JPS60156659A - 3-alkoxy-3-aminopropionic acid derivative - Google Patents

Abstract

NEW MATERIAL:A compound shown by the formula I [R1 is 3-6C alkyl; R2 is H, or methyl; R3 is COOR5 (R5 is lower alkyl, or benzyl), or cyano; R4 is lower alkyl; X is lower alkanoyl, or lower alkoxycarbonyl]. EXAMPLE:3-(N-Cyclohexyl-N-ethoxycarbonyl)amino-3-methoxypropionic acid methyl ester. USE:An intermediate for preparing drugs, agricultural chemicals, and perfume compounds. PREPARATION:A compound shown by the formula II is electrolytically oxidized in an alcohol (e.g., methanol, ethanol, etc.) shown by the formula R4OH to give a compound shown by the formula I . The compound shown by the formula II is obtained by adding isopropylamine, etc. to an alpha,beta-unsaturated ketone, etc. through 1,4 addition, converting N of the addition product to a lower alkanoyl group. Tetraethylammonium tosylate, etc. is used as the supporting electrolyte.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing ftT gold compound compound 1 of 2 R4 1.
The symbols have the following meanings. □ R1 represents an alkyl group having 3 to 6 carbon atoms (7), and 1 represents an iso7@o pyl group, a cyclohexyl group, or the like.

R2 represents a hydrogen atom or ε represents a methyl group.

R31 represents a co'ois or cyano group, and R5 represents a lower alkyl group such as a methyl group, ethyl group, or propyl group.

R4 represents a lower alkyl group such as a methyl group, ethyl group, or propyl group.

X represents a lower alkanoyl group such as an acetyl group or a propionyl group, or a lower alkoxycarbonyl group such as an ethoxycarbonyl group.

The compound of formula (1) is a compound of formula R40H (in the formula, the symbols are the same as above).
(In the formula, R4 is the same as above.) It can be produced by electrolytic oxidation in alcohol.

R4 Ma(n) (1) The compounds of formula (1) are derived from malondialdehyde and malonitrile, respectively, and are not only useful as synthetic intermediates for pharmaceuticals, agricultural chemicals, and fragrance compounds, but also for dealcoholization and deacetalization. By doing so, it is possible to induce water-soluble polymers. In addition, the enamine form produced by deacetalizing the above alkoxyamino form is
It has a wide range of uses as an intermediate for organic synthesis.

The present inventors used an electrolytic oxidation method to solve the process of converting the α-position of the nitrogen atom into an acid and alkoxylating it, which is difficult to do with conventional chemical reactions.
Aminopropionic acid ester or 3-alkoxy-3
- High yield of aminopropionitrile as a new compound,
As a result of diligent efforts to achieve highly selective synthesis, the present invention has been completed.

Up until now, examples of electrolytic alkoxylation of carbon at the α-position of a nitrogen atom include N,N-dimethylaniline expressed by general formula (1) (yield 73%). Geinberg and
E, ^, Brown, , ; , J, Org
,, Chew,, Vo, 131.405B (19
66, )) or electrolytic oxidation (T, 5ho) of the carbamate represented by general formula (2) in methanol
no, Y., MatsuIlura, K., Tsu.
bata and J,, Takata, Chew
, Lett.

1121 (1981), (2) and electrolytic methoxylation of N-furkylcarbamate esters represented by general formula (3) (T, 5hono).

Y., Matsumura, and S. Kashi, m.
ura, J, Org, Chem, +48, 3338 (
1983) ), but there are few examples that have been applied to polyfunctional organic compounds.

(3) The present invention produces 3-alkoxy-3- The purpose is to synthesize aminopropionic acid ester or 3-alkoxy-3-aminopropionitrile. In addition, the alkoxylated product obtained in nature can be derived into an enamine by solvolysis or dealcoholization.

In the present invention, first, isopropylamine, cyclohexy)
Alkylamines such as raremine are converted into acrylic esters: methacrylic esters and acrylonitrile, etc. α,β-unsaturated ketones (or □α, ゛β) of the formula (′■) of ゛□
-unsaturated nitrile), and then the nitrogen atom of the adduct is converted into lower alkanoylation or carbamate using acetic anhydride, acetyl chloride, ethyl chloroformate, etc. according to the lightning method to form formula (II). Let it be a compound of

(IV) (III) (If) Methyl acrylate as the α,β-unsaturated ester,
Compounds such as ethyl acrylate, methacrylate, acid mer and acrylonitrile are used.

Next, the amide or carbamate of formula (II) is added to 4
Dissolve in ~100 times the amount of alcohol, preferably 5 times the amount, ~20 times the amount of alcohol, and add a supporting electrolyte such as tetraethylammonium tosylate to this solution at a concentration of 1.0 times the amount of the substrate.
~5.0 mol% was added and 2 Faraday (
When an amount of electricity of F)/mol to 7F1 mole is applied using a constant DC current, one methylene group at the alpha position of the nitrogen atom is selectively and quantitatively alkonated. Examples of the alcohol used in this electrolytic melt include lower alcohols such as methanol and ethanol.

In addition to tetraethylammonium tosylate, the supporting electrolyte includes tetraethylammonium verchlorate, tetraethylammonium verchlorate, lithium perchlorate, sodium perchlorate, tadium tetrafluoroborate, and the like.

Although this reaction may be carried out at a reaction temperature in the range of 0°C to 50'C, it is preferable to keep the liquid temperature around room temperature.

After removing the alcohol solvent under reduced pressure, the electrolytic reaction product is extracted by adding benzene, toluene, diethyl ether, or ethyl acetate, washed with saturated brine or saturated salt water to remove the supporting salt, concentrated, and then distilled. The biological father of the present invention is listed below.

Example 1 9.9 g (0.10 mol) of cyclohexylamine and ethyl acrylate (0.10 mol) were placed in a two-necked flask with a capacity of 50 mm and equipped with a condenser, and stirred with a magnetic stirrer. The liquid temperature will be ~50℃, but if you continue stirring for 4 to 5 hours and distill under reduced pressure, you will obtain the Eichel adduct (2■, R1 = cyclohexyl,
R2=H, R3=COOCI+3) is obtained. (Yield 17.6g, yield 95%, boiling point 95℃72.5 ++
nHg') This adduct 7. Qg (37.8 mmol),
8 parts of water and 10 parts of diethyl ether are placed in a flask equipped with a condenser, the flask is cooled with ice water, and 4.12 g (38 mmol) of di-4-methyl chloroformate is added dropwise while stirring the reaction solution with a magnetic cooler. When about half the amount is dropped, add 40% sodium hydroxide aqueous solution 2.2
Start dropping 8d at the same time, and make sure to finish dropping both at the same time. Dripping takes 20 minutes. Next, the reaction solution is neutralized, the aqueous layer is extracted twice with diethyl ether, the oil layer and the extract are dried over anhydrous sodium sulfate, and then concentrated to yield a carbamate (formula IIR1=cyclohex', t) Lt,
=C0CH3, R2=H, R3=C0OCH3) is 8
．． 95g (yield 92.1%, boiling point 144°C/mmHg)
is obtained.

3.0 g (11.67 mmol) of the above carbamate was dissolved in 30 parts of methanol, and a supporting electrolyte of tetraethylammonium tosylate (Et4 N0Ts) was added to the solution.
) 0.132g (0.4M liquid) was added and the whole was placed in a 170-m circular electrolytic cell. Electrolysis-5
Attach the second carbon temporary mold m (i'617).

While cooling the electrolytic cell from the outside on an ice water bath,
Continuing to have a strong relationship with Senyu-ryu.゛7 When 1 mole of electricity is applied, is it thin? ') 4 Stop the electrolysis, which has authorized that the raw materials have been tied together.

The methanol of the reaction medium was distilled off, the residue was washed with ethyl acetate 50-base oil, and the first solution was washed with saturated saline solution to remove the supporting salt. After drying over dttrium acid and concentrating it under reduced pressure, the organic 3-(N--/
'robexyl-N''-methyloxycarbonyl)amino-2-3-nimethoxypropionate (compound N
a1) 3.115 g (10.85 mmol, yield '93゜0%, boiling point 106-107℃/0.02 r
smHg> is obtained.

Infrared absorption spectrum (meat) r (C=O)1
700, 1740 cm −', reverse symmetry r of methoxy group (C-0-C) 1130 (2) Pe, H-NMR (C
CI! 4) , δt, oa (an, t).

61.0 ~ 2.0 (IIH, broad), δ
2.6.5 (2H, m).

δ3.30 (3H, S, OCH3), δ3.65.
(38,S,0COCH3).

δ4.15 (2H, q), δ5.65 (LH, t
).

The following examples follow the method of Example 1.

Example 2 An adduct (2 m
, R1=isopropyl, R2=H, R3=COOC1+
3) 27.55 g (yield 95.θ%, boiling point 92
"C/ 23 mmmm 1l is obtained. Adduct 2.8
8 g (0°02 mol) and 2.19 g (0.02 mol) of acetic anhydride
The reaction mixture was distilled separately under reduced pressure to obtain the acetyl compound (2〇, R1 = isopropyl).

X=C0C113, R2=H, R3=C0OCH3)
3.705g (yield 99.6%, boiling point 112℃/3
+++wHg) is obtained. 3.0g of this acetyl body (
16,13 mmol) and Et4 N0Ts 0.182
g (0.60.5 mol) and methanol 30. d
Electrolytic oxidation was performed in the same manner as in Example 1 using the following. 7. When 1 mole of electricity is applied, 3.453 g (yield 99
．． 1%.

A boiling point of 120°C/2 mdg) is obtained.

Examples 3 to 8 and IO to 11 Following Example 1, 3-amino-3-alkoxypropionic acid ester and 3-amino-3-alkoxypropionitrile derivative of formula (I) were synthesized. The results are shown in Table 1, and Compound Arashi 1- obtained in Example 1-11.
The boiling point and elemental analysis measurements of No. 11 are shown in side 2.

Example 9 Adduct of 11.8 g (0.2” mol) of isopropylamine and 10.6 g (0.2 mol) of acrylonitrile (formula I, R1=isopropyl, R2=H, R3=CH)
21.73g (yield 97.0%, boiling point 92°C/23+
mHg) is obtained. Adduct 5.6 g (0.05 mol)
and diethyl ether 10 + ae were placed in a two-necked flask with a condenser, the flask was cooled with ice water, and the liquid was stirred with a magnetic stirrer.
g (0.05 mol) was gradually added over 10 minutes and stirring was continued for a further 1 hour. When diethyl ether and acetic acid are distilled off from the reaction solution, a white solid remains. When this is recrystallized from ethyl acetate, acetyl compound (formula n, R] = shisopropyl is obtained as white crystals.

X=COCH3, R2=l(, R3=CH) yield 96
．． 7% (melting point 55-5!C). .

3.0 g (19.48 mmol) of acetyl compound.

Et4 N0Ts 220g+g and methanol 30
Electrolytic oxidation was performed in the same manner as in Example 1 using d. 7.0
When 1 mole of electricity is applied, 3.513 g of 3-(N-isopropyl-N-acetyl)amino-3-methoxypropionitrile (compound Na9) (yield 98.0%, boiling point 146-148°C/3. 0 m+110 g) is obtained.

(Leaving space below) Procedural amendment 1 Commissioner of the Japan Patent Office 1 Indication of the case Patent Application No. 011517 of 1982 2゜ Title of the invention 3-Alkoxy-3-aminopropionic acid derivative 3 Person making the amendment Relationship to the case Patent applicant name: Osaka Organic Chemical Industry Co., Ltd. 4, agent address: Koei Building, 2-40-4 Awajicho, Higashi-ku, Osaka
, Voluntary action 6, Number of inventions increased by amendment None 7, Detailed explanation of the invention subject to amendment 8, Contents of amendment 1 as shown in the attached sheet, The formula on page 7 of the specification is corrected as follows.

□ (IV) (II) (■) 2. “Tatium tetrafluoroborate” on page 8, line 6 of the same
I corrected Kuzu to "lithium tetrafluoroborate."

3, page 9, line 16 of the same, "-t form (formula n R1 = cyclohex, sil, X
70COC2J,, [-t form (formula n Rs = cyclohexyl, X = C0
Correct it to 0C2J.

4. "Infrared absorption spectrum (sweat) r (C=O
) J and [Infrared absorption spectrum (neat) v (C=0)
Correct J and δ1.

5. [Inverse symmetry γ(C-0-C)] on page 10, line 19
Correct J to [inverse symmetry ν(C-0-C) J.

6, page 11, line 2 [δ3.30 (311,S, 0CH3), δ3.
65 (3fl, S, 0COC) Is) J, [63,30 (311, S, 0CH3), δ3.6
5 (3H, S, C00CH3) Correct as J.

7. In the 4th line of page 13, the statement "R" = shisopropyl is corrected to "R1 = isopropyl."

8゜ Replace Table 1-b and Table 2 with those on the attached sheet.

Claims (1)

[Claims] tit formula, , R4 R1-N-C1 (-C1l-R3, ,,, 〶)3゜1 strand, R2. (In the formula, R1 is an alkyl group having 3 to 6 carbon atoms (7), R2 is a hydrogen atom or
S is a lower arykyl group or a pen or zyl group;
is a cyanogen 1゜ group, and R4 is! X is a salary class, alkano. , , represents an yl group or a lower alkoxycarbomole group, respectively.1. :, thing 0. ．． ．． . (2), 2-,. (In the formula, R11R2, R3, and X are the same as above.) North gate←
, Sakai R40H (in the formula, R4 is the same as above.)
7) A formula characterized by a single solution in the Lt column'i blindness, ``□゛'' R4,1,1 (In the formula, the symbols are the same as the oke and the notation. ), a method for producing a compound.