DE1217386B - Process for the preparation of 2,4-disubstituted 6-amino-1,3,5-triazines - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

Int. Cl .:

C07d

GERMAN

PATENT OFFICE

EDITORIAL

German class: 12 ρ -10/05

Number: 1 217 386

File number: F 41524IV d / 12 ρ

Filing date: December 12, 1963

Opening day: May 26, 1966

So far it has been difficult to prepare certain aminotriazines with two identical substituents on the ring.

US Pat. No. 2,769,809 gives a process for the preparation of some 2,4-disubstituted aminotriazines in which nitriles R ₁ - CN are reacted with guanidine. However, this process is only suitable for very few nitriles R ₁ CN, namely for aromatic nitriles in which R _{1 stands} for an aromatic radical which a) either has to be unsubstituted or has to have electron-withdrawing groups on the ring or in the ring (e.g. B. a p-chlorophenyl, p-nitrophenyl or pyridyl radical and b) must not carry any substituents of any kind in the o-position to the nitrile group. According to US Pat. No. 2,769,809, other nitriles do not react or react to form non-cyclic reaction products.

It has now been found that 2,4-disubstituted aminotriazines substituted in the amino group are obtained if, in a modification of the process for the preparation of 2,4-disubstituted 6-amino-1,3,5-triazines by heating guanidine with at least the double molar amount of a carboxylic acid nitrile of the general formula R ¹ - CN, in which R ^{1 is} a cycloalkyl radical, an alkyl radical optionally substituted by a cyano group, one in the m- and / or p-position by halogen atoms, alkyl, alkoxy, methylenedioxy or dimethylamino radical Substituted phenyl radical, which can optionally also carry a halogen atom in the o-position, in the presence of an alkali metal alcoholate or an alkali metal hydroxide, in particular in amounts of 0.05 to 0.2 mol per mol of guanidine, the cyclocondensation at 50 to 200 "C and optionally carried out in the presence of a solvent, according to patent application F 38685 IVd / 12 ρ (German Auslegeschrift 1 242 547), instead of guanidine subst ituted guanidines of the general formula

R ₂

HN

NH ₂ Process for the preparation of 2,4-disubstituted 6-amino-1,3,5-triazines

Addition to registration: F 38685IV d / 12 ρ - Auslegeschrift 1 212 547

Applicant:

Paint factories Bayer Aktiengesellschaft, Leverkusen

Named as inventor:

Dr. Hans-Joachim Kabbe, Leverkusen; Dr. Karl Eiter, Cologne-Stammheim

2

product of the general formula

Ri

/ R ₃

C-Ri

isolated.

The course of the reaction proceeds in such a way that the s-triazine ring is closed with elimination of ammonia will:

R ₂ R ₃

\ / R ₂ R ₃

N \ /

HN
Ri-C

NH ₂
C-Ri

-NH ₃₎

N N

wherein R ₂ and R ₃ individually represent identical or different, optionally substituted alkyl, aryl or heterocyclic radicals, R ₂ also represent hydrogen and R ₂ and R ₃ together with the nitrogen atom represent a heterocycle, and the process

Ri

Nitrile polymerization reactions, which are known to take place under acidic catalysis not possible.

bcher

609 570/533

The following can in particular be used as nitriles: acetonitrile, propionitrile, butyronitrile, isobutyronitrile, Cyclopropyl cyanide, cyclohexanecarboxylic acid nitrile, p-methoxybenzonitrile, 3,4-methylenedioxybenzonitrile, p-dimethylaminobenzonitrile.

The following guanidines substituted in the amino group can be used for the process according to the invention, for example: n-butylguanidine, n-dodecylguanidine, p-methoxyphenylguanidine, m- and p-nitrophenylguanidine, jo-phenylethylguanidine, pentamethylene guanidine, γ - (N - morpholino) - propylguanidine Ν, Ν-dimethylguanidine, N-morpholinoamidine and N'-methyl-N-piperazinylamidine, optionally also as salts, such as sulfates or hydrochlorides.

Suitable solvents are those that are effective both against the reactants and against the basic catalyst used are inert and, if you want to work under normal pressure, at least have a boiling point that corresponds to the reaction temperature, i.e. hydrocarbons such as benzene, Toluene and xylene, ethers such as dibutyl ether and glycol diethyl ether and chlorinated hydrocarbons such as tetra carbon, dichloroethane and chlorobenzene. Although the reaction can be carried out without a solvent their use is particularly favorable when the starting materials dissolve well and the end product is insoluble, which is often the case with this condensation.

Alkali hydroxides or alcoholates are used as catalysts, ζ. B. Sodium or Potassium Hydroxide, methylate, ethylate and tert-butylate; they are used in amounts of 0.01 to 1 mole per mole Guanidine used.

The process is carried out at temperatures between 50 and 200 ⁰ C. The reaction temperature is, in some cases at 60 ⁰ C, in other to 100 ⁰ C, 'but can also amount to 180 ° C. If possible, it is chosen so that the reaction is complete in a few minutes to a few hours; the end of the reaction can be recognized by the fact that the evolution of ammonia ceases.

The optimal ratio of the reactants is the stoichiometric, i.e. nitrile to guanidine such as 2: 1. Excess nitrile can be used as a solvent for low-boiling products, but it is more difficult in the case of high-melting starting materials, the work-up.

Most aminotriazines are obtained in crystalline form in high purity and can be obtained by recrystallization, optionally also be purified by distillation.

The method according to the invention has a number of advantages. It achieves high yields. the Starting materials are easily accessible; it is very suitable because of the simple reaction conditions good for large-scale implementation.

The substituted amino-s-triazines which can be prepared according to the invention are new compounds. You serve as intermediates in the manufacture of dyes and as pharmaceuticals.

B e i s ρ i el 1

83 g of N-dodecylguanidine sulfate are refluxed with 25 g of sodium methylate and 300 ml of absolute ethanol for 1 hour. The solution is separated off by suctioning off sodium sulfate and concentrated in vacuo. The residue is then stirred with 50 g of propionitrile for 50 hours at 100 ^° C., cooled, treated with 200 ml of water and the organic part is extracted with methylene chloride. Fractional distillation gives 75 g (= 78% of theory) 2,4-diethyl-6-dodecylamino-s-triazine, colorless crystals which boil at 160 ° C./0.05 Torr and melt just above room temperature.

Analysis: C ₁₉ H _se N ₄ .

ίο Calculated ... C 71.20%, H 11.32%:
found ... C 71.59%, H 11.67%.

Example 2

63.6 g of β-phenylethylguanidine sulfate, 25 g of sodium methylate and 300 ml of alcohol are reacted as in Example 1 and the residue is reacted with 50 g of propionitrile. 40 g (= 55% of theory) of 2,4-diethyl-6 - /? - phenylethylamino-s-triazine are obtained. M.p .: 65 to 70 ⁰ C, b.p. _oils 160 to 165 ° C.

Analysis C ₁₅ H ₂₀ N ₄ • 0.2 CH ₃ OH, from methanol.

• Calculated ... C 69.50%, H 7.99%, N 21.34%;
found ... C 69.50%, H 7.89%, N 21.38%.

B e i s ρ i e 1 3

53 g of N-pentamethylene guanidine, 25 g of sodium methylate and 300 ml of alcohol are treated as in Example 1 and reacted with 50 g of propionitrile. The resulting 2,4-diethyl-6-N-piperidyl-s-triazine is a colorless oil, bp. _{0, 05} 95 ° C.

Analysis: C ₁₂ H ₂₀ N • 0.2 H ₂ O.

Calculated ... C 64.37%, H 9.20% / N 25.02%;
found ... C 64.08%, H 9.26%, N 25.08%.

Example 4

Analogously to Example 1, 2,4-diethyl-6- (N'-methyl) -N-piperazinyl-s-triazine was obtained from N'-methyl-N-piperazinyl-amidine in a yield of 30%. Colorless oil, b.p. ₀ , ₀ 5 100 to 110 ⁰ C.

Analysis: C ₁₂ H ₂₁ N ₅ .

Calculated ... C 61.25%, H 8.99%, N 29.76%;
found ... C 61.14%, H 8.84%, N 29.63%.

Example 5

A mixture of 25 g of sodium methylate, 150 ml of n-pentane oil, 59 g of γ- (N-morpholino) propylguanidine and 40 ml of acetonitrile is heated to boiling under reflux until the evolution of ammonia is noticeable has subsided. Then the solution is mixed with 500 ml of water and the organic portion extracted with methylene chloride. Fractional distillation gives 17 g of a colorless, at 155 boiling up to 163 ° C / 0.03 torr. Oil obtained from 2- [y- (N-Morpholino) propyl] -4,6-dimethyl-s-triazine consists.

Analysis: C ₁₂ H ₂₁ N ₅ O.

Calculated ... C 57.35%, H 8.42%;
6c. found ... C 57.28%, H 8.72%.

Example 6

64 parts by weight of p-methoxyphenylguanidine sulfate, 25 parts by weight of sodium methylate and 300 parts by volume of ethanol are converted as in the "example.!. The Residue is stirred with 50 parts by weight of propionitrile for 48 hours at reflux temperature. Man contains 17 parts by weight (= 24% of theory) 2,4-di-

ethyl - 6 - ρ - methoxyphenylamino - s - triazine; Bp. _{0> 01} 155 "C.

Analysis: C ₁₄ H ₁₈ N ₄ O (MS = 258.32).

Calculated ... C 65.09%, H 7.04%;
found ... C 65.52%, H 7.22%.

Example 7

98 parts by weight of n-butylguanidine sulfate, 38 parts by weight of sodium hydroxide and 500 parts by volume of ethanol are reacted as in Example 1, then with 100 parts by weight of propionitrile at 100 ° C for 48 hours Brought reaction. The 2,4-diethyl-6-n-butylamino-s-triazine obtained (35 parts by weight = 38% of theory) boils at 100 ° C / 0.05 Torr.

Analysis: C _n H ₂₀ N ₄ (MS = 208.30).

Calculated ... C 63.42%, H 9.68%, N 26.90%;
found ... C 63.07%, H 9.79%, N 26.93%.

Example 8

55 parts by weight of 2-ethylhexylguanidine (prepared from the sulfate), 10 parts by weight of sodium methylate and 48 parts by weight of propionitrile are stirred for 2/2 days at reflux temperature. The resulting mixture is mixed with ice and extracted _{several times with CH 2} Cl _2. After two distillation, 46 parts by weight (= 58% of theory) of 2,4-diethyl-6- (2 ') -ethylhexylamino-s-triazine are obtained; Kp. ₀ , ₀₇ 12O ⁰ C.

Analysis: C ₁₅ H ₂₈ N ₄ (264.41).

Calculated ... C 68.13%, H 10.69%, N 21.19%;
found ... C 67.79%, H 10.88%, N 21.15%.

Example 9

94 parts by weight of S-dimethylamino-ethylguanidine sulfate, 60 parts by weight of sodium methylate and 800 parts by volume of ethanol are converted. The residue is stirred with 54 parts by weight of cyclopropyl cyanide at HO ⁰ C for 48 hours. 35 parts by weight (= 36% of theory) of 2,4-dicyclopropyl-6- / 3-dimethylaminoethylamino-s-triazine are formed; Sdp. ₀ , ₀₁ 130 to 140 ⁰ C.

Analysis: C ₁₃ H ₂₁ N ₅ .

Calculated ... C 63.13%, H 8.56%;
found ... C 63.77%, H 8.79%.

Example 10

The same guanidine as in Example 9 gives after 48 hours of conversion with 75 parts by weight of cyclopentyl cyanide 48 parts by weight (= 40% of theory) ^ -dicyclopentyl-o-zS-dimethylaminoethylamino-s-triazine; 160 to 165 ° C / 0.01 torr.

Analysis: C ₁₇ H ₂₉ N ₅ .

Calculated ... N 23.08%;
found ... N 23 ', 12%.

Example 11

The same guanidine as in Example 9, with parts by weight of 2,2-dimethylcyclopropyl cyanide, gives 48 parts by weight (= 40% of theory) 2,4-di- (2 ', 2') -dimethylcyclopropyl -6-ß- dimethylaminoethylaminos-triazine. Bp 150 ° C / 0.005 torr.

Analysis: C ₁₇ H ₂₉ N ₅ .

Calculated ... N 23.08%;
found ... N 23.33%.

Claims (1)

Claim: Modification of the process for the preparation of '5 2,4-disubstituted 6-amino-1,3,5-triazines by Heating of guanidine with at least twice the molar amount of a carboxonitrile of the general kind formula R ₁ -CN
^x wherein R ₁ denotes a cycloalkyl radical, an alkyl radical optionally substituted by a cyano group, a phenyl radical substituted in the m- and / or p-position by halogen atoms, alkyl, alkoxy, methylenedioxy or dimethylamino radical, which is optionally also substituted in the o-position Can carry halogen atom, in the presence of an alkali metal alcoholate or an alkali metal hydroxide, in particular in amounts of 0.05 to 0.2 mol per mole of guanidine, the cyclocondensation being carried out at 50 to 200 ⁰ C and optionally in the presence of a solvent, according to patent application F 38685 IVd / 12p, characterized in that, instead of guanidine, substituted guanidines of the general formula R ₃ N C. HN NH ₂ where R ₂ and R ₃ individually represent identical or different, optionally substituted alkyl, aryl or heterocyclic radicals, R ₂ also represent hydrogen and R ₂ and R ₃ together with the nitrogen atom represent a heterocycle, and the product of the general formula is used R ₂ \ Ri-C ; Cs Il C-Ri isolated.