Dihydroimidazoles

Napamezole (68) is a dihydroimidazole derivative with antidepressant activity probably as a result of its combined a 2 adrenergic receptor blockuig and serotonin uptake blocking proper ties It can be synthesized by Wittig olefination of p-tetralone (65) with diethyl (cyanomethyl) phosphonate (66) and base to give nitnle 67 Imidazoline construction on the latter was smoothly... 

Second-generation ruthenium-carbene complex, (tricyclohexylphosphine-[l,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene][benzylidene]ruthenium (IV) dichloride),4e was purchased from Strem Chemicals. 

Tricyclohexylphosphine[l,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene][benzylidene]ruthenium... 

Increasing steric bulk at one of the NHC side groups will cause interference with the active site of the complex and generate an amplifying effect on alternation control. A methyl substituted one-carbon spacer like in l-mesityl-3-((rR)-l-phenylethyl)-4,5-dihydroimidazol-2-yhdene is enough to dramatically improve the alternation rate [129]. In Fig. 3.31 the steric impact on monomer coordination for different situations is rationahsed. 

Reaction of the dihydroimidazole ring of the tricyclic system 55 with w-chloroperbenzoic acid (MCPBA) results in oxidation of the iminium nitrogen with concomitant ring opening to generate the tertiary nitro compound 56 (Equation 7) <1997BML1381>. 

Apart from imidazol-2-ylidene carbenes, other electron-rich carbenes such as (L27)—generated by deprotonation of a 4,5-dihydroimidazole—have been tested for cross-coupling reactions, but gave much poorer results. The only reported exception is in the cross-coupling of arenediazonium salts with arylboronic acids, in which (L27) (used as hydrochloride) proved to be efficient.369... 

In 2002 Mehnert and co-workers were the first to apply SILP-catalysis to Rh-catalysed hydroformylation [74], They described in detail the preparation of a surface modified silica gel with a covalently anchored ionic liquid fragment (Scheme 7.7). The complex N-3-(3-triethoxysilylpropyl)-4,5-dihydroimidazole was reacted with 1-chlorobutane to give the complex l-butyl-3-(3-triethoxysilylpropyl)- 4,5-dihydroimidazolium chloride. The latter was further treated with either sodium tetrafluoroborate or sodium hexafluorophosphate in acetonitrile to introduce the desired anion. In the immobilisation step, pre-treated silica gel was refluxed with a chloroform solution of the functionalised ionic liquid to undergo a condensation reaction giving the modified support material. Treatment of the obtained monolayer of ionic liquid with additional ionic liquid resulted in a multiple layer of free ionic liquid on the support. 

The reaction of 2-chloro-4,5-dihydroimidazole 347 with hydroxylamine-O-sulfonic acid gives 2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate 348, which reacts with aldehydes and cyclic ketones to give the imidazo[l,2-f] fused 4,5-dihydro-l,2,4-oxadiazoles 350 (Scheme 58). Mechanistically, the reaction may be explained by the reaction of an imidazoline NH with the carbonyl followed by intramolecular electrophilic amination of the anionic oxygen present in the resultant intermediate 349 and elimination of the sulfate group <2003JOC4791>. 

In 1991 Arduengo and co-workers42 reported the isolation and characterization of the first stable carbene, l,3-di(l-adamantyl)-2,3-dihydroimidazol-2-ylidene. Since that time many substituted nucleophilic carbenes have been prepared.43 From ab initio studies it can be shown that cyclic electron delocalization is partly responsible for the extraordinary stability of 2,3-dihydroimidazol-2-ylidenes.44... 

A second example of homochiral columns formed by discotics are the complexes of tetrazoles (59 and 60) with l,3,5-tris(4,5-dihydroimidazol-2-yl)benzene (61).74 Four molecules self-assemble to give a supramolecular disc and these discs subsequently form columns in nonpolar solvents. Chiral discs were obtained from the self-assembly of the chiral tetrazole (60) with 61. The chirality of the side chains was found to induce a bias in the helic-ity of the supramolecular assembly. Sergeants-and-soldiers measurements75 were performed for which chiral (60) and achiral (59) molecules were mixed. The experiments showed no amplification of chirality, thus revealing that in these systems chirality transfer from the side chains into the column is... 

Synthesis and Activity of a New Generation of Ruthenium-Based Olefin Metathesis Catalysts Coordinated with 1,3-Dime-sityl-4,5-dihydroimidazol-2-ylidene Ligands, M. Scholl, S. Ding, C.W. Lee, et al, Org. Lett. 1999, 7, 953-956. 

Synthesis and Metathesis Reactions of a Phosphine-Free Dihydroimidazole Carbene Ruthenium Complex, S. Gessler,... 

The saturated imidazolidinium salts can be obtained by alkylation of dihydroimidazole or by selected cyclization reactions [22]. A multicomponent reaction leading to unsymmetric derivatives of type 2 has also been reported (Fig. 3c) [30]. 

Fusion of the imidazole ring to pyrrolo-benzothiadiazepine 340 can be achieved by straightforward TosMIC cycloaddition approach (Scheme 72, Section 4.2 (1994JHC1033)). An alternative sequence starts with the addition of nitromethane to the C-N double bond on the thiadiazepine ring, nitro group reduction and manganese oxide oxidation of the intermediate dihydroimidazole derived from amine 342 and tiiethyl ortho formate. 

Imidazo[l,2-a]pyridine , imidazo[5,l-a]isoquinoline and imidazo[2,l-a]iso-quinoline rings were successfully obtained from pyridine or isoquinoline oximes or their ethers. Thus, oxime ethers 130 were converted to imidazopyridines 131 in the presence of EtsN in methanol (equation 57). Esoquinoline oxime 132 by treatment with ethylenediaminetetraacetic acid (EDTA)/HgO and then AC2O gave imidazoisoquinoline 133 (equation 58). Similar mercury(EE)/EDTA mediated cyclization of pyridine oximes afforded fused dihydroimidazoles... 

The reaction of 2-aminobenzyl alcohol 376 with 2-chloro-4,5-dihydroimidazole afforded [2-(4,5-dihydro-177-imidazol-2-ylideneamino)phenyl]methanol hydrochloride 377, which upon treatment with carbon disulfide gave l-(477-3,l-benzoxazin-2-yl)imidazolidine-2-thione 378 (Scheme 71). The assumed reaction mechanism involved the initial formation of the dithiocarbamate 379, which underwent intramolecular nucleophilic addition to furnish the unstable thiazetidine 380. By nucleophilic attack of the hydroxy group on the carbon atom of the thiazetidine ring, thiocarbamate derivative 381 was formed, which gave the final 3,1-benzoxazine 378 by an intramolecular cyclocondensation with the evolution of H2S <2006H(68)687>. 

During studies on the use of amidines as azomethine ylide sources, Jones et al. (67-69) reported in a series of papers the application of their general strategy to an asymmetric process. Quatemization of the dihydroimidazole 214 with an a-halo ester followed by DBU-induced ylide formation and subsequent cyclization furnished a range of nitrogen heterocycles in a one pot generation and cyclization protocol (70) (Scheme 3.73). 

Synthesis oe Heterocyclic Compounds. In some cases, dehydroamino acids obtained from unsaturated 5(477)-oxazolones have been used as intermediates to prepare other heterocyclic compounds. For example, reaction of 2-benzoylamino-3-substituted-2-alkenoic acids 485 with alkyl or arylisothiocyanates affords 4-aryl-methylene-l,2-disubstituted-5-oxo-4,5-dihydroimidazoles 486 (Scheme 7.155). ... 

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