DE1493904A1 - Process for the preparation of basic substituted phenylacetonitriles - Google Patents

Description

Process for ■ the production of basic substituted phenylacetonitrile (Addition to patent 1 154 Ö1O and 1 158 083)

The subject of patents 1 154 Ö1O and 1 1> 8 083 are processes for the production of basic substituted phenylacetonitrile of the general formula

in which A, B and Ö are hydrogen or halogen atoms, low molecular weight alkyl or alkoxy groups, whereby in the latter case two adjacent groups can also jointly form a methylenedioxy group, R a low molecular weight aliphatic radical, R ₁ a low molecular weight alkyl radical, a saturated or unsaturated, cyclic or bicyclic hydrocarbon radical or the benzyl or phenyl group, η denotes the number 2, 3 or 4 and m denotes the number 1, 2 or 3.

Following the procedures of these patents, the connections are made by that in the presence of basic condensing agents

a) Phenylacetonitriles of the general formula

A ■

-C = H '

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KNOLL AG.

CHEMICAL FACTORY

with a compound of the general formula

AX - (CH ₂ ) _n - N - (CH ₂ ) '

₂ ) _n

₂ ) _m

wherein X represents a reactive acidic residue, converts or b) Phenylaoetonitriles of the general formula A A

C = N

> n - f - ( ^CH 2) m

with compounds of the general formula R - \ to react or

c) Pheny / acetonitriles of the general formula

CH,

with compounds of the general formula

A /

X - (CHg) _n - W - (UH ₉ X

and compounds of the general formula R ₁ -X converts, or

d) Phenylacetonitriles of the general formula A -

C - (CH ₀ ) - X

L. ⁿ

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BATH ORIGINAL

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KMOLL AG.

CHEMICAL FACTORY

with compounds of the general formula

= 2 * - ^ ³ Z>

m -4

H-N-j

reacts or

e) Pheny / acetonitriles of the general formula

G 5 N

λ I.

- χ

with compounds of the general formula

, B

reacted and introduced into the obtained sweet luniären amines the remainder R by alkylation in a known per se Vfeise, wherein in the above formulas, the symbols A, B, C, R, R .., η and m have the meaning indicated above and X is a means reactive acid residue. ''""':

It has now been found that in a further development of the processes mentioned new valuable compounds are obtained if such starting compounds are reacted according to patent 154810 and latent 1558 08J at least one of the reaction components instead of the group

A / "

3,

the group ^J F * ~ \

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KNOLL A. G.

CHEMICAL FACTORY

carries and / or instead of starting compounds in which R. a Benzyl or phenyl group, corresponding trifluoromethylbenzyl or trifluoromethylphenyl compounds react.

The new compounds have low toxicity significant coronardilatatorische effectiveness and should findene as medicinal use of the compounds of patents 1,154,810 and 1 I58 083 they also differ in terms of blood pressure-lowering properties _o

The invention is explained below on the basis of exemplary embodiments.

example 1

α-Isopropyl-α- ^ (N-methyl-N-β-3-trifluoromethylphenylethyl) -y-aminopropyl7-3-trifluoromethylphenylacetonitrile

In a three-necked flask equipped with a stirrer, reflux condenser and dropping funnel, 22.7 8 (0.1 mol) of α-isopropyl-3-trifluoromethylphenylacetonitrile are dissolved in 200 ml of toluene and mixed with the solution of 1-chloro-3- (lI -methyl-N-ß-34; rifluoromethylphenylethyl) aminopropane in 200 ml of toluene and heated. At 90 ° C., 13 g of a 30% sodium amide suspension in toluene are introduced over the course of 20 minutes and the mixture is then heated to the boil for 4 hours.

The cooled solution is mixed with 200 ml of water, the toluene layer separated off, dried with anhydrous magnesium sulfate, and the toluene was distilled off and the residue fractionated in vacuo.

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IS O L L AG.

CHEMICAL FACTORY

41.2 g of α-isopropyl-ci- ^ U-methyl-IT-β-J-trifluoromethylphenylethyl) -y-aminopropyl / -3- rIfluoromethylpheny / acetonitrile are obtained as a yellow, viscous oil. Yield 88 fo the theory, bp 0.1 - 205 - 210 ° C. Acid oxalate F ■ 188 ° C.

The starting compounds were prepared by condensation of 3-trifluoromethylphenylacetonitrile and isopropyl bromide and by release, respectively the chlorine base from the corresponding acidic oxalate

In the same way, the compounds described in the table were made manufactured

Kp ° 0

yield

(acid in ^c ß> the oxalate, ⁰ O) theory

Sv r

C ₃ H ₇

CH.
CH ₃ O

ClT 0-

CH,

OCH,

(CH) -N- (CH ₂ ) ₂

195-200 / 0.1 mm I58

195-200 / 0.1 mm I47

232-235 / 0.3mm

79

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KM DLL AG

CHEMICAL FACTORY

Bp ° C

(sour

Yield in ^a / o the

Oxalate, Q, theory

H ₁

OH

OF,

■ OH, 235-240 / 0.05 mm x 105

(Decomp.)

CN CH

CH

207-210 / 0.01mm 142

CN CH,

.C- (CH ₂ ) ₅ -1T- (CH ₂ ) _J

210-215 / 0.01mm 111

202-204 / 0.1 mm 121

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CHEMICAL FACTORY

Example 2

α-Isopropyl-α- / Xli-niethyl-N-homoveratryl) -y-aminopropyl _> 7-3-trifluorioethylphenylacetonitrile

According to the method described in Example 1, 93.6 g (0.223 mol) of a- / Xli-methyl-lI-homoTeratryl) -y-aminopropyl / -5-trifluoromethylphenylacetonitrile are dissolved in 500 ml of toluene, 30.8 g (0, 25 mol) of isopropyl bromide are added and 32.5 8 30-year old sodium amide suspension in toluene is slowly added dropwise at 70 ° C. The mixture is then kept boiling for 3 hours, cooled, 150 ml of water are added and the separated toluene layer is shaken twice more It is dried with anhydrous magnesium sulfate, the toluene is removed and the residue is fractionated.

You get 89.5 S ct-I

3-trifluoromethylphenylacetonitrile as a yellow, viscous oil. Yield 87 fo the theory. Bp 0.1 = 195 - 200 ° C. Sour salat F. = I58 - I59 ⁰ 0.

The starting compound is prepared by condensation of 3-trifluoromethylphenylacetonitrile and N- ^ ethyl-ii-homoveratrylaniino-y-chloropropane in Presence of sodium dinamide. , ·

example

a-Isopropyi-a- _> /(lT-i..ethyl-lI-homoveratryl)-y-aminopropyl7-3-trifluoromethyl v! acetonitrile

30 & (C-, 1. l.ol) f.-13oprC'pyl-c (- (3'-chlorpiOpyl) -3-trifluoromethylphenylaceto- "-iivL! .; Nd J- .. .0.2 Γ, ΐοΐ ¹¹ Iv-Ietr.jihonoveratrylamin are in an oil bath

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K IST Ό Ii-L AG.

CHEMICAL FACTORY

Heated to 130-150 ° C for 7 hours. The glassy solidified melt is heat-treated with 1 1 of benzene, "whereupon the hydrochloride of the N-Methylhomoveratrylamina precipitates and is suctioned off. The filtrate is washed with 10 follower sodium hydroxide solution, dried with anhydrous magnesium sulfate, distilling off the benzene and the residue fractionated.

Kp / (N-methyl-N-homoveratryl ^ y-aminopropyl / -3-trifluoromethylphenylacetonitrile as a yellow viscous oil Yield 79 i ° of the theoretical 0.1 - - is obtained 36.5 g of a-isopropyl-a.. 195-200 ° C. Acid Oxalate F - 158 ° C. The salt is identical to the oxalate described in Example 2.

cc-Isopropyl-cc- (3 ^L -chlorpropyl) -3-trifluoromethylphenylacetonitrile is produced by the condensation of i-chloro-3-bromopropane or 1,3-dichloropropane with α-isopropyl-3-trifluoromethylphenylacetonitrile in the presence of sodium amide.

Example 4

o-Isopropyl-o- ₁ / (IT-methyl-F-homoveratryl) -y-aminopropyl7-3-trifluoromethylphenylacetonitrile

45 g (0.15 mol) of a-isopropyl-o- (3 ^l -ohlorpropyl) -3-trifluoromethylphenylacetonitrile and 55 g (0.3 mol) of homoveratrylamine are heated to 130-150 ° C. for 7 hours. The cooled, glassy, solidified melt is treated with 1 l of benzene in the heat, whereupon the homoveratrylamine hydrochloride precipitates and is filtered off with suction. ■ '"-'

The filtrate is washed with 10 $ strength sodium hydroxide solution, with anhydrous

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CHEMICAL FACTORY

Magnesium sulfate dried, the solvent was distilled off and the Fractionated residue.

This gives 45 S ct-isopropyl-a - / (lJ'-homoveratryl) - '/ - aminopropyl / -5'-trifluoromethylphenylacetonitrile as yellow viscous Cl. Yield 68 fo the theory »bp 0.1-203-208 ° G.

45 g of the secondary base obtained are dissolved in 100 ml of methanol and 40 ml of 35% aqueous formaldehyde solution and methylated in the heat by adding 7.5 g (0.2 mol) of sodium borohydride in portions. During the reaction, the solution heats up to the boil. The batch is then stirred for a further 2 hours without the supply of heat. The methanol solution is evaporated to dryness, the residue is mixed with 200 ml of water and extracted with ether. The dried iither solution is again evaporated and the residue is distilled.

30.5 g of α-isopropyl-α - / ^ lJ-methyl-IT-homoveratryl) -y-aminopropyl / -3-trifluoromethylphenylacetonitrile are obtained as a viscous yellow oil. Yield 66 -fo of theory. Bp 0.1 = 195-200 ° C. Acid oxalate F 158 ° C. The salt is identical to the oxalate described in Examples 2 and 3.

The methylation can also be done with formaldehyde / formic acid or by action of hydrogen in the presence of palladium or Mxckel catalyst or amalgamated aluminum among those in Example 3 of patent 1 1 ^ 8 083

♦.

conditions described are carried out.

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Claims (1)

CHEMICAL FACTORY
Claim. Further development of the process for the production of basic substituted Phenylacetonitrile of the general formula B C in which A, B and O are hydrogen or halogen atoms, low molecular weight Alkyl or alkoxy groups, in the latter case two adjacent groups can also together form an Ivlethylendioxygruppe, R a low molecular weight aliphatic radical, R. a low molecular weight alkyl radical, a saturated or unsaturated, cyclic or bicyclic hydrocarbon rest or the benzyl or phenyl group, η the number 2, 3 or 4 and m denotes the number 1, 2 or 3, according to patent 1,154,810 and patent 1,158,083, characterized in that starting 3 compounds are reacted in which at least one of the reaction components instead of the group the group carries and / or instead of starting compounds, in Wbijhen R. a benzyl or phenyl group, corresponding trifluoromethylbenzyl or trifluoromethylpheny! compounds lets react. BATH ORIGINAL 909825 / U82.