SU353421A1 - Method of producing derivatives of 4,5,6,7-tetrahydrin benzimidazole - Google Patents

Description

This invention relates to the preparation of derivatives of 4,5,6,7-tetrahydrobenzimidazole, valuable corrosion inhibitors and antioxidants.

The difficulty of catalytic hydrogenation of benzimidazoles is well known: benzimidazole is not hydrogenated either with nickel at high pressure and 200 ° C, nor with platinum at 100 ° C in the presence of various solvents. However, it was possible to hydrogenate the benzimidazole derivatives placed in position 2, namely 2-methyl-, 2-ethyl-, 1,2-dimethyl- and 2-phenylbenzime "dazole, with the aid of adlat according to Adams in glacial acetic acid, obtaining the corresponding 4,5,6,7-tetrahydrobenzimidazoles. Hydrogenation of the benzimidazo substituted only 13 position 1, as well as benzimidazoles substituted in position 2, carrying substituents in the benzene residue of benzimidazole, was not crowned with success.

In order to increase the yield and expansion of the assortment of the target product, a method for the preparation of 4,5,6,7-tetragichrobenzimidazole derivatives of general formula 1 is described.

  R

where RI is a hydrogen atom, an unbranched or branched alkyl residue with 1 to 18, preferably 1-4 carbon atoms, oxyalkyl or carboxyalkyl radical with 1-4 carbon atoms in the alkyl residue, a 5- or 6-membered cycloalkyl, alkylcycloalkyl or cycloalkylalkyl residue, an arylalkyl residue with I-4 carbon atoms in the alkyl residue, glycosyl, arabinosyl, xplosyl, ribosium or other, formed from hexoses, pentoses or tetrosis, a sugar residue, or RI means the A – Z residue, where A is unbranched or times branched alkplei residue with 1-4 carbon atoms, and Z - amino, lower monoalkylamino, lower dialkylamino, morpholino, N-pyrrolidino-, N-piperidino, N-piperazino-, N-alkanol- piperazino- , N- (co-hydroxy-lower alkyl) N-piperazino- or M- (y-hydroxyalkoxy-lower alkyl) -M-piperazine group; R2 is a hydrogen atom, a linear diacetoxypropionic acid, dialkylaminoethylamide diacetoxypropionic acid with 1-4 carbon atoms in alkylamino residue, the residue tetraoxival eripic acid, polyoxyalkyl residue with 4-6 carbon atoms, cyclopentyl or cyclohexyl residue, alkylcyclohexyl residue with 1-4 carbon atoms in the alkyl residue, carboxycyclohexyl residue, 2-, 3- or 4-piperidine residue, phenyl, mono- or dialkylphenyl residue with 1-4 carbon atoms in the alkyl residue, mono- or dialkoxyphenyl, mono- or dialkoxybenzyl or mono- or dialkoxyphenylethyl residue with 1-4 carbon atoms in the alkoxy residue, 3,4-methylenedioxyphenyl, 3,4-methylenedioxybenzyl or 3,4-methylepdioxyphenyl residue, tetrahydrofuryl group, acylaminophenyl residue, where the acyl group is derived from aliphatic carbopic acid with 1-3 carbon atoms, fluorophenyl residue, 4,5,6,7-tetrahydrobenzimidazolyl - (2) -1 , 2-dioxyethyl or 4,5,6,7-tetrahydrobenzimidazolyl (2) -1,2,3,4-tetraoxybutyl residue, imidazolylalkyl triazolylalkyl or tetrazolylalkyl residue with 1-4 carbon atoms in the alkyl residue; Ks is a hydrogen atom, an unbranched or branched alkyl group with 1 to 18 carbon atoms, preferably 1 or 2 carbon atoms, a carboxyl or alkoxycarbonyl group with 1-4 carbon atoms in the alkoxy residue, and R4 is a hydrogen atom or a linear or branched alkyl residue with 1 - 4 carbon atoms, or their salts, consisting in the fact that the corresponding benzimidazole derivatives of general formula II

 iG) n,

K :, N

R.

where RI, R2, Hz and R4 are as follows, or are their hydrogenated, unsaturated precursors, or their salt is hydrogenated in the presence of rhodium or catalysts containing rhodium in the overwhelming majority. The desired product is isolated in the free state or in the form of a salt by known methods.

The novel method of preparation according to the invention is benzimidazolbenzene nuclear hydrogenation in the complete absence of substitution effects. Other suitable aromatic residues at normal pressure are not affected at all or very difficultly.

Since rhodium has no tendency to

hydrogenolytic dissociation according to

A new method can be hydrogenated and such

benzimidazoles that carry alkylphenyl substituents.

In this way, 2- (4-megoxyphenyl) -, 2- (4-methoxycyclohexyl) -, 2- (3methoxyphenyl) -, 2 - (3 - methoxycyclohexyl) -, 2 - (2 - methoxyphenyl) -, 2 - { 2 - methoxycyclohexyl) -, 2- (4-ethoxyphenyl) -, 2- (4-ethoxycyclohexyl) -, 2- (4-butoxyphenyl) -, 2- (4-butoxycyclohexyl) - 4,5,6,7 - tetrahydrobenzimidazole , 2- (3,5-dimethoxyphenyl) -, 2- (3,5-diethoxyphenyl) -, or 2- (3,4-methylenedioxyphenyl) -, 2 - (3,4 - dimethoxycyclohexyl), 2- (3, 4-dimethoxyphenylmethyl) -, and 2- (3,4-dimethoxyphenylethyl) -4,5,6,7-tetrahydrobenzime "Dazole.

As catalysts, conventional rhodium catalysts can be used in pure form OR on various supports. Preferably, supported rhodium catalysts are used. As such 1; ostelit use silicic acid, diatomaceous earth, alumina, pumice, asbestos,

coal, titanium dioxide, barium sulfate, vermiculite, and silica gel. Preferably, active coal, barium sulfate, titanium dioxide, alumina and silica gel are used. In catalysts on carriers catalyst

usually contained in amounts of about 2-10%. Catalysts can be used several times with thorough washing, for example, with water, methanol, or glacial acetic acid.

The method is carried out in a solvent or diluent 1 in which the starting benzimide sol is at least partially soluble. The applicable solvents are water, acetic acid, propionic acid,

lower aliphatic alcohols, glycol ethers, tetrahydrofuran, or mixtures thereof.

A wide temperature range can be used at normal or elevated pressures from about OS to t. Bale.

solvent or diluent used. In the case of overpressure, in appropriate cases, the existing aromatic substituents can also be hydrogenated. Hydrogenation can be carried out at normal pressure up to about 120 kg / cm or higher. Hydrogenation is also possible at higher pressures and higher temperatures if the products or hydrogenation products to be hydrogenated allow or require this. Some substituted benzimidazole compounds may undergo changes at elevated reaction temperatures. For example, the hydrogenation temperature during hydrogenation

benzimidazolyl- (2) -acetic acid should not exceed approximately 80 ° C, since decarboxylation will take place at higher temperatures, in which case 2-methyl-4,5,6,7-tetraB is formed. Figure 1 shows the results of hydrogenation of be 1 zimidazole using various catalysts.

1.2 g of benzimidazole are hydrogenated in 30 ml of AcOH under normal pressure or 2.4 g of benzimidazole in 50 ml of AcOH at 60 atm.

Table 1

It is confirmed that platinum is not able to hydrogenate benzimidazole, even at elevated pressures and temperatures (runs 1, 2, 3, and 8).

A mixed catalyst (rhodium – platinum), usually recommended for nuclear hydrogenations (see F. Zymalkowsky, “Catalytic Hydrogenation in an Organic Chemical Laboratory, Ferd. Enke, Stuttgart, FRG, 1965, p. 28) is worse than rhodium. Only part of the benzimidazole is subjected to hydrogenation at a slow rate, and after 20 hours, the hydrogenation stops (experiment 4).

Only with the use of a rhodium catalyst is benzimidazole completely hydrogenated, although at a normal pressure relatively slowly (test 5-7), and only at elevated pressure and temperature very quickly and smoothly (test 9).

A significant part of the invention is the correct choice of the appropriate solvents. In addition to acetic acid or other lower carboxylic acids, it is generally possible to use water or other polar solvents, such as lower aliphatic alcohols, glycol ethers, diester esters or tetrahydrofuran. If the compound is to be hydrogenated in the form of its salt with an inorganic or organic acid, then these acids must be added in an amount of at least 1 eq. on the main group. If an insufficient amount of acids is used, there will be no hydrogenation of the vehicle or it will not flow completely.

In tab. 2 shows the results of hydrophobic intakes depending on the use of various amounts of HC1. Hydrogenation of 2.4 g of benzimidazole is carried out with 100 ml of water with 0.5 3 rhodi / coal (5% rhodi) at 120 ° C and 60 kg / cm.

table 2

In water at normal pressure, hydrogenation has no place. At elevated pressure and elevated temperature, hydrogen is very slowly observed, but after a while hydrogenation is suspended (Table 2, experiment 1).

The same result is obtained if only a part of the benzimidazole is converted to the hydrochloride, despite the initial high speed (experiment 2). With the addition of 1 mole. hydrochloric acid hydrogenation is carried out quickly and completely (experiment 3); By excess of hydrochloric acid, hydrogenation is further accelerated (run 4).

In tab. Figure 3 shows the effect of various systems (acid / solvent) on the rate of hydrogenation reaction. The benzimidazole is hydrogenated using 5% rhodium / carbon table. 3 it can be seen that the reaction rate depends on the type of solvent used, as well as on the temperature n and pressure.

This results in preferred and cost-effective hydrogenation conditions. Hydrogenation is best carried out using supported rhodium catalysts in glacial acetic acid, dilute acetic acid, or water, orienting with at least an equimolar amount of strong acids (for example, hydrochloric, sulfuric), all of which have basic nitrogenous groups neutralized by acid and even acid may be in excess, at 20-120 ° C and at a hydrogen pressure of 1 - 80 KzJcM. Hydrogenation in water is particularly cost-effective when strong acids are added at elevated pressure and temperature. Salts of tetrahydrobenzimidazoles are formed.

Methods for obtaining free bases.

Hydrogenation methods.

A) 1 weight. the compounds to be hydrogenated are hydrogenated with 0.01-1 weight. h .. 5% supported on a carrier rhodium catalyst in 2-20 weight. including solvent at normal pressure in a fitted Muggle in 30 ml of solvent at normal pressure or 50 ml of solvent at elevated pressure.

Table 3

nitric stirrer flask or under increased pressure in the autoclave.

On absorption of the calculated amount of hydrogen, the catalyst is filtered off, the filtrate is concentrated. The residue is then dissolved in water, adjusted to caustic with caustic soda; the hydrogenation product is filtered off or, in extreme cases, extracted with a solvent. The crude product is recrystallized from an appropriate solvent.

B) Hydrogenation is carried out according to A). The catalyst is filtered off, the filtrate is concentrated. The residue is dissolved in water, the solution is made alkaline, the product

hydrogenations are extracted with chloroform, trichlorethylene, benzene or other solvents that are not miscible with water. The extract is dried over a drier, the solvent is distilled off, the liquid product is distilled.

in high vacuum or converted to hydrochloride. AT). Hydrogenation according to A). After filtering off the catalyst and concentration of the solvent, the residue is diluted with water, alkali is added to it, equivalent to

filtered off. D). After filtering off the catalyst, the filtrate is concentrated, an alkali equivalent amount of inorganic acid is added, and the solution is evaporated to dryness. The residue is extracted with methanol or acetone, the extract is concentrated and, if the hydrogenation product does not crystallize, is precipitated with ether or another appropriate solvent.

Methods for Preparing Quaternary Ammonium Salts:

E) For tetrahydrobenzimidazoles of the general structural formula I, but where Ri is different from hydrogen, 1 mol of the tetrahydro compound is dissolved in a small amount of methanol, 1 mol of an alkyl, cycloalkyl or arylalkyl halide is added to the solution; then either the reagents are allowed to react for a long time at room temperature, or a shorter time when heated. On distilling off the solvent, the quaternary ammonium salt remains almost pure.

E) For tetrahydrobenzimidazoles of general structural formula I, but where Ri is a hydrogen atom, 1 mol of tetrahydro compounds is introduced into reaction D) with 1 mol of alkyl, cycloalkyl or arylalkyl halide. Then 1.1 mol of sodium hydroxide is added and the reaction mixture is heated under reflux for 1 hour. After further addition of 1 mol of alkyl-, cycloalkyl- or arylalkyl halide, the mixture is refluxed for 1 hour,

the precipitated sodium salt is then filtered off and the solvent is distilled off. Quaternary ammonium salt remains.

The starting compounds, the hydrogenation conditions and the physical data of the resulting tetrahydrobenzimidazoles are listed in the table below. four.

Tetrahydrobenzimidazoles are clearly characterized by an infrared spectrum. Aromatic vibrations of the benzene ring characteristic of unhydrogenated benzimidazoles

(depending on the type of substitution between 670 and 900 cm-) hydrogenated compounds do not. Characteristic of the imidazole core (HL) associated absorption1-o (between 2400 and 3500) remains.

Thin-layer chromatograms of hydrogenated products, with the exception of rare compounds, share common patterns. More basic hydrogenation products are carried out on Merck silica gel H (solvent: benzene / methanol 7/3 or chloroform / / methanol 8/2; visualization of sunspots in the iodine chamber) is slower, their Rf coefficients are smaller than unhydrogenated starting compounds.