Aziridine Reaction with azide

The commonest of these for oxirane opening are amines and azide ion [amide ions promote isomerization to allylic alcohols (Section 5.05.3.2.2)]. Reaction with azide can be used in a sequence for converting oxiranes into aziridines (Scheme 49) and this has been employed in the synthesis of the heteroannulenes (57) and (58) (80CB3127, 79AG(E)962). 

Unsubstituted benzyl 4-(9-benzyl-2,3-dideoxy-2,3-epimino-(3-D-/yv o- (341) and -ot-D-n )o-pyranoside (342) have been used by Paulsen and Patt in 1981 in cleavage reactions with azide. By the action of a mixture of sodium azide and ammonium chloride in a butanol-water system, the aziridine-ring cleavage proceeded exclusively at C-3, thus exhibiting anti-Furst-Plattner regioselectivity for both epimines. No explanation for this preference was given in the paper. 

The steroidal JV-cyanoaziridine (546) reacted with a variety of nucleophiles to give rm/i5-diaxial ring-opened products. In the reaction with thiocyanate anion final ring closure occurs to give the thiazolidine (547). An analogous reaction of the aziridine (548) with azide anion, followed by reduction, provides a stereospecific route to trans-diaxidl- 2j9,3a-diaminocholestane (549). Similar reactions of the isomeric iV-benzoylaziridines (550) and (551) provide mixtures of azides and oxazolines. 

More examples of dual-functionalized reagents inclnde the reaction of 2-acyl-aziridines 93 with azides and alkynes. In this case, a three-component synthesis of 2-imino-5-arylidene-3-pyrrolines 94 was achieved snccessfnlly (Scheme 5.61) [61]. 

The azidohydrins obtained by azide ion opening of epoxides, except for those possessing a tertiary hydroxy group, can be readily converted to azido mesylates on treatment with pyridine/methanesulfonyl chloride. Reduction and subsequent aziridine formation results upon reaction with hydrazine/ Raney nickel, lithium aluminum hydride, or sodium borohydride/cobalt(II)... 

When unacylated azides are used as nitrene precursors, the first reaction with an alkene is a cydoaddition, generating the corresponding 1,2,3-triazoline, which often eliminates N2 under the fierce reaction conditions to give an aziridine product (Scheme 4.9 ). 

The ring-opening reactions of aziridines 16 with amines deserve special attention. Unlike ring-openings with the other nucleophiles examined, they do not require added base, and they do not produce stoichiometric byproducts (as with azide). In certain cases, they do not even require a solvent, as exemplified by the ring-opening of aziridine 18 (Table 12.12, entries 1-3). In addition, the reactions... 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

Cycloaddition reactions of dimethyl benzylidenemalonate 262 with azides provide triazolines 263. All compounds 263, except one with R = Ph, are stable in xylene at 110 °C. The phenyl derivative eliminates molecular nitrogen to give dimethyl l,3-diphenylaziridine-2,2-dicarboxylate 264. At elevated temperature, the aziridine system is not... 

In molecules containing two cyclobutenes, addition of organic azides 26 yielded two adducts, e.g. reaction with 50 with benzyl azide 56 produced the cr-isomer 57a in which the (V-benzyl substituents were sy -aligned and the C2-isomer 57b in which they were anti-orientated (Scheme 7). The structure of syn-isomer 57a was confirmed by X-ray (Figure 2). The fact that both isomers yielded the same fns-aziridine 58 upon photolysis made separation of the individual triazoline isomers unnecessary. 

Dichlorocarbene reacts exothermically under soliddiquid two-phase conditions with azides to produce, initially, isocyanide dichlorides, RN=CC12, which can react further to give A-alkyltetrachloroaziridines [50], The aziridines are the major products (60-70%) with simple alkyl azides, but the reaction tends to stop at the isocyanide step (50-60%), when the alkyl group is highly fluorinated. 

In another approach, 2-(alkylamino)alcohol is employed as starting material for aziridine syntheses with the aid of dihalogenophosphoranes (70BCJ1185). Intramolecular transformation of 3-azidopropyloxirane 73 results in a simultaneous formation of a condensed aziridino[l,2-a]pyrrol-idine system (Scheme 39). The azide group is first transformed into imino-phosphorane 74, the nucleophilic N atom cleaves the oxirane to form betaine 75 [as in the Mitsunobu reaction (81S1)], and the phosphorus is shifted from N to O and then eliminated as phosphane oxide under simultaneous cyclization to bicyclic 76 (89JA7500). 

Monocyclic 1,3-oxazepines (325) with aryl substituents at the 2-, 4- and 7-positions can be prepared in moderate yield (20-40%) by the reaction of aliphatic diazo compounds with 1,3-oxazinium perchlorates (324) (74S187). Tetra- and penta-phenyl-l,3-oxazepines (328 R = H or Ph) have been obtained via the reaction of azide with pyrylium salts (326) (78H(l 1)331). This principle had earlier been applied to the preparation of 1,3-benzoxazepines (74CR(C)(278)1389> and more recently to 3,1-benzoxazepines (81JHC847). The preparation of 2-phenyl-1,3-oxazepine.(331) by the UV irradiation of (329) is mechanistically interesting in that it apparently involves an intermediate (330) of the same type as (327) (73TL1835), but the method has only been used in this one case. One of the few examples of a dihydro-1,3-oxazepine (333) has been prepared by the thermolysis of the aziridine (332) (68JOC4547). 

Simple carbon-carbon double bonds react slowly with azides and frequently take more than a week to react at 25 C. Increasing the reaction temperature is restricted by the thermal lability of most triazolines. In fact, some classes of triazolines decompose spontaneously at room temperature with the extrusion of nitrogen.189 The principal decomposition modes involve the formation of aziridines and imines and are outlined in Scheme 55. Usually, just a few of these modes operate in any particular system.190... 

The strained double bonds in Dewar benzene and thiophene make them good dipolarophiles in 1,3-cycloadditions. The hexamethyl,148 1,3,5-trimethyl, and perfluoro-1,3-dimethyl122 Dewar benzenes all yield a monoadduct by reaction with phenyl azide. The hexafluoro derivative, however, gives, depending on the conditions, either a monoadduct (19) or a mixture of mono-and bisadducts accompanied by an aziridine resulting from thermolysis of the triazoline ring system (Scheme 19).146... 

The nitrogen heterocycles, aziridines, can be made by displacement of an alcohol by an amine after activation. In their synthesis of the antitumour and antibiotic compound 30, whose active region is the aziridine, J. P. Michael and group opened the cyclic sulfite 28 with azide ion. Reaction occurred at the allylic position and with inversion. Activation of the alcohol as a mesylate gave 29 and reduction of the azide to an amine was followed by base-catalysed cyclisation, again with inversion.4... 

Similarly to the reaction with diazomethane, [3 + 2] cycloaddition of alkyl azides to C70 affords three constitutionally isomeric adducts (87, 88, and ( )-89) 46.226,227 Thermal elimination of N2 from the fullerene-fused triazolines showed a preference for the formation of 6-5 open azahomofullerene structures (types 90 and ( )-91) as compared to the 6-6 closed aziridine isomers corresponding to 92 and 93 (Scheme 1.9).226,227... 

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