s-CIf(CH3)CH(CH3)-, etc., and -CH2-CHl- is particularly preferred.

n is a number of 6 or more on average, and x and y are numbers of 0 or more such that the sum of both is 6 or more on average, but it is preferable that at least one of them is 6 or more. R1 is a hydrocarbon group having 1 to about 30 carbon atoms (preferably about 4 to about 20 carbon atoms), preferably an aliphatic hydrocarbon group (e.g., hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, cetyl, stearyl, oleyl, etc.) ), aliphatic hydrocarbon-substituted aromatic hydrocarbon groups (e.g. nonylphenyl, decylphenyl, undecyl, dodecyl phenyl, etc.)
etc., and R2 and R4 are hydrogen atoms or hydrocarbon groups having 1 to about 20 carbon atoms (preferably lower alkyl groups)
, an acyl group (preferably a lower acyl group), a trialkylsilyl group (preferably a trimethylsilyl group), a mono-Rogge 7-substituted hydrocarbon group (preferably a chloro-substituted alkyl or aryl group), and R3 is a hydrogen atom weight or It is a hydrocarbon group (preferably an aliphatic hydrocarbon group) having 1 to about 20 carbon atoms, and the total number of carbon atoms of R1 to R4 in one molecule is about 50 or less, preferably about 40 or less. Gayo.

The values of n and (x+y) are integers for one molecule, but in the general manufacturing method of polyoxyalkylene compounds, the values of n or (x+y) between individual molecules are not uniform due to polyoxyalkylenization. Usually, a mixture of polyoxyalkylene compounds (strictly speaking, a mixture of polyoxyalkylene compounds) is obtained, and in the present invention, such a polyoxyalkylene compound is used as it is without particular separation, and the polyoxyalkylene compound is It is possible to use them separately in a suitable molecular weight range, and n and (x+y) in each of the above formulas are understood to mean the average number of oxyalkylene units per molecule. Should. and such n and (x
+y) is no longer necessarily an integer. n and (x+
Although there is no critical upper limit for y), there is no need to intentionally use polyoxyalkylene compounds with extremely large values;
) is preferably about 50 or less. In consideration of reaction results, product separation after reaction, price and physical constants (properties) of the polyoxyalkylene compound, a particularly preferred range of n and (x+y) is about 7 to about 20. All of the alkylene groups A in the same molecule do not need to be the same, and may be partially different alkylene groups, such as the covalent forces of ethyl oxide and propylene oxide. Regarding the polyoxyalkylene compound not represented by any of the above general formulas, the number of oxyalkylene units it should have, the type of oxyalkylene units, etc. are the same as described above. An example of a polyoxyalkylene compound not represented by the above general formula includes a compound such as polyoxyalkylene di(trimethylsilyl)ether. In consideration of catalytic ability, thermal and chemical stability, ease of availability including price, and wide range of application, preferred polyoxyalkylene compounds include glycols of the general formula (1), particularly polyethylene glycol. , and R1 in the general formula () which can be obtained by polyaddition reaction of aliphatic alcohol or aliphatic hydrocarbon-substituted phenol with ethylene oxide or propylene oxide (especially ethylene oxide) or subsequent etherification. is an aliphatic hydrocarbon group or an aliphatic hydrocarbon-substituted phenyl group, and R2 is a hydrogen atom or a lower alkyl group (particularly a methyl group). In the method of the present invention, the amount of the polyoxyalkylene compound as described above is usually a so-called catalytic amount (about 0.001 mol to about 1 mol, preferably about 0.01 to 0.3 mol per mol of organic reactant). It is fine, but there is no harm in using an excess amount.

When applying the method of the present invention to carry out an organic ion reaction on an industrial scale, it is usually desirable to carry out the reaction in an organic solvent solution. As the solvent used in this case, a suitable organic compound or a mixture thereof should be selected depending on the type of organic ion reaction, but commonly used solvents include hydrocarbons, ethers, nitriles, esters, and alcohols. etc. The organic ion reactions to which the method of the present invention is applicable will be explained below.

1. Carbene reactions, ylide reactions, and ring-closing reactions due to the elimination of hydrogen halides Bases act catalytically on the de-hydrogen-halide reactions, but they do not react with the pre-formed mono-hydrogen halides. It is then consumed.

For this reason, the base used is usually referred to as a dehydrohalogenating agent. This type of reaction generally involves n-butyllithium,
Phenyllithium, Grini. Organometallic compounds of alkali or alkaline earth metals such as Jarl's reagent, sodium ethoxide, potassium t-butoxide,
It is also contacted by alkali metal alcolades or phenolades such as sodium phenoxide, but it is industrially disadvantageous to use these alkali metal compounds in stoichiometric amounts relative to organic monologen compounds. It is. However, according to the method of the present invention, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, which are cheaper and easier to handle than the above-mentioned alkali metal compounds, can be used as dehydrohalogenating agents. The industrial value of the invented method is extremely large. Carben is one.
It is generated by α-dissociation of mono- and halogenated hydrocarbons from halogenated hydrocarbons and their derivatives.

Example: CHX3-→:CX, (X is halogen) The conventional industrial method for generating dihalocarpenes is to carry out an α-dissociation reaction of the corresponding monoform in a non-aqueous system in the presence of a strong base such as potassium t-butoxide. However, according to the method of the present invention, carbene can be generated under mild conditions using an inexpensive alkali metal hydroxide.

The carpene reaction is well known as cyclopropane ring formation, ring expansion, )C=S, 2C=0. ] It is applied to addition reactions to C=N- bonds, etc., and is one of the basic reactions as a method for synthesizing industrially useful compounds. The carbene reaction is usually carried out in the presence of a solvent and in the presence of an excess of the unsaturated compound to be added. When the method of the present invention is applied to a carbene reaction, the above base acts catalytically on the elimination reaction itself, but reacts with the eliminated mono-hydrogenide to produce the corresponding metal mono-hydrogen. Because it becomes a chemical compound, it is ultimately consumed in a stoichiometric amount relative to the amount of carpene generated.
In a sense, the ylide production reaction can be regarded as a reaction in the same category as the carbene reaction, and is one of the preferred reaction examples to which the method of the present invention can be applied.

When a base is applied to an adduct of a phosphine or phosphite and a mono-logenated hydrocarbon, such as triphenylphosphine, trialkylphosphine, or trialkylphosphite, a highly reactive ylide intermediate is produced, and the reaction from the carbonyl compound is It is used for olefin synthesis (called Wlttig reaction). Similarly, 8-ylide obtained by reacting a base with a sulfide or sulfoxide such as dialkyl sulfide or dialkyl sulfoxide and a mono-logenated hydrocarbon is added to a carbonyl compound to form the corresponding epoxy compound. It is known to cause

In these ylide reactions, organometallic compounds of alkali or alkaline earth metals and alcocalates are generally used as catalysts, but according to the method of the present invention, cheaper alkali metal hydroxides can be used. It becomes possible to use it.

The ring-closing reaction by de-monohydrogenide is also an industrially useful reaction, and an example of this type of reaction is described in JP-A No. 51-3, for example.
No. 2543, No. 51-39647, No. 51-6573
4, No. 51-65733, and No. 51-59839.

The reason why the ring-closing reaction takes place at a practical yield in preference to the β theory is, for example, when the carbon with a halogen to be eliminated in the starting organic halogen compound is set as the α-position carbon, hydrogen is not attached to the β-position carbon. Alternatively, the hydrogen attached to the γ-position carbon may be activated by an electron-withdrawing group. (X is Ce or Br, R is an alcohol residue such as an alkyl group, Y and Z are hydrogen, monologen or a hydrocarbon group such as a methyl group, a vinyl group, etc.)
According to the method of the present invention, the ring-closing reaction described above can be carried out smoothly even under mild conditions (e.g., room temperature to 80°C) using an inexpensive alkali metal hydroxide or an alcoholade in a nonpolar solvent such as a hydrocarbon. can proceed to.

The method of the present invention also exhibits excellent effects in addition reactions of α-haloesters and α-nitrile to carbonyl compounds (referred to as Danens reaction) as exemplified by the following formula. Base (R is an alcohol residue, such as an alkyl group)2. Substitution reaction of active hydrogen in active hydrogen compounds with organic groups Active hydrogen atoms (α-hydrogen) attached to carbons bonded to electron-withdrawing atomic groups represented by carbonyl groups, cyano groups, alkoxycarbonyl groups, etc., alcohols, Organic compounds containing active hydrogen (active hydrogen compounds), such as hydrogen atoms bonded to oxygen or sulfur in thiols, etc., and hydrogen atoms bonded to nitrogen in amines, amides, etc., are converted into organic monologenides in the presence of a base. When reacted, the halogen atom in the organic halide can be replaced with a carbanion, an alkoxy anion, a thiol anion, or an N anion generated from the above-mentioned active hydrogen compound.

There are countless examples of such base-catalyzed substitution reactions, and the following 1) Sako reaction can be cited as a representative example.
However, in the above formula (1)-{v), R and R'&i are the same or different and represent a hydrogen atom or an organic group represented by an alkyl group, a cycloalkyl group, an aryl group, an alkenyl group, an acyl group, a cyano group, etc. , R are generally hydrocarbon groups, such as alkyl groups.

R7 is a primary or secondary hydrocarbon group and does not include a substituted or unsubstituted phenyl group or vinyl group. x is a halogen atom, which from an industrial point of view is a chlorine atom and a bromine atom. In the reactions of this section represented by Qi) to Qi) above, the base is required in a stoichiometric amount relative to the organic monologenide.

This point is exactly the same as in the case of each organic ion reaction mentioned in the previous section 1, and if the method of the present invention is applied to these reactions, it is possible to use inexpensive alkali metal hydroxides, alcoholades, or phenolades. The reaction can proceed smoothly. 3. Addition reaction of active hydrogen compounds to unsaturated compounds Carpenions generated from active hydrogen compounds in the presence of a base turn into olefinic compounds activated (polarized) by carbonyl groups, alkoxycarbonyl groups, nitro groups, cyano groups, etc. Addition is well known, with Michael addition being a representative example.

There are many reactions of this type, and in general, alkali metal alcolades, alkali or alkaline earth metal organometallic compounds, and the like are used as catalysts, usually in an amount of several mol % or less based on the organic reactant. By applying the method of the present invention, cheaper alkali metal hydroxides can be used as base catalysts. Furthermore, by applying the method of the present invention to the case where an alkali metal alcoholade is used as a catalyst, the catalyst can be further activated, and for example, it is possible to lower the reaction temperature and lower the catalyst concentration. Yes, side reactions can be suppressed. Typical examples of such addition reactions catalyzed by a very small amount of base include the following reactions. Among the addition reactions, some addition reactions proceed at a practical reaction rate only in the presence of a large amount of base, and in these addition reactions, the feature of method a of the present invention is prominently exhibited. In this case, specific examples of industrially valuable bases include sodium hydroxide, potassium hydroxide, sodium alcoholade, potassium alcoholade, sodium phenolade, potassium phenolade, sodium amide, potassium amide, and the like. these. Bases generally have extremely low solubility in common organic solvents, and in conventional methods the reaction does not proceed at a practical rate unless a special solvent is used in combination, but the method of the present invention facilitates such reactions. proceed. Among the addition reactions of active hydrogen compounds to unsaturated bonds that are contacted in the presence of a large amount of base, the addition reaction of acetylene compounds to carbonyl compounds (the following (see formula). Here R
and R' is usually a hydrocarbon group such as an alkyl group, allyl group, or substituted allyl group, and R〃 is usually a hydrogen atom or a hydrocarbon group such as an alkyl group, alkenyl group, alkynyl group, aryl group, or cycloalkyl group. be.

These hydrocarbon groups may be appropriately substituted with a different atom (hezero atom) or an atomic group containing this to the extent that no harm is caused. Conventionally, the reaction represented by the above formula has been carried out using, for example, potassium hydroxide in liquid ammonia as a catalyst, but by applying the method of the present invention, as will be seen in the examples below, the reaction can be carried out using a general organic solvent solution. The reaction proceeds smoothly even inside. 4. Condensation reactions between carbonyl compounds themselves and between different species The reactions mentioned above are typified by aldol condensation (including self-condensation and cross-aldol condensation between different carbonyl compounds), Claisen condensation, and penzoin condensation.

These condensation reactions generally use alkali or alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide, pallium hydroxide, sodium alcolade, potassium alcolade, sodium phenolate, sodium cyanide, potassium cyanide, etc. as catalysts. is used. For example, aldol condensation of acetaldehyde, aldol condensation of n-butyraldehyde, crossaldol condensation of formaldehyde and acetaldehyde,
Aldol condensation of acetone is also carried out industrially, and in these cases the reaction is carried out using a very small amount of a base catalyst and under relatively mild reaction conditions. In the condensation reactions of carbonyl compounds that are extremely susceptible to condensation, as in these examples, the features of the method of the present invention are not necessarily apparent, but if the method of the present invention is applied, the reaction can be carried out even in a nonpolar solvent solution. , for example, side reactions such as the Kanisotuaro reaction can be suppressed, and product separation can be facilitated. On the other hand, the advantage of applying the method of the present invention is noticeable in condensation reactions that have conventionally been carried out only in the presence of a large amount of base or under severe reaction conditions. For example, as seen in the Examples, the Penthorne condensation of pesosaldehyde proceeds extremely smoothly even at room temperature according to the method of the present invention. Condensation reactions of esters and condensation reactions of esters and carbonyl compounds (Stobe reaction) are also suitable examples of reactions to which the method of the present invention is applied. 5. Rearrangement Reaction Via Calcunion From an industrial standpoint, there are not necessarily many examples of rearrangement reactions catalyzed by bases to which the present invention can be applied, but the present invention can be applied to some base-catalyzed rearrangement reactions. This method is effective.

Specific examples of these include the following benzylic acid rearrangement, rearrangement of allyl ethers and benzyl ethers, and Oxycope reaction. Penzylic acid rearrangement reaction has conventionally been carried out at high temperatures in the coexistence of sodium hydroxide or potassium hydroxide, but according to the method of the present invention, this reaction proceeds extremely smoothly and selectively even at room temperature.

Allyl ethers and benzyl ethers are generally n
- It is known that in the presence of a stoichiometric amount of an organometallic compound represented by butyl lithium, the other organic group of the ether is rearranged to the alcocarate of a secondary alcohol at the allyl and penzyl positions. (Wittig
(called dislocation).

According to the method of the present invention, this rearrangement reaction can be carried out using sodium amide, which is cheaper and easier to handle, instead of using a concentrated metal compound.
This can be carried out smoothly using potassium amide or the like.
It has recently been revealed that the Oxycope reaction proceeds at extremely low temperatures in the presence of a base, and the method of the present invention can also be suitably used for this Oxycope reaction.

Hereinafter, the present invention will be explained with reference to Examples, but these only show a part of the present invention, and the present invention is not limited by these Examples.

Example 1 Contents 100 with thermometer, stirrer and reflux condenser
60 mmol of finely powdered potassium hydroxide, 30 mmol of styrene, and 5.0 r of chloroform in the Yotsuro flask of d.
fLt and C,8H3,O(C2H4O),. 5CH
31.0 mmol was added, and the reaction was allowed to proceed for 2 hours under stirring at room temperature.

After the reaction, isobutylbenzene was added as an internal standard substance, and the product was analyzed and quantified using gas chromatography. As a result, it was found that 1,1-dichloro-2-phenylcyclopropane was produced at a yield of 78% based on the added styrene. Examples 2 to 7 and Comparative Examples 1 to 2 The same reaction apparatus as in Example 1 was used, and at least one of the alkali metal compound and the polyoxyalkylene compound was changed, but in exactly the same manner as in Example 1. , an addition reaction of dichlorocarpene to styrene was carried out.

These results are shown in Table 1 below along with comparative examples. In addition, in all the experiments shown in Table 1, the reaction time was 1.0 hour, and the reaction temperature was room temperature. Example 8 In the same reactor as in Example 1, 20 mmol of benzoic acid amide, 40 mmol of micronized potassium hydroxide, 10 mmol of chloroform, and C,2H2,O (C2H4O),
1.0 mmol of 0C4H was added, and the mixture was reacted at 50° C. for 4 hours with stirring.

After the reaction, the reaction mixture was analyzed by gas chromatography, and it was found that benzonitrile was produced in a yield of 80% (based on the added benzoic acid amide). Example 9 and Comparative Example 3 In the same reaction apparatus as in Example 1, 3,3-dimethyl-4
, ethyl 6,6-trichloro-5-hexenoate 10 mmol, sodium ethylate 20 mmol, benzene 1
0 g and 7 mmol were added, and the reaction was allowed to proceed for 1.5 hours under stirring at room temperature.

Analysis of the reaction mixture using gas chromatograph JC revealed that ethyl 2,2-dimethyl-3-(2',2'-dichlorovinyl)cyclopropanecarboxylate had been added to 3,3-'methyl-4,6 , 6-trichloro-5-hexenoate in a yield of 52% based on ethyl ethyl 6-trichloro-5-hexenoate. For comparison, the reaction was carried out for 1.5 hours under the same reaction conditions without adding any polyoxyalkylene compound (Comparative Example 3).
The yield of ethyl (2',2'-dichlorovinyl)cyclopropanecarboxylate was only 9%.

Example 10 and Comparative Example 4 In the same reactor as in Example 1, 3,3-dimethyl-4,6,6-trichloro-5-
10 mmol of ethyl hexenoate, 25 mmol of micronized sodium hydroxide, 10" of benzene, and C8Hl
7O(C2H4O),. ,C8H,,O. 5 mmol was added, and the reaction was allowed to proceed for 3 hours at room temperature with stirring.

When the reaction mixture was analyzed by gas chromatography, it was found that ethyl 2,2-dimethyl-3-(2',2'-dichlorovinyl)cyclopropanecarboxylate was added to the 3,3
It was found that -dimethyl-4,6,6-trichloro-5-hexenoic acid was produced at a yield of 40% based on ethyl 4,6,6-trichloro-5-hexenoate. For comparison, 2,2-dimethyl-3 in the case where no polyoxyalkyne compound was added (Comparative Example 4)
The yield of ethyl -(2',2'-dichlorovinyl)cyclopropanecarboxylate was only 3%.

Example 11 In the same reaction apparatus as in Example 1, while substituting dry nitrogen gas, 40 mmol of pulverized potassium hydroxide, 20 mmol of benzaldehyde, and methyltriphenylphosphonium iodide [C6H, which had been separately synthesized and purified in advance] were added.
,)3p(CH,)(I)], 10 qL of methylene chloride, and 10 mmol of methylene chloride were added, and the reaction was carried out at 40° C. for 18 hours with thorough stirring.

When the reaction mixture was analyzed using a gas chromatograph, it was found that styrene was 64q based on the amount of benzaldehyde added.
It was found that it was produced in a yield of 1I. Example 12
And Comparative Example 5 In the same reaction apparatus as in Example 1, 40 mmol of micronized potassium, 20 mmol of penzaldehyde, and 1 mmol of trimethylsulfinium iodide synthesized separately in advance [(C
H,),s(1-)]25 mmol, C,8H,,O(
C, H4O), C8Hl, l. 0 mmol and 10rfLt of methylene chloride and stirred vigorously for 4 hours.
The reaction was carried out at 5°C for 5 hours.

After the reaction, the reaction mixture was analyzed by gas chromatography, and it was found that styrene oxide was produced in a yield of 91% based on the benzaldehyde added.
Note that no formation of benzyl alcohol or benzoic acid was observed. On the other hand, when the same reaction as in Example 12 was repeated without adding any polyoxyalkylene compound (Comparative Example 5), styrene oxide was not produced at all in the reaction at 45°C for 5 hours, and benzoin 47% acid and 47% benzyl alcohol (both based on added benzaldehyde) were produced.

That is, when a polyoxyalkylene compound is added, styrene oxide is produced as the main product, whereas when a polyoxyalkylene compound is not added, only the Kanitssoaro reaction takes precedence. Thus, the effects of the method of the present invention are extremely significant. Example 13 Into the same reaction apparatus as in Example 1, 120 mmol of octanal, 40 mmol of finely divided sodium hydroxide, and allyldimethylsulfinium chloride [(
CH,)21(CH2O₂CH2)(Ce-)]20 mmol, C8Hl,O(C,H,O),C8H,,l.
0 mmol and 10 WLt of benzene were added, and the reaction was carried out at 40° C. for 10 hours with vigorous stirring at t$.

As a result of analysis by reaction mixture Wlk gas chromatography, the corresponding oxirane compound, n-C7Hl, CH-C
It was found that H-CH=CH2 was produced in a yield of 70% based on the added octanal-1.

Example 14 In the same reactor as in Example 1, 60 mmol of micronized potassium hydroxide, 30 mmol of prenyl chloride, 5i1 of acetone, and a time reaction were carried out.

After the reaction, the reaction mixture was analyzed by gas chromatography, and it was found that methylhebutenone was produced at a yield of 6% based on the added prenyl chloride.
Example 15 In the same reactor as in Example 1, 20 mmol of micronized potassium hydroxide, 10 mmol of benzyl cyanide, 12 mmol of ethyl bromide, 5i acetate, and C8H! , O(C2H4O)10C4H, 1.0 mmol, were added thereto, and the reaction was carried out under reflux and stirring for 3 hours.

After the reaction, the reaction mixture was analyzed by gas chromatography, and it was found that α-ethylpenzyl cyanide was produced in a yield of 85% based on the added benzyl cyanide. Example 16 Into the same reactor as in Example 1, 20 mmol of micronized potassium hydroxide, 12 mmol of ethyl bromide, 10 mmol of ethyl phenyl acetate, 10-1 J mole of acetonitrile, and ~1 J mole were added and stirred vigorously under reflux. The reaction was continued for 10 hours.

After the reaction, the reaction mixture was analyzed by gas chromatography, and it was found that 4.8 mmol of α-ethylphenyl ethyl acetate was produced. Example 17 and Comparative Example 6 Into the same reaction apparatus as in Example 1, 68 mmol of finely powdered potassium hydroxide, 34 mmol of n-octyl bromide,
68 mmol of ethyl alcohol, 10 mmol of acetonitrile
, and mol were added and allowed to react under reflux and stirring for 15 hours.

After the reaction, the reaction mixture was analyzed by gas chromatography, and it was found that n-octyl ethyl ether added n-
It was found that the yield was 87% based on octyl bromide. Note that when the reaction was carried out for 15 hours under the same reaction conditions without adding any polyoxyalkylene compound (Comparative Example 6), the yield of n-octylethyl ether was only 6%.

Example 18 In the same reactor as in Example 1, 20 mmol of micronized sodium hydroxide, 10 mmol of indole, 10 mmol of benzene 20a1 ethyl iodide, and C8H1,
0(C,H40)6.5C4H, l. 5 mmol was added and the reaction was allowed to proceed at 50° C. for 5 hours with stirring.

Analysis of the reaction mixture by gas chromatography revealed that 8.8 mmol of N-ethylindole was produced. Example 19 In the same reactor as in Example 1, n-butyraldehyde 5
0 mmol of potassium cyanide, 2.0 mmol of potassium cyanide, ~==', and 10 d of toluene were added, and the mixture was stirred at room temperature for 10 hours.

When the reaction mixture was analyzed by gas chromatography, it was found that 2-ethyl-3-hydroxyhexanal-1 was produced in a yield of 93% based on the added n-butyraldehyde. Example 20 In the same reactor as Example 1,
50 mmol of benzaldehyde, 20 mmol of potassium cyanide, 10 rlLt1 of acetonitrile and C8Hr!
Add 1.5 mmol of O(C2H40)10CH,
After the reaction was vigorously stirred at room temperature for 6 hours, the reaction mixture was analyzed by gas chromatography, and it was found that benzoin was produced in a yield of 70% based on the added benzaldehyde.

Examples 21 to 29 and Comparative Examples 7 to 8 Benzoin condensation was carried out under exactly the same reaction conditions as in Example 20, except that one or both of the solvent and the polyoxyalkylene compound in Example 20 were changed.

The results obtained are shown in Table 2. In addition, in Table 2, the benzoin yields are all based on added penzaldehyde (50
mmol) standard. Example 30 Into the same reaction apparatus as in Example 1, 60 mmol of pulverized potassium hydroxide, 30 mmol of ethyl acetate, 10 WLt, and mol of ethyl alcohol were added, and the mixture was allowed to react under reflux and stirring for 18 hours.

After the reaction, the reaction mixture was treated according to a conventional method and then analyzed by gas chromatography.

As a result, it was found that ethyl acetoacetate was produced at a yield of 43% based on the added ethyl acetate. Example 31 Into the same reactor as in Example 1, 40 mmol of micronized potassium hydroxide, 20 mmol of benzaldehyde, 25 mmol of ethyl chloroacetate, and 10 rf diethyl ether were added.
Lt, and C, Hl, O(C2H4O)6. ,C8H
, 1.0 mmol was added, the flask was immersed in a dry ice acetone bath, and stirring was started.

Thereafter, the reaction temperature was gradually raised to room temperature, stirring was continued, and the reaction was carried out for a total of 3 hours. After the reaction, the reaction mixture was analyzed using gas chromatography, and it was found that β-
It was found that ethoxycarbonyl-styrene oxide was produced in a yield of 68%. Example 32 In a reactor similar to Example 1, 10 mmol of pulverized potassium hydroxide, 10 mmol of phenylacetylene, 5 mtl of acetone and Cl8H3,O (C2H4O),
1.0 mmol of 0C4H was added, and the mixture was reacted at 50° C. for 4 hours with vigorous stirring.

After the reaction, the reaction mixture was treated according to a conventional method and analyzed by gas chromatography, which revealed that 7.6 mmol of 1-phenyl-3-methyl-1-butyn-3-ol was produced. I understood. Example 33 In the same reactor as in Example 1, 10 mmol of micronized potassium hydroxide, 10 α of benzene, and C8Hl,O(
C, H4O)6. , C8H,, 1.0 mmol, and while stirring at room temperature, acetylene gas was added at 1 e/Hr.
It was injected at Q speed for 1 hour.

Thereafter, while continuing to introduce acetylene gas, a solution of 50% acetone in benzene (10 -) was gradually added over 1 hour while stirring at room temperature. Thereafter, the reaction mixture was treated according to a conventional method, and the product was analyzed by gas chromatography. 3-Methyl-1-butyn-3-ol is 5.
2 mmol was obtained. Example 34 and Comparative Example 9 In the same reactor as in Example 1, 73 mmol of micronized potassium hydroxide, 24 mmol of penzyl acetonitrile, and 20 T! Lt and C, Hl, -0(C2H4O
),. , C.H., l. 0 mmol was added and stirred for 10 minutes at room temperature.

After the reaction mixture was treated in a conventional manner, the reaction product was analyzed by gas chromatography, and it was found that 9 pendylic acids were present.
It was produced with a yield of 8%. On the other hand, the reaction was carried out for 1 hour under the same reaction conditions (room temperature) as in Example 34 except that no polyoxyalkylene compound was added (Comparative Example 9), but no benzylic acid was produced.

Example 35 Using the same reaction apparatus as in Example 1, while thoroughly purging the inside of the flask with dry nitrogen gas, 40 mmol of sodium amide, 20 mmol of benzyl methyl ether, 10 i of n-hexane, and Cl, H2, O (C2H4O) were added. 10C
1.2 mmol of 8H was added and the reaction was allowed to proceed for 10 hours at 0° C. with vigorous stirring.

After the reaction, the reaction mixture was treated in a conventional manner, and the reaction product was analyzed by gas chromatography. 4.6 mmol of α-methylpenzyl alcohol was obtained. Example
36 Using the same reaction apparatus as in Example 1, the inside of the flask was thoroughly replaced with dry nitrogen gas, and then 40 mmol of potassium amide, 10 mmol of 2,7-octadienyl allyl ether, and C8Hl7O(C,H4O)7C4H,1 were added. .5 mmol and 20 tfLt of diethyl ether were added, and the reaction was allowed to proceed at -40°C for 10 hours with vigorous stirring.

Claims (1)

[Claims] 1. (1) carbene reaction by elimination of hydrogen halide, which is contacted by a basic alkali metal compound (excluding organometallic compounds having a carbon-metal bond) in an organic liquid; ylide reaction or ring-closing reaction, (2) substitution reaction of active hydrogen of an active hydrogen compound with an organic group, (3) addition reaction of an active hydrogen compound to an activated unsaturated compound, (
4) When performing an organic ion reaction selected from the group consisting of an addition reaction of an acetylene compound to a carbonyl compound, (5) a self- or heterogeneous condensation reaction of a carbonyl compound, and (6) a rearrangement reaction via a carbanion, the formula ▲
There are mathematical formulas, chemical formulas, tables, etc. (However, A has 2 carbon atoms.
- 4 (representing a straight chain or branched alkylene group), a polyoxyalkylene compound having an average of 6 or more structural units without forming a cyclic polyether structure is present in the reaction system. A method for promoting a base-catalyzed organic ion reaction, characterized by: 2 The polyoxyalkylene compound is an aliphatic alcohol,
The method according to claim 1, which is a polyaddition reaction product of an aliphatic hydrocarbon-substituted phenol or aliphatic amine and ethylene oxide or propylene oxide, or an etherified product of the polyaddition reaction product. 3. The method according to claim 1, wherein the alkali metal compound is a hydroxide, an alcoholate, or a phenolate.