DD293584A5 - PROCESS FOR PREPARING NEW 3,5,5-TRISUBSTITUTED 1- (BENZIMIDAZOL-2-YL) -IMIDAZOLIDIN-2,4-DIONES BZW. -4-ON-2-thiones - Google Patents

Abstract

The invention relates to a process for the preparation of new * * or -4-one-2-thiones from * with isocyanates or isothiocyanates in the presence of molar amounts of alkali metal hydride. As another variant, in the first step, the * is synthesized in the presence of equimolar amounts of sodium hydride in the o. G. Be relocated connection. It is an object of the invention to provide such compounds, which are to be considered as potential herbicides or fungicides, via a selective route. They can also find use as drugs against hypertension. {* * * * Isocyanate; isothiocyanate; alkali metal hydride; Herbicide; Fungicide; Pharmakum}

Description

RN = C = X

in the

R is AkIyI, aryl or substituted aryl, and

X: S or O,

with a 2,2-disubstituted 1 (9) H-2,3-dihydroimidazo / 1,2-a / benzimidazol-3-one of general formula III,

III

in the

R ¹ and R ^{2 is} alkyl or (CH ₂ J _n with "preferably 5, is reacted in the presence of alkali metal hydride.

2. The method according to claim 1, characterized in that a 2,2-disubstituted 1-carbamoyl or i-thiocarbamoyl ^ S-dihydro-imidazo / i ^ -a / benzimidazole-S-on is reacted with alkali metal hydride.

3. The method according to claim 1 and 2, characterized in that is used as the alkali metal hydride sodium hydride.

Field of application of the invention

The invention relates to a process for the preparation of novel 1- (benzimidazol-2-yl) -imidazolidine-2,4-diones or -4-one-2-thiones from the readily available 1 (9) H-2,3- Dihydro-imidazo / 1,2-a / benzimidazol-3-ones with isocyanates or isothiocyanates or from the primary preparable 1-carbamoyl or i-thiocarbamoyl ^^ - dihydro-imidazo / i ^ -a / benzimidazole-S- tions. The compounds can be used as herbicides and fungicides in the phytosanitary sector, but are also used as drugs against hypertension.

Characteristic of the known state of the art

Hydantoins or thiohydantoins are generally synthesized from α-amino acids and isocyanate or isothiocyanate under acidic catalysis (W.J. Boyd, Biochem., J. 27, 1838/1933 /).

In order to obtain 1-benzimidazolyl derivatives, aryl or alkyl isocyanate or isothiocyanates must be reacted, the primary attack of which always takes place on the endo-nitrogen of the benzimidazoles with a-benzimidazolylglycine derivatives and thus leads to other secondary products (H. Graubaum et al. , J. prakt. Chem. 324,809 / 1982 /). Similarly, the problem with the method of Moskal et al. (Moskal J., A. Moskal, P. Milart, Tetrahedron 38, 1787/1982), the azomethine of 2-aminobenzimidazole and a 1,2-dicarbony compound are reacted with isocyanates or isothiocyanates, so that the Endosubstitution on benzimidazole leads to other derivatives. The synthesis of the Bucherer-Bergs synthesis requires a high selectivity in the

desired direction, but which is not given by the possibility of involvement of the ring nitrogen of benzimidazole. Here, too, compounds which are unsubstituted in the 3-position are obtained via this route (J.N. Coker et al., J. Org. Chem. 27, 3201/1962 /). All other ways, e.g. with 3-dimethylamino-2H-aziridine, lead to the unsubstituted compounds, which must first be alkylated secondarily, but in turn raises selectivity problems (E. Schaumann, E. Kausch, W. Walter, Chem. Ber. 110,820 / 1977 / and CA Lopez, GG Trigo, Adv. Het. Chem. 1985, 177).

Object of the invention

It is an object of the invention to develop a process for the preparation of novel 3,5,5-trisubstituted 1- (benzimidazol-2-yl) -imidazolidine-2,4-dione or -4-one-2-thiones, which is selective, does not require complicated process steps and allows a wide range of substituents in positions 3 and 5.

Explanation of the essence of the invention

The object of the invention is to achieve the aim of the invention by using a suitable starting material. This object is achieved by a process for the preparation of novel 3,5,5-trisubstituted 1- (benzimidazol-2-yl) -imidazolidine-2,4-diones or -4-on-2-thiones of the general formula I,

OCh

ν-Γ

in the

R: aryl, alkyl, substituted aryl

R ¹ , R ² : alkyl or pentamethylene and

in that, according to the invention, a heterocumulene of the general L-ormel II,

RN = C = X II

in the

R: aryl, alkyl, substituted aryl and

with a 2,2-disubstituted 1 (9) 4-2,3-dihydro-imidazo / 1,2-a / benzimidazol-3-one of general formula III,

in which R ¹ , R ^{2 is} AIkyI or (CH ₂ I _n with η preferably 5, in the presence of alkali metal, the, preferably sodium hydride is reacted.

Optionally, the compound of the formula III is also first acylated with the heterocycle of the formula II to give 1-carbamoyl-2,3-dihydro-imidazo / 1,2-a / benzimidazol-3-one which is obtained in the presence of an alkali metal hydride, preferably NaH, is converted into the compound of formula I. The work-up is carried out in the usual way.

If one sets e.g. the compound of general formula III in molar amounts with isocyanate and sodium hydride and allowed to react for 24 hours, the reaction proceeds according to the following scheme:

+ -M.K / CO

H * j .H

fie

Optionally, the 1-carbamoyl compound can be isolated and analogously 24 hours with an alkali metal hydride, preferably NaH, in molar amounts at 0 to 80 ° C in a solvent, u. a. cyclic ethers, preferably tetrahydrofuran, at RT

The structure of the reaction products obtained results from the elemental analyzes, mass, ¹ H and ¹³ C-NMP spectra.

embodiments

version 1

3,5,5-trisubstituted 1- (benzimidazol-2-yl) -imidazolidine-2,4-diones (Table 1)

To 10 mmol of i-carbamoyl-S-dihydro-imidazo / i 1 -α / benzimidazole-S-one are added in 10 cm ^{3 of} absolute THF 10 mmol of NaH. After 24 hours, the solution is mixed with 10 cm ^{3 of} water and the resulting precipitate is filtered off with suction, dried and recrystallized.

Variant 2

3,5,5-trisubstituted 1- (benzimidazol-2-yl) -imidazolidine-4-pn-2-thiones (Table 2) 10mmol 1,2-disubstituted 1 (9) H-2,3-dihydro-imidazo / 1,2-a / benzimidazol-3-one and 10 mmol isothiocyanate in 10 cm ³ abs. THF are added in portions with 10 mmol sodium hydride. After 24 hours, the solution is mixed with 10 cm ^{3 of} water and the resulting precipitate is filtered off with suction, dried and recrystallized.

Table 1

3,5,5-trisubstituted 1- (benzimidazol-2-yl) -imidazolidine-2,4-diones (variant 1)

at X R ¹ R ² R ³ method Yield. ° / c , Mp ( ⁰ C) Molecular formula Analysis Ber./Gef. H N game molar mass C (Ber./gef.) 5.46 21.69 1 O CH ₃ CH ₃ CH ₃ Α, Β 82 155-156 C ₁₃ H ₁₄ N ₄ O ₂ 60.45 5.47 21.74 (258.3 / 258) 60.28 5.03 17.49 2 O CH ₃ CH ₃ C ₆ H ₅ Α, Β 85 163-164 C ₁₈ H ₁₆ N ₄ O ₂ 67.49 5.16 17.29 (320.4 / 320) 67.55 6.12 15.46 3 O CH ₃ CH ₃ 4- (CH ₃ ) ₂ CH-C _e H ₄ Α, Β 94 175-176 C ₂₁ H ₂₂ N ₄ O ₂ 69.59 6.10 15.37 (362.4) 69.52 4.26 15,79 4 O CH ₃ CH ₃ 4-ChC ₆ H ₄ Α, Β 69 228-231 C ₁₈ H ₁₆ CIN ₄ O ₂ 60.93 4.49 15.44 (354.8) 61.12 3.62 14.39 5 O CH ₃ CH ₃ 3,4-CI ₂ -C ₆ H ₃ Α, Β 77 216-217 C ₁₈ H ₁₄ CI ₂ N ₄ O ₂ 55.54 3.64 14.36 (389.3) 55.66 4.90 15,30 6 O CH ₃ CH ₃ Naphth-1-yl Α, Β 90 186-187 C ₂₂ H ₁₈ N ₄ O ₂ 71.34 4.89 15.06 (370.4) 71.29

Table 2

3,5,5-trisubstituted 1- (benzimidazol-2-yl) -imidazolidin-4-one-2-thione (variant 2)

\ f

X R ¹ H R ² ir R ³ *O % Yield. Fp- ( ⁰ C) Molecular formula Analysis Ber./Gef. H. N at method molar mass C game (Ber./gef.) 5.14 20.42 S CH ₃ CH ₃ CH ₃ 73 124-125 C ₁₃ H ₁₄ N ₄ OS 56.91 5.15 20.32 7 B (274.4 / 274) 57.07 4.49 16.65 S CH ₃ CH ₃ C ₆ H ₆ 60 184-185 C ₁₈ H ₁₆ N ₄ OS 64,26 4.82 16,66 8th B (336.4) 64.42 4.08 15.11 S CH ₃ CH ₃ 4-CI-C ₆ H ₄ 71 150-151 C ₁₈ H ₁₆ CIN ₄ OS 58.29 4.09 15,12 9 B (370.9) 58.47

Claims (1)

claims: 1. A process for the preparation of novel 3,5,5-trisubstituted 1- (benzimidazol-2-yl) -imidazolidine-2,4-diones or -4-on-2-thiones of the general formula I, in the mean R: aryl, alkyl, substituted aryl R ¹ , R ² : alkyl or pentamethylene and X: O, S characterized in that a heterocumulen of the general formula II,