JPH0364489B2 - - Google Patents

Description

[Detailed description of the invention]

(Technical Field of the Invention) The present invention relates to a method for synthesizing β-alkoxy alcohol, which is a protected glycol derivative important in organic synthesis, by ring-opening addition of alcohol to an epoxy compound. (Prior art and problems) Conventionally, by adding alcohol to epoxide, β-
It is already known that the reaction to form an alkoxy alcohol can be carried out using various acids, and it has also been proposed to simplify the operation by using a heterogeneous catalyst (Japanese Patent Publication No. 47-197- Publication No. 20606,
Tetrahedron Lett.3597 (1975) etc.). However, the products obtained by any of these methods differ in the addition position of the alkoxy group as shown in the reaction formula () below.
The result was a mixture of (1) and (2), which was not satisfactory as a method for synthesizing highly regioselective β-alkoxy alcohols. (Objective of the Invention) The present invention provides a method capable of producing one of the β-alkoxy alcohols in an extremely selective manner that has not been possible with the prior art. (Structure of the Invention) The present invention involves the addition of an organic tin compound selected from the group (A) below and a complete or partial alkyl ester of a phosphoric acid selected from the group (B) below when ring-opening addition of an alcohol to an epoxide. This is a method for synthesizing β-alkoxy alcohol, characterized by the presence of a thermal condensation product as a catalyst. Group (A); RaSnX ₄ -a (A-1) (However, in the above formula (A-1), R is an aliphatic or aromatic hydrocarbon group having 1 to 12 carbon atoms, and these groups are , may have a substituent containing a hetero atom.Also, when a=2 or more, R may be the same or different.X is a hydrogen atom, a halogen atom, a hydroxy group, an alkoxy group, an aryloxy group, and acyloxy group, and when a=2 or 1, X may be the same or different. a is an integer of 1 to 4.) In formula (A-2), R is (A-
It is the same as R in formula 1). d is 1 or 2
, when d=1, e=3/2, and when d=2, e
=1. Moreover, the compound of formula (A-2) is (A-
It may form a complex with the compound of formula 1). ) (B) group; (HO) ₃ P=O (B-1) The above-mentioned catalyst used in the present invention is a part of catalysts already disclosed by the present applicant as ring-opening polymerization catalysts for three-membered ring epoxides (US Pat. No. 3,773,694). The method of the invention has a very high degree of regioselectivity. Although the reason for this is not clear, it is thought that it is related to the fact that a polymer having extremely high stereoregularity can be obtained by ring-opening polymerization of epoxide using the above catalyst. Conventionally, it is known that the acid strength of organic tin compounds is usually extremely low, and their function as general acid catalysts is extremely low and almost unknown. In contrast, the organic tin-phosphoric acid alkyl ester thermal condensation product of the present invention exhibits high acid strength and exhibits unique functions as an organic tin compound. Specific examples of the group (A) organotin compounds of the catalyst of the present invention include the following. Representative compounds belonging to the above general formula (A- ₁ ) include ( _{C2H5 ) 4Sn ,} ( _C2H5 ) _SnBr3 , ( _C2H5 ) _3SnF ,
( _CH3 ) _3SnCl , ( _{C4H9 ) 3SnCl} , ( _C6H5 ) _{4Sn ,}
( _C8H19 ) _{3SnCl ,} ( _CH3 ) _{3SnBr ,} ( _C4H9 ) _{2SnCl2 ,}
(C ₄ H ₉ ) ₃ SnOC ₄ H ₉ , (C ₈ H ₁₇ ) ₃ SnOCOCH ₃ , Examples include (C ₆ H ₅ ) ₃ SnOH. Compounds belonging to the above general formula (A-2) include (CH ₃ ) ₂ SnO, (C ₄ H ₉ ) ₂ SnO, (C ₈ H ₁₇ ) ₂ SnO,
Examples include (C ₆ H ₅ ) ₂ SnO, CH ₃ SnO3/2, and C ₄ H ₉ SnO3/2. Further, examples of complexes of compounds of general formula (A-1) and general formula (A-2) include:
(CH ₃ ) ₂ SnO・(C ₂ H ₅ ) ₂ SnBr ₂ , (CH ₃ ) ₂ SnO・
(CH ₃ ) ₂ SnCl ₂ , CH ₃ [(CH ₃ ) ₂ SnO] ₂ OCH ₃・
Examples include (CH ₃ ) ₂ SnBr ₂ and the like. In the present invention, specific examples of complete or partial alkyl esters of phosphoric acids of group (B) include the following. (C ₂ H ₅ ) ₃ PO ₄ , (C ₃ H ₇ ) ₃ PO ₄ , (C ₄ H ₉ ) ₃ PO ₄ ,
(C ₈ H ₁₇ ) ₃ PO ₄ , (C ₁₂ H ₂₅ ) ₃ PO ₄ , (ClCH ₂ −
CH ₂ ) ₃ PO ₄ , (Cl ₂ C ₃ H ₅ ) ₃ PO ₄ , (C ₂ H ₅ ) ₂ HPO ₄ ,
( _{C4H9 ) 2HPO4 ,} ( _{C4H9 ) H2PO4 , ( C4H9 ) 4P2O7 ,}
(C ₄ H ₉ ) ₂ H ₂ P ₂ O _7In the present invention, the component (B) constituting the catalyst is (B)
A catalytic reaction product having a similar catalytic effect can also be obtained by directly adding a combination of component compounds capable of forming a catalytic reaction together with component (A) to the catalyst production reaction system. Examples of combinations of component compounds that can form such component (B) include (a) a combination of phosphorus oxyhalide and an alcohol having 1 to 12 carbon atoms and an epoxide; (b) a combination of the above general formula A combination of a phosphoric acid selected from (B-1) and (B-2) or a partial alkyl ester thereof and an alcohol having 1 to 12 carbon atoms or an epoxide (c) Phosphoric anhydride and an alcohol having 1 to 12 carbon atoms Examples include combinations with other groups. Examples of the oxyhalogenated phosphorus in (a) above include POCl ₃ , POBr ₃ , POI ₃ , (C ₂ H ₅ O)P(O)Cl,
Examples include (C ₈ H ₁₇ O) ₂ P(O)Br. Examples of alcohols include CH ₃ OH, C ₂ H ₅ OH, C ₃ H ₉ OH, C ₄ H ₉ OH,
C ₆ H ₁₃ OH, ClCH ₂ −CH ₂ OH, HOCH ₂ −
Examples of epoxides include CH ₂ OH.

【formula】

【formula】

【formula】

[Formula] etc. As the alcohols and epoxides in the above (b), the same ones as in the above (a) can be exemplified. The most preferable phosphoric anhydride in (c) above is P ₂ O ₅ . Further, examples of alcohols include those mentioned in (a) above. The thermal condensation product used in the present invention is usually 100%
It is produced by mixing and heating component (A) and component (B) or a combination of component compounds capable of forming component (A) and component (B) at ~300°C. A solvent may be used if necessary. Components (A) and (B) are used so that the ratio of tin atoms to phosphorus atoms contained is usually in the range of 1:10 to 10:1. In the reaction product obtained by the thermal condensation reaction as described above, various relatively simple substances are generated and eliminated by the condensation reaction, depending on the type of components. The resulting condensate exhibits the desired activity at various stages of the degree of condensation. The optimal degree of condensation varies depending on the type and ratio of components (A) and (B), but can be easily determined experimentally. Generally, condensates are initially soluble in various solvents such as hexane, benzene, and ether, but become insolubilized as the condensation reaction progresses. Any of these condensates, insoluble or soluble, can be used as a catalyst for the ring-opening addition reaction of the present invention. In particular, when an insoluble thermal condensate is used, the catalyst can be separated by simply filtering the reaction mixture after the addition reaction and can be used again. Epoxides applicable to the present invention include, for example, olefin oxides such as ethylene oxide, propylene oxide, and butadiene monoxide, alicyclic oxides such as cyclohexene oxide, aromatic oxides such as styrene oxide, butyl glycidyl ether, and allyl glycidyl oxide. Ethers, glycidyl ethers such as phenyl glycidyl ether, glycidyl esters such as glycidyl acetate, glycidyl propionate, glycidyl benzoate, ethylene glycol-bis-glycidyl ether, 4,4'-bisphenolmethane diglycidyl ether, butadiene Examples include polyepoxides such as diepoxide, glycidyl phthalate, and diglycidyl ether. Examples of alcohols that can be used for addition in the present invention include alcohols such as methanol, ethanol, propanol, butanol, allyl alcohol, hexanol, octanol, cyclohexanol, benzyl alcohol, and ethylene chlorohydrin, phenol, cresol, and naphthol. Examples include phenols, polyhydric alcohols such as ethylene glycol, and diethylene glycol. The ring-opening addition reaction of the present invention is accomplished by bringing a mixture of epoxide and alcohol into contact with the thermal condensation product. The amount of catalyst used, reaction temperature, etc. can be arbitrarily determined during implementation. The use of solvents is also optional. The alcohol is usually used in excess of the epoxide, and the ratio can be easily selected from a practical standpoint. (Effects of the Invention) The present invention has a high degree of regioselectivity in the ring-opening addition of an alcohol to an epoxide, so the desired product can be obtained easily and in high yield, and the present invention can be used as a method for producing raw materials for organic synthesis reactions. Useful. (Example) Examples 1 to 10 Using epoxides and alcohols shown in Table 1, in the presence of 1 g of a thermal condensation product of an organotin compound shown in (a) to (d) below and a phosphoric acid ester as a catalyst. perform a reaction. In Table 1, when the alcohol was methanol, 10 ml of methanol was used, and this itself was used as the solvent. In cases other than methanol, predetermined amounts of epoxide, alcohol, and catalyst were added to 10 ml of hexane and reacted. The reaction temperature was room temperature in Examples 2 and 6, and under reflux in the others. After the reaction was completed, the catalyst was filtered off and the product was purified by distillation or silica gel chromatography. The yield shown in Table 1 is the total amount of all addition compounds;
The other values are calculated values obtained by silica gel chromatography purification, and (1) and (2) in the product molar ratio represent (1) and (2) in the above reaction formula (), respectively. In Table 1, Ph represents a phenyl group and Ac represents an acetyl group. <Catalyst manufacturing method> Mix 0.1 mol of the organic tin compounds shown in (a) to (d) below and 0.2 mol of phosphoric acid ester, and heat to 240 to 260 mol under a nitrogen stream.
Heated under stirring at 0C for 30 minutes. At this time, a large amount of desorption products were distilled out. The residual pale yellow solid was cooled and pulverized for use. (B) (C ₄ H ₉ ) ₂ SnO+2 (C ₄ H ₉ ) ₃ PO ₄ (B) (C ₄ H ₉ ) ₃ SnCl+2 (C ₄ H ₉ ) ₃ PO ₄ (C) (C ₆ H ₅ ) ₂ SnCl+2(C ₂ H ₅ ) ₃ PO ₄ (d) CH ₃ SnO _3/2 +2(C ₄ H ₉ ) ₂ HPO ₄

【table】

[Table] Main products (1) obtained in each example and their
The analysis results by ¹ H-NMR characteristic absorption and thin layer chromatography (TLC) are shown below.

【table】

【table】

【table】

【table】

【table】

【table】

Claims (1)

[Claims] 1. When ring-opening addition of alcohol to epoxide, heat is applied between an organotin compound selected from the group (A) below and a complete or partial alkyl ester of a phosphoric acid selected from the group (B) below. Synthesis of β-alkoxy alcohol characterized by the presence of a condensation product as a catalyst. Group (A); RaSnX ₄ -a (A-1) (However, in the above formula (A-1), R is an aliphatic or aromatic hydrocarbon group having 1 to 12 carbon atoms, and these groups are , may have a substituent containing a hetero atom.Also, when a=2 or more, R may be the same or different.X is a hydrogen atom, a halogen atom, a hydroxy group, an alkoxy group, an aryloxy group, and acyloxy group, and when a=2 or 1, X may be the same or different. a is an integer of 1 to 4.) In formula (A-2), R is (A-
It is the same as R in formula 1). d is 1 or 2
, when d=1, e=3/2, and when d=2, e
=1. Moreover, the compound of formula (A-2) is (A-
It may form a complex with the compound of formula 1). ) (B) group; (HO) ₃ P=O (B-1)