ABSTRACT
In situ derived acyclic and cyclic 1,2-diaza-1,3-dienes (DDs) were engaged in interceptive [4 + 1] annulation strategy with diazo esters (DEs). The catalytic activity of inexpensive copper(II) chloride allows the direct synthesis of mono-, bi-, and tricyclic 4,5-dihydropyrazole-5-carboxylic acid derivatives in a process that circumvents the use of an anhydrous and inert atmosphere.
ABSTRACT
A novel and simple one-pot synthesis of 3-substituted 2,5,6,7-tetrahydro-1H-1,4-diazepin-2-ones from 1,2-diaza-1,3-dienes (DDs) and N-unsubstituted aliphatic 1,3-diamines is described. Here we also report a procedure to selectively obtain alkyl 5H-1,4-benzodiazepine-3-carboxylates from the DDs and 2-aminobenzylamine. Both processes occur by means of sequential 1,4-conjugated addition followed by regioselective 7-exo cyclization. The behavior of N-methyl- and N,N'-dimethyl-1,3-diaminopropanes toward the DDs furnished pyrazol-3-ones and bis-α-aminohydrazones, respectively.
Subject(s)
Benzodiazepines/chemical synthesis , Chemistry, Pharmaceutical/methods , Diamines/chemical synthesis , Psychotropic Drugs/chemical synthesis , Alkanes/chemistry , Aza Compounds/chemistry , Benzodiazepines/analysis , Carboxylic Acids/chemistry , Chromatography, Thin Layer , Cyclization , Diamines/analysis , Drug Discovery , Humans , Hydrazones/chemical synthesis , Magnetic Resonance Spectroscopy , Molecular Mimicry , Peptides/chemistry , Psychotropic Drugs/analysis , Pyrazolones/chemical synthesis , StereoisomerismABSTRACT
1,2-Diaza-1,3-dienes (DDs) react as Michael acceptors with primary amines to afford α-aminohydrazone derivatives that were in situ coupled with isocyanates. Intramolecular ring closure of the asymmetric urea derivatives so formed allows for a selectively substituted hydantoin ring to be obtained. The hydrazone side chain introduced by the conjugated heterodiene system at the 5-position of the heterocycle represents a valuable functionality for accessing novel 5-acyl derivatives difficult to obtain by other methods.
Subject(s)
Alkenes/chemistry , Amines/chemistry , Aza Compounds/chemistry , Hydantoins/chemical synthesis , Catalysis , Combinatorial Chemistry Techniques , Hydantoins/chemistry , Molecular StructureABSTRACT
The kinetics of the reactions of 1,2-diaza-1,3-dienes 1 with acceptor-substituted carbanions 2 have been studied at 20 °C. The reactions follow a second-order rate law, and can be described by the linear free energy relationship log k(20 °C)=s(N+E) [Eq.â (1)]. With Equation (1) and the known nucleophile-specific parameters N and s for the carbanions, the electrophilicity parameters E of the 1,2-diaza-1,3-dienes 1 were determined. With E parameters in the range of -13.3 to -15.4, the electrophilic reactivities of 1a-d are comparable to those of benzylidenemalononitriles, 2-benzylideneindan-1,3-diones, and benzylidenebarbituric acids. The experimental second-order rate constants for the reactions of 1a-d with amines 3 and triarylphosphines 4 agreed with those calculated from E, N, and s, indicating the applicability of the linear free energy relationship [Eq.â (1)] for predicting potential nucleophilic reaction partners of 1,2-diaza-1,3-dienes 1. Enamines 5 react up to 10(2) to 10(3) times faster with compounds 1 than predicted by Equation (1), indicating a change of mechanism, which becomes obvious in the reactions of 1 with enol ethers.
