Imidazoles, ring-closure

Two different c-fused [l,2,4]thiadiazines were synthesized nearly at the same time, and the syntheses are shown in Scheme 30. Boverie et al. <2001JPL973> reported a procedure for the imidazole ring closure, which is fairly... 

Nitropyridine 166 in the Barton-Zard condensation behaves specifically affording tricyclic compound 167 (00SL213). Evidently, 4-azaisoindole derivative 168 formed in the first step reacts further with another molecule of nucleophile that results in imidazole ring closure (Scheme 50). Under the same conditions 4-nitro-pyridine remains unchanged. 

Triacanthine (17) has been isolated from Holarrhena mitis Details on the structure and total synthesis of eritadenine (18), a hypocholesterolemic alkaloid from Lentinus edodes, have been reported.An unsuccessful attempt to improve the imidazole ring-closure reaction in a total synthesis of eritadenine, which has been previously discussed, was also reported in this study. Concentrations of both caffeine and theobromine in the cocoa bean were shown to increase most markedly in the time period from flowering to harvest. ... 

Structural studies presented by Chibata and by Kamiya included similar total syntheses of eritadenine, each consisting of the condensation of 4-amino-6-chloro-5-nitropyridine with 4-amino-4-deoxy-2,3-C)-isopropyli-dene-D-erythromic acid, followed by catalytic reduction of the ni-tro group and imidazole ring closure by formic acid or its amide. This can be exemplified by Kamiya s procedure (400) shown in Scheme 83. Soon improved syntheses were reported from both laboratories by Kawazu et al. (401) and Kamiya et al. (402), each starting from adenine and methyl 2,3-0-isopropylidene-5-0-tosyl-)8-D-ribofuranoside or d-erythronolactone acetonide, respectively (Schemes 84 and 85). Kamiya... 

There were some previous reports on the preparation of the PPBIs in PPA that resulted in low IV polymers or incomplete imidazole ring closure [ 102, 103]. In the present study, the initial polymerizations using diadd monomers without further purification gave PPBIs with IVs less than l.OdLg", as shown in Table 2. Based on the Carother s equation, monomer purity and accurate stoichiometry are crucial to obtain high IV polycondensation polymers. Therefore, a detailed study of the monomer purity and purification method was carried out on aU the diadd monomers. DSC scans were employed to monitor the relative purity of the monomers. They confirmed the improved monomer purity after purification. Table 2 shows that all diadd monomers polymerized to yield high IV PPBIs after appropriate purification of starting materials and careful manipulation of polymerization conditions. 

Synthesis of 2-thioxopenams (76) has also been realized usiag a [sulfur, C-5] ring closure (117). Cyclization of 4-(3)-chloroazetidinone [88816-44-8] (77, R = R = SCOCH ), C22H22ClN20gS2, usiag imidazole ia aqueous dioxane proceeded stereospecifically to give the 5-(R)-thioxopenam [83362-57-6]... 

An alternative method involves reaction of an a-acylaminoketone (12) with a primary amine and subsequent ring closure of the resultant Schiff s base (13) with phosphoryl chloride. This enables the introduction of a 1-substituent as in (14) to be carried out efficiently, and if the amine were replaced with a monosubstituted hydrazine, the imidazole derivative (IS) resulted (78LA1916). 

Sulfur may also be alkylated under appropriate conditions. On formation, the N-/3-chloroethylthiazolidine-2-thione (307) underwent spontaneous ring closure to the tetrahy-drothiazolo[2,3-6]thiazolylium chloride (308) (71CHE1534) and a similar reaction occurred in the imidazole series. 

Isoxazoles (478) in the presence of base undergo ring opening to a-ketonitriles (479). When the reaction was carried out in the presence of hydrazines, 5-aminopyrazoles (480) were obtained. The reaction is also a convenient source of imidazoles, For example, when the 1,2-benzisoxazole (481) was treated with phenylhydrazine, decarboxylation initially occurred with subsequent ring closure to (482) (see Chapter 4.16). 

Most frequently the synthetic routes to imidazoquinolines involve the ring closure of pyridine ring starting from aminobenzimidazoles. Ring closure of the imidazole ring is preferred when starting from o-diaminoquinolines. 

The cyclization of o-substituted amides 206 was used for the preparation of a series of purine derivatives 207. In this case, the amine behaved as a nucleophile toward the amide function followed by ring closure to the imidazole ring (Scheme 75) [133]. 

However, similar NHC architectures employing aromatic side chains have shown more encouraging results. In 2000, Nolan and co-workers reported the synthesis and characterisation of the NHC-Ru complex 20 bearing a sterically more demanding N,N -bis-[2,6-(di-/xo-propyl)phenyl]imidazol-2-ylidene (IPr) ligand [27, 28] (Fig. 3.5). Standard RCM substrate 1 was used to test the catalytic performance of 20. The ring closure was found to be complete after 15 min by using 5 mol% 20 as catalyst at room temperature. Under identical conditions, 15... 

Treatment of the tetrahydropyrano[l,6]naphthyridine 303 with phosphorus oxychloride results both in closure of the imidazole ring and rearrangement of the pyran ring to give the spiro-cyclopropano compound 304 (Equation 104) <1996JHC49>. 

The Suzuki coupling of soluble polyethylene glycol (PEG)-bound bromothiophene 71 and p-formylphenylboronic acid provided biaryl 72 [56]. Due to the high solubilizing power of PEG, the reaction was conducted as a liquid-phase synthesis. Treatment of 72 with o-pyridinediaminc resulted in a two-step-one-pot heterocyclization through an imine intermediate. Nitrobenzene served as an oxidant in the ring closure step. Finally, transesterification with NaOMe in MeOH resulted in l//-imidazole[4,5-e]pyridine 73. 

Imidazole-fused dithiazines were synthesized by Brzozowski and Saczewski <2002JME430>. The ring-closure reaction of the acetal 181 took place in sulfuric acid to yield the tricyclic product 182 in almost quantitative yield. 

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