JPH0617319B2 - Method for producing hydroxy compound - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for releasing a hydroxyl group from an organic compound such as alcohol, phenol or the like having a hydroxyl group protected.

(Prior Art) Generally, when synthesizing a plurality of organic compounds, it is often necessary to protect a hydroxyl group in a molecule. Therefore, a tetrahydropyranyl group or a silyl group is widely used as a useful protecting group. These protecting groups must be easily eliminated as necessary to restore the hydroxyl group, and the elimination / removal method for this purpose has conventionally been to remove acid catalysts such as sulfuric acid, hydrochloric acid, sulfonic acids and ion exchange resins. Is used. However, in many cases, these acid catalysts are not suitable for acid-sensitive compounds, and there is a disadvantage that they cause, for example, dehydration reaction, isomerization reaction, and tar formation. Further, the usual acid catalyst requires complicated steps such as neutralization and liquid separation operations in order to remove it from the reaction solution, and these steps may also cause the above-mentioned undesirable side reaction.

Further, if hydrofluoric acid is used as the method for removing the silyl group, it may be dangerous and requires special consideration. In addition to the above acid catalyst, lithium tetrafluoride, tetra-n-fluoride fluoride
Although a special reagent such as butylammonium is used, the reagent is expensive and a large amount is required for the silyl ether, which is economically disadvantageous.

Further, in general, a compound having two or more kinds of protected groups that are easily removed by an acid, for example, a compound containing a pyranyl etherified hydroxyl group and an acetalized aldehyde group is used to selectively remove only the pyranyl group. To date, there is no disclosure of a highly selective and highly active elimination catalyst in the reaction of releasing the hydroxyl group.

(Problems to be Solved by the Invention) The present invention generally provides a substance useful for depyranylation or desilylation in a reaction of an acid-sensitive compound, and therefore, a hydroxyl group available for the acid-sensitive compound. The aim is to provide a means of protection and a means of selective depyranylation and desilylation.

(Means for Solving Problems) The present invention provides the following general formula (I). (Wherein R ¹ , R ² and R ³ represent a hydrogen atom or a group selected from an alkyl group, an alkenyl group, an aryl group and an arylalkenyl group each having 1 to 12 carbon atoms,
R ¹ and R ² may be bonded to each other to form a cyclic structure.
Y represents a protective group for a hydroxyl group selected from a tetrahydropyranyl group and a silyl group.) When the protective group is removed from the organic compound to release the hydroxy compound, the following general formulas (i) and (i
a mixture of an organotin compound selected from i) and an alkyl phosphate ester is heated to 150 to 300 ° C. to obtain a condensation product having a tin atom to phosphorus atom ratio of 1:10 to 10: 1. A method for producing a hydroxy compound characterized by being used as a catalyst.

R _a SnX _4-a (i) (In the formula (i), R is an optionally substituted alkyl group having 1 to 12 carbon atoms, an alkenyl group, a cycloalkyl group, an aryl group and an aralkyl group. More preferably, X is a halogen atom, an alkoxy group, an aryloxy group, an acyloxy group, or a partial ester residue of phosphoric acid, and a is an integer of 1 to 4. When 2 or more, R may be the same or different, and when a is 1 or 2, X may be the same or different.) R _b SnO _c (ii) (provided that in the formula (ii), , R are the same as R in the formula (i), b is 1 or 2, when b is 1, c is 3/2, and when b is 2, c is 1. Also, i
The i) formula compound may form a complex with the (i) formula compound. ) This invention relates to U.S. Pat. No. 3,773,6 owned by the applicant.
The heat condensation product of the specific organotin compound (A) and the phosphoric acid alkyl ester (B) described in Japanese Patent No. 94 selects a protective group of a hydroxy compound protected by a tetrahydropyranyl group or a silyl group. By removing
It is based on the finding that it is very useful for the production of hydroxy compounds.

The following can be mentioned as specific examples of the organotin compound (A) of the formulas (i) to (ii) used in the present invention.

The compounds belonging to general formula _{(i), (C 2 H} 5) 4 Sn, (C 6 H 5) 4 Sn, (CH 3) 3 SnF, (C 4 H 9) 3 SnCl, (CH 3) 3 _{SnBr, (C 8 H 17)} 3 SnCl, (CH 3) 2 SnF 2, (C 4 H 9) 2 SnCl 2, (C 12 H 23) 2 SnBr 2, (cyclo-C 6 H 11) 2 SnI 2 _{, (C 4 H 9) SnF} 3, (C 8 H 17) SnCl 3, (C 4 H 9) 3 SnOC 4 H 9, _{(C 8 H 17) 3 SnOCOCH} 3, (C 8 H 17) 2 Sn (OCOC 17 H 35) 2, And so on.

The compounds belonging to general formula _{(ii), (CH 3)} 2 SnO, (C 4 H 9) 2 SnO, (C 8 H 17) 2 SnO, (C 6 H 5) 2 SnO, CH 3 SnO 3 / ₂ , C ₄ H ₉ SnO _{3/2 and the} like, and examples of the complex of the compounds of the general formula (i) and the general formula (ii) include (CH ₃ ) ₂ SnO. (C ₂ H ₅ ) ₂ SnBr _2, and the like _{(CH 3) 2 SnO · (} CH 3) 2 SnCl 2, CH 3 _{[(CH 3)} 2 SnO] _{2 CH 3 · (CH 3)} 2 SnBr 2.

As the phosphoric acid alkyl ester (B) which is another component constituting the catalyst of the present invention, a complete or partial ester of orthophosphoric acid represented by the following general formula (II) is particularly preferably used.

(R ² O) ₃ P = O (II) (In the formula (II), R ² is hydrogen or an alkyl group, an alkenyl group or a cycloalkyl group having 2 or more carbon atoms, and at least one of R ² is selected. is a group other than a hydrogen atom.) specific examples of the above formula (II) _{is, (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, (CH 2 = CH-CH 2) 3 PO 4, (C 6 H 11) PO 4, (ClCH 2 -CH 2) 3 PO 4, (Cl 2 C _{3 H 5) PO 4, (} C 2 H 5) 2 HPO 4, (C 4 H 9) 2 HPO 4, and the like _{(C 4 H 9) H 2} PO 4.

The catalyst of the present invention is obtained as a condensation product by heating a mixture of the organotin compound (A) and the phosphoric acid alkyl ester (B) in a temperature range of 150 ° C to 300 ° C.
The solvent may be used if necessary. The above-mentioned components (A) and (B) are used so that the ratio of tin atoms and phosphorus atoms usually contained is in the range of 1:10 to 10: 1.

In the catalyst formation reaction, various relatively simple substances are formed and eliminated by the condensation reaction according to the types of the component (A) and the component (B). The obtained condensate exhibits the desired activity at various stages of the degree of condensation. The optimum condensation degree varies depending on the types and ratios of the component (A) and the component (B), but they can be easily determined experimentally. The condensate is generally soluble in a solvent such as hexane or benzene at the initial stage, but becomes insoluble as the condensation reaction proceeds.

The organic compound that can be used in the present invention is a chain hydrocarbon, a cyclic hydrocarbon or an aromatic hydrocarbon represented by the above general formula (I), which may have a substituent and has one of the skeletons. Parts may be replaced by heteroatoms.

Representative examples include various alcohol compounds such as primary to tertiary alcohols, monohydric or polyhydric alcohols, phenol compounds, enol compounds and the like, in which the hydroxyl group is protected with Y.

Specific examples of Y include a tetrahydropyranyl group, a trialkylsilyl group represented by trimethylsilyl, triethylsilyl, tribenzylsilyl, and triphenylsilyl, a triaralkylsilyl group, or a triarylsilyl group.

The amount of the catalyst used is not particularly limited and can be selected within a wide range, but in general, the range of 10 to 200% by weight, preferably 50 to 150% by weight with respect to the substrate is most suitable.

When carrying out the present invention, as the solvent, hydrocarbons, halogenated hydrocarbons, ethers, alcohols and the like are used, and particularly, alcohol compounds such as methanol, ethanol, propanol and ethylene glycol monomethyl ether, or alcohols thereof. It is preferable to use a mixed solvent containing the compound.

The reaction temperature in the present invention is not particularly limited, but is generally 10 to 200 ° C, and usually 40 to 100 ° C is suitable.

Examples of the present invention will be shown below.

Production Example 1 of catalyst In a three-necked flask equipped with a stirrer, a thermometer and a distillation apparatus, 12.5 g of dibutyltin oxide and 2 of tributylphosphate were added.
6.6 g was added, and the mixture was heated at 250 ° C. for 20 minutes while stirring under a nitrogen stream to distill off the distillate, and a solid condensation product (1) was obtained as a residue.

Production Example 2 of Catalyst A solid condensation product (2) was obtained in the same manner as in Production Example 1 except that 10.5 g of tributyltin chloride and 17.4 g of tributyl phosphate were used and the reaction conditions were 250 ° C. for 30 minutes.

Examples 1 to 2 In a flask equipped with a stirrer, a thermometer and a reflux condenser, 200 m each of the above condensation product (1) or (2) as a catalyst was used.
g and 1 mmol of the hydroxy compound having a protecting group shown in Table 1 were added to 7 ml of methanol, and the reaction was carried out for 2 hours while heating under reflux with stirring. The reaction mixture was subjected to gas chromatography analysis to confirm that a hydroxy compound was produced. Examples 2, 6, 7, 1
In 0 and 11, the catalyst was further separated from the reaction mixture, the solvent was removed under reduced pressure, and then hexane: ethyl acetate = 10: 1.
Silica gel column (φ20mm x
The desired hydroxy compound was isolated by passing through 30 cm). . The results are shown in Table 1.

In Table 1, THP indicates a tetrahydropyranyl group, and the yield indicates the yield by gas chromatography (however, the isolated yield in parentheses).

Examples 13 to 15 Exactly the same as Examples 1 to 12 using equimolar amounts (1 mmol each) of a hydroxy compound protected by a tetrahydropyranyl group and a hydroxy compound protected by another substituent (excluding a silyl group). The reaction was carried out under various conditions. After the reaction, the hydroxy compound protected by a group other than the tetrahydropyranyl group remained unreacted.

The results are shown in Table 2.

Example 16 Using the catalyst recovered in Example 2, the same reaction as in Example 2 was carried out to obtain dodecyl alcohol in a yield of 90%.

(Effect of the Invention) According to the present invention, by using a specific catalyst, depyranylation or desilylation in a reaction of an acid-sensitive compound, which is disadvantageous in conventional acid catalysts, can be effectively performed. In addition, these reactions can be selectively and efficiently performed even when other reactive groups are present. Therefore, when a tetrahydropyranyl group or a silyl group is present as a protecting group for a hydroxy compound, the elimination reaction of these groups can be carried out smoothly, which is extremely useful in organic synthetic reactions.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical indication C07C 33/02 8827-4H 33/22 8827-4H 35/18 8827-4H // C07B 61/00 300

Claims (1)

[Claims] 1. The following general formula (I): (Wherein R ¹ , R ² and R ³ represent a hydrogen atom or a group selected from an alkyl group, an alkenyl group, an aryl group and an arylalkenyl group each having 1 to 12 carbon atoms,
R ¹ and R ² may combine with each other to form a cyclic structure. Y represents a protective group for a hydroxyl group selected from a tetrahydropyranyl group and a silyl group.) When the protective group is removed from the organic compound to release the hydroxy compound, the following general formulas (i) and (i
a mixture of an organotin compound selected from i) and an alkyl phosphate ester is heated to 150 to 300 ° C. to obtain a condensation product having a tin atom to phosphorus atom ratio of 1:10 to 10: 1. A method for producing a hydroxy compound, which is used as a catalyst. R _a SnX _4-a (i) (In the formula (i), R is an optionally substituted alkyl group having 1 to 12 carbon atoms, an alkenyl group, a cycloalkyl group, an aryl group and an aralkyl group. The group selected from X, X is an atom or a group selected from a halogen atom, an alkoxy group, an aryloxy group, an acyloxy group and a partial ester residue of phosphoric acid, and a is an integer of 1 to 4. a is 2 In the above case, R may be the same or different, and when a is 1 or 2, X may be the same or different.) R _b SnO _c (ii) (provided that in the formula (ii), R is the same as R in the formula (i), b is 1 or 2, c is 3/2 when b is 1 and c is 1 when b is 2.
The i) formula compound may form a complex with the (i) formula compound. )