Benzimidazole 1-hydroxy- from

The only case of this type reported in the literature concerns the preparation of the substituted hydroxy-thiazolo [3,2 -a -benzimidazole 408 from 2-aminothiazole 407 and 1,4-benzoquinone in glacial acetic acid (Equation 185)... 

In this paper, we briefly review the results of our work on the iodine interaction with the thioamides benzothiazole-2-thione (BZT) (1), 6-n-propyl-2-thiouracil (PTU) (2), 5-chloro-2-mercaptobenzothiazole (CMBZT) (3), N-methyl-benzothia-zole-2-thione (NMBZT) (4), benzimidazole-2-thione (BZIM) (5), thiazolidine-2-thione (TZD) (6), 2-mercapto-pyridine (PYSH) (7), 2-mercapto-nicotinic acid (MNA) (8), 2-mercapto-benzoic acid (MBA) (9) and 2-mercapto-pyrimidine (PMT) (10), selenoamides, derived from 6-n-propyl-2-thiouracil (RSeU) (R= Me- (11), Et- (12), n-Pr- (13) and i-Pr- (14)) and amides 2-hydro -pyridine (PYOH) (15) and 2-hydroxy-pyrimidine (PMOH,+ Cl ) (16)... 

Poly(arylene ether benzimidazole)s have received more attention than any other PAE containing heterocyclic units. This is due primarily to their unique combination of properties even at relatively low molecular weights and their potential for use in several high performance applications. The initial report in 1991 involved polymers from the reaction of 3 different bis[(4-hydroxy-phenyl)benzimidazole]s with various activated aromatic difluoro monomers as shown in Eq. (10) [37]. The bis[(4-hydroxyphenyl)benzimidazole]s were prepared from the reaction of aromatic bis(o-diamines) and phenyl-4-hydroxybenzoate in diphenyl sulfone. The use of 4-hydroxybenzoic acid would obviously reduce the... 

Apart from the chemistry of the 4-hydroxy derivative (see p. 126) relatively little investigation in this area has been conducted. Thiocoumarin-3-carbonyl compounds have proved to be effective precursors for the synthesis of the pharmaceutically useful 3-(2-benzimidazolyl) derivatives. Thus, on interaction of the 3-carboxamide with o-phenylenediamine or the 3-aldehyde with o-nitroanilines, the above benzimidazoles or their TV-oxides are formed. 

The 2-(oMo-polyhydroxyalkyl) benzimidazoles are weak bases derived from o-phenylenediamine by condensation with an aldonic or closely related hydroxy acid. The present review includes substances of this type containing hydroxylated side chains of one to seven carbon atoms in length. Typical is the benzimidazole from D-glucose via D-gluconic acid. The side chain is attached at position 2 of the benzimidazole nucleus,... 

Thioazolidinediones have by now achieved a major role in the treatment of Type II, also called adult onset diabetes. A recent example includes a benzimidazole moiety as part of the structure. One of the syntheses for this compound starts by nucleophihc aromatic displacement of fluorine in p-fluorobenzaldehyde (151) by the anion from treatment of the hydroxy-methylbenzimidazole (150) with strong base. The product (152) is then... 

Base-induced conversion of lV,iV-disubstituted-o-nitroanilines (59) into benzimidazole A/-oxides may occur provided that one of the carbon substituents can be removed subsequently (e.g. cyano or arylsulfonyl). The reaction products, however, may well differ from those obtained from the monosubstituted analogues, e.g. cyclization of lV-alkyl(or aryl)-iV-cyanomethyl-onitroanilincs gives not the 2-cyanobenzimidazole M-oxides, but the 2- hydroxy derivatives [148J. These processes do not seem to have great synthetic utility. 

In the uncondensed imidazoles the standard method reacts an a-aminocarbonyl compound with a thiocyanate (see Section 4.1 and Table 4.1.1). If a 2-alkylthioimidazole is required directly, one can combine an N-alkyT or A -arylcarbonimidodithioate in refluxing acetic acid with the aminocarbonyl substrate (see Section 4.1 and Scheme 4.1.3). Alternatively, reaction between thiourea and a two-carbon synthon (ot-hydroxy-, a-halogeno-, a-dicarbonyl) leads to imidazoline-2-thiones (see Section 4.3). In sulfuric acid, 3-butynylthiourea cyclizes to 4,5-dimethylimidazolin-2-thione (see Section 2.2.1). 1-Substituted 2-methylthioimidazoles can be made, albeit in rather poor yields, from appropriately substituted 2-azabutadienes (see Section 3.2 and Scheme 3.2.3), and 2-arylthioimidazoles are available in moderate yields from benzyl isocyanides and arylsulfenyl chlorides (see Section 4.2 and Scheme 4.2.12). Ring transformations of 5-amino-2-alkylaminothiazoles and 2-acylamino-5-aminothiazoles may have occasional applications (see Section 6.1.2.7). The ease with which a thiol group or imidazole or benzimidazole can be alkylated, in comparison with the annular nitrogens, usually makes it more convenient to prepare alkylthioimidazoles from the thiols (or thiones). 

A synthesis of a benzimidazole in which the final step consists of the formation of a bond between a nitrogen atom and a ring-carbon atom was used to synthesize 6-hydroxy-1,2-diarylbenzimidazoIes from the benzamidine (44.1). Naphthylguanidines undergo oxidative cyclization at temperatures below 0°C to form a new 2-iminoimidazole ring. In this example, simultaneous oxidation and bromination occurs elsewhere in the molecule. LTA has also been used as the oxidant. 

The synthesis of substituted benzimidazolone analogues (Xi H) was started from appropriate 2-chloronitrobenzenes (VII) as outlined in Scheme 3. The reaction of VII with aminoalkanols in an inert solvent afforded N-hydroxy-alkyl-2-nitroanilines (VIII). Catalytic hydrogenation of the nitro group resulted in o-phenylene-diamines (IX) which reacted with urea to give the N-hydroxyalkyl-benzimidazol-2-ones (X). After treatment of Xwith thionylchlo-ride, the desired chloroalkylbenzimidazol-2-ones (I) could be isolated. 

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