JPS59222433A - Production of tertiary alcohol derivative - Google Patents

Abstract

PURPOSE:To obtain easily the titled compound without using an expensive silver salt, by reacting a carboxylic acid, an alcohl or phenol in the form of an o- trialkylsilyl derivative with a halide corresponding to a tertiary alcohol. CONSTITUTION:A compound of formula I (Y is a residue when a carboxylic acid, alcohol or phenol is expressed by YOH; R is hydrocarbon group) obtained by trialkylsilylating the carboxylic acid, etc. is reacted with a halide of formula II(X is halogen) corresponding to a tertiary alcohol of the formula Z3COH (Z is hydrocarbon group) if necessary in the presence of a Lewis acid, e.g. tetrafluorosilane, to afford the aimed tertiary alcohol derivative of formula III. The introduction of the triphenylmethyl group having improved property as a protecting group can be easily carried out.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) This invention relates to a novel reaction for obtaining tertiary alcohol derivatives of carboxylic acids, alcohols or phenols.

More specifically, a tertiary carbon is introduced onto the oxygen atom of carboxylic acid, alcohol or phenol to produce triphenyl methyl ester of carboxylic acid, tertiary butyl ester of carboxylic acid, triphenyl methyl ether of alcohol or haphenol, etc. This invention relates to a method for producing a tertiary alcohol derivative.

Triphenylmethyl group has excellent properties as a protective group, such as being easily removed under mild conditions and having good crystallinity of derivatives, and is suitable for carboxylic acids, alcohols, or phenols. esterification, which introduces
Etherification reactions are useful in the field of synthetic organic chemistry. Tertiary alcohol derivatives are also useful in their own right, such as triphenylmethyl methacrylate, which is used as a monomer to create polymers with optical resolution capabilities.

(Prior art) The reaction to produce carboxylic acids, alcohols, or alcohol derivatives of phenol is known as esterification or etherification reaction, and in the case of the group to be introduced is a group bonded at a primary carbon or secondary carbon, - This can be accomplished by a dehydration reaction using alcohol or secondary alcohol.

On the other hand, esterification and etherification using tertiary alcohols are different from those using primary and secondary alcohols, and dehydration reactions are extremely difficult. Particularly in the case of triphenylmethyl ester of carboxylic acid, it is known that the hydrolysis reaction, which is the reverse reaction, proceeds rapidly, and triphenylmethylation by dehydration reaction is generally impossible. Therefore, the conventional method has been to react triphenylmethyl ester with triphenylmethyl bromide and a carboxylic acid salt in a nonpolar solvent. In particular, in cases where side reactions are likely to occur, such as polymerizable acrylic esters, it is necessary to carry out the reaction using expensive silver salts.

For example, triphenylmethyl methacrylate is
r represents a triphenylmethyl group. ) Conventional methods that use small amounts of silver or bases as dehydrohalogenation agents have various problems, and despite their excellent properties as protecting groups, the triphenylmethylation reaction is difficult. It was not widely used.

The present inventor carried out a dehexaalkyldisiloxane reaction with a 0-tl alkylsilyl derivative of a carboxylic acid, alcohol, or phenol using a triphenylmethylating agent that was previously trialkylsilylated.
It has been discovered that o-triphenylmethylation, which is difficult to perform with dehydration reactions, can be easily carried out. This reaction is not limited to triphenylmethylation, but can be generally applied to reactions that produce tertiary alcohol derivatives, such as t-butylation. ) Based on the above-mentioned prior art, the present invention provides a method for producing tertiary alcohol derivatives that is easier to realize without using silver salts.A representative example of the present invention uses triphenylmethyl fluoride. However, the hydrogen fluoride used in the production of this starting material is easily obtained by the sulfuric acid decomposition of fluorite, which is currently the most widely used fluorine resource.Furthermore, 5IF4 used in the catalyst is produced from phosphate rock. It is an unused resource contained in waste gas during the process of manufacturing fertilizers.In this way, the present invention is a part of 7 elemental chemistry, which is expected to develop in the future.

(Structure of the Invention) The present invention provides (1) using a carboxylic acid, alcohol, or phenol in the form of an O-)I) alkylsilyl derivative as a substrate for a reaction such as triphenylmethylation, and (2) using this as a substrate for a reaction such as triphenylmethylation. (3) This is a manufacturing method to obtain a tertiary alcohol derivative corresponding to the substrate by reacting the tertiary alcohol with a halide corresponding to the substrate.A tertiary alcohol derivative is one in which a carbon atom bonded to three different carbon atoms is bonded to an oxygen atom. It means a bonded compound yoc2, (where Z is a group bonded through a carbon atom, and Y represents a residue when carboxylic acid, alcohol, or phenol is expressed as YOH).

The reaction of the present invention can be expressed as a general formula as shown in formula (2).

YOS i Rs 10Zs CX-+YOCZs +R
s S I The carboxylic acid, alcohol, and phenol may be polyvalent. R is a hydrocarbon group such as an alkyl group, a phenyl group, or a benzyl group, and examples of the alkyl group include lower alkyl groups such as methyl, ethyl, and butyl.

2 is a hydrocarbon group such as aryl, aralkyl, alkyl, or cycloalkyl, and may have a substituent such as alkoxy, acyloxy, halo, or dialkylamino that is inactive under the reaction conditions of the present invention; Z may be the same or different.

By selecting Z, it is possible to introduce groups with various tertiary carbons such as triphenylmethyl, t-butyl, p-methoxyphenyldiphenylmethyl, 1,1-bis(p-methoxyphenyl)benzyl, and naphthyldiphenylmethyl. The invention can be applied. X is a halogen atom, especially fluorine,
Bromine or chlorine.

Therefore, Z and CX are halides corresponding to the tertiary alcohol Z and (C)H.

In the present invention, if necessary, the reaction is carried out in the presence of tetrafluorosilane or other Lewis acid catalyst, but the reaction will be explained in a separate section.

(Raw materials) Carboxylic acid shown in the previous section (1), alcohol 31t phenol O-)! J alkylsilyl derivative, YO8i
R= is essentially the same as that used in the prior art described by the inventor Mangu, and is obtained by trialkylsilylation of YOH such as carboxylic acid.

For Z and CX, a chloride such as triphenylmethyl chloride used in the silver salt method shown in reaction formula (1) can be used, but in the present invention, which is characterized in that it is reacted with YO8iR3, the reaction Inferior to fluoride in terms of selectivity (Z
, COH is produced as a by-product). Bromide is also good in terms of selectivity, but fluoride is practically the best because triphenylmethyl bromide has low solubility in acetonitrile.

(Reaction conditions) The reaction is usually carried out in an inert organic solvent. A typical solvent is acetonitrile.

Others include paraffinic hydrocarbons such as n-pentane and n-hexane, halogenated hydrocarbons such as methylene chloride, chloroform, and 1゜2-dichloroethane, aromatic hydrocarbons such as benzene and toluene, and nitroalkanes such as nitromethane. Illustrated.

When using chloride or bromide as Z, CX,
The reaction can also proceed without a catalyst. However, when a fluoride is used, a catalyst is used since the reaction cannot be carried out quickly without a catalyst.

A typical catalyst is tetrafluorosilane SiF.
, is. Other Lewis acids, such as trimethylsilyl triflate (CHs )s 5iO8O= CF=
, BF-.

AICL I TiCL r 5TIC14 and the like are also effective as catalysts for this reaction. Among these, T iC1
Since 4 and 5nC14 reacted with acetonitrile to form a precipitate, they were reacted in a methylene chloride solvent. The amount of catalyst used is, for example, about 5 molti based on the substrate, but it may be increased or decreased as necessary. Generally, when a catalyst having a molar ratio of about 1 to 10 is used, the reaction can be carried out under mild conditions around room temperature or below. Of course, if there are no problems such as side reactions, the reaction temperature may be selected from a wider range of degrees, for example 0 to 100 degrees Celsius.

Example 1. (Triphenylmethyl methacrylate = TrMA)
Methacrylic acid trimethylsilyl ester (1.25 g,
7.91 mmol) and triphenylmethyl fluoride (2,07y, 7.91 mmol) in dry acetonitrile (2+-1') under an argon atmosphere at 141°C, tetrafluorosilane (0.08 mol/
diacetonitrile solution, 4.9cr71.0.3.9
6 mmol) was added. After stirring for 6 hours at the same temperature, the resulting yellow mixture was stirred with a phosphate buffer solution (80c4) containing potassium fluoride (8,02) at pH 7.4 at 0°C.
Pour into the mixture while stirring vigorously. The aqueous solution was extracted twice with a 2:1 mixture of ether/hexane (50c4) and the combined organic phases were washed with aqueous Na HCOs and brine, dried over anhydrous sodium sulfate and evaporated in vacuo.

When the remaining solid was recrystallized from hexane, TrMA
(2,42!F, 94% yield) was obtained as colorless columnar crystals.

Touch point 98-99℃ (literature value 101-102℃); IR (
CC14) 1725.1490.1140Crn-';
'HNMR (CDCl2) 61.99 (31(, dd
, J=1.0, 1.4Hz), 5.60 (LH
, m).

6.23 (LH, m), 7.2-7.5 (15H
, m); MS rrv/z 328 (M+).

260.259,243,183,165,105,8
5.83°77.

The above reaction was carried out in acetonitrile-d3 for 6 hours, and HNMR analysis of the reaction mixture revealed that the theoretical trimethylfluorosilane (δ0.21.d.

J(+H,F=7.' 5 Hz) was found along with triphenylmethyl methacrylate.

Example 2 (triphenylmethyl decanoate) Decanoic acid trimethylsilyl ester (232η.

0.95 rr+mol), triphenylmethyl fluoride (249ml+.

0.95 mol) and SiF, (0.08 mol/dm'
Acetonitrile solution 0.62crt1.0.05. mm
ol) was dissolved in acetonitrile (2.5 crl) and stirred at 16°C for 6 hours. The reaction mixture was treated in the same manner as in Example 1, and an oily residue was obtained, which was chromatographed on silica gel coated with triethylamine (2%) using a mixture of hexane and ether (5:1) as the developing solution. Pure triphenylmethyl decanoate was obtained as a colorless oil (361 cm, 88%).

IR (CC14') 1760.1500.1150
cm-';'H' NMR (cDcl,) δ0.8.
7 (3H, br t, J=6.0 Hz), 1.
0.7-1.73 (14H, m)2.43 (2
H,t,J, =6.8Hz) 7.1-7,.
4 (15H,, m); MS, m/z 414 (M
+L 260.259°244.243,165,78
．． 77.

Example 3 (triphenylmethyl benzoate) Benzoic acid trimethylsilyl ester (372+++y.

1.92 mmol) + triphenylmethyl fluoride (5
03rq, 1.92mmol) + and tetrafluorosilay (0.08mol/d-acetonitrile solution, 1
．． 2c40.11 lesson o1) in acetonitrile (4cJ)
and stirred at 16°C for 4 hours. Example 1 reaction mixture
and recrystallized from a 10:1 mixture of hexane and benzene to give triphenylmethyl benzoate (671 m
r, 96%) was obtained as colorless platelets. mp 170-
171℃, (literature value 168-170℃); IR(C
C14) 1740.1600, 1500°1270
C1n-';'HNMR (CDC13) 67.1-7.
6 (18H, m).

8.13 (2H, dd, J= 1.j, 7.8.
Hz) ; MS-364 (M+), 260.25
9.244.243.85.83.

Example 4 (n-octylt IJ phenylmethyl ether) triphenylmethyl fluoride (210my, 0.8mmo
l) to tetrafluorosilane (0.04 mol/mountain zeacetonitrile solution, 1 crtl, 0.04 mmol)
) was added to the resulting yellow solution, and n-octyltrimethylsilyl ether (162,my, 0.8 plate o1
) is added dropwise at 18° C. at a rate that does not cause the yellow color to disappear (it takes about 1.5 hours) to complete the reaction. The reaction mixture was treated in the same manner as in Example 2.
(2, 90%) was obtained as a colorless oil.

IR (CCI4) 1590, 1480. 108
0, 1060crn-'; InNMR (CDC1
．． ) δ 0.85 (3H., t, J = 6Hz)
, 1.1-1, 7. (12H,'m), 3.03(
2H, t, J = -6Hz), 7.1 -7, 5 (15H
, m).

Example 5 (Phenyltriphenylmethyl ether) Phenyltrimethylsilyl ether (166η.

1,0 mmol), triphenylmethyl fluoride 1
, 0rnmol) + and SiF. (0.0 8 mol/dn? Acetonitrile solution + 0.6 3C4,
o. o 5 mmol) in acetonitrile (2 ctd)
and stirred at 15°C for 24 hours. The procedure was repeated in the same manner as in Example 2, and the desired product (286 ml, 85%) was obtained as a colorless oil (developing solution: hexane-ethyl 30:1 mixture). When this oil was recrystallized from an ethanol solution, colorless columnar crystals were obtained.

mp103-104℃ (literature value 103℃); IR (
CCI4) 1600, 1500. 1450. 12
20z-': 'H NMR (CDCl2) δ6,6-
7,1 (5H, m) 7.1-7.5 (1 5
H, m); MS m/z244, 243,165
,94.

Example 6 (Catalyst) Trimethylsilyl methacrylate and triphenylmethyl fluoride were reacted in the same manner as in Example 1 using a colored catalyst instead of tetrafluorosilane.

Unless otherwise specified, as in the case of S i F4, the catalyst has a 5 molar ratio to the substrate, the solvent is acetonitrile, and the reaction temperature is room temperature.

(1) (CH3)ssiOsOzcFi 80% yield of target product TrMA after 6 hours reaction (2) AlCl2 Target product TrMA after 14 hours reaction
MA yield: 85% (3) BF3/OEt2 After overnight (18 hours) using 5 mol of catalyst, the reaction reached 40%. It took an additional 4 hours to complete. TrMA yield: 86 cm (4) Since the catalyst of TiCl- (4) (5) reacted with acetonitrile to form a precipitate, methylene chloride was used as the solvent.

The reaction solution becomes colorless after 4 hours at room temperature. The reaction had already finished.

TrMA yield 89% (5) SnCl- methylene chloride solvent, short time (
Condensation progressed in less than 0.5 hours), but when the same treatment as in Example 1 was carried out, it decomposed to become tidriphenylmethyl alcohol.

(6) Even when a large amount of HF (100 to 120 mol%) was used, the reaction did not proceed.

The TrMA obtained in (1) to (4) was confirmed by 'H NMR and melting point matching that of the standard product.

Column 7 Trimethylsilyl methacrylate (158■, 1■01)
and triphenylmethyl bromide (323 mr, 1 mmol
) was dissolved in acetonitrile (30 mg) and incubated at 16°C.
Stir for hours. It was confirmed by thin layer chromatography that the target product was quantitatively produced.

Example 8 Trimethylsilyl methacrylate (158+++p, 1
mrnol) and triphenylmethyl chloride (279rq
, 1 mmol) was dissolved in acetonitrile (30 yd) and stirred at 16°C for 2 hours. It was confirmed by thin layer chromatography that the target substance TrMA and triphenylmethyl alcohol were produced in a ratio of 6:4.

Claims (1)

[Claims] A method for producing a tertiary alcohol derivative of a carboxylic acid, alcohol, or phenol, which comprises reacting an O-trialkylsilyl derivative of a carboxylic acid, alcohol, or phenol with a halide corresponding to the tertiary alcohol.