Synthesis of monocyclic diaziridines and their fused derivatives

Abstract

Diaziridines and their fused analogues have a wide-range potential as a test subjects for theoretical and practical application. This review covers our investigations focused on the development of optimal methods for the synthesis of monocyclic and fused diaziridine derivatives. Several approaches to the preparation of monocyclic diaziridine derivatives were developed: (1) a synthesis of 3,3-di-and 1,3,3-trialkylmono-and α,ω-bis(diaziridin-1-yl)alkanes from ketoxime O-sulfonates and ammonia, and primary aliphatic amines, respectively, as well as of practically previously inaccessible 3-monoalkyldiaziridines from ammonium salts of aldoxime O-sulfonic acids and ammonia (2) a synthesis of diaziridines from carbonyl compounds, primary aliphatic amines, and aminating reagents in water (or a water-MeOH mixture) at controlled pH of the medium, as well as from carbonyl compounds, amines and N-chloroalkylamines in aprotic solvents in the presence of K 2 CO 3, and (3) a synthesis of 1,2,3-trialkyldiaziridines from Nchloroalkylamines without carbonyl compounds in the presence of primary aliphatic amines at high pressure. As regards fused diaziridine derivatives, general and simple methods were developed to prepare four types of these structures: 1,5-diazabicyclo[3.1.0]hexanes, 1,6-diazabicyclo[4.1.0]heptanes, 1,3,5-triazabicyclo[3.1.0] hexanes, including the parent compound and 2,4-nonsubstituted structures, and 1,3,6-triazabicyclo[3.1.0]hexanes, the latter being previously unknown. The diastereomers have been isolated for 3,3′-bi-and 1,1′-alkylenebisdiaziridines. As a whole the investigations performed in our laboratory have resulted in the simple and general methods for preparing any kind of monocyclic and fused diaziridine derivatives that give high opportunities in the study of their chemical and stereochemical properties, and applications.

New Trends in Diaziridine Formation and Transformation (a Review)

“…Three key approaches are known for the construction of monocyclic diaziridines 4, and these were summarized by Makhova et al in their previous 2008 review of diaziridine (Figure 2) [20]. First, the reaction of primary aliphatic amines or ammonia 5 with the condensation products of carbonyl compounds 6 and aminating reagents.…”

“…A possible pathway for this is through the generation of carbenium-iminium cations, which subsequently react with the aminating reagent (HOSA) to form an intermediate compound of an aminal type. The presence of base would rapidly cyclize this intermediate to result in diaziridine [20]. The addition of base to the process was followed by diastereoselective synthesis of N-monosubstituted diaziridines coupled with neurotransmitter amino acid 102 [86].…”

“…As for N,N-disubstituted diaziridine 3, these valuable heterocycles have also been used as a versatile reagent via selective C-N or N-N cleavage in organic synthesis, particularly their bicyclic analogues of 1,5-diazabicyclo[3.1.0]-hexanes, which possess a strained cis-N,Ndisubstituted diaziridine fragment for 1,3-dipolar cycloaddition [17]. The advancements in substituted diaziridine with respect to its nitrogen atom(s) synthesis and applications have been summarized in several reviews [3][4][5][18][19][20]. On the basis of these excellent reviews, only a few studies have been fully dedicated to investigating the potential properties diaziridine with respect to its monocyclic synthetic methods [20] or its reactivity of these excellent reviews, only a few studies have been fully dedicated to investigating the potential properties diaziridine with respect to its monocyclic synthetic methods [20] or its reactivity towards electrophilic reagents [5].…”

“…The advancements in substituted diaziridine with respect to its nitrogen atom(s) synthesis and applications have been summarized in several reviews [3][4][5][18][19][20]. On the basis of these excellent reviews, only a few studies have been fully dedicated to investigating the potential properties diaziridine with respect to its monocyclic synthetic methods [20] or its reactivity of these excellent reviews, only a few studies have been fully dedicated to investigating the potential properties diaziridine with respect to its monocyclic synthetic methods [20] or its reactivity towards electrophilic reagents [5]. Here in this review, the scope is limited to the current formation and transformation of diaziridines.…”

Recent Advances in the Preparations and Synthetic Applications of Oxaziridines and Diaziridines

“…Similarly, preparations and synthetic applications of diaziridines were reviewed by Makhova et al. in 2008 and in 2011 [2a,b] . Despite few more articles [2c–e] were reported independently by Lumb and Makhova, discussing various features of diaziridines, including structural and biological applications, the comprehensive account on the synthesis and applications were not accounted post 2011.…”