2- benzimidazole, structure

Firefly lucifenn is an example of an azole that contains a benzene ring fused to the five membered ring Such structures are fairly common Another example is benzimidazole present as a structural unit m vitamin B12 Some compounds related to benzimidazole include purine and its ammo substituted derivative adenine one of the so called het erocychc bases found m DNA and RNA (Chapter 28)... 

In the course of the investigations directed at the structural characterization of another type of aza analog of sesquifulvalene, the X-ray structure of the triaza derivative 72a was determined (89CC1086). Tire molecule is effectively planar, the torsion angle between the pyridine and benzimidazole... 

The simple methyl compounds do indeed contain methyl groups, e.g., methylthiazoles exist as such and not in the methylene form."" The structures of compounds of the pyrophthalone type containing a benzimidazole and benzthiazole nucleus, e.g. 228, have been discussed. Bis (benzimidazolyl) methanes (229) absorb light in the... 

Therapeutic Function Anthelmintic Chemical Name 2-(4-thiazolyl)-1 H-benzimidazole Common Name -Structural Formula ... 

Since a substituted benzimidazole was first reported to inhibit the H,K-ATPase by covalent binding [ 1 ], many PPIs have been synthesized and are in clinical use. These all have a similar core structure, 2-pyridy lmethylsulfinyl benzimidazole moiety except tenatoprazole. Tenato-prazole has 2-pyridylmethylsulfinyl pyridoimidazole moiety. 

Substituted benzimidazole inhibitors show slightly different effects depending on the inhibitor structure. Omeprazole binds to cysteines in the extracytoplasmic regions of M5/M6 (cys-813) and M7/M8 (cys-892). 

Only one example in this category has been described in recent years (as of 2003). Treatment of o-phenylenediamine (396) with 3,4,5,6-tetrachloropyridazine (397) in A-methylpyrrolidine at 115°C for 17 h gave a separable mixture of products, one of which was 2,3-bis(benzimidazol-2-yl)quinoxaline (398) (unstated yield). The structure (398) was confirmed by X-ray analysis,and a mechanism for its formation was suggested. ... 

Due to the steric requirement of these substituents the formation of a columnar structure with infinite M M interactions is inhibited, and only the association of pairs of molecular units is allowed. The Ni Ni distance is 3.21 A [164]. If the same compound is crystallized in the presence of benzimidazole, the [Ni(dmg-BF2)2]2 dimer units are sandwiched between sheets of benzimidazole molecules due to n-n interactions resulting in an increased Ni Ni separation of 3.358 A [165]. With anthracene the n-n interactions seem to be stronger, because in this case the parent dimer molecule is cleaved. Each monomer now has a conformation of type B (Fig. 32) and is sandwiched by anthracene molecules [166]. Compound 121 has the same configuration [163d]. 

Fig. 3.10 Recognition of the DNA minor groove with benzimidazole derivatives, (a) Structure of the dimeric core for Py-benzimi-dazole (Bi), Py-hydroxybenzimidazole (Hz) and Py-imidazopyridine (Ip) (left) in comparison with the five-membered ring system (right). H-bonding surfaces along the recogni-...

In this chapter, an attempt has been made to present a total number of 20 QSAR models (12 QSAR models for topo I inhibitors and eight QSAR models for topo II inhibitors) on 11 different heterocyclic compound series (an-thrapyrazoles, benzimidazoles, benzonaphthofurandiones, camptothecins, desoxypodophyllotoxins, isoaurostatins, naphthyridinones, phenanthridines, quinolines, quinolones, and terpenes) as well as on some miscellaneous heterocyclic compounds for their inhibition against topo I and II. They have been found to be well-correlated with a number of physicochemical and structural parameters. The conclusion, from the analysis of these 20 QSAR, has been drawn that the inhibition of topo I is largely dependent on the hydrophobicity of the compounds/substituents. On the other hand, steric parameters (molar refractivity, molar volume, and Verloop s sterimol parameters) are important for topo II inhibition. 

A mass spectrometric study was carried out to establish tbe structure of compoimd 69. Its mass spectrum contains tbe molecular ion peak m/z 252 (16.98%) and a base peak (100%) at m/z 210, corresponding to 2-(2-hydroxypbenyl)benzimidazole (70). A tendency towards decreasing the heterocycle size is characteristic of the mass spectrometric behavior of 1,5-benzodiazepin-2-ones [61] and consequently the mass spectra of these compounds contains intense peaks of the corresponding benzimidazoles. It is also known that the mass spectrometric fragmentation of 1,5-benzodiazepines is similar to their thermal or acid decomposition. In fact, refluxing compound 69 in concentrated sulfuric acid yields benzimidazole 70 as the main product. 

Table 7 shows the structures of representative azole compounds and several structurally related compounds such as benzimidazoles, thiazoles and imidazolines. 

Other patent reports covering PDF inhibitors from structural classes different from those discussed above include hydrazides (43) [118], aryl-substituted pyrrolidines (44) [119], benzimidazoles (45, 46) [120-121], hydantoins (47) [122] and oxo-pyrrolidines (48) [123], A prodrug approach utilising PDF has been published by Pei, and patents have been published by NewBiotics, but in this case the compounds of interest are used as substrates rather than inhibitors (49) [124-126]. 

P2j Z = 2 D = 1.57 R = 0.048 for 931 intensities. The base exists in the thioxo form, with C-8=S and N-7 protonated. The 8-thio substituent causes the base to assume the syn (—102.6°) orientation. The o-ribosyl group is 2T3 (174.8 °, 44.1 °). The exocyclic, C-4 -C-5 bond orientation is trans (—173.2°). This does not favor intramolecular hydrogen-bonding of 0-5 to N-3 of the syn base. The C=S distance is 166.8 pm. The S atom is involved in a weak, acceptor hydrogen-bond to a water molecule, S H-O(w) = 361 pm. The bases are stacked head-to-tail, with overlap of the C=S bonds and the purine ring, in contrast to the known, related structure l-/ -D-ribofuranosyl-2-thioxo-3ff-benzimidazole,197 where similar head-to-tail stacking of the bases involves overlap of the base rings only. 

In analogy to the reaction of CDI with carboxylic acids, the even more reactive NJf -carbonyldi-1,2,4-triazole 5bl has been used instead of CDI in cases where specific structural effects require a higher reactivity of the azolide. On the other hand, the example of the last paragraph of the preceding section showed that A -carbonyldi-benzimidazole 151 141 and AyV -carbonyldibenzotriazole 151 have been useful for the syntheses of azolides with reduced reactivities when these are essential and sufficient for the specific reaction in question. 

A trinuclear system, whose structure was published,555 was formed in high yield by the cyclometalation of a l,3-bis(alkylbenzimidazol-2-yl)benzene ligand, followed by the trimerization of the unit, which possesses a vacant coordination site on the palladium atom and a pendant noncoordinated benzimidazole moiety. The resulting product forms a cup-shaped trimer or tricorn, presented in Figure 46, that includes a molecule of acetonitrile in the crystal structure.556... 

A trimeric species was formed with one equivalent of a bis(benzimidazole) ligand in the presence of benzylthiolates (59) (Figure 10). Zinc-zinc distances were in the range 3.069-3.958(2) A.126 Other zinc-thiolate trinuclear compounds include Zn3(CH2SiMe3)3(SC6H2iPr3)3 and Zn3(o-phen)2(toluene-3,4-dithiolate)3 but have little structural similarity.81,525... 

Figure 10 Molecular structure of a zinc trimer (59) with bridging benzyl thiolates and a bis(benzimidazole)...

Some interesting organic chemistry is involved in the synthesis of chlorite-resistant brighteners for acrylic fibres. None of these compounds is easy to make and methods for preparation of the starting materials can be complex. Much manufacturing know-how is involved. One route for introduction of the benzimidazole nucleus into structure 11.55 is shown in Scheme 11.22. Preparation of the chemically rather simpler benzoxazole grouping in product 11.56 is shown in Scheme 11.23. 

Potent IRAK-4 inhibitors have been reported by several groups including some structurally related benzimidazoles (e.g., 34-36) as well as alternative fused heterocycles such as the imidazopyridine (37) and imidazopyridazine (38) [102-107]. Such compounds are... 

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