JPH0692978A - Production of organogermanium compound - Google Patents

Abstract

PURPOSE:To simply and inexpensively obtain a compound by hydrolyzing an azulactone body and then adding a trihalogermanium to the hydrolyzate. CONSTITUTION:An azulaction body of formula I [R<1> to R<3> are H or lower alkyl; R4 is lower alkyl or formula II (Z is H, OH or acetoxy)] is hydrolyzed to afford an unsaturated compound of formula III and a trihalogermanium of the formula X3GeH (X is halogen) is added thereto to provide the compound of formula IV. Furthermore, the compound of formula I is obtained by adding, e.g. a halide of formula VI (Y1 and Y2 are halogen) to an amino compound of formula V in the presence of a base and heating the resultant additional product in acetic anhydride.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing an organic germanium compound.

[0002]

2. Description of the Related Art An organic germanium compound has a germanium propionate derivative and an oxygen atom of 2: 3.
Of carboxyethyl germanium sesquioxide (Ge—CH ₂ —CH ₂ —COO)
H) ₂ O ₃ has been known for a long time (Japanese Patent Publication No. 46-249).
No. 8) recently, many organic germanium compounds having structures other than the above have also been synthesized.

For example, Japanese Patent Laid-Open No. 02-62885 discloses

[Chemical 20] (R represents a hydrogen atom, a lower alkyl group or a phenyl group), has an amino group at the α-position of a carboxyl group, and thus discloses an organic germanium compound having an amino acid structure.

In this prior art, the above-mentioned organic germanium compound has been produced, for example, by the method shown in the following reaction formula.

[Chemical 21] That is, for unsaturated compounds, trihalogermane (X in the formula
Represents a halogen atom) to form a trihalo body,
The trihalo compound was hydrolyzed to germanium sesquioxide and then deacetylated, or deacetylated and then hydrolyzed to germanium sesquioxide.

[Problems to be Solved by the Invention]

However, many of the above unsaturated compounds are difficult to obtain, or even if they are available, they are extremely expensive. Therefore, it is possible to obtain an organic germanium having the above amino acid structure without using the unsaturated compound as a starting material. It has been desired to develop a method capable of producing a trihalo compound that can be easily converted into.

[0006]

The present invention has been made in view of the above-mentioned prior art, and

[Chemical formula 22] (In the formula, R _{1 to} R ₃ represent a hydrogen atom or a lower alkyl group,
R ₄ is a lower alkyl group or

[Chemical formula 23] (In the formula, Z represents a hydrogen atom, a hydroxyl group or an acetoxy group), the azlactone derivative represented by the formula:

[Chemical formula 24] (Wherein R _{1 to} R ₄ are as described above), and trihalogermane X ₃ GeH (in the formula, X represents a halogen atom) is added to the unsaturated compound. An expression characterized by

[Chemical 25] The present invention provides a method for producing an organogermanium compound represented by the formula (wherein R _{1 to} R ₄ and X are as described above).

The present invention also provides the formula

[Chemical formula 26] (In the formula, R _{1 to} R ₃ represent a hydrogen atom or a lower alkyl group,
R ₄ is a lower alkyl group or

[Chemical 27] (Wherein Z represents a hydrogen atom, a hydroxyl group or an acetoxy group) respectively, and trihalogermane X ₃ GeH (in the formula, X represents a halogen atom) is added to the azlactone form. Do, expression

[Chemical 28] The present invention provides a method for producing an organogermanium compound represented by the formula (wherein R _{1 to} R ₄ and X are as described above).

The present invention will be described in detail below.

In the manufacturing method of the present invention, first, the above formula (1) is used.
The azlactone form represented by (hereinafter, also represented as the compound (1)) is synthesized. Here, the substituents R _{1 to} R ₃ in the formula are a hydrogen atom or a lower alkyl group such as a methyl group, an ethyl group and a propyl group, and the substituent R ₄ is the same lower alkyl group as R ₁ or a formula.

[Chemical 29] (Z represents a hydrogen atom, a hydroxyl group or an acetoxy group).

This reaction is based on H. Kurita, Y. Chigira, N.
Masaki and M. Ohta et al.'S method (Bull. Chem. Soc.
an), 41, 2758-2762 (1968)) and JC Sheaham and W.
The method of E. Deggins et al. (J. Am. Chem. Soc., 72, 2475-24
77 (1950)). That is, in the presence of a base, for example the formula

[Chemical 30] (Wherein R ₁ and R ₄ are as described above), for the amino compound (5),

[Chemical 31] (In the formula, R ₂ and R ₃ are as described above, and Y ₁ and Y ₂ represent a halogen atom.) A halogen compound (6) is added, and the adduct is added in acetic anhydride. It heats.

Examples of the amino compound (5) used in the above reaction include various amino acids, and examples of the halogen compound (6) include chloroacetyl chloride. The halogen compound that can be used in the present invention is halogen. Of course, the compounds are not limited to these.

The mechanism of the above reaction is as follows, for example, in the case of adding chloroacetyl chloride to the amino compound (5):

[Chemical 32] The azlactone body represented by is once produced, and then a dechlorination reaction and an isomerization reaction occur to produce an azlactone body having the above structure.

Further, the azlactone derivative (1) represented by the above formula has the formula

[Chemical 33] (Wherein R ₁ and R ₄ are as described above), with respect to the amino compound (7),

[Chemical 34] (In the formula, R ₂ and R ₃ are as described above) The acid anhydride (8) can be acted on to cyclize, and further, in the azlactone (1) form, Especially R
₁ is a hydrogen atom, R ₄ is

[Chemical 35] (Wherein Z ′ represents a hydroxyl group or an acetoxy group) is represented by the formula

[Chemical 36] For the aldehyde (9) represented by

[Chemical 37] It can also be obtained by acting a carboxylic acid (10) represented by

By hydrolyzing the azlactone derivative (1) obtained as described above, a compound of the formula

[Chemical 38] An unsaturated compound (3) represented by At this time, it is preferable to adopt mild conditions such as adding water after forming the acetone solution.

The unsaturated compound (3) thus obtained is obtained.
By adding trihalogermane X ₃ GeH (wherein X is as described above) to the formula

[Chemical Formula 39] A trihalogen compound (4) represented by

On the other hand, by adding trihalogermane X ₃ GeH directly without isolating the azlactone derivative (1) obtained as described above, the trihalogen compound (4 ) Can be.

The trihalogen compound (4) thus obtained is hydrolyzed to germanium sesquioxide, and then the amide bond is cleaved, or the amide bond is cleaved and then hydrolyzed.

[Chemical 40] Represented by germanium sesquioxide (11)
It can be

[0018]

INDUSTRIAL APPLICABILITY In the present invention, trihalogermane X ₃ GeH is allowed to act after or without hydrolyzing an azlactone form, and this azlactone form can be derived also from ordinary amino acids. It becomes possible to produce a trihalo compound that can be easily converted into an organic germanium compound having an amino acid structure without using a compound that is difficult to obtain or expensive as a starting material.

[0019]

EXAMPLES The present invention will be described in more detail below with reference to examples.

Example 1 Synthesis of Compound of the Present Invention Represented by Formula (1) a) L-Leucine 131.0 g (1.0 mol) and sodium hydroxide 40.0 g (1.0 mol) in 800 ml
113.0 g (1.0 mol) of chloroacetyl chloride and 1050 ml of a 1N aqueous sodium hydroxide solution were added dropwise at the same time, and the mixture was stirred at room temperature for 3 hours. After filtering the insoluble matter, the pH was adjusted to about 1 with concentrated hydrochloric acid, the mixture was extracted with 1000 ml of ethyl acetate, the ethyl acetate layer was dried over anhydrous sodium sulfate, and then concentrated to dryness to precipitate light yellow crystals. When this was recrystallized from acetone and hexane, N-chloroacetylleucine became 1
29.0 g (yield 62.2%) was obtained. Melting point: 130 to 131 ° C Anal.Calcd .: C 46.64; H 6.80; N 6.75 Found: C 46.65; H 6.72; N 6.74 IR ν KBr / max cm ^-1 : 3314 (NH), 1709, 1636 (C =
O) ¹ H-NMR (Aceton d-6) δ: 0.94, 0.95 (3H × 2, d × 2,
(C H ₃ ) ₂ ), 1.71 (3H, m, (CH ₃ ) ₂ -C H -C H ₂ ), 4.14 (2H, s,
C H ₂ Cl) 4.54 (1H, dd, C H -N), 7.64 (1H, br, N- H )

41.5 g (0.2 mol) of N-chloroacetylleucine synthesized as described above was added to acetic anhydride 3
00 ml was added and heated at 80 ° C. for 30 minutes. When acetic anhydride was distilled off and vacuum distillation was carried out, 4-isobutylidene-2-methyl-5-oxazolone (in the formula (1), R ₁ = R ₂ = R ₃ = H was obtained as a fraction at 57 ° C./3 mmHg. , R ₄ =
11.9 g (compound of CH (CH ₃ ) ₂ ) (yield 38.9)
%) Obtained. Anal.Calcd .: C 62.73; H 7.24; N 9.14 Found: C 62.50; H 7.00; N 8.96 IR ν KBr / max cm ^-1 : 1809 (C = O) ¹ H-NMR (CDCl ₃ ) δ: 1.40 ( 6H, d, (C H ₃ ) ₂ ), 2.32 (3
H, s, N = CC H ₃ ), 3.15 (1H, m, (CH ₃ ) ₂ -C H 6.40 (1H, d,
C H = C)

B) L-valine 1 in the same manner as in the above a)
62 g / 1.0 by adding 17 g (1.0 mol) to N-chloroacetylvaline and heating it in acetic anhydride.
As a fraction of 3 mmHg, 4-isopropylidene-2-
Methyl-5-oxazolone (in the formula (1), R ₁ =
8.27 g (yield 59.5%) of R ₄ ═CH ₃ and R ₂ ═R ₃ ═H) were obtained. Anal.Calcd .: C 60.42; H 6.52; N 10.07 Found: C 60.40; H 6.44; N 9.87 IR ν KBr / max cm ^-1 : 1800 (C = O) ¹ H-NMR (CDC ₁₃ ) δ: 2.30, 2.38, 2.42 (3H × 3, s ×
3, (C H ₃ ) ₂ ), C H ₃ changeable)

C) In the same manner as in the above a), 49.78 g (0.38 mol) of L-isoleucine was used as N-chloroacetylisoleucine, and this was heated in acetic anhydride to obtain a fraction at 70 ° C./4 mmHg. As 4- (1
- In methylpropylidene) -2-methyl-5- oxazolone (formula _{(1), R 1 = CH} 3, R 4 = CH 2 CH 3
22.75 g of R ₂ = R ₃ = H compound) (yield 74.3)
%) Obtained. This compound was a mixture of isomers. Anal.Calcd .: C 62.73; H 7.24; N 9.14 Found: C 62.51; H 7.09; N 9.04 IR ν KBr / max cm ^-1 : 1805, 1775 (C = O) ¹ H-NMR (CDCl ₃ ) δ: 1.15, 1.16 (3H × 2, t × 2, C H ₃ ) 2.21, 2.26, 2.31 (3H, 6H, 3H, S × 3, C H ₃ -C = C, N = CC
H ₃ changeable) 2.64, 2.81 (2H × 2, q × 2, CH ₃ -CH ₂ )

D) Norvaline 1 in the same manner as in a) above.
By adding 17.0 g (1.0 mol) of N-chloroacetyl norvaline to this in acetic anhydride, 7
As a fraction of 7 ° C / 15 mmHg, 4-propylidene-
2-methyl-5-oxazolone (in the formula (1), R
₁ = H, the compound of _{R 4 = CH 2 CH 3,} R 2 = R 3 = H) was obtained 8.93 g (31.7% yield. Note that this compound was a mixture of isomers. Anal.Calcd .: C 60.42; H 6.52; N 10.07 Found: C 60.19; H 6.38; N 9.92 IR ν KBr / max cm ^-1 : 1800 (C = O) ¹ H-NMR (CDCl ₃ ) δ: a) 1.11 (3H, t, C H ₃ -CH ₂ ), 2.28 (3H, S, N = C-CH ₃ ), 2.
54 (2H, dq, CH ₃ -C H ₂ ) 6.53 (1H, t, C H) b) 1.11 (3H, t, C H ₃ -CH ₂ ), 2.25 (3H, S, N = C-CH ₃ ), 2.
74 (2H, dq, CH ₃ -C H ₂ ) 6.64 (1H, t, C H )

D) In the same manner as in the above a), 99 g (0.60 mol) of phenylalanine was converted into N-chloroacetylphenylalanine, which was heated in acetic anhydride, sublimated and purified to give 4-benzylidene-2. -Methyl-5-oxazolone (in the formula (1), R ₁ = H,
13.23 g of R ₄ ═C ₆ H ₅ , R ₂ ═R ₃ ═H)
(Yield 59.0%) was obtained. Melting point: 155 ° C (sublime) Anal.Calcd .: C 70.58; H 4.85; N 7.48 Found: C 70.29; H 4.77; N 7.31 IR ν KBr / max cm ^-1 : 1780 (C = O) ¹ H-NMR ( DMSO d-6) δ: 2.45 (3H, s, C H ₃ ), 7.21 (1
H, S, H C = C), 7.51, 8.20 (3H 2H, mm, C ₆ H ₅ )

Example 2 Synthesis of the compound of the present invention represented by formula (3) a) 4-isobutylidene-2-methyl-5-oxazolone (6.12 g, 0.04 mol) was added to 10 ml of water for 20 hours. After leaving it for a while, if the precipitated crystals are collected,
4.8 g of colorless and transparent crystals of 2-acetamido-4-pentenoic acid (compound of R ₁ = R ₂ = R ₃ = H and R ₄ = CH (CH ₃ ) _{2 in} the formula ( ₃ )) (yield 70.2%) was obtained. Melting point: 143 ° C (dec) Anal.Calcd .: C 56.13; H 7.65; N 8.18 Found: C 56.10; H 7.55; N 8.02 IR ν KBr / max cm ^-1 : 3300 (NH), 1700, 1660 (C =
O) ¹ H-NMR (CD ₃ OD) δ: 1.13 (6H, d, (C H ₃ ) ₂ ), 2.15 (3
H, s, CO-C H ₃ ), 2.71 (1H, d sept, (CH ₃ ) ₂ -C H ) 6.62 (1H, d, (CH ₃ ) ₂ -CC H )

B) In the same manner as in a) above, 4-isopropylidene-2-methyl-5-oxazolone was added to water and allowed to stand, and then the precipitated crystals were separated to obtain 2
-Acetamido-3-methyl-2-butenoic acid (formula (3)
In was obtained colorless transparent crystals of R ₁ = R ₄ = CH ₃ Compound of R ₂ = R ₃ = H) is 5.03 g (72.8% yield). Melting point: 196 ° C (dec) Anal.Calcd .: C 53.49; H 7.05; N 8.91 Found: C 53.25; H 6.91; N 8.80 IR ν KBr / max cm ^-1 : 3320 (NH), 1700 (C = O) ¹ H-NMR (CD ₃ OD) δ: 1.83, 2.03, 2.13 (3H × 3, s ×
3, (C H ₃ ) ₂ ), C H ₃ changeable)

Example 3 Synthesis of Compound of the Present Invention Represented by Formula (4) (1) a) 3.42 g of 2-acetamido-4-pentenoic acid
(0.02 mol) was suspended in 30 ml of concentrated hydrochloric acid, and 4.50 g (0.02 mol) of trichlorogermane Cl ₃ GeH was added.
(5 mol) dissolves and crystals precipitate after a while, so after stirring for 19 hours, the crystals are separated to give 2-acetamido-4-methyl-3- (trichlorogermyl) pentanoic acid (formula In (4), R ₁ =
4.62 g (yield 65.8%) of white crystals of R ₂ = R ₃ = HR ₄ = CH (CH ₃ ) ₂ ) were obtained. Melting point: 119-120 ° C Anal.Calcd .: C 27.36; H 4.02; N 3.99 Found: C 27.39; H 4.01; N 3.99 IR ν KBr / max cm ^-1 : 1720, 1620 (C = O), 415 (Ge -C
l) ¹ H-NMR (CDCl ₃ + CD ₃ OD) δ: 1.19, 1.23 (3H × 2, d,
(C H ₃ ) ₂ ), 2.07 (3H, s, CO-C H ₃ ), 2.33 (1H, d sept,
(CH ₃ ) ₂ -C H ) 2.93 (1H, dd, Ge-C H ), 5.16 (1H, d, CO-C H )

B) In the same manner as in a) above, 1.57 g (0.01%) of 2-acetamido-3-methyl-2-butenoic acid.
mol) with trichlorogermane to give 2-acetamido-3-methyl-3- (trichlorogermyl) butanoic acid (in formula (4), R ₁ = R ₄ = C
3.05 g of white crystals of H ₃ , R ₂ = R ₃ = H)
(Yield 90.5%) was obtained. Melting point: 150 ° C (dec) Anal.Calcd .: C 24.94; H 3.59; N 4.15 Found: C 24.93; H 3.58; N 4.07 IR ν KBr / max cm ^-1 : 3330 (NH), 1725, 1605 (C =
O), 405 (Ge-Cl) ¹ H-NMR (CD ₃ OD) δ: 1.40 (6H, s, (C H ₃ ) ₂ ), 2.07 (3
H, s, CO-C H ₃ ), 5.00 (1H, s, CO-C H )

C) 4-propylidene-2-methyl-5-
0.84 g (0.006 mol) of oxazolone was suspended in 20 ml of concentrated hydrochloric acid, and trichlorogermane Cl ₃ Ge was added.
When 1.20 g (0.0066 mol) of H was added, crystals began to precipitate immediately, so after stirring for 44 hours continuously, the crystals were separated to give 2-acetamido-3- (trichlorogermyl) pentanoic acid. (In the formula (4), R ₁
= R ₂ = R ₃ = H, R ₄ = CH ₂ CH ₃ compound) 1.49 g (yield 73.7%) was obtained. Melting point: 163-164 ° C Anal.Calcd .: C 24.94; H 3.59; N 4.15 Found: C 24.81; H 3.50; N 3.99 IR ν KBr / max cm ^-1 : 3300 (NH), 1720, 1640 (C =
O), 430 (Ge-Cl) ¹ H-NMR (Aceton d6) δ: 1.17 (3H, t, C H ₃ -CH ₂ ), 1.
86 (1H, ddq, CH ₃ -C- H a), 2.00 (1H, ddq, CH ₃ -C- H b) 2.08 (3H, s, CO-C H ₃ ), 2.90 (1H, ddd, Ge- C H ), 5.10
(1H, d, C H -CO)

D) In the same manner as in c) above, 11.43 g of 4-isobutylidene-2-methyl-5-oxazolone
2-acetamido-4-methyl-3- by reacting (0.075 mol) with trichlorogermane.
16.0 g of white crystals of (trichlorogermyl) pentanoic acid (a compound of the formula (4) where R ₁ = H, R ₄ = CH (CH ₃ ) ₂ and R ₂ = R ₃ = H) (yield 60 .1%) was obtained. Melting point: 119-120 ° C Anal.Calcd .: C 27.36; H 4.02; N 3.99 Found: C 27.39; H 4.01; N 3.99 IR ν KBr / max cm ^-1 : 1720, 1620 (C = O), 415 (Ge -C
l) ¹ H-NMR (CDCl ₃ + CD ₃ OD) δ: 1.19, 1.23 (3H × 2, d,
(C H ₃ ) ₂ ), 2.07 (3H, s, CO-C H ₃ ), 2.33 (1H, oct (C H ₃ ) ₂
-CH) 2.93 (1H, dd, Ge-C H ), 5.16 (1H, s, CO-C H )

E) 4- (1-methylpropylidene) -2-methyl-5-oxazolone 2 in the same manner as in c) above.
By reacting 2.6 g (0.15 mol) with trichlorogermane, 2-acetamido-3-methyl-
30.87 g of white crystals of 3- (trichlorogermyl) pentanoic acid (compound of R ₁ ═CH ₃ , R ₄ ═CH ₂ CH ₃ R ₂ ═R ₃ ═H in formula (4)) (yield 59. 4%) was obtained. This compound was a mixture of isomers. Melting point: 163 to 164 ° C Anal.Calcd .: C 27.36; H 4.02; N 3.99 Found: C 27.05; H 4.19; N 3.88 IR ν KBr / max cm ^-1 : 3360 (NH), 1725, 1660 (C =
O), 410, 395 (Ge-Cl) ¹ H-NMR (CDCl ₃ + CD ₃ OD) δ: 1.12, 1.17 (3H × 2, t ×
2, CH ₂ -C H ₃ ), 1.37, 1.42 (3H × 2, s × 2, Ge-CC H ₃ ) 1.89 (2H × 2, q, CH ₃ -C H ₂ ), 2.10 (3H × 2, s, CO-C H ₃ ),
5.18 (1H × 2, s, CO-C H )

E) 18.70 g of 4-benzylidene-2-methyl-5-oxazolone in the same manner as in c) above
By reacting (0.10 mol) with trichlorogermane, 2-acetamido-3-phenyl-3-
36.8 g (yield 95.6) of white crystals of (trichlorogermyl) propanoic acid (a compound of the formula (4) in which R ₁ = H, R ₄ = C ₆ H ₅ , and R ₂ = R ₃ = H). %) Obtained.
This compound was a mixture of isomers. Anal.Calcd .: C 34.30; H 3.14; N 3.64 Found: C 34.21; H 3.00; N 3.45 IR ν KBr / max cm ^-1 : 1735, 1630 (C = O), 420 (Ge-C
l) ¹ H-NMR (Aceton d-6) δ: a) 1.97 (3H, s, C H ₃ ), 4.37 (1H, d, Ge-C H ), 5.46 (1
H, d, CO-C H ), 7.40 (5H, s, C ₆ H ₅ ) b) 1.91 (3H, s, C H ₃ ), 4.33 (1H, d, Ge-C H ), 5.20 (1
H, d, CO-C H ), 7.36 (5H, s, C ₆ H ₅ )

Example 4 Synthesis of Compound of the Present Invention Represented by Formula (4) (2) 11.9 g of threonine was dissolved in an aqueous solution containing 4.0 g of sodium hydroxide, and acetic anhydride 10. Two
g and an aqueous solution containing 4.0 g of sodium hydroxide were added simultaneously, and the mixture was stirred as it was for 3 hours. After completion of the reaction, dilute hydrochloric acid to 1
Ethanol was added to the colorless syrup obtained by removing the solvent with an evaporator and distilling off the solvent with an evaporator, the precipitate was filtered off, and the ethanol layer was concentrated to obtain N-acetylthreonine as a colorless syrup almost quantitatively. It was

The obtained N-acetylthreonine was dissolved in a large excess of acetic anhydride and stirred at room temperature for 16 hours to give an azlactone form. After completion of the reaction, the precipitate was filtered, and the azlactone was hydrolyzed by pouring the filtrate into a large amount of water little by little, and the solvent was distilled off with an evaporator to quantitatively give 2-acetamido-2-butenoic acid as a yellow gum. Obtained as a substance.

4.3 g of the obtained 2-acetamido-2-butenoic acid was dissolved in chloroform, 9.2 g of trichlorogermane was added, and the mixture was stirred at room temperature for 19 hours. After completion of the reaction, the solvent was distilled off to give 2-acetamido-3- (trichlorogermyl) butanoic acid (in the formula (4), R ₁ =
H, R ₄ = CH ₃ , and R ₂ = R ₃ = H) were quantitatively obtained. IR ν KBr / max cm ^-1 : 1720, (C = O), 400 (Ge-Cl) ¹ H-NMR (CD ₃ OD) δ: 1.33, 1.37 (total 3 H, d ×
2, CH-C H ₃ ), 2.04 (3H, s, CO-C H ₃ ) 2.5 to 2.9 (1H, m, Ge-C H ), 4.90, 4.94 (1H, d × 2, CO-
CH)

Example 5 Synthesis of compound of the present invention represented by formula (4) (3) To 25.0 g of p-hydroxybenzaldehyde, 29 g of N-acetylglycine, 8.2 g of sodium acetate and 60.6 g of acetic anhydride were added and heated. It was made to melt | dissolve and was refluxed for 1 hour. After completion of the reaction, the reaction mixture was left overnight at room temperature, the formed cake-like solid was washed with water, dissolved in 450 cc of acetone, 170 ml of water was added, and the mixture was heated under reflux for 3 hours to hydrolyze the formed azlactone.

When left at room temperature, 13.74 g of yellow crystals
2.87 g by further subjecting the reaction solution to an operation such as cooling, and an acetone washing solution of these precipitated crystals and 7.5 g by subjecting the remaining reaction solution to a purification operation, for a total of 24.11 g of yellow crystals. Got The yield was 44.7%.

2.22 g of the obtained compound was suspended in chloroform, 2.9 g of trichlorogermane was added dropwise, and then,
Stir at room temperature for 4 hours. After the reaction was completed, the insoluble matter was filtered off,
By concentrating the filtrate, 2-acetamido-3-
(Para-hydroxyphenyl) -3- (trichlorogermyl) butanoic acid (in the formula (4), R ₁ = H, R ₄ = para-hydroxyphenyl, R ₂ = R ₃ = H)
2-acetamido-3- (paraacetoxyphenyl) -3- (trichlorogermyl) butanoic acid (formula (4)
In, a mixture of R ₁ = H, R ₄ = paraacetoxyxyphenyl, R ₂ = R ₃ = H) was obtained. Parahydroxyphenyl IR ν KBr / max cm ^-1 : 1755, 1650 (C = O), 410 (Ge-C
l) ¹ H-NMR (CD ₃ OD) δ: 1.85, 1.99 (total 3 H, s ×
2, CO-C H ₃ ), 3.93 (1H, d, Ge-C H ), 5.24 (1H, d, NC
H ) 6.76, 7.13 (2H × 2, d × 2, ph- H ) paraacetoxy phenyl IR ν KBr / max cm ^-1 : 1755, 1650 (C = O), 410 (Ge-C)
l) ¹ H-NMR (CD ₃ OD) δ: 1.82, 1.96 (total 3 H, s ×
2, N-CO-C H ₃ ), 2.26 (3H, q, O-CO-C H ₃ ), 4.02 (1H,
d, Ge-C H ) 5.29 (1H, d, NC H ), 7.09, 7.34 (2H × 2, d × 2, ph- H )

Reference Example Synthesis of Compound of the Present Invention Represented by Formula (11) 2-acetamido-3- (paraacetoxyphenyl)-
3-trichlorogermylpropanoic acid (in the formula (4), R ₁ = H, R ₄ = paraacetoxyphenyl, R ₂ = R ₃
= H compound) (969 mg), concentrated hydrochloric acid was added, and the mixture was stirred at room temperature for 2 days. After the reaction was completed, the contents were poured into a large amount of water and impurities were filtered. The residue obtained by concentrating the filtrate was dissolved in distilled water, and the cation exchange resin Amberlite IR120B was used.
1-parahydroxyphenyl-2-amino-2-carboxyethyl germanium sesquioxide (formula (11)) by adsorbing (trade name) [H + type] and eluting with 5% ammonia water and concentrating the eluate Where R
₁ = H, R ₄ = p-hydroxyphenyl, R ₂ = R ₃ = H
To obtain 200 mg as a pale yellow powder. Yield: 46.2% (mixture of diastereomers) Melting point: 300> ° C (dec.) Anal.Calcd .: C 39.06; H 3.64; N 5.06 Found: C 39.22; H 3.71; N 5.20 IR ν KBr / max cm ^-1 : 3700 to 2200 (NH ₃ +), 1605 (C =
O), 885, 845 (Ge-O) ¹ H-NMR (D ₂ O) δ: 3.38 (1H, d, Ge-C H ), 4.33 (1H,
d, CO-C H ), 6.87 (2H, d, ortho position of OH) 7.14 (2H, d,
(OH meta position)

Claims (5)

[Claims] 1. The formula: (In the formula, R _{1 to} R ₃ represent a hydrogen atom or a lower alkyl group,
R ₄ is a lower alkyl group or (In the formula, Z represents a hydrogen atom, a hydroxyl group or an acetoxy group), the azlactone derivative represented by the formula: (Wherein R _{1 to} R ₄ are as described above), and trihalogermane X ₃ GeH (in the formula, X represents a halogen atom) is added to the unsaturated compound. Characterized by the formula: (Wherein R _{1 to} R ₄ and X are as described above), and a method for producing an organogermanium compound. 2. The formula: (In the formula, R _{1 to} R ₃ represent a hydrogen atom or a lower alkyl group,
R ₄ is a lower alkyl group or (Wherein Z represents a hydrogen atom, a hydroxyl group or an acetoxy group),
Trihalogermane X ₃ GeH (wherein X represents a halogen atom) is added, and the compound is represented by the formula: (Wherein R _{1 to} R ₄ and X are as described above), and a method for producing an organogermanium compound. 3. The formula: (In the formula, R _{1 to} R ₃ represent a hydrogen atom or a lower alkyl group,
R ₄ is a lower alkyl group or (Wherein Z represents a hydrogen atom, a hydroxyl group or an acetoxy group),
Formula For the amino compound represented by the formula (wherein R ₁ and R ₄ are as described above), (Wherein R ₂ and R ₃ are as described above, and Y ₁ and Y ₂ represent a halogen atom), and are obtained by reacting with a halogen compound and then cyclizing. A method for producing an organic germanium compound according to claim 1 or 2. 4. The formula: (In the formula, R _{1 to} R ₃ represent a hydrogen atom or a lower alkyl group,
R ₄ is a lower alkyl group or (Wherein Z represents a hydrogen atom, a hydroxyl group or an acetoxy group),
Formula For the amino compound represented by the formula (wherein R ₁ and R ₄ are as described above), The production of the organogermanium compound according to claim 1 or 2, which is obtained by acting an acid anhydride represented by the formula (wherein R ₂ and R ₃ are as described above) and cyclizing. Method. 5. The formula: (In the formula, R ₁ is a hydrogen atom, R ₂ and R ₃ are hydrogen atoms or a lower alkyl group, and R ₄ is (In the formula, Z ′ represents a hydroxyl group or an acetoxy group), and the azlactone form is represented by the formula: For the aldehyde represented by the formula: The method for producing an organogermanium compound according to claim 1 or 2, which is obtained by acting a carboxylic acid represented by the formula (wherein R ₂ and R ₃ are as described above) to cyclize. .