Author: Dylan Innes
Innes, Dylan, 2020 Synthesis and reactivity of novel molecular scaffolds from N,N-Dialkyl-N'-Chlorosulfonyl Chloroformamidines, Flinders University, College of Science and Engineering
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This research represents an extension to an expanding body of work on the use of
N,N-dialkyl-N0-chlorosulfonyl chloroformamidines (1) to generate novel, low molecular
weight heterocyclic compounds. The regioselective reactions of 1 with the 1,3-N-C-Cbis-
nucleophilic 1H-benzimidazole-2-ylacetonitriles 94 and related compounds produced the
benzo[4,5]imidazo[1,2-b][1,2,6]thiadiazine dioxides 96, 117, 119a and 121, all of which are
representatives of a new ring system. Reaction of the dichlorides 1 with the trifluoroacetyl
derivative 107 afforded benzo[4,5]imidazo[1,2-c]pyrimidines 127 and 128. An N-acyl and
some N-alkyl derivatives of benzimidazo-thiadiazines 96 were prepared to demonstrate the
potential of this new ring system as a novel scaffold for synthetic and medicinal chemistry
applications. Treatment of the 4-cyano-5-methyl-benzimidazo-thiadiazine 135c with LiAlH4
resulted in an unexpected and remarkable conversion of the nitrile to give the 4,5-dimethylbenzimidazo-
thiadiazine 142.
The N,N-dimethyl-N0-chlorosulfonyl chloroformamidine 1a also underwent reactions with
various anilines. In addition to the benzo[e][1,2,4]thiadiazine dioxides 29 and bis-anilino
adducts 145, some unexpected products were formed, particularly when sterically hindered
or electron-poor anilines were used. In these cases, products such as the [1,3,2,4,6]dithiatriazine
1,1,3,3-tetraoxides 151 and occassionally, the N,N,5-trimethyl-4-(arylimino)-4,5-
dihydro-[1,3,5]triazin-2-amines 149 were produced in significant yields. Reaction of the
dichloride compound 1a with 3-bromoaniline afforded the unusual eight-membered-ring
product 2,6-bis(3-bromophenyl)-3,7-bis(dimethylamino)2H,6H-[1,5,2,4,6,8]dithiatetrazocine
1,1,5,5-tetraoxide 163, in addition to the dithiatriazine tetraoxide 151l.
A brief investigation into the reactions between the N,N-dialkyl-N0-chlorosulfonyl chloroformamidines
(1) and the 1H-benzimidazol-2-yl-2-methylamines 95 as 1,4-N-C-C-N
bis-nucleophiles produced the first derivatives of the new benzo[4,5]imidazo[2,1-f ]-
[1,2,4,7]thiatriazepine 1,1-dioxide ring system 98. The potential for this new ring system
as a novel scaffold was demonstrated by reaction of 98b with 4-chlorobenzylbromide to afford
the alkylated product 167. Compounds 98 represent the first optically active compounds to be
produced from the dichlorides 1.
All of these uncommon heterocyclic structures are of interest for bioactive molecule discovery
screening programs.
Keywords: N,N-dialkyl-N'-chlorosulfonyl chloroformamidines, heterocyclic, benzimidazole, aniline, thiadiazine
Subject: Chemistry thesis
Thesis type: Doctor of Philosophy
Completed: 2020
School: College of Science and Engineering
Supervisor: Michael Perkins