JPS61148186A - Production of organic germanium compound - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a medicinal drug having hypotensive activity and antitumor activity, easily in high yield, without forming a trialkoxy compound as an intermediate, by reacting an organic germanium compound with triethanolamine. CONSTITUTION:The compound of formula II having atrane skeleton can be produced by reacting an organic germanium compound of formula I (R1-R3 are H, lower alkyl such as methyl, ethyl, etc., or phenyl; Y is amino or O-lower alkyl such as methyl, ethyl, etc., or phenyl; Y is amino or O-lower alkyl alkyl; Z is O or S) with triethanolamine of formula N(CH2-CH2-OH)3 in a solvent such as benzene, optionally under refluxing, and post-treating the reaction product by conventional method.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing an organic germanium compound.

[Conventional technology]

Germanium Ge, a type of metal, has long been the subject of research as a semiconductor, but recently there has been research into its organic compounds.

Research results have become actively published1.
For example, a compound called carboxyethyl germanium sesquioxide, represented by the formula (GeCH2CH1C○0HhOJ), has extremely strong hypotensive effects and anti-11!
On the other hand, it exhibits physiological activities such as tumor action.

Germanium
In particular, these organic compounds have attracted attention from various technical fields.

On the other hand, the inventors of the present invention have been involved in research on organic germanium compounds for a long time. He has completed the invention of germanium compounds and has already applied for a patent (see Japanese Patent Publication No. 43479/1983).

[Problem that the invention seeks to solve]

However, in the invention related to the above patent application, as shown in the reaction formula below, trichlorogermylpropionic acid derivative (■) is treated with an alkoxide in alcohol to form a trialkoxy compound (■), which is then reacted with triethanolamine. However, since the above-mentioned atran-type compound (2) was obtained, there were still some points that needed to be improved.

In other words, as long as the above synthetic route is adopted, it is necessary to pass through the trialkoxy form (2) as an intermediate, but since this trialkoxy form (2) is relatively unstable, the total yield of the atran-type compound (2) is limited. The yield was not good and the synthesis procedure was complicated, and furthermore, since alkoxide was used in the synthesis of the trialkoxy derivative (■),
When the oxygen functional group of the trichlorogermylpropionic acid derivative (1) is a free carboxylic acid, there is a problem in that the desired atlane-type compound cannot be obtained directly.

[Means for solving problems]

The present invention was made against the background of the above-mentioned circumstances, and is composed of the general formula (wherein R, R, and RB are hydrogen atoms, lower alkyl groups such as methyl group and ethyl group, or substituted or unsubstituted a phenyl group, Y represents a hydroxyl group, an amino group, or a 〇-lower alkyl group, and Z represents an oxygen atom or a sulfur atom, respectively), and triethanolamine N (CHz (: Hl OH)3 ...(II
By reacting with I), a compound of the general formula (wherein R1 to R3 and Y are the same as defined above) can be obtained.

) is characterized by producing an organic germanium compound represented by:

The present invention will be explained in detail below.

The production method of the present invention uses germanium sesquioxide (Z=○ in (■)) or germanium trisulfide (Z=S in (■)) as a starting material as described above. Since an organic germanium compound with an atran skeleton is synthesized in one step, we will first explain germanium sesquioxide (■'), which is one of the starting materials. , R3
A compound in which a substituted germylpropionic acid derivative in which a and an oxygen functional group COY are bonded and an oxygen atom are bonded in a ratio of 2:3, and as shown in Reaction Formula 1 below, It can be easily synthesized by adding trichlorogermane C1,1GeH and then subjecting it to a hydrolysis reaction.

Reaction formula 1 In addition, the remaining starting material germanium sesdisulfide (II
), the last hydrolysis reaction in the above reaction formula 1 may be replaced with a reaction using hydrogen sulfide, as shown in reaction formula 2 below.

Reaction formula 2 In any case, the substituents R1 to R3 represent a hydrogen atom or a lower alkyl group such as a methyl group, an ethyl group or a propyl group, a substituted or unsubstituted phenyl group, and an oxygen functional group. The substituent Y therein represents a hydroxyl group, an amino group, or a 〇-lower alkyl group formed by the same alkyl group as above.

The compound to be reacted with this germanium sesquioxide (■') or germanium sesdisulfide (■) is triethanolamine N (CH, CH2LOH), (m), and this triethanolamine (m) is used as a reagent. Commercially available ones can be used.

The above-described reaction of germanium sesquioxide (■') or hakelmanium sesdisulfide (TI) with triethanolamine (m) can be carried out in an appropriate solvent 2, for example, benzene.
The organic germanium compound (1) having an atran skeleton can be obtained by carrying out refluxing as necessary and post-processing according to a conventional method.

The structure of the obtained organic germanium compound (H) was determined in part by comparing various physicochemical data with that published in the patent publication mentioned above, and in other respects by comparing various physicochemical data measured. This was confirmed by analyzing the data.

(Effects of the Invention) According to the present invention, it is possible to synthesize an atran skeleton compound (summer) without going through the trialkoxy compound, which is relatively unstable and reduces the total yield. Since the operation can be simplified, the total yield can be expected to improve, and there is no need to use an alkoxide, a compound (T) having a free carboxyl group, etc.
However, it has the advantage of being easily synthesized.

[Example] 1゜ Examples of the Nariki invention will be described.

■Synthesis of 71-ran-type compound from germanium sesquioxide ■Compound (general formula (1) L: inte, R+ =F?-a=)-1
-Rz4.

3-germyl-3-phenylpropionic acid triliethanolamine 3 g (0.02 mo1.) and 100 m1
．． (7) The mixture was placed in a Kolben, and 50 ml of benzene was added thereto, heated to reflux, and the reaction was carried out for 8 hours while removing the azeotropic water-benzene mixture from the reaction system. The powdered crystals obtained by distilling off the solvent were recrystallized from ethanol-hexane to obtain 4.38 g of the target compound. The yield was 60%.

Melting point = 178°C [R: 1650,900,620,580 Elemental analysis: HN Calculated value 48.97 5.75 3.81 Experimental value 49.11 5.78 3.78 ■Synthesis operation almost same as above ■ As a result, other atlan-type compounds were also synthesized from germanium sesquioxide, and these compounds and physicochemical data are illustrated below.

Conflict-a, Compound N (CHzCHzO)i GeCII, C
H, COOH yield: 80% NMR: 1.56 (2H, t) 2.46 (
21,t,) 3.46(6H,t) 3.93(
6H,t,)IR: 1670,920,910
,900,580 Melting point: 228℃ Elemental analysis: CHN Calculated value 49.10 6.04 7.63 Experimental value 49.13 6.11 7.7ON M
R: 2.70 (so, t) 2.95 (2H
, d) 3.00 (IH, t,) 3.65 (6)
1. t,)IR: 3410-3200,31
00.1680~1650 Melting point = 177℃ Elemental analysis: HN Calculated value 37.16 6.19 9.63 Experimental value 37.22 6.11"9.77N M R
: 1.08(2H,t,) 2.38(
211, t) 2.91 (611, t) 3.75
(6H,t)IR: 3520-3200,16
60,1620.9002, Synthesis of atlan-type compound from germanium sesdisulfide ■Compound (in general formula (1), R1=R3=H, R2=0°3-germyl-3-phenylpropionic acid attriethanol) 3.00 g (0.02 mol) of amine was heated under reflux in benzene for 7 hours. After the reaction, the precipitated crystals were collected by filtration and recrystallized from methanol-ether to obtain 3.1 g of the above compound. The yield was 86
%Met.

Put 2.7 g (0,0185 mo, L) of tritriethanolamine (3-gelmyloyl-3-phenylpropionic acid) into a 100 ml container, add 30% benzene,
The mixture was heated under reflux for 8 hours. The crystals obtained by distilling off the solvent were recrystallized from ethanol-hexane to obtain 3.6 g of the desired compound. The yield was 53%.

In addition, the physicochemical data of the obtained compound are as described in l-■ above.
This was consistent with the data obtained.

・3I Other 71-ran type compounds could be synthesized from germanium sesdisulfide by the same synthetic procedure as in (1) above, and the physicochemical data of these compounds were consistent with those described above.

Since the present invention is as described above, it is extremely excellent as a method for producing organic germanium compounds.

Claims (1)

[Claims] General formula▲ Numerical formulas, chemical formulas, tables, etc.▼・・・・・・(II) (In the formula, R_1, R_2, R_3 are hydrogen atoms or lower alkyl groups such as methyl group, ethyl group, etc. or a substituted or unsubstituted phenyl group, Y represents a hydroxyl group, an amino group, or an O-lower alkyl group, and Z represents an oxygen atom or a sulfur atom, respectively. CH_2-OH)_3...(
By reacting with III), an organic germanium compound represented by the general formula ▲mathematical formula, chemical formula, table, etc.▼...(I) (wherein R_1 to R_3 and Y are the same as defined above) A method for producing an organic germanium compound, the method comprising: producing an organic germanium compound.