DE1670798A1 - Process for the preparation of heterocyclic compounds - Google Patents

Description

PAINT FACTORY ^{BAYERAG 1670738} LEVERKU S EN-B * yeiwwk

p «ent-Abteiiunf February 10, 1967 Fy / Bi

Process for the preparation of heterocyclic compounds

It has been found that heterocyclic compounds are obtained when guanidine derivatives of the formula

I ¹

'NH - Ar
in which

Ar denotes an optionally substituted aryl radical, and in which the radicals

-RJ, R ₂ and R, can be identical or different and • in addition to hydrogen are an optionally substituted alkyl or aryl radical and

η means the number 2 or 3 ,

optionally in the presence of an inert organic solvent to about 80 to about 250 ^° C., optionally under reduced pressure, and after distilling off the split off aromatic amine or the solvent, the heterocyclic compound formed is isolated under reduced pressure. The method according to the invention is explained using the following example:

0-CH ₂

N = C-NH-CH ₉ -CH ₅ -OH -4 f> -N = C <^ | +

I ^cc N = / ^N NH— Γ "

NH

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In a particular embodiment of the invention The process is not based on isolated guanidine, but that is used in the preparation of the substituted one Guanidines e.g. from diarylcarbodiimide and alkanolamine in the usual way Way obtained crude arylguanidine derivative without intermediate isolation for possible purification, if necessary after prior removal or replacement of the solvent directly heated against a higher boiling point.

The optionally substituted aryl radicals Ar, which can be identical or different, contain at least one. of these radicals at least one unoccupied o-position to the imino nitrogen atom. Aryl radicals are those with up to 10 carbon atoms in the ring system, and two of these aromatic radicals can also be linked via oxygen, sulfur, -CH ₂ -, -CH ₂ -CH ₂ -, NH or also directly via a CC bond .

Examples of substituents on the aromatic radical are

called: halogens (preferably fluorine, chlorine, bromine), alkoxy- or -S-alkyl with 1-12, preferably 1-4 carbon atoms, Carbalkoxy (alkyl with preferably 1-4 carbon atoms), straight-chain or branched alkyl radicals with up to 12 carbon atoms, preferably 1-4 carbon atoms, nitro, Cycloalkyl, preferably with 5-6 carbon atoms in the ring system, which is optionally also by lower alkyl groups may be substituted, dialkylamino having 1-6 carbon atoms per alkyl group, these alkyl radicals optionally

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together they can also be constituents of a carbocyclic 5- or 6-membered ring.

As radicals R ₁ are in addition hydrogen, optionally substituted alkyl radicals having 1-20 carbon atoms, preferably 1-4 and 16-18 carbon atoms, and optionally substituted cycloaliphatic radical having 5-12, preferably white ^"3 5, called 6 and 8 carbon atoms. Suitable substituents on the alkyl or cycloalkyl radical are the same as those listed above for the aryl radicals. R ₁ can furthermore stand for an optionally substituted aryl radical with the scope of meaning given above.

Rp and R can stand for identical or different radicals. In addition to hydrogen, the following may be mentioned, for example: optionally substituted alkyl radicals preferably having 1-18 carbon atoms, the total number of carbon atoms in the radicals R1 and R2 should not be more than 30; as substituents on the alkyl radical R _? bsw. R ~ may be mentioned: alkoxy- and -S-alkyl with 1-4 carbon atoms, alkoxyalkoxy with preferably 1-4 carbon atoms, cycloalkyl with preferably 5-6 carbon atoms in the ring system, tetra- or decahydronaphthyl optionally substituted by lower alkyl radicals;

R ₂ or R can furthermore stand for an aralkyl radical (aryl, preferably phenyl and naphthyl) with an alkylene chain of 1-4, preferably 1-2, carbon atoms which is optionally substituted in the nucleus.

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Substituents which can be used on the aromatic part of the aralkyl radical are essentially those mentioned for the aryl radicals as far as they are inert under the reaction conditions are to be seen.

As aryl radicals R ₂ and R, the optionally substituted aryl radicals listed under Ar come into consideration, but the total number of carbon atoms of R ₀ and R should not be more than 30.

The ones used for the method according to the invention Guanidines can be prepared in a known manner, e.g. by reacting arylcarbodiimides such as diphenylcarbodiimide, di- (ortho-toluyl) -carbodiimide, Di- (m-toluyl) -carbodiimide, di- (p-toluyl) -carbodiimide, di- (o-chlorophenyl) -carbodiimide, di- (3,4-dichlorophenyl) -carbodiimide, Di- (p-nitrophenyl) -carbodiimld, N- (4-chlorophenyl) -N "- (2,6-diisopropylphenyl) -carbodiiraid, Di- (c ^ -naphthyl) -carbodiimide,

with alkanolamines, such as ethanolamine, diethanolamine, propanolamine-1,3, propanolamine-1,2, N-ethyl-ethanolamine, N-phenylethanolamine, N- (p-chlorophenyl) ethanolamine, ephedrine and the like (reports from the Germans Chemical Society, volume j3, p.1395 (18/3); volume χ, p.10 and 1306 (1874); volume J_9, p.2404 (1886)).

The inventive method is in the temperature range of about 80 to about 25O ° C, preferably 120-160 ⁰ C is performed. The aromatic amine liberated in the reaction is expediently removed during the reaction. This will be

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for example, under reduced pressure, preferably below 100 torr, worked. The choice of the reduced pressure naturally depends on the type of arylamine liberated. It may be appropriate to carry out the reaction in the presence of sufficiently high-boiling organic solvents. Preference is given to those boiling above about 110 ° 0, such as toluene, xylene, chlorobenzene, o-dichlorobenzene, 1,2,4-trichlorobenzene, tetrahydronaphthalene, decahydronaphthalene and chlorinated naphthalenes or mixtures of such solvents. When working with the concomitant use of a Λ such a solvent, it may be advantageous to initially without applying heat of a vacuum and then set in the freedom aromatic amine along with the solvent, optionally under reduced pressure ,. Remove £ u.

The compounds obtainable by the process according to the invention are mostly obtained in good purity. If necessary, they can be further purified by recrystallization for special areas of application with the highest purity requirements. The heterocyclic compounds obtainable by the process are valuable intermediates for further reactions, but can also be used directly as hydrolysis protection agents for esters, in particular polyesters and polyurethanes.

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1670788

example 1 r

126 g N, N'-diphenyl-N "-beta-hydroxyäthylguanidin were 25 minutes at 1 Torr to 150 -. Heated 160 ⁰ C It distilled 45.9 g of aniline (98.5 $> of theory) from 80 g (. 88.7 $ of theory) of 2-phenylimino-oxazolidine were obtained of a viscous residue in the form of water After recrystallization from F .: 119 -. 120 ⁰ C.

The N, N'-diphenyl-N ⁿ -β-hydroxyethylguanidine was obtained as follows:

A solution of 97 g of diphenylcarbodiimide in 250 ml of benzene was added dropwise to 30.5 g of ethanolamine. After one hour of heating to 70 ^° C., the mixture was cooled. The resulting N, N'-diphenyl-N "-β-hydroxyethylguanidine was filtered off. Yield: 126 g (99 # of theory); mp .: 75-88 ° C.

Example 2

60 g N, N'-diphenyl-N "- (2-hydroxypropyl) guanidine were heated in an oil bath at 1 torr at 160 ⁰ C were recovered 20 g (100% of theory) of aniline and 38 g (95%. theory) 2-phenylimino-5-methyl-oxazolidine obtained. F .: 134 - 135 ° C (from benzene)
Analysis: C _1O ^H 12 ^N 2 ° (molecular weight 176)

68 C. 6th H N 9 Ber .: 68 , 2% 6th , 82 1> 15, 67 Found: .25 * , 92 # 15,

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Example 3 ^

The crude guanidine obtained by reacting 39 g of N-methylethanolamine in 50 g of benzene with a mixture of 100 ml of benzene and 97 g of diphenyl carbodiimide was heated ^{to 160 ° C. after removal of the benzene in an oil bath under water jet pressure.} 93 $> of the theoretical amount of aniline were distilled off under vacuum and the residue was added 43 g (98% of theory) of the crystalline 2-phenylimino-3-methyloxazolidin, F .: 74 ° C (from hexane or water) was obtained. Analysis: G ₁₀ H ₁₂ N ₂ O (molecular weight: 176)

GHN
Calc .: 68.2 # 6.82 # 15.9 1 * Found: 68.11 $ 6.97 % 15.12%

Example 4

The crude guanidine obtained by reacting 0.5 mol of di-p-toluylcarbodiimide with 0.5 mol of 2-hydroxypropylamine was heated to 170.degree.-150.degree. C./4 torr. 0.48 mol of p-toluidine distilled off. The residue was recrystallized from cyclohexane. Yield of 2-p-toluyl-5-methyloxazolidine 66.2 $ of theory; F .: 115 ° C.
Analysis: C ₁₀ H ₁₄ N ₂ O (molecular weight 190)

CHN
Calculated: b9.4 % 7.37 t 14.7 96 Found: $ 69.7 7.49 % $ 14.38

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Example 5 λ

The DARCH reacting 1 mol of di-p-ethoxy-phenylcarbodiimide and 1 mol Äthylaminoäthanol guanidine was obtained (about 2 Torr) heated under reduced pressure at 140 ⁰ C and distilled phenetidine. The residue was redissolved from hexane. Yield of 2-p-ethoxyphenyliminooxazolidine 86 % of theory; F .: 53 - 54 ⁰ C. (F .: 53 ° C German Reich patent 694 133).

Example 6

The N obtained from 37.5 g of 3-hydroxypropylamine-1 and 97 g diphenylcarbodiimide, N ^s-diphenyl-N "-3-hydroxypropylguanidin (130 g) was heated to 160 - 18O ⁰ C (14 Torr) and 45 g of aniline abd The residue remained 84 g of 2-phenylimino-1,3-tetrahydrooxazine, viscous oil, identified by IR and NMR spectra.

Example 7

The g from 137.0 N-Phenyläthanolamin and 194 g of diphenyl N obtained, N ^1, N "-triphenyl-N-2-hydroxyäthylguanidin (300 g) was heated to 14 Torr to 190 ⁰ C / 70 g, distilling off aniline. 228 g of crude 2-phenylimino-3-phenyloxazolidine were obtained, mp: 124 ° 0 (from methanol).
Analysis: C ₁₅ H ₁₄ N ₂ O (molecular weight: 238)

CH N
Calculated: 75.6% ■ 5.88 # 11.78 %
Found: 75.59 % 5.94 ° h 11.77 %

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Example 8 a

The N, N'-diphenyl-N "- (1-methyl-3-hydroxy -) propylguanidine (P .: 106 -108 ⁰ g) was heated to 160 - 18O ⁰ g and heated under a water jet vacuum distilled 46 g of aniline Ale residue remained 95 g of 2-phenylimino-4-methyl -.. tetrafunctional] iydro-1,3-oxazin raw i ^1st : 98 - 105 ⁰ C.

Example 9

The N, N'-diphenyl-N "- (β-hydroxyethyl) -guanidine (298 g; P. 95-98 ° C.) obtained from 194 g (1 mol) of diphenylcarbodiimide with 105 g (1 mol) of diethanolamine was obtained 140 - 180 ⁰ C and warmed aniline (92 g) under reduced pressure (1 Torr), 204 g of 2-phenylimino-3- (ß-hydroxyethyl) oxazolidine were obtained as an oily residue (99 $> of theory) of P.. : 73 - 74 ° C (from hexane or carbon tetrachloride). Analysis: G ₁₁ H ₁₄ N ₂ O ₂ (molecular weight 206)

CHN
Calc .: 64.0 1 <> 6.8 % 13.6 #
Found: 64.94 # 6.8% 13.48 #

Example 10

Consisting of 37 "5 g (0.5 mole) of 2-hydroxy-propylamine-1 and 147 g (0.5 mol) of di-nL-naphthylcarbodiimide guanidine obtained was 140 - 180 ⁰ C heated and distilled under vacuum cL-naphthylamine and 117 g (100 $> of theory) 2 - (^ .- naphthylimino- 5-methyloxazoldine obtained as residue. Resin-like solidified; identified by IR and nuclear magnetic resonance spectra.

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Example 11

The g of 18.8 N-methylethanolamine and 65.7 g of di-p-Chlorphenylcarbodiimid obtained crude guanidine (F.:-126 - 129 ° C) was heated to 160 - 180 ^c heated C / 4 Torr while 31 g chloroaniline by distillation severed. 51 g (97 # of theory) of a crude p-chlorophenyl-imino-3-niethyloxazolidine remained as residue. F .: 126 ° C (from cyclohexane).

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Claims (1)

Claim ι » Process for the preparation of heterocyclic compounds, characterized in that one guanidine derivatives of the formula ^ N - (G H- _o R _o R,) - 0H Ar - N = C <" ^{n 2n} ~ ^{2 2 5} ^ NH - Ar in which Ar denotes an optionally substituted aryl radical, and in which the radicals R ^, Rp and R-z can be the same or different and, in addition to hydrogen, represent an optionally substituted alkyl or aryl radical and η means the number 2 or 3, optionally in the presence of an inert organic solvent to about 80 to about 250 ^C , optionally under reduced pressure, and after distilling off the split off aromatic amine or the solvent, the heterocyclic compound formed is isolated under reduced pressure. 109813/191
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