DE1111188B - Process for the preparation of heterocyclic nitrogen-containing bases arylated in the ª-position to the nitrogen atom and having a double bond in the 1, 2-position and salts thereof - Google Patents

Description

BMTERNAT.KL. C 07 d

GERMAN

PATENT OFFICE

F2835irVb / 12p

REGISTRATION DATE: 30 A P R I L 1959

NOTICE
THE REGISTRATION
AND ISSUE OF
EDITORIAL: JULY 20, 1961

2-Arylpyrroline with a double bond in the 1,2-position have already been produced in various ways. Almost all of these procedures have in common that the last stage before the ring closure is γ-aminoalkylaryl ketones appear.

The invention relates to a simple, one-step process for the production of previously only more cumbersome Because of the accessible heterocyclic, nitrogen-containing, in -position to the nitrogen atom by aryl radicals substituted bases with a double bond in 1,2-position and their salts.

It has been found that heterocyclic, nitrogen-containing bases arylated in the α-position to the nitrogen atom with a double bond in the 1,2-position and their salts can be prepared if aromatic compounds which contain at least one group - XR in the X is an oxygen or sulfur atom and R is a hydrogen atom, an alkyl radical or a radical - R1X1 - in which X _{1 is} an oxygen or sulfur atom bonded in the o-position to X and K _{1 is} an ethylene radical or X _{1 is} an aromatic radical bonded oxygen or sulfur atom and K _{1 is} an alkylene radical, and which have at least one hydrogen atom in o- or p-position to such a group —XR, in the heat, dissolved in polyphosphoric acid, with primary γ- or ^ -amino carboxylic acids, their Esters and / or their salts condensed with inorganic acids or bases and, if appropriate, the bases obtained after introducing the reaction mixture into water and alkalizing m treated with acids.

The alkyl radicals R and the alkylene radical R _x are particularly short-chain radicals, in particular those with

0-CH ₃

Method of manufacture

of heterocyclic nitrogenous,

arylated bases with a double bond in the α-position to the nitrogen atom

in the 1,2-position and their salts

Applicant:

Farbwerke Hoechst Aktiengesellschaft

formerly Master Lucius & Brüning,

Frankfurt / M., Brüningstr. 45

Dr. Walter Koller, Frankfurt / M.,

and Dr. Paul Schlack, Frankfurt / M.-Höchst,

have been named as inventors

1 to 4 carbon atoms, preferably 1 or 2 carbon atoms, are possible.

The aromatic compounds used as starting materials for the reaction according to the invention can differ from benzene or any other aromatic base material, for example naphthalene, Anthracene and phenanthrene.

In the reaction according to the invention, when γ-aminocarboxylic acid is used, 2-aryl- ^{Zf 1 -pyrrolines are formed;} for example from resorcinol dimethyl ether and γ-aminobutyric acid in the sense of the reaction equation

Q-CH ₃ CH ₂ -CH ₂

CH, -O-

> + HOOC-CH ₂ CH ₂ -CH ₂ -NH ₂ + CH ₃ -O _N CH ₂ + 2H ₂ O

2- (2 ', 4'-dimethoxyphenyl) -Zl ¹ -pyrrole. from thioanisole and <5-aminovaleric acid hydro

When using ^ -aminocarboxylic acids ent- chloride in the sense of the equation
are 2-ΑτγΙ-Α ^ tetrahydropyridines, for example

CH ₂

CHo- S- <

:> + HOOC CH ₂ -CH ₂ -CH ₂ -CH ₂ NH ₂ - »- CH ₃ -S- :;

-c

sCH ₂

2H ₂ O

2- (4'-methylmercaptophenyl) -Zl ¹ -tetrahydropyridine. smooth and with high yield, so that bases the

The reactions usually proceed through the process of the invention, as mentioned in the extraordinarily mentioned type

109 648/375

3 4

are very easy to produce, if reactive also, the implementation at lower temperatures

capable aromatic compounds of the formula. However, it is generally useful

Ar (XR) «, in which η is a lower whole number, in particular to choose the temperature as high as possible,

which represent 1 to 3, is assumed. In advance without undesired side reactions in

Setting for the feasibility of the invention 5 significant scope occur. It then succeeds in

proper implementation is a solubility of the reac- a relatively short time, very good, often almost

tion components in polyphosphoric acid. To achieve particularly quantitative yields,
The alkyl aryl ethers and alkyl ethers behave favorably. In individual cases, the reaction takes place in the

aryl thioethers, the alkyl groups of which are from 1 to 3 carbons polyphosphoric acid with dealkylation of an o-stän-

There are substance atoms, probably because of their better io-ended alkyl ether group, such. B. in the implementation

Solubility in polyphosphoric acid compared to that of desPyrogaUol-trimethyläthersmity-aminobutyric acid

ethers containing higher alkyl radicals. Lower ones above 50 ⁰ C.

Yields are obtained with free phenols and the aromatic mercaptans. The process is diluted with water and the base formed according to the invention is deposited as aminocarboxylic acids, 15 by neutralizing or making alkaline, for example the following: γ- amino If the reaction products are phenolic in character, butyric acid, γ-aminovaleric acid, γ-methyl y-amino-, it is usually expedient to avoid an excess of alkali leading to the formation of valeric acid, ό-aminovaleric acid and <5-amino-phenolates, caproic acid or its salts. The nature of the salt-forming component, unless it succeeds and is intended, the Umden component is important for the reaction even without a settlement product as a sparingly soluble alkali metal phenolate. There are salts of the aminocarboxylic acids with isolate. In many cases, the bases can be any inorganic acids or bases, e.g. B. partially separated as sparingly soluble salts with other acids hydrochloric or hydrofluoric acid, phosphoric acid or potassium or sodium hydroxide from the reaction mixture diluted with water, z. B. as perchlorates or picrates. The compounds according to the invention are suitable, provided they can only be dissolved in polyphosphoric acid, at least in the heat. This can take on a particularly pure form.
Dissolve in the polyphosphoric acid, if necessary. The salts of the bases obtained by the process of the invention with expulsion of a volatile acid, such as chlorine, are usually made with hydrogen or hydrogen fluoride. Instead of excellent crystallizability. Most of the free aminocarboxylic acids can also be found in bases. Some of the new basic den, z. B. the methyl or ethyl esters or their heterocycles show strong fluorescence in short hydrochloride. wavy light.

As an aromatic reactant the general- A very remarkable property of the bases is

my formula Ar (XR) _n are z. B. the following conspicuously in view of their imine structure

bonds used: o-cresol, p-cresol, anisole, resistance to strong acids, even in the

o-chloroanisole, p-cresol monomethyl ether, phenetol, heat. The compounds produced according to the invention

/? - Bromoethyl-phenylether, butylphenylether, p-tert.- gen are in contrast to the behavior of the

Butylphenyl methyl ether, resorcinol dimethyl ether, higher analogues with seven ring members, (e.g.

Veratrole, benzodioxane, pyrogallol-1,2-dimethyl ether, 40 aza-cycloheptenes) with double bond in 1,2-place

Pyrogallol - trimethyl ether, 1 - methoxynaphthalene, lung, which is very easily produced by acids, even at room temperature

2-methoxynaphthalene, 2-methoxyanthracene, methyl temperature, to the salts of the corresponding amino

phenyl sulfide, ethyl phenyl sulfide. Particularly valuable ketones are broken down.

and reactive are the phenyl ethers and phenyl The bases with alkylthioether groups in o- and thioether. The naphthalene p-position to the heterocyclic substituent react less easily with derivatives. The lower yields of naphthalene in concentrated strong acids, such as sulfur derivatives, in contrast to simple benzene derivatives, acid or perchloric acid, with an intense color, whereby quinoid sulfonium compounds evidently form quinoid sulfonium compounds due to their lower solubility in polyphosphorus. The reduced reaction rate- These rearrangements are reversible,
speed then presumably favors side reactions, 50 The accessible by the method of the invention z. B. the formation of lactams. Strongly negative sub-bases or their salts are valuable intermediate substituents, such as free carboxyl, nitro, sulfo or products, e.g. B. for the production of pharmaceutical sulfone groups should be used in the aromatic starting compounds. The products of the process are not contained, at least not then, and can also act as optical brighteners if they are characterized by strong fluorine if only one reactivating group —XR is present. Find UV absorbers use. From different

The implementation is usually carried out in the manner of textile fibers, e.g. B. those with acidic groups, such as

made that the reaction components, polyacrylonitrile fibers, the bases are made of warm,

one of which was vigorously absorbed by the aqueous liquor used in excess,
can be, in about 4 to 8 times the weight 60

amount of polyphosphoric acid, which should be an example 1

Content of 75 to 85 percent by weight of P ₂ O ₅ on 10.31 g of y-aminobutyric acid,

has heated for some time until the reaction has ended and 13.82 g of Veratrol

is. The implementation conditions can be with regard to 180 g of polyphosphoric acid (P ₂ O ₅ content 80%)

The temperature and time, depending on the reactivity of the 65, are ^{heated to 100 °} C. for 3 hours with stirring.

Aromatics vary within relatively wide limits.

ken. As a rule, a syrupy reaction mixture is worked into 400 ecm of water at temperatures.

between 60 and 150 ^° C. In some cases it succeeds after removing the unreacted veratrole

5 6

by shaking out the phosphoric acid solution with Example 4

Ether is the solution with water to three times 10.31 g of y-aminobutyric acid,

diluted to the subsequent addition with 16.82 g of pyrogallol trimethyl ether and

Alkali leads to the precipitation of alkali phosphates 180 g polyphosphoric acid (P ₂ O ₅ content 80%)

prevent. It is then alkaline with 10 η sodium hydroxide solution and ^{heated to 40 °} C. for 72 hours with stirring.

(Ph> 10) made, whereby the pyrroline base becomes oily, The dark red, syrupy solution becomes, as in the case of

partly emulsified. Specified from the mixture of game 1, worked up. By evaporation

if the base is extracted with ether, the ether solution of the ether extracts is obtained the 2- (2 ', 3', 4'-tri-

Washed alkali-free with water and dried over sodium methoxyphenyl-Z ^ -pyrroline as a brown oil,

dried sulfate, after evaporation of the solution which solidifies in crystalline form on cooling. After the loading

by means of 2- (2 ', 3'-dimethoxyphenyl) - ^ l * -pyr- treatment with activated charcoal crystallizes the compound

rolin as a greenish-yellow colored oil, which is produced from petroleum ether in pale yellowish needles from

Cooling solidified crystalline. After dissolving in ether F. 48 ⁰ C.

and treating the ether solution with active carbon Yield: 18.6 g (79.2 ° / ₀ of theory).

colorless crystals with a melting point of 89 ^° C. are obtained. The base 15 The base distills at 0.03 mm in a bulb tube

distilled at 0.03 mm in a Kugelrohr at 108 ⁰ C air 107 ° C air bath.

bath temperature. Hydrochloride: F. 160 ⁰ C, colorless, thin prisms

The yield is 19.6 g (95.5%). from methyl ethyl ketone alcohol.

Hydrochloride: mp 255 ° C (decomposition), colorless perchlorate: mp 181 ° C, colorless needles made of water.

Prisms made of alcohol, made by adding 20. With a reaction time of 17 hours, the

Hydrogen chloride — ether for the ether solution of the base. Yield 62% of theory.

Perchlorate. F. 241 ⁰ C, colorless needles from water, at higher temperatures is obtained under Enthergestellt by dissolving the base in dilute hydrochloric methylation of a methoxyl group, the 2- (2'-oxy acid and addition of 35% strength perchloric ^he 3 ' , 4'-dimethoxyphenyl) - ^ d ^ pyrroline depending on the

If the γ-aminobutyric acid is replaced by its chosen reaction temperature in a mixture with the

Hydrochloride or its ethyl ester and works in the trimethoxy compound, for example at 55 ⁰ C, or as

the rest as stated, the same reaction ^{- the only reaction product, for example at 75 °} C. - is formed; yellow

product in slightly lower yield. Needles with a ^{temperature of 101 °} C. made of ligroin after treatment

with activated carbon.

Example 2 3 ° hydrochloride: mp 184 to 185 ° C, colorless prisms

from alcohol — ether.

10.31 g of γ-aminobutyric acid, perchlorate: F. 223 ^° C., colorless needles made of water. 13.82 g resorcinol dimethyl ether and

180 g of polyphosphoric acid (P ₂ O ₁ content 80%) Example 5

10.31 g of y-aminobutyric acid are added to 35 10.31 g of y-aminobutyric acid for 3 hours with constant stirring,

100 ⁰ C heated. The purple colored reaction mixture 12.41 g of thioanisole and

is as indicated in Example 1, worked up. 180 g of polyphosphoric acid (P ₂ O ₅ content 80%)

yield the 2- (2 ', 4' ⁽¹ DhnethoxyphenyrM -pyrrolin by heated under stirring for 3 hours at 100 ⁰ C.

Evaporation of the ether extracts first as thick, one lets cool and then carries the yellow, syrupy

red-brown colored oil, which after treatment with 40 reaction mixture in 600 ecm of water. After this

Activated charcoal from petroleum ether in colorless rhombuses from thinning with water three times and dissolving

F. 51 ⁰ C crystallized. The base is distilled at 0.05 mm, the solution is treated with 10 η sodium hydroxide solution under ice

in the bulb tube at 106 to 108 ⁰ C air bath temperature. cooling made alkaline (pn> 10), whereby the

Yield: 16.4 g (80.0% of theory). Pyrroline base for the most part in solid form on the

Hydrochloride: F. 207 to 208 ⁰ C, colorless prisms 45 surface separates. The solution with the Niederaus alcohol ether. shock is shaken out with ether, the ether phase

Perchlorate: mp 197 ° C, colorless needles made of water. Washed alkali-free with water and dried over sodium

. . ₁ sulfate dried. By evaporating the solution

Example J by means of the 2- (4'-methylmercaptophenyl) -

10.31 g of γ-aminobutyric acid, 50 Zl ^ pyrroline as almost colorless crystals. After this

10.81 g of anisole and recrystallization from petroleum ether colorless needles

180 g of polyphosphoric acid (P ₂ O ₅ content 80%), melting at 102 ° C, bp. _{0, 02,} 105 ° C air bath,

^{are heated to 100 °} C. for 12 hours with stirring. Yield: 17.1 g (89.6% of theory, based on

The red colored reaction mixture is, as in aminobutyric acid).

Example 1 indicated, worked up. A 10% excess is used by evaporation

the ether extracts if the 2- (4 ₆ -methoxy-thioanisole is obtained, then the yield increases, based on

phenyl) - /! ^ pyrroline initially as a pale green colored γ-aminobutyric acid, to 95.3%

Oil that solidifies in crystalline form after cooling. The hydrochloride: mp 222 ° C, colorless needles

Binding crystallizes from ether in colorless needles alcohol.

from 73 to 73.5 ° C. The base distills at 0.03 mm 60 perchlorate: F. 201 ⁰ C, colorless needles from water,

in a bulb tube at 95 ⁰ C air bath. . .

Yield: 13.8 g (78.8% of theory). Example 6

If anisole is used in excess of 100%> 10.31 g of γ-aminobutyric acid,

so the yield after 3 hours of heating is 12.21 g of 2-methoxytoluene and

96.0% of theory. 65 180 g polyphosphoric acid (P ₂ O ₅ content 80%)

Hydrochloride: mp 208 ° C, colorless needles from Aiko- are heated to 100 ° C for 3 hours while stirring,

get — petroleum ether. The wine-red, syrupy solution is, as in Example 1

Perchlorate: F. 190 ⁰ C, colorless needles made of water. specified, worked up. One obtains by

7 8

the ether extracts evaporate the 2- (4'-methoxy-3'-me-F. 106 ° C. from petroleum ether. The base distills at

thylphenyl) -Zl ¹ -pyrroline as a brown oil, the 0.03 mm in the bulb tube at 118 ° C air bath temperature.

Cooling solidified crystalline. After treatment with yield: 13.6 g (50.8% of theory).

Activated carbon colorless needles, melting at 51 ⁰ C from petroleum hydrochloride: mp 155.5 to 156 ° C, colorless needles

The base distills at 0.03 mm in the Kugelrohr 5 from alcohol-ether.

at 88 ° C air bath temperature.

Yield: 15.7 g (83.0% of theory). Example 10

Hydrochloride: F. 271 ⁰ C, colorless needles from 10.31 g γ-aminobutyric acid,

Alcohol. 10.81 g p-cresol and

Perchlorate: F. 148 ^C C, colorless needles made of water. 180 g polyphosphoric acid (P ₂ O ₅ content 80%)

If 4-methoxytoluene is used instead of, the mixture is ^{heated to 130 °} C. for 48 hours while stirring.

2-methoxytoluene, the 2- (2'-methoxy- The yellow-green, syrupy reaction mixture is obtained, like

5'-methylphenyl) -J ^ pyrroline in 73.0% yield i§ ^it. indicated in Example 1, worked up. Instead of

After distillation in a bulb tube at 0.03 mm ether, however, it is advantageous to extract a colorless 15 ^{with methylene chloride and an air bath temperature of 78 3 C.} The 2- (2'-oxy-5'-methylphenyl>

Hydrochloride: F. 204.5 to 205 ⁰ C, colorless prisms zF-pyrroline as a dark red, greasy oil, which

from alcohol — ether. solidified in crystalline form on cooling. After treatment

Perchlorate: mp 283 ° C, colorless needles made of water. with activated charcoal and recrystallization from petroleum ether

. . ₁ 20 become yellow-green, strongly fluorescent in UV light

^{ΰεΐδριε1} 'prisms from F. 80.5 to 8I ⁰ C obtained. The base

10.31 g of y-aminobutyric acid, distilled at 0.03 mm in a bulb tube at 105 ⁰ C air

13.61 g catechol ethylene ether and bath temperature.

180 g of polyphosphoric acid (P ₂ O ₅ content 80%) Yield: 11.25 g (64.2% of theory),

^{are heated to 100 °} C. for 3 hours with stirring. 25 Hydrochloride: F. 258 to 259 ⁰ C (decomposition), yellow-

The dark red, syrupy solution is, as in the case of green fluorescence in UV light,

game 1 specified, worked up. The perchlorate is obtained: mp 251.5 to 252.5 ° C, yellowish needles,

2- (3 ', 4 ₆ -äthylenedioxyphenyl) -Zl ^ pyrroline by yellow-green fluorescence in UV light,

the ether extracts evaporate as a yellow oil, which becomes o-cresol after a reaction time of 3 hours

solidified in crystalline form on cooling. 30 at 100 ⁰ C the 2- (4'-oxy-3'-methylphenyl) -il ¹ -pyrroline

Yield: 90.4 g (95.7% of theory). obtained in 24% yield. Yellow-green, in the UV

After distillation in a bulb tube with 0.03 mm light, strongly fluorescent needles with a temperature of ^{86 ° C}

and 105 ⁰ C air bath temperature and recrystallization of petroleum ether after treatment with activated charcoal,

from ether-petroleum ether with addition of activated carbon Kp. _{0, 03} 88 ⁰ C air bath,

colorless needles are obtained, melting at 8O ⁰ C. ₃₅ Hydrochloride: M.p. 192 ° C, colorless needles made of alcohol

Hydrochloride: mp 205 ° C, colorless crystals of hol-ether.

Alcohol — petroleum ether. Perchlorate: F. 189.5 to 19O ⁰ C, colorless needles off

Perchlorate: mp 149.5 ° C, colorless needles made of water. Water.

Example 8 ₄₀ Example 11

10.31 g γ-aminobutyric acid, 15.36 g (3-aminovaleric acid hydrochloride,

14.26 g of 2-chloroanisole and 10.81 g of anisole and

180 g polyphosphoric acid (P ₂ O ₅ content 80%) 180 g polyphosphoric acid (P ₂ O ₃ content 83%)
are heated to 100 ° C. for 24 hours while stirring. are heated to 100 ° C with stirring, the chlorine-The reddish-colored, syrupy reaction mixture is, 45 hydrogen escapes. After a reaction time of 3 hours as indicated in Example 1, worked up. The dark red-colored reaction mixture is worked up, as indicated in the vapor residue of the ether extracts, the 2- (3'-chlorine example 1. The 4'-methoxyphenyl) -zl ¹ -pyrroline is obtained, initially a yellow, 2- ( 4'-methoxyphenyl) - / l ¹ -tetrahydropyridine due to greasy oil, solidifies on cooling. After steaming the ether extracts as a light brown oil, which, when treated with activated charcoal from petroleum ether, colorless 50 solidifies in crystalline form on cooling.
Needles with a temperature of 74.0 ° C. The base distills with a 0.3 mm yield: 16.4 g (86.7% of theory),
in a bulb tube at 118 ° C air bath temperature. By recrystallization from petroleum ether with a yield: 15.05 g (72.0% of theory). The addition of activated charcoal gives colorless needles hydrochloride: mp 244 ° C, colorless needles from mp 60 ° C, which gradually turn brown. The alcohol. 55 base distilled at 0.3 mm in a Kugelrohr at 118 ° C perchlorate: F. 16O ⁰ C, colorless needles from water. Air bath temperature.

_. . ,. Hydrochloride: mp 213.5 to 214.0 ° C, colorless needles

^Beis P ^ie19 made of alcohol-ether.

10.31 g of γ-aminobutyric acid, perchlorate: mp 137 to 137.5 ° C, colorless needles

20.10 g of phenoxyethyl bromide and 60% water.

180g polyphosphoric acid (P ₂ O ₅ content 80%) Example 12
are heated to 100 ° C. for 3 hours with stirring.

The yellow-brown, syrupy reaction mixture, such as 15.36 g of ö-aminovaleric acid hydrochloride,

indicated in Example 1, worked up. The 2- (4'- 13.82 g veratrole and

/ 3-Bromäthoxyjphenyl) - / J ¹ -pynOlin is 65 180 g polyphosphoric acid (P ₂ O ₅ content 83%)
evaporation of the ether extracts obtained as a green yellow oil are heated with stirring to 100 ⁰ C, wherein Chlordas solidified crystalline on cooling. After the hydrogen escapes. After one hour of reaction with activated charcoal, colorless needles from time to time, the wine-red, syrupy reaction mixture,

9 10

as indicated in Example 1, worked up. The dark red, syrupy reaction mixture is obtained in time,

the 2- (3 \ 4'-dimethoxyphenyl) -zl ¹ -tetrahydropyridine as indicated in Example 1, worked up. You get

by evaporation of the ether extracts. First the 2- (2 \ 3 ^ 4Vtrimethoxyphenyl) -zl ¹ -tetrahydropyridine

yellow oil crystallizes after prolonged standing. by evaporation of the ether extracts than initially Yield: 16.6 g (75.7% of theory). 5 green-yellow oil, after distillation in the bulb tube

Still weak by recrystallization from petroleum ether below 0.03 mm and 100 ⁰ C air bath temperature

The addition of activated charcoal results in colorless, long yellowish oil, which gradually turns brown

Needles from F. 78 ⁰ C. The base distilled at 0.03 mm discolored,

in a Kugelrohr at 109 ⁰ C air bath. Yield: 16.1 g (64.6% of theory).

Hydrochloric !: F. 215.5 to 216.5 ⁰ C, colorless needles io Hydrochloric: F. 131.5 to 132 ° C, colorless small

from alcohol — ether. Needles made of dimethylformamide — ether and alcohol—

Perchlorate: F. 223 to 223.5 ⁰ C, colorless needles made of ether.
Water. Perchlorate: F. 139 ° C, colorless needles made of water.

Example 13 ^Alcohol1

15.36 g o-aminovaleric acid hydrochloride,

13.81 g resorcinol dimethyl ether and 10.31 g γ-aminobutyric acid,

180 g of polyphosphoric acid (P ₂ O ₅ -GeImIt 83%) 16.62 g of methyl 2-methoxybenzoate and
are heated with stirring to 100 ° C, whereby chlorine- 180 g polyphosphoric acid (P ₂ O ₅ content 83%)
hydrogen escapes. After 3 hours of heating ao 3 hours under stirring heated to 100 ⁰ C, duration is allowed to cool, and operates the wine-red, The brown syrupy reaction mixture is worked up as described in syrupy reaction mixture, such as starting in Example 1. Example. 1 By entering, on. The 2- (2 ', 4'-dimethoxy vapor of the ether extracts is obtained, the 2- (4'-mephenyl) - ^! ¹ -tetrahydropyridine is obtained by evaporating the thoxy-3'-carbmethoxy) -Zl ¹ -pyrroline as yellow-green oil, ether extracts as red-brown, thick oil, which crystallizes out after prolonged standing.
Distillation in a bulb tube at 0.03 mm and 115 ^° C. Yield: 8.2 g (35.2% of theory).
Air bath temperature is obtained almost colorless, but after recrystallization from ether one gets dark again after a short time. colorless, irregular crystals with a melting point of 58 to 60 ° C. Yield: 19.6 g (89.4% of theory). Hydrochloride: F. 20FC, colorless, small needles

Hydrochloride: mp 188 ⁰ C, colorless diamonds of 30 from alcohol-petroleum ether.

Alcohol — ether. Perchlorate: F. 222 ⁰ C colorless needles and irregular

Perchlorate: F. 187 ⁰ C, colorless needles made of water. moderate crystals of water-alcohol.

Picrat: F. 142 ⁰ C.

Example 17

35 10.31 g of γ-aminobutyric acid,

15.36 g δ- aminovaleric acid hydrochloride, 15.82 g 1-methoxynaphthalene and

12.42 g thioanisole and 180 g polyphosphoric acid

180 g of polyphosphoric acid (P ₂ O ₅ content 83%) are heated to 75 ° C for 12 hours while stirring,

are heated to 75 ^° C. with stirring, with chlorine- After cooling, the dark brown-green

hydrogen escapes. After a reaction time of 3 hours, pour 40 colored reaction mixture into ice water, whereby

the green, syrupy reaction mixture, as in the 2- (l'-methoxynaphthal) -4 ¹ -pyrroline as yellow-

Example 1 indicated, worked up. The brown, initially greasy phosphate is deposited,

2 - (4 '- Methylmercaptophenyl) -Δ ¹ - tetrahydropyridine which then to remove impurities in

dissolved as green-yellow dilute hydrochloric acid by evaporation of the ether extracts and extracted with ether.

Oil, which crystallizes in needles on cooling. 45 is shaking. The clear, hydrochloric acid solution becomes

Yield: 14.6 g (71.2% of theory). Obtaining the pyrroline base with 10 N NaOH alkaline

After treatment with activated charcoal made crystallized and etherified. Likewise, with the phos-

remove the base from petroleum ether in colorless flakes from the phosphoric acid solution. The pyrroline base will

F. 70 ⁰ C. as evaporation residue of the combined, with water

The base dissolves in concentrated strong acids, washed 5 ° and dried with sodium sulfate,

such as sulfuric acid and perchloric acid with deep green-blue ether extracts initially obtained as a yellow-brown oil,

Color, apparently due to the formation of a quinoid which crystallizes on cooling to room temperature

Sulfonium salt. Failed when diluting with water.

the color disappears again. Yield: 10.5 g (46.6% of theory).

Kp.o, o3 105 ⁰ C air bath temperature. 55 By recrystallization from ligroin with addition

Hydrochloride: mp 192.5 to 193.5 ° C, colorless needles of activated charcoal are obtained from colorless needles

from alcohol — ether. 104-105 ° C. The base distills at 0.015 mm

Perchlorate: F. 160.5 to 161 ° C, colorless needles in a Kugelrohr at 121 ⁰ C air bath.

Water. Hydrochloride; F. 203 to 205 ⁰ C, colorless rhombuses

At a reaction ^{temperature of 100 °} C., 60 is obtained from alcohol — ether,

a yield of only 15.6% perchlorate: mp 197 to 199 ⁰ C, colorless needles from

_. · , ,, Water.

Example 15

,,. ,,, .... . ..,, ,,., Example 18

15.36 g of o-aminovalenaic acid hydrochloride,

16.88 g pyrogallol trimethyl ether and 65 10.31 g y-aminobutyric acid,
180 g of polyphosphoric acid (P ₂ O ₅ content 83%) 16.7 g of 1,2-diphenoxyethane and

are heated with stirring to 75 ⁰ C, with chlorine 90 g polyphosphoric acid (P ₂ O ₅ content 83%)

hydrogen escapes. After three hours of reaction, the mixture is ^{heated to 110 °} C. for 6 hours with stirring.

The light brown, syrupy reaction mixture is worked up as indicated in Example 1. Instead of ether, however, the pyrroline base is shaken out with methylene chloride. The 1,2-bis [4'-J ^a -pyrrolinyl- (2 ") -phenoxy] -ethane is obtained as almost colorless crystals.
Yield: 16.2 g (93.0% of theory).

After recrystallization from methylene chloride or methanol, colorless, irregular crystals with a melting point of 225 ^° C. are obtained.

Perchlorate: F. 274 ³ C, colorless needles and fibers.

Example 19

10.31 g of γ-aminobutyric acid,
16 gl, 4-bis (2-methoxyphenoxy) butane and
90 g polyphosphoric acid (P ₂ O ₅ content 83%)
^{are heated to 100 °} C. for 3 hours with stirring. The red-colored, syrupy reaction mixture is worked up as indicated in Example 1. The 1,4-bis [2'-methoxy-4'-zl ¹ -pyrrolinyl- (2 ") - phenoxyj-butane is obtained as an evaporation residue of the ether extracts as a red-brown oil which solidifies in crystalline form after some time.

Yield: 11.15 g (51.1% of theory).

After recrystallization from ligroin or benzene, colorless needles with a mp of 147 ° C. are obtained.

Claims (1)

PATENT CLAIM: Process for the preparation of heterocyclic, nitrogen-containing bases arylated in the α-position to the nitrogen atom with a double bond in 1,2-position and their salts, characterized in that aromatic compounds which contain at least once the group -XR in the X is an oxygen or sulfur atom and R is a hydrogen atom, an alkyl radical or a radical —X ₁ Ri - in which X _{1 is} an oxygen or sulfur atom bonded to X and R _{1 is} an ethylene radical or X _{1 is} one to another aromatic radical bonded oxygen or sulfur atom and R ₁ denotes an alkylene radical, and which have at least one hydrogen atom in o- or p-position to such a group —XR, in the heat, dissolved in polyphosphoric acid, with primary γ- or ^ -aminocarboxylic acids , their esters and / or their salts with inorganic acids or bases, condensed and optionally after the reaction mixture has been introduced into water and alkalized holding bases treated with acids. © 109 648/375 7.