Benzimidates

In 1997 the first asymmetric aza-Claisen rearrangement was reported by Overman et al. [55], which made use of diamines as bidentate ligands for Pd(II), allowing for moderate enantioselectivities. In the same year, Hollis and Overman described the application of the planar chiral ferrocenyl palladacycle 38 as a catalyst for the enantioselective aza-Claisen rearrangement of benzimidates 39 (Fig. 19) [56]. A related ferrocenyl imine palladacycle provided slightly inferior results, while a benzylamine palladacycle lacking the element of planar chirality was not able to provide any enantioselectivity [57]. 

Fig. 19 Asymmetric Azti-Claisen Rearrangement of benzimidates 39 using amino palladacycle 38...

A significant breakthrough was achieved by Overman and Donde in 1999 they reported the first highly selective catalyst 41 for the aza-Claisen rearrangement of benzimidates 39 (Fig. 20) [58]. Enantioselectivities were in most cases good to very good. 

Fig. 20 Asymmetric azti-Claisen rearrangement of benzimidates using oxazoline palladacycle precatalyst 41...

Fig. 21 Asymmetric crza-Claisen rearrangement of benzimidates using bispalladacycle precatalyst 42...

Pd-centers as catalysts for the rearrangement of benzimidate substrates. While the enantioselectivity reached a practical value, the yield was only moderate (Fig. 22). 

Fig. 22 Asymmetric tiza-Claisen rearrangement of benzimidate 39a using the trispalladium species 43...

A related planar chiral Co-based oxazoline palladacycle COP-X (46) was later found to be of higher synthetic utility as it permitted the use of benzimidates, [62] as well as allylic trifluoro- [63] and trichloroacetimidates [64, 65]. 46 was found to be superior to its ferrocene analogue 41 [61] in a number of aspects such as ease of... 

Fig. 16 Excess acidity plot against X according to equation (60) for the hydrolysis of methyl benzimidate at several temperatures, showing the involvement of two water molecules. Data from ref. 253.

The discovery of oxazoline hydroxamates as potential inhibitors of LpxC was the result of high-throughput screening of large libraries of compounds at the Merck Research Laboratories in collaboration with the Department of Biochemistry, Duke University Medical Center [95]. The lead compound, L-573,655, was a racemic mixture of 4-carbohydroxamido-2-phenyl-2-oxazoline, which had been previously made by Stammer et al. [96] as a precursor in the chemical synthesis of cyclosporine. Namely, (R,S)-serine methyl ester hydrochloride (149) is converted into (R,S)-4-carbomethoxy-2-phenyl-2-oxazoline (150) via treatment with ethyl benzimidate using the Elliot procedure [97]. Treatment of this ester with one equivalent each of hydroxylamine and sodium methoxide in methanol at room temperature affords the desired (R,S)-4-carbohydroxamido-2-phenyl-2-oxazoline (151), as depicted in Scheme 30. 

Some general aspects of linked bis-tacn, bpta and bis-benzimidazole-pyri-dyl ligand and their Fe(II)Fe(II) compounds have been mentioned in Sect. 2.1 and Sect. 2.2 [21, 22, 28]. Only the helical [Fe2L3]4+ bis-benzimid-azole-pyridyl complex shows SCO and it was studied in solution. We are pursuing work on weakly linked compounds, with Toftlund, using a butane-linked dinitrile ligand, and this is mentioned in Sect. 6. 

The excellent solvent and migration fastness which is typical of all benzimid-azolone pigments probably results from this singular structural principle, which has not yet been discovered in any other azo pigment class. 

Pankova and Tichy prepared all four stereoisomeric 4-rerr-butyl-2-aminomethyl-l-cyclohexanols and cyclized them with ethyl benzimidate to hexahydro-l,3-benzoxazines 158-161 (74CCC1447). From the A-acyl O-mesylate derivatives 162 and 163 on thermal cyclization or thionyl chloride treatment, ring closure occurred with inversion and resulted in 158 and 159 (74CCC1447). 

In the reactions of cis- and rrans-2-aminomethyl-l-cyclohexanol or -1-cycloheptanol or cis- and trans-2-hydroxymethyl-l-cyclohexylamine or -1-cycloheptylamine with ethyl 4-chlorobenzimidate, the stereo- and regio-isomeric derivatives and homologs 164 and 165 were prepared (79T799). The amidine intermediate 166 of the benzimidate ring closure was also... 

Because some of the compounds with general structure 316 have noteworthy pharmacological activities, a number of alternative methods have been developed for the synthesis of the 2-substituted and 2,3-disubstituted derivatives 316. 2-Substituted derivatives of 316 cis, n = 1, 2, 3, 4 trans, n = 2, 3, 4) were prepared (77GEP2643384 80AUP507798) from 312-315 with ethyl benzimidates. The attempted ring closure of trans-2-amino-l-cyclopentanecarboxylic acid to rra/w-fused derivatives failed. In this reac-... 

Nucleophilic attack at the C-5 carbon atom of 1,2,4-thiadiazoles has been proposed as a reaction mechanism for many of the ring transformations described throughout this chapter. Thus, 2-methyl-3,5-diphenyl-1,2,4-thiadiazolium fluorosulfate (33) is cleaved by alkoxide giving the benzimidate (34) in the case of hydroxide ions, reaction continues to the benzoylamidine stage (35) (Scheme 10) <82AHC(32)285>. 

Aliphatic and aromatic nitriles are often converted to the corresponding imidates that then react with amino alcohols to provide oxazolines. This two-step process offers milder conditions. Generally, a mixture of the imidate (free base or hydrochloride) is allowed to react with the amino alcohol in a solvent (alcohols, CH2CI2, CHCI3) with or without a tertiary base. As expected, the cylization proceeds with retention of stereochemistry when chiral amino alcohols are used. Representative examples are shown in Table g 17 33,62,63,139,216-225 ready availability of benzimidates and trimethyl orthobenzoates make them ideal surrogates for benzonitrile. ... 

Via a same intermediate, the action of sodium cyanamide on phenylchloroxime or the action of hydroxylamine on ethyl-N-cyano-benzimidate, yields 3-phenyl-5-amino oxadiazole (61a, 33c). 

Das einfach protonierte Benzimidazolium-tetrafluoroborat( ) liegt dimer vor mit dem Proton in einem asymmetrischen Minimum bei 2,787(3) A zwischen den beiden Ringsystemen678. Die unterschiedlichen N, —C- bzw. C -N-,-Bindungslangen in (2-Naphthyloxy-methyl)-benzimid-azol werden erwartungsgemaB egalisiert, wenn man mit Methyliodid 3-Melhyl-l-(2-naphthyl-oxy-methyl)-benzimidazolium-iodid (II) erzeugt25 (vgl. a. Lit.679). 

Bei der Photolyse von l-(2,4-Dinitro-phenyl)-4-phcnyl-imidazol in Ethanol wird der Heterocyclus in einer intramolekularen Redox-Reaktion gespalten. Unter Recyclisierung erhalt man 2-Benzoyl-6-nitro-benzimid-azol [50% Schmp. 255° (Zers.)]326. 

Im Gegensatz zur normalen Cyclisierung von Kohlensaure-Derivaten zu 2-Hydroxy-benzimid-azolen reagieren Kohlensaure-dialkylester in Anwesenheit von Cyanid-Ionen mit o-Diamino-arenen zu 2-Alkoxycarbonylamino-benzimidazolen34 5 z.B. ... 

Fiir die Herstellung von antibakteriell wirksamen 2-(l-Pyridiniono-methyi)-benzimid-azolen I werden o-Diamino-arene mit 2-Pyridiniono-dithioessigsaure-estem kondensiert. Nach dieser Methode erzielt man bessere Ausbeuten als durch Substitution der 2-Chlormethyl-benzimidazole mit Pyridinen267,268. 

Die Umsetzung mit Seleno-carbonsaure-O-ethylestern liefert zwar bei 20° gute Ausbeuten an Benzimid-azolen, die Methode hat sieh aber nicht weiter durchgesetzt336. 

Oxidativ werden 1-Amino-benzimidazole mit Kalium-hexacyanoferrat(III) in lH-Benzimid-azole umgewandelt444. 

Acyl-2-amino-benzimidazole werden durch Pyridin (100° 1 h) zu 2-Acylamino-benzimid-azolen umacyliert (s.a. S. 351, 3S6)447. 

Methyl-benzimidazol dimerisiert ebenfalls bei der Acylierung mit Benzoylchlorid und Tri-ethylamin als Base zu 3-Benzoyl-l-methyl-2-(l-methyl-2-benzimidazolyl)-2,3-dihydro-benzimid-azol (I 37% Schmp. 170-171°). Fuhrt man die Umsetzung statt bei 20° bei 140° (Ampulle) durch, so isoliert man 2-Benzoyl-1-methyl-benzimidazol (II 92% Schmp. 71 - 72°)417. Das Di-mere I laBt sich thermisch ebenfalls zu 2-Benzoyl-l-methyl-benzimidazol ( 61%) spalten. Die basische Oxidation des Dimeren I liefert dagegen fast quantitativ 1, Y-Dimethyl-2,2-bi-(benzimidazolyl) (III)417. 

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