DE1443913B - Process for the preparation of N-cyanoiminocarbonic acid ester amides - Google Patents

Description

in which R is a haloalkyl or an optionally substituted aromatic or heterocyclic radical and χ is an integer from 1 to 3, at temperatures between -50 and 10O ⁰ C, preferably from -20 to 80 ⁰ C, optionally in a diluent and optionally in the presence of a base, with cyanamide, its salts or with thiourea.

It has been found that N-cyano-iminocarbonic acid ester amides are obtained when cyanic acid esters are used the general formula

R (OCN) _x

in which R is a haloalkyl or an optionally substituted aromatic or heterocyclic group, and χ is an integer of 1 indicates to 3, at temperatures between -50 and 100 ^0C, preferably from -20 to 8O ⁰ C, optionally in a diluent and if appropriate in the presence of a base, with cyanamide, its salts or with thiourea.

The compounds obtainable by this process are new and have the general formula

in which R and χ have the meaning given above.

The aromatic radicals R are 5- and 6-membered aromatic hydrocarbon radicals with up to 20 carbon atoms in question.

Suitable heterocyclic radicals R are, for example, 5- and 6-membered aromatic ring systems, which contain one or more nitrogen, oxygen or sulfur atoms.

The aromatic or heterocyclic radicals can have as substituents, for example: alkyl, Aryl, alkylamino, acylamino, nitro, halogen, alkoxy, aroxy, acyloxy, carbonyl, carboxyl, Carbon ester, amide, sulfonyl, sulfonic acid ester, amide, acyl, cyano, rhodanide, alkyl mercapto, Aryl mercapto or acyl mercapto residues.

The cyanate ester used as starting compounds can be prepared according own earlier proposals by the reaction of hydroxyl-containing compounds at temperatures Halogencyaniden are preferably prepared below +65 ⁰ C, optionally in a solvent in the presence of a base.

It can be used for the inventive method, for. B. the following cyanic acid esters are used:

Phenyl cyanate, mono- and polyalkylphenyl cyanates, such as

3-methyl-, 4-isododecyl-, 4-cyclohexyl-, 2-tert-butyl-, 3-trifluoromethyl-, 2,4-dimethyl-, 3,5-dimethyl-, 2,6-diethyl-,
4-allyl-2-methoxyphenyl cyanate; Arylphenylcyanates, such as 4-cyanatodiphenyl,

4,4'-biscyanatodiphenyl;
Dialkylaminophenylcyanates, such as 4-dimethylamino,

4-dimethylamino-3-methylphenyl cyanate; Acylaminophenyl cyanates, such as acetylamino-

phenyl cyanate;
Nitrophenyl cyanates, such as 4-nitro-, 3-nitro-,

4-nitro-3-methyl,
3-nitro-6-methylphenyl cyanate; Halophenyl cyanates, such as 2-chloro, 3-chloro,

4-chloro, 2,4-dichloro,
2,6-dichloro-, 3-bromo-, 2-chloro-6-methyl-phenyl cyanate;

Cyanatophenylcarboxylic acid, esters, amides, such as 4-cyanatobenzoic acid, 2-cyanatobenzoic acid

ethyl ester,
2-cyanatobenzoic acid morpholide and diethylamide;

Cyanatophenylsulfonic acid, esters, amides, such as 4-cyanatobenzenesulfonic acid;
Alkoxyphenyl cyanates, such as 2-methoxy,

3-methoxy, 4-isopropoxyphenyl cyanate; Phenoxyphenyl cyanates, such as 4-cyanatodi-

phenyl ether;
Acyloxyphenyl cyanates such as 3-acetoxyphenyl cyanate;

Acylphenyl cyanates such as 4-acetylphenyl cyanate; Cyanatophenyl cyanates, such as 2,3-dicyano-1,4-di-

cyanatobenzene;
α- and ß-naphthyl cyanate, anthrachinyl cyanate,

such as 1,4-dicyanatoanthraquinone; Quinoline cyanates such as 5-cyanatoquinoline; Cyanatopyrazoles, such as 5-cyanato-l-phenyl-3-methylpyrazole,

1,4-phenylenedicyanate, 1,5-naphthylendicyanat, 1,3,5-tricyanatobenzene, 4,4'-bis-cyanatodi-

phenyldimethylmethane,
4,4'-biscyanatodiphenylcyclohexane-1,1;2,2'-biscyanato-dinaphthyl, 4-methyl mercaptophenyl cyanate,

S-NjN-dimethylcarbamylphenyl cyanate and the cyanic acid esters of the following alcohols: β, β, β-Τή- chloroethanol, "^, ^, / S-trifluoroethanol, β, β, β-Ίή- bromoethanol, / S ^ -dichlorethanol.

The cyanamide can be converted in free form, but also in the form of its alkali or alkaline earth metal salts will. Instead of cyanamide, thiourea can also be used.

As a solvent, for. B. organic solvents such as alcohols, ketones, ethers, nitriles, Esters, amides, aromatic and aliphatic, optionally nitrated or halogenated hydrocarbons or water. Examples include: methanol, ethanol, acetone, diethyl ether, Acetonitrile, ethyl acetate, dimethylformamide, benzene, petroleum ether, nitrobenzene, nitromethane, chloroform, Carbon tetrachloride, chlorobenzene. One can use the components to carry out the

Combine the process in any order, preferably in one of the diluents mentioned. In general, the reactants are used in approximately equivalent amounts. The products of the process are usually removed by suction, if appropriate after the solvent has been concentrated

OCN + H ₂ NC-NH ₂

isolated. The addition of a base such as NaOH, Na ₂ CO ₃ , triethylamine or pyridine can be advantageous for the reaction.

If thiourea is used instead of cyanamide, the reaction proceeds according to the following example Equation from:

O - C-NH ₂ +
I.

NH

Il

I-C-NH-CN
II

In this case, 2 moles of cyanate ester are required to produce one mole of the new compound II are applied. In general, the thiourea reacts first with the cyanate ester to I, which can be removed from the reaction mixture (suction). Then the 2nd mole reacts Cyanic acid ester with the cyanamide formed to give compound II.

The new N-cyano -iminokarbonic acid ester amides are valuable intermediate products for the production of pharmaceuticals.

example 1

11.9 g (0.1 mol) of phenyl cyanate are added to a solution of 4.5 g (0.107 mol) of cyanamide in 100 ml of ether and 5 drops of triethylamine. After standing

overnight is the _XTr ,

JN ri

O - C - NH - CN

precipitated and is isolated by suction. Yield: 8.4 g, mp 158 ° C. Obtained from the filtrate by concentrating a further 5.5 g of the same product, also with a temperature of 158 ° C. So overall yield 13.9 g (= 86% of theory).

Analysis: C ₈ H ₇ N ₃ O (161).
Calculated:

C 59.6, H 4.36, N 26.1, O 9.93%;
found:

C 59.60, H 4.49, N 26.16, 010.22%.

The IR spectrum shows a strong band at 4.55 μ on.

Example 2

26 g (0.22 mol) of phenyl cyanate are added to a solution of 8.3 g (0.11 mol) of thiourea in 50 ml of acetone. The temperature rises to about 30 ° C,

O - C - NH ₂

precipitates out and is isolated by suction filtration (14.5 g; mp 134 ° C.). The acetone evaporates from the filtrate on suction. It is diluted again with a little alcohol and a few drops of triethylamine are added. The temperature rises again (up to about 35 ⁰ C), the

NH

9.7 g; F. 158 ° C. The product is identical to that obtained according to Example 1. (Mixed melting point; IR spectrum). Note: If you carry out the reaction without Intermediate isolation of the thiocarbamic acid ester ^ by adding base in one go, the The two products are separated as follows: The N-cyano-imidocarbonic acid phenylesteramide is dissolved with dilute NaOH out of the mixture as Na salt and it becomes acidic again (pH 3 to 4).

Example 3

The same compound as in Example 1 is obtained when using 2-pentachlorophenyl isothiourea Reacts in ether with phenyl cyanate. The components dissolve; after an exothermic reaction, the product falls from the reaction solution, is precipitated again by taking up in dilute NaOH and acidification and isolated. F. 157 ° C. IR spectrum identical to sample according to example 1 or 2.

Example 4

Analogously to Example 1, cyanamide and 3-chlorophenyl cyanate in methanol as a solvent without the addition of a base give the _cl

40 NH
γ \ - η - c - μη -

NH-CN

from a melting point of 184.5 to 185 ^° C. in a yield of 76% of theory.
IR spectrum: strong band at 4.55 μ.

Analysis: C ₈ H ₆ ClN ₃ O (195.5).

Calculated:

C 49.1, H 3.07, N 21.5, O 8.18, Cl 18.15%;
. found:

C 49.20, H 3.19, N 21.18, O 8.37, Cl 18.00%.

Example 5

_{A cold aqueous solution of 13.6 g (0.1 mol) of KHSO 4 is} poured into a cold aqueous solution of 8.6 g (0.1 mol) of disodium cyanamide and then an acetone solution of 14.7 g ( 0.1 mol) of 2,4-dimethylphenyl cyanate was added dropwise. After the reaction has ended, dilute H ₂ SO ₄ .

neutralized, filtered off with suction, washed and dried.

15.3 g (= 81% of theory) of the

CH ₃

O-C-NH-CN

precipitates and is isolated by suction. Yield:

H ₁ C

NH

Il

O - C - NH - CN

with a temperature of 142 ° C are obtained in this way.
IR spectrum: strong band at 4.55 μ.

Example 6

Analogously to Example 1, / S, / S, /? - trichloroethyl cyanate is obtained and cyanamide with a little soda instead of triethylamine as the base

NH CLC - CH ₂ - O - C - NH - CN

from 191 ° to 193 ° C. in a yield of 62% of theory.

IR spectrum: strong band at 4.55 μ.

Example7

Analogously to Example 5, from 2 MoINaHN — CN and 1 mol of 1,4-phenylene biscyanate without the addition of _{KHSO 4, the}

NH
NC-NH-C-O- ^

NH

Il

) —C — NH — CN

vom F .: Decomposition from 280 ° C in a yield of 54% of theory. IR spectrum: strong band at 4.55 μ.

Example 8

4.2 g (0.1 mol) of cyanamide and 13.3 g (0.1 mol) 4-methylphenyl cyanate are refluxed for 2 hours with the addition of a little triethylamine in 30 ml of acetone cooked. After cooling down, you suck up the failed

NH

35

C - NHCN

away. After stirring with water, suctioning off, washing and drying, a yield of 14 g is obtained (= 80% of theory). M.p. 150 to 151 ° C.

Analysis: C ₉ H ₉ N ₃ O (175).

Calculated ... C 61.70, H 5.18, N 23.99, O 9.13%; found .... C 61.83, H 5.43, N 24.17, O 9.28%.

Example 9

16.9 g (0.1 mol) of a-naphthyl cyanate and 4.2 g (0.1 mol) Cyanamide are dissolved in 50 ml of acetone. After adding one milliliter of triethylamine, the temperature rises up to the boiling point of the mixture (58 ° C). The temperature is held for 10 minutes, after which The solvent is stripped off when cooling, the crystalline residue is stirred with water and adjusted to pH 3 with HCl and washed. Yield: 19.1 g (90.5% of theory) of the "

O-C-NHCN

from 184 to 185 ° C.
Analysis: C ₁₂ H ₉ N ₃ O (211).

Calculated:

C 68.23, H 4.30, N 19.90, O 7.58, molecular weight 211;

60

65 found:

C 67.51, H 4.31, N 19.35, 0 8.08%,
Molecular weight 216.

Example 10

Analogously to Example 8, “is obtained from cyanamide
4-Acetylphenylcyanat das

O NH

10 H, C - C

C - NHCN

from F. 200 to 201 ⁰ C.

Analysis: C ₁₀ H ₉ N ₃ O ₂ (203).

Calculated:

C 59.10, H 4.46, N 20.68, O 15.75%,

Molecular weight 203;
found:

C 59.46, H 4.62, N 20.43,016.19%,

Molecular weight 201.

Example 11

To an aqueous solution of 0.055 mol of the triethylammonium salt of cyanamide is added dropwise Solution of 10.5 g (0.05 mol) of 2-cyanatodibenzofura: in 50 ml of acetone at room temperature. Nad After stirring for 1 hour, the reaction mixture is neutralized and then the final product which has precipitated out is duct vacuumed and washed. 11.5 (= 92% of theory) N-cyano-iminocarbonic acid are obtained (2-dibenzofuranylester -) - amide with a melting point of 23 to 234 ° C. With further heating, the enamel becomes solid again as a result of polymerization.

The IR spectrum shows the pronounced, slender CN band of the cyanamide group at 4.6 μ.

Elemental analysis: C ₁₄ H ₉ N ₃ O ₂ (mole 251).

Calculated ... C 67.0, H 3.58, N 16.7, O 12.75%; found .... C 67.0, H 3.6, N 17.1, O 12.4%.

Example 12

Analogously to Example 11, 3-cyanatocarbazole is obtained with 74% of the theoretical yield of N-cyanine iminocarbonic acid (3-carbazolyl ester) amide with a melting point of 244 to 245 ° C. The melt is be further heating as a result of polymerization wiede solid.

The IR spectrum shows the pronounced, slender CN band of the cyanamide group at 4.6 μ.

Example 13

Analogously to Example 11, 0.0825 mol of Triäthy! ammonium salt of cyanamide with 6.7 g (0.025 Mo i 1,3,5-Tricyanatobenzene implemented. After suctioning off the precipitated reaction product and working up: of the filtrate, 4.5 g (= 55% of theory tris - [N - cyano - iminocarbonic acid - (1,3,5 - trioxobene zolester) amide], which melts from 160 ° C and polymerizes and becomes solid again.

The IR spectrum shows the pronounced * CN band of the cyanamide group at 4.6 μ.

The solution used in Examples 11 to 13; of the triethylammonium salt of cyanamide was prepared as follows: 4.7 g (0.055 mol) of sodium cyanamid were dissolved in 40 ml of ice water. The base was released by adding dilute hydrochloric acid set and then transferred with 3 ml of triethylamine i the triethylammonium salt.

Claims (1)

Claim: Process for the production of N-cyano-iminocarbonic acid ester amides, characterized in that cyanic acid esters of the general formula R (OCN) _x