New Synthetic Approaches to Functionally Substituted 4,5-Dihydro-1,2,3-oxadiazole 2-Oxides

Abstract

A practical procedure has been proposed for the synthesis of functionally substituted 4,5-dihydro-1,2,3-oxadiazole 2-oxides on the basis of sulfamic acid derivatives.Functionally substituted 4,5-dihydro-1,2,3-oxadiazole 2-oxides were synthesized for the first time by alkaline hydrolysis of the corresponding N-nitrosulfamides [1,2] or functionalized N-nitro-2-cyanoethylalkylamines [3]. In both cases, the initial materials were difficultly accessible compounds. Taking into account recent data, such compounds attract interest as nitrogen oxide donors [4], as well as components of gas-generating compositions.The goal of the present work was to develop a practical procedure for the preparation of both previously known and new functionally substituted 4,5-dihydro-1,2,3-oxadiazole 2-oxides. We previously studied in detail reactions of sulfamic acid salts with epoxy derivatives [5,6] and found that this transformation can be used to obtain a wide series of the corresponding N-(2-hydroxyalkyl)sulfamates (compounds IaIc and Ie) in high yields. Some compounds I can be subjected to further modification. For example, by nucleophilic substitution of the chlorine atom in Ic we obtained compounds Id and If (Scheme 1). The latter were brought into further syntheses without additional purification, for it was difficult to separate them from inorganic salts.The next stage of our study was aimed at selecting optimal conditions for nitration of compounds I. The nitration was performed using a mixture of nitric and sulfuric acids. Only in the reaction with N-(3-azido-2-hydroxypropyl)sulfamate Id we used a mixture of nitric acid and acetic anhydride to avoid replacement of the azido group by nitrate moiety. The yields of the corresponding N-nitro amines II varied from 70 to 90%. Nitroamines II were then converted into ammonium salts III by saturation of their solutions in diethyl ether with gaseous ammonia. It should be emphasized that this stage was simultaneously the final stage of purification of compounds II from nitrolysis products. Salts III were subjected to cyclization in methanol in the presence of an equimolar amount of alkali or in the absence of it. As a result, we isolated a series of 4,5-dihydro-1,2,3-oxadiazole 2-oxides IV having functional substituents in the 5-position; the overall yield was about 50% (Scheme 2). +1 &+ &+&+ &O 62 0 2+ ,F 1D1 &+ 1+62 0 2+ +1 &+ &+&+ 1 62 0 2+ ,G +1 &+ &+&+ 1&+ 62 0 2+ 62 0 ,I '0) +1 &+ &+5 62 0 2+ ,D B ,I 12 +1 &+ &+5 12 212 ,,D B ,,I 1+ 1 1 2 5 2+ 0H2+ 2 ,9D B ,9I 1+ 1 1&+ &+5 2 2 212,,,D B ,,,I M = Na, K; R = R' = H (a), CH 2 OCH 3 (b), CH 2 Cl (c), CH 2 N 3 (d); R = CH 2 OH, R' = CH 2 ONO 2 (e); R = CH 2 N(SO 3 M)CH 3 , R' = CH 2 N(NO 2 )CH 3 (f). M = Na, K. Scheme 1. Scheme 2.

Oxadiazoles

“…Recently, a new synthetic approach to functionally substituted 4,5-dihydro-1,2,3-oxadiazolo 2-oxides 34 has been described, starting from sulfamic acid derivatives 33 (Scheme 13.8) [26]. 72-88% R = n-C 8 H 17 , Ph, -(CH 2 ) 3 OBn, -CH 2 OCH 2 CCPh CH 2 N(p-Ts)CH 2 CHCH 2 Scheme 13.6…”

Sulfamic Acid and Its N- and O-Substituted Derivatives

“…N-Substituted aminomethyl-1,4-dioxane 30 and 2,5-bis(aminomethyl)-1,4-dioxane 31 have been prepared in generally good yields by cyclization of the corresponding potassium N-[3-(2-chloroethoxy)-2hydroxypropyl]sulfamates 32. 135 Cyclodehydration of potassium dihydroxyalkylsulfamates in concentrated H 2 SO 4 gave 2-substituted morpholines and 1,4oxazepines, 136 nitration of 2-hydroxyalkylsulfamates, and subsequent conversion of the nitroamines formed into ammonium salts followed by cyclization in methanolic alkali gave 4,5dihydro-1,2,3-oxadiazole 2-oxides 33 137 in moderate yield and reaction of 2-hydroxyethylsulfamate and 2-substituted acetaldehydes gave rise to N-nitrooxazolidines 34. 138 Dinitramidic acid and its ammonium salt have been prepared by nitration of ammonium sulfamate with fuming HNO 3 using solid acid catalysts such as montmorillonite clay.…”

“…Cyclodehydration of potassium dihydroxyalkylsulfamates in concentrated H 2 SO 4 gave 2-substituted morpholines and 1,4-oxazepines, nitration of 2-hydroxyalkylsulfamates, and subsequent conversion of the nitroamines formed into ammonium salts followed by cyclization in methanolic alkali gave 4,5-dihydro-1,2,3-oxadiazole 2-oxides 33 in moderate yield and reaction of 2-hydroxyethylsulfamate and 2-substituted acetaldehydes gave rise to N -nitrooxazolidines 34 …”

Aliphatic nitramino alcohols and their derivatives

“…91 Another promising starting com pound is 2 nitroxyethylnitramine, which is easily accessi ble by the nitration of N (2 hydroxyethyl)sulfamic acid with a mixture of nitric and sulfuric acids. 92, 93 2 Nitroxyethylnitramines with polynitroalkyl substi tuents at the nitrogen atom of the amino group are high energy blasting powders. The typical representatives of this group are 1,1,1,3 tetranitro 6 nitroxy 3 azahexane 8 and 1,1,1,3 tetranitro 6 nitroxy 5,5 bis(nitroxymethyl) 3 azahexane.…”