JPS59161347A - 3-amino-2-alkenenitrile and its preparation - Google Patents

Abstract

NEW MATERIAL:A compound of the formula (R<1> is H, alkyl, aryl; R<2> is alpha- alkoxyalkyl). EXAMPLE:4-(2-Tetrahydropyranoxy)-3-amino-2-pentenitrile. USE:It is used as a synthetic intermediate of aminosugar, after reduction and hydrolysis. It is also used as a key intermediate of heterocyclic ring syntheses. PREPARATION:The reaction of a nitrile of the formula: R<1>CH2CN with a metal compound of the formula: MX (X is alkyl, phenyl, dialkylamino, bistrimethylsilylamino) is conducted in a solvent such as tetrahydrofuran or diethyle ether at -100-50 deg.C, preferably -78 deg.C- room temperature. Then, an alpha-alkoxyalkanenitrile of the formula: R<2>CN is made to act on to give the compound of the formula.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to monoamino-2-alk This invention relates to nitrile and its manufacturing method.

6-amino-2 represented by the general formula (1) of the present invention
-Alkenenitrile can be reduced and hydrolyzed to become a direct intermediate for amino sugar synthesis (see reference side).

Furthermore, it is used as a key intermediate for Peter ring synthesis (J
, Org, Chem, 37.3030 (1972) and J.

kn, clem,, soc, , 96, 2010
(1974)].

Conventionally, to synthesize amino sugars, alkoxyalkane nitrile was reacted with magnesium enolate of acetate (Tetrahedron Lette).
rs, 1597 (1982)], the yield of the product obtained by this method was low and its stability was also poor. Furthermore, it has been previously proposed to react a second nitrile with a nitrile anion to form a β-amino-2-alkenenitrile, but this was considered impractical due to the generation of large amounts of by-products. [J. O
rg, Chem, .

15.165 (1950)]. As a result of studies to overcome these conventional drawbacks, the present inventors discovered and completed the present invention.

The production method of the present invention uses a nitrile represented by the general formula % formula % () (in which R is the same as above) and a nitrile represented by the general formula % formula % () (where M is an alkali metal atom and X is an alkyl group, phenyl group, dialkylamino group, or bistrimethylsilylamino group. 6-amine-2-alkenenitrile represented by general formula CI) is obtained by reacting α-alkoxyalkane nitrile represented by formula CI).

That is, the production method of the present invention can be expressed by the following reaction formula.

(In the formula, ■ is also 1, l ('', M and It causes a reaction.

The nitrile represented by the general formula (If), which is a raw material in this step, is a compound that is industrially easily available, such as acetonitrile, propionitrile, butyronitrile, allyl cyanide, benzyl cyanide, phenyloxyacetonitrile, benzyloxyacetonitrile, Examples include trimethylsilylacetonitrile.

The total bending compounds represented by the general formula (IID) which are the reactants in this step are butyllithium, methyllithium phenyllithium, lithium diimpropylamide, lithium hexamethyldisilazane, sodium hexamethyldisilazane, potassium hexamethyldisilazane, and potassium hexamethyldisilazane. Examples include silazane.

The non-step process is preferably carried out using molten IA, and for example, ether solvents such as tetrahydrofuran, dimethoxyethane, and diethyl ether can be used. The reaction is 11
It can be carried out at a temperature of 00°C to 50°C, preferably -78°C to room temperature.

[Second process]

In this step, the reaction product obtained in the first step is reacted with the α-alkoxyalkane nitrile represented by the general formula (IV), and 3-
Amino-2-alkene nitride/L/ is refined.

The alkoxyalkane nitriles represented by the general formula (rV) that are raw materials for this step include 0-ethoxyethyl lactonitrile, O-tetrahydropyranyl lactonitrile, 0-trimethylsilyl lactonitrile, 0-ethoxyethylmanzolonitrile, 0-Tetrahydropyranylmanzolonitrile, 0-trimethylsilylmantelonitrile, α-ethoxypropionitrile, methoxyacetonitrile, 0-ethoxyethylacetone cyanohydrin, 2,6-cyclohexyritenedioxybutanenitrile, 2.3-(2, Examples include 2-zolobylidene)dioxybutanenitrile and Zl-(diphenylmethylene)dioxybutanenitrile/l/.

This step is the same as the first step regarding conditions such as solvent and reaction temperature. After the reaction, the 3-amino-2-alkenenitrile represented by general 2 (I) can be obtained by neutralizing the reaction system using, for example, an aqueous ammonium chloride solution.

Considering the reaction mechanism of the production method of the present invention, the carbonyl anion heel stabilized with nitrile is easily reacted with the specific α-alkoxyalkane nitrile used in the present invention, and the by-product r It can be seen that the desired product can now be obtained in one step without the occurrence of any oxidation. In light of this extremely controversial fact, it is clear that the nitrile represented by the general formula (II) and the metal compound represented by the general formula (ffO) of the present invention can be widely used.

Hereinafter, the present invention will be explained in further detail based on Examples and Reference Examples.+JJ
K.Explain.

A solution of acetonitrile (2.06 g, 5 QmmOI) in tetrahydrofuran was cooled to -78°C, and with stirring, butyllithium (50 mmol, 1.61-4 hexane solution) was brushed. The reaction system became cloudy. 15 minutes (
When 2(2-tetrahydropyranoxy)prono(nitrile (7,75,!i!, 50 mmol) was added, the cloudiness immediately disappeared and the solution became pale (1!) with a uniform color. An aqueous ammonium solution was added and extracted with diethyl ether. After drying over anhydrous magnesium sulfate, it was concentrated and distilled using a Kugelrohr. 70 g (yield 99%) was obtained.

Boiling point = 161°C (bath temperature) / Q, 4 Torr.

IR(neat): 3450, 3340, 3230,
2180°1625, 1580cIn.

” H-NMR (CC14): δ1.3-2° [1(
m, 91().

3.2-5.4 (m, 7H).

Example 2-6 几2CN＋R1CH2CN 1. In the same manner as in Example 1. An lNpl-aminoacrylonitrile derivative was synthesized. The results and physical properties of the product are shown in Cloth 1. Note that the spectrum data is shown in Table 2.

Reference example NH2 ↓ cNH GcNH Yu (4s95S wood)-6-amino-4,5-diphenylmethylenedioxy-2-hexenenitrile (606m41
．． An ethanol solution of 1 mmol), sodium cyanoborohydride (126m 9.2 mmol), and a trace amount of bromocresol green was cooled to 0°C. Initially, the solution was blue in color, but when one drop of concentrated hydrochloric acid was added while stirring, the solution turned yellow.

Concentrated hydrochloric acid was added dropwise to maintain the yellow color and the reaction was followed by TLC. After the starting materials disappeared, 40% aqueous sensitized sodium solution was added, and the mixture was extracted with ether. The extract was washed with an aqueous sodium bicarbonate solution, dried, and concentrated, followed by preparative thin layer chromatography to obtain (4s+5S*)-3-amino-4,
Two isomers of 5-(sif-nylmethylenedioxy)hexanenitrile were isolated (216 mm, total yield 69%).
). R,f (ethyl acetate) of 0.63 and 0.57
The ratio with that of
IrL.

NMR (CD C13) δ1°40 (d, 3H),
1.96 (brs, 2H), 2-65 (d, 2H), 2
゜7-3.1 (m, IH), 3゜64 (dd, IH
).

4.09 (dq, IH), 7.1-7゜6 (m,
10f().

Isomer IR (neat) of 几fO,57 3400, 2240, 1665m
.

NMR (CDC13) δ 1. ro3 (d, 3
H), 2.06 (brs, 2H), 2゜56 (d
,, 2l-1), 2.9-3.2(m, IH),
5.75 (dd, 1.H).

4.22(d(1,1H), 7.1-7.6(m, l0
H).

(48 wood, 58 end) Rf of -6-amino-4,5-(diphenylmethylenedioxy)hexanenitrile
Q. Component 57 (123m9, 0.4mmol) K acetic anhydride and pyridine were added once each, and the mixture was stirred at room temperature for 5 hours. After removing excess acetic anhydride and pyridine under reduced pressure, ci(4S water, 58-terminal)-6-acetylamino-4,5-(diphenylmethylenedioxy)hexanenitrile was isolated by preparative thin layer chromatography. I did (1
2ro η, Section 88).

Soil is also fQ. 60 (ethyl acetate).

mp 140-142°0 IR (neat) 3400, 2250, 1675.15
25cm.

NMR (CDCl2) δ1°40 (d, 2H), 1
．． 49 (S.

roH), 2゜71 (d, 2H), 3゜8-4.5 (
m.

ro) (), 5.3-5゜7 (br, I H) +
7.2-7,7 (m, 10IL).

(4s end, 58*)-3-acetylamino-4,5-(
diphenylmethylenedioxy)hexanenitrile (10
The TI (F (2 m solution) of 5"F + O -3 mmof) was cooled at -78 ml, and while stirring, diisobutylaluminum hydride (1 iV THF solution, 0.6 mA) was slowly added, and then the mixture was heated to room temperature. The temperature was raised and the mixture was stirred for 6 hours (~). It was treated with 5% sulfuric acid and extracted with ether. After drying and concentration, it was extracted with PLO.
5-(diphenylmethylenedioxy) hegigahesho λtaka≦
I was obtained in 5 (75m9.71%).

Rf O, 46 (ethyl acetate) mp 159-162'0, [R(neat) 3380, 1730.1665 concentration
.

NMR (C1) C13) δ 1°32 (d, filter 14)
+ 1-90 (s.

3H), 2.7-2.9 (m, 2H), 3.7-4゜5
(m, RoH), 5.9-6.2 (br, IH), Otsu 2
-Z6 (m, 10H), 9.71 (brs, in)
.

(4S*, 58 bottles) -6-acetamido-4,5-(diphenylmethyledioxy)hexanal hydrochloric acid was added to approx.
I set it to 01N. After stirring at room temperature for 6 hours, add hydrogen carbonate)
A small amount of IJum was added to neutralize the mixture, and the precipitate was filtered. (±)-N-acetyl 1-nosamine methyl ether was isolated by concentration and preparative diluent chromatography at 474 N (297#, 71%) OR, f 0056
(Acetone) IIL (neat) Ro310, 1650.1535
cm.

NMR (CDCI.) δ1°22 (d, 3H), 1.7
-1.9 (m, 2l-i), 1.96 (s, 3H), 2
゜15 (S.

IH), 3.31 (s, 3H)% 5.55 (m, IH
).

6゜8-4.4 (m, 2H), 4.75 (
dd, IH).

5.8-6.3 (br, in).

Amendment of the Proceeding of Procurement of Proprietor, January 31, 1981 l) Ko1 Revised Secretary Kazuo Wakasugi 1, Indication of Tenant's Work lj"fl] 5 B 4E 'i'!r M'
r wish 'j'! 35904 No. 2, Title of the invention 3-amino-2-alkenyl-1-lyl and its θ) Production method 3o Relationship with tenant making amendment Column 5 of “Detailed description of the invention” in the patent applicant specification column, Amendment Contents (1) “Benzyl cyanide” on page 6, line 3 of the specification of the present application
Delete "," and replace "phenyloxy..." in lines 4 to 6.
・Delete "Silylacetonitrile".

(2) On page 7, lines 9 and 10, "[0-11J methylsilylactonitrile,"] is deleted, and on line 12, "0-trimethylsilylmanzolonitrile," is deleted.

(3) Equation 1 of actual rotation example 2 in Table 2 on page 12 of the same page % (4) Lines 7 to 8 and 17 of page 16μ of the same page, page 6 of the same page 17
Correct “acetylamino” to “acetamide” in lines ~7 0

Claims (1)

[Scope of Claims] 6-amine-2-alkenenitrile represented by the general formula (wherein R is an aqueous atom, an alkyl group, or an aryl group, and H
F is an α-alkoxyalkyl group. ). (2) The nitrile represented by the general formula % is reacted with the metal compound represented by the general formula A method for producing ro-amino-2-alkenenitrile represented by the general formula (wherein R is a hydrogen atom, an alkyl group, or an aryl group, R2 is an α-alkoxyalkyl group, M is an alkali metal atom, and X is (alkyl group, phenyl group, dialkylamino group or bistrimethylsilylamino group).