Chlorin building blocks incorporating a geminal dimethyl group in the reduced ring and synthetic handles in specific patterns at the perimeter of the macrocycle are expected to have utility in biomimetic and materials chemistry. A prior route employed condensation of a dihydrodipyrrin (Western half) and a bromodipyrromethane-monocarbinol (Eastern half), followed by oxidative cyclization of the putative dihydrobilene-a to form the meso-substituted zinc chlorin in yields of approximately 10%. The limited stability of the dihydrodipyrrin precluded study of the chlorin-forming process. We now have refined this methodology. A tetrahydrodipyrrin Western half (2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin) has been synthesized and found to be quite stable. The condensation of the Western half and an Eastern half (100 mM each) proceeded smoothly in CH(3)CN containing 100 mM TFA at room temperature for 30 min. The resulting linear tetrapyrrole, a 2,3,4,5-tetrahydrobilene-a, also is quite stable, enabling study of the conversion to chlorin. Refined conditions for the oxidative cyclization were found to include the following: the tetrahydrobilene-a (10 mM), AgTf (3-5 molar equiv), Zn(OAc)(2) (15 molar equiv), and 2,2,6,6-tetramethylpiperidine (15 molar equiv) in CH(3)CN at reflux exposed to air for 4-6 h, affording the zinc chlorin. The chlorin-forming process could be implemented in either a two-flask process or a one-flask process. The two-flask process was applied to form six zinc chlorins bearing substituents such as pentafluorophenyl, 3,5-di-tert-butylphenyl, TMS-ethyl benzoate, iodophenyl, or ethynylphenyl (deprotection of the TMS-ethynyl group occurred during the oxidative cyclization process). The stepwise yields (isolated) for the condensation and oxidative cyclization processes forming the tetrahydrobilene and zinc chlorin were 32-72% and 27-62%, respectively, giving overall yields of zinc chlorin from the Eastern and Western halves of 12-45%. Taken together, the refinements introduced enable 100-mg quantities of chlorin building blocks to be prepared in a facile and rational manner.
Treatment of N-acetoxy-N-alkoxyamides or N-alkoxy-N-chloroamides with sodium azide in aqueous acetonitrile results in S N 2 displacement of chloride and the formation of reactive N-alkoxy-N-azidoamides. The reaction with N-acetoxy-N-benzyloxybenzamide has been studied kinetically (k 294 = 2 L mol Ϫ1 s Ϫ1 ) and azidation of N-formyloxy-N-methoxyformamide has been modeled computationally at the pBP/DN*//HF/6-31G* level of theory. The anomeric amides N-alkoxy-N-azidoamides decompose intramolecularly and spontaneously to esters and two equivalents of nitrogen. This extremely exothermic process facilitates the formation, in excellent yields, of highly hindered esters.
N,NЈ-Diacyl-N,NЈ-dialkoxyhydrazines are HERON amides that exhibit theoretical and physical properties of bisheteroatom-substituted amides. Amide nitrogens are pyramidal and they adopt a preferential conformation which permits an anomeric interaction in which one nitrogen overlaps strongly with the adjacent N-O σ* orbital. A crystal structure of N,NЈ-di(p-chlorobenzoyl)-N,NЈ-diethoxyhydrazine 4d has been obtained which confirms these properties in the solid state. Infrared data for ten such hydrazines indicate unusually high carbonyl stretch frequencies in accord with pyramidality at nitrogen. Diastereotopic resonances and dynamic 1 H NMR studies indicate both a significant N-N rotational barrier of between 65 and 72 kJ mol Ϫ1 , which is consistent with a strong anomeric interaction, as well as a much smaller than usual amide rotation barrier of 54 kJ mol Ϫ1 , a direct consequence of pyramidality at nitrogen.
Abstract:The origin of the HERON reaction is reviewed from a historical perspective and shown to have its foundation in the unusual properties of bisheteroatom-substituted amides, so-called anomeric amides. The reaction involves migration of anomerically destabilized oxo-substituents on an amide nitrogen to the amide carbon and dissociation of the amide bond. Computational work providing a theoretical basis for the reaction is presented, together with physical organic measurements that support results therefrom. The rearrangement has been observed in a number of chemical transformations of N-alkoxy-N-aminoamides, reactions of 1-acyloxy-1-alkoxydiazenes, N-alkoxy-N-aminocarbamates, Nalkoxyhydroxamic acids, as well as in the gas-phase reactions of N-acyloxy-N-alkoxyamides.Key words: HERON reaction, anomeric amides, rearrangements, hindered esters, concerted reactions. Résumé :On a fait une revue historique de l'origine de la réaction HERON et on montre que sa base réside dans les propriétés inhabituelles des amides portant des substituants bishétéroatomiques, les amides dits anomères. La réaction implique la migration de substituants oxo anomériquement déstabilisée de l'azote d'un amide vers le carbone de l'amide accompagnée d'une dissociation de la liaison amide. On présente un ensemble de calculs théoriques qui sert de base pour expliquer la réaction ainsi que des mesures de chimie organique physique qui supportent les résultats de ces calculs. Le réarrangement a été observé dans un certain nombre de transformations chimiques de N-alkoxy-N-aminoamides, dans les réactions de 1-acyloxy-1-alkyoxydiazènes, de N-alkoxy-N-aminocarbamates et d'acides N-alkoxyhydroxamiques ainsi que dans les réactions en phase gazeuse de N-acyloxy-N-alkoxyamides.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.