JPH02172967A - Production of carbonic acid ester - Google Patents

Abstract

PURPOSE:To obtain the subject compound useful as an introducing reagent in high yield and efficiency in an easily separable state by reacting di-t-butyl dicarbonate with a p-dialkyl-sulfoniophenol in the presence of a specific amine. CONSTITUTION:The objective carbonic acid ester of formula II (t-Bu is t-butyl) can be produced by reacting d-t-butyl dicarbonate with a p-dialkylsulfoniophenol of formula I (R<1> and R<2> are alkyl; Y<-> is halogen anion, perchlorate radical, etc.; X is H, halogen, etc.) in the presence of three kinds of amines comprising secondary amines having a structure containing two secondary alkyl groups bonded to N atom (e.g. dicyclohexylamine or di-sec-butylamine) or tertiary amines having the above structure (e.g. dicyclo-hexylmethylamine) and pyridine derivatives having substituents at 2 and 6-sites (e.g. 2,6-lutidine). The compound of formula II exhibits excellent acylating action in aqueous solution.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing a carbonate ester. More specifically, the present invention relates to a method for producing a carbonate ester represented by the following general formula (1).

X (In the above general formula (I), t-Bu is a t-butyl group. R1 and R2 are the same or different alkyl groups. X is a hydrogen atom, a halogen atom, or an alkyl group. .Y- is a halogen anion, perchlorate group, alkyl sulfate group, hydrogen sulfate group, or p-
It is either a 1-luenesulfonic acid group. ) The carbonate ester of the present invention exhibits an excellent acylation effect in an aqueous solution, so it is used as a protecting group in the field of organic synthetic chemistry such as peptide synthesis.
-BuOCO-1 (hereinafter abbreviated as Boc) is a useful compound as a reagent for introducing a group.

[Conventional technology and its problems]

The compounds produced according to the invention belong to mixed carbonate esters containing phenolic components.

Conventionally, the method of esterifying a compound having a phenolic hydroxyl group such as p-dimethylsulfoniophenol/methyl sulfate as a phenol component involves using an acid halide in the presence of a tertiary amine such as triethylamine. A method is known from JP-A-63-8365.

However, when applying the above method to a sulfonium compound such as p-dimethylsulfoniophenol methylsulfate to synthesize p-(t-butyloxycarbonyloxy)phenyldimethylsulfonium methylsulfate, the corresponding acid As the halide, an alkyloxycarbonyl halide such as t-butyloxycarbonyl chloride is used, but since this compound is generally a very unstable substance, the target compound can only be obtained in low yield by conventional methods. do not have. In addition, because the solubility of the target product in various solvents is similar to that of the by-product organic amine hydrochloride, it is difficult to separate it from the organic amine hydrochloride, requiring a complicated purification process, making it uneconomical. There was a point.

Furthermore, Chemistry [! xpress, Vol. 3, No. 1, pp. 45-48 (1988), di-t-butyl dicarbonate and p-dimethylsulfoniophenol methyl sulfate were reacted in the presence of triethylamine, and the present invention p-(t
-butyloxycarbonyloxy)phenyldimethylsulfonium methyl sulfate was obtained, but the yield remained low.

The present invention provides a method for efficiently obtaining a highly pure target product without using the conventionally used acid halopanide, in which the product can be easily separated.

[Means for solving problems]

As a result of intensive studies to solve the above-mentioned problems, the present inventors discovered an advantageous method for synthesizing the carbonate ester of the present invention represented by the following general formula (I), and completed the present invention. I ended up letting it happen.

That is, the present invention combines di-t-butyl dicarbonate and p-dialkylsulfoniophenol represented by the following general formula (II) into the following (A), (B) or (C
) is a method for producing a carbonic acid ester represented by general formula (I), which is characterized in that the reaction is carried out in the presence of at least one amine selected from the group defined by formula (I).

(In the above general formulas (I) and (n), t-Bu is t-
It is a butyl group. R' and R'' are alkyl groups that are the same or different from each other. X is a hydrogen atom, a halogen atom, or an alkyl group.

Y- is either a halogen anion, a perchlorate group, an alkyl sulfate group, a hydrogen sulfate group, or a p-)luenesulfonate group. ) (A) A secondary amine having a structure in which two secondary alkyl groups are bonded to a nitrogen atom.

(B) A tertiary amine having a structure in which two secondary alkyl groups are bonded to a nitrogen atom.

(C) A pyridine derivative having a substituent at the 2.6-position.

The amines specified as (A), (B), and (C) above used in the present invention generally have "two carbon chains branched on the first carbon bonded to the nitrogen atom". It can also be defined as "an amine having a structure".

As such amines, for example, those belonging to (A) include synchhexylamine, di-5ec-butylamine, diisopropylamine, dimethylpiperidine, and 2,5-dimethylpyrrolidine, and those belonging to (B) include synchhexylmethyl. Amine, diisopropylethylamine, synchhexylethylamine, (C
) include 2.6-lutidine, 2.4.
Examples include 6-collidine.

The alkyl groups R1 and R2 in the above general formulas (1) and (II) are preferably lower alkyl groups having 1 to 4 carbon atoms, and among these, methyl groups are particularly preferable. Substituent X in general formula (I) and general formula (n) is preferably a hydrogen atom, but is appropriately selected depending on the solubility and acylation reactivity of the target compound represented by general formula (I).

When X is an alkyl group, a lower alkyl group having 1 to 4 carbon atoms is preferred.

In addition, the anion Y- in the general formula (I) and the general formula (II) is preferably an alkyl sulfate group or a hydrogen sulfate group from the viewpoint of water solubility of the target compound represented by the general formula (I). The methyl sulfate group is particularly preferred.

The method for producing a carbonate ester according to the present invention includes, as described above, a sulfoniophenol represented by the general formula (n);
Di-t-butyl dicarbonate (hereinafter referred to as (Boc) 20
This method involves reacting the above-mentioned (A) with a sulfoniophenol dissolved in a solvent.
, (B) and (C), and (BOC) 20 is added to this mixture, but the order of addition is limited to this. However, the order of addition may be changed.

The amount of (Boc) used in the present invention, 0 is the general formula (
The p-dialkylsulfony represented by II) is 1.0 to 2.0 times the mole amount, preferably 1.0 to 1.5 times the mole amount, relative to t-phenol.

The amount of amine used is determined by p of the general formula (n).
-0.5 to 2 for dialkylsulfoniophenol
．． 0 times the mole, preferably 1.0 to 1.5 times the mole.

The solvent used in the reaction of the present invention is preferably one that can dissolve the raw material sulfoniophenols to some extent. Examples of such solvents include aprotic polar solvents such as acetonitrile and N,N-dimethylformamide, ethers such as ether and tetrahydrofuran, and halogenated hydrocarbons such as dichloromethane.

Among these, acetonitrile and N,N-dimethylformamide are particularly preferred solvents.

A preferable amount of the solvent is 1 to 15 β, particularly preferably 3 to 10 Il, per mole of the sulfoniophenol represented by the general formula (If).

In the method of the present invention, if the reaction temperature is too low, the reaction will be slow, and if it is too high, it will be an exothermic reaction, making it difficult to control the reaction. , it is particularly suitable to carry out the reaction in the range of -1O<0>C to 30<0>C.

In addition, the reaction time depends on the reaction temperature, but is usually 1 to 20
The time is appropriate.

By the method of the present invention, a sulfoniophenol represented by the general formula (II) and (BOC) 20 are reacted, and after the reaction is completed, if solid is generated in the reaction solution, the solid is filtered. After that, the desired product is obtained as crystals by concentrating and adding a poor solvent such as ethyl acetate.

[Example] The present invention will be specifically explained below using Examples.

Example 1 1.33 g of p-dimethylsulfoniophenol methyl sulfate (5,0 mm
ol), dry acetonitrile 40 rnl, 2.6-
0.536 g (5,0 mmol) of lutidine was added in this order, and the mixture was stirred at room temperature for 1 hour under a nitrogen stream.

This reaction solution was cooled to 0°C, and (Boc) 20 1.3
Add 1g (6,0rnrnol) and return to room temperature 5
After stirring for an hour, the reaction solution was concentrated to about 10 parts, and 10 parts of ethyl acetate was added to obtain crystals of the product.

The product p-(t-butyloxycarbonyloxy)
The yield of phenyldimethylsulfonium methyl sulfate was 1.73 g (4.72 mmol, yield 94.4%).

Melting point: 118-121℃ (decomposition) 'H-NMR: δ=1.54 (9tl, s,
t-Bu) (CDC1,) 3,43
(6B, s, ”5ue) 3.66 (3■.

? , 39 (2) 1゜ 8.17 (2B.

IR (KBr): 1760cm-'1245c
m-'1160cm-'.

s, MeSO4-' d, J=10Hz, Ph) d, J=10Hz, Ph) (υC=O).

1230cm-'101101O' Examples 2 to 6 The same operation as in Example 1 was performed except that the amines shown in Table 1 were used. The results are shown in Table 1 (however, in the case of synchlohexylamine and diisopropylamine, a filtering operation was required).

Table 1 (Synthesis of p-(t-butyloxycarbonyloxy)phenyldimethylsulfonium methyl sulfate) [Effects of the invention] According to the method of the present invention, it can be used widely as a protecting group in the field of organic synthetic chemistry such as peptide synthesis. It is possible to efficiently produce a highly pure carbonate ester represented by the general formula (I), which is a compound useful as a reagent for introducing the t-butyloxycarbonyl group used.

Patent applicant: Mitsubishi Gas Chemical Co., Ltd. Agent: Patent attorney: Sadafumi Pediatrics Procedural amendment July 1999 lfL day

Claims (2)

[Claims] (1) In the presence of at least one amine selected from the group defined by (A), (B) or (C) below,
1. A method for producing a carbonate ester represented by general formula (I), which comprises reacting t-butyl dicarbonate and p-dialkylsulfoniophenol represented by general formula (II) below. (A) A secondary amine having a structure in which two secondary alkyl groups are bonded to a nitrogen atom. (B) A tertiary amine having a structure in which two secondary alkyl groups are bonded to a nitrogen atom. (C) A pyridine derivative having substituents at the 2 and 6 positions. General formula (I): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ General formula (II): ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the above general formulas (I) and (II), t-Bu is t
-butyl group. R^1 and R^2 are the same or different alkyl groups. X is a hydrogen atom, a halogen atom or an alkyl group. Y^- is either a halogen anion, a perchlorate group, an alkyl sulfate group, a hydrogen sulfate group, or a p-toluenesulfonate group. ) (2) In claim 1, the amine belonging to the above (A) is synchhexylamine, di-sec-butylamine, diisopropylamine, dimethylpiperidine, 2
,5-dimethylpyrrolidine, and the amines belonging to (B) are synchhexylmethylamine, diisopropylethylamine, and synchhexylethylamine, and (
The amines belonging to C) are 2,6-lutidine, 2,4,5-
2. The method according to claim 1, wherein the collidine is collidine.