Diazirine compounds

Diazirine and several of its 3-substituted homologues, formally cyclic azo compounds, are explosive on heating or impact [1]. The shock-sensitivity of all diazirine compounds and the inadvisability of their handling in the undiluted state have again been stressed [2], In a description of the synthesis of 27 3-(4-substituted)halodiazirines, the need is stressed to handle the compounds at below 30°C to prevent thermal decomposition, or, for the pure compounds, explosion [3],... 

The original investigators of the diazirine compound shown in Fig. 6.22 claim that the following features can be found in that figure ... 

Carbene generation from photolysis of diazirine compounds leads to efficient insertion into C—H or N—H bonds and also causes addition reactions with points of unsaturation within target molecules. Diazirine-containing photoaffinity probes have... 

Trifluoromethyl Imines, Oximes, Hydrazones, Imidoyl Chlorides, Nitrones, Diazo and Diazirine Compounds... 

Derivatives of Cgo for photoaffinity labelling studies have been synthesized, including the cis and treats diazirine compounds (21a). The photochemical properties of these are currently being studied in various applications. An... 

All the thermal protocols discussed above initially form singlet carbenes, as do the photolysis of diazo and diazirine compounds. For cases where the triplet is the ground state, relaxation to the triplet state can occur in competition with additions and insertions. In addition, it is possible to use a photochemical sensitizer (see Chapter 16) to produce a triplet state directly. Here, the sensitizer is a photo-excited triplet state of an additive that transfers its energy to the carbene precursor, creating the triplet carbene directly. 

Whereas oxaziridine and diaziridine were partial subjects of comprehensive theoretical studies on cyclic compounds (73MI50800), diazirine and some of its simple derivatives were the special target of quantum chemical investigations. Since diazirine, the lowest molecular weight heterocycle, has only five atoms and is of high symmetry, there was a chance for ab initio calculations, which followed some semiempirical studies. 

Even more recent calculations using STO-3G and 6-31G basis sets could not safely predict diazomethane as the more stable compound in comparison with diazirine, although there is an experimental energy difference of 125 kJ moP 79JST(52)275). 

The energy difference between diazirine and diazomethane, interesting from the point of view of their isomerism, came from MS measurements (63JCP(39)3534). The appearance potentials of the CH2 ion, common to both compounds, yielded a difference in heats of formation of 125kJmor A strong peak in the mass spectrum of 3-chloro-3-methyl-diazirine (50) with relative mass 55 was ascribed to the methyldiazirinium ion (51). 

It was not their reactivity but their chemical inertness that was the true surprise when diazirines were discovered in 1960. Thus they are in marked contrast to the known linear diazo compounds which are characterized by the multiplicity of their reactions. For example, cycloadditions were never observed with the diazirines. Especially surprising is the inertness of diazirines towards electrophiles. Strong oxidants used in their synthesis like dichromate, bromine, chlorine or hypochlorite are without action on diazirines. Diazirine formation may even proceed by oxidative dealkylation of a diaziridine nitrogen in (186) without destruction of the diazirine ring (75ZOR2221). The diazirine ring is inert towards ozone simple diazirines are decomposed only by more than 80% sulfuric acid (B-67MI50800). 

Diazirines (3) smoothly add Grignard compounds to the N—N double bond, giving 1-alkyldiaziridines. Reported yields are between 60 and 95% without optimization (B-67MI50800). The reaction is easily carried out on a preparative scale without isolation of the hazardous diazirines and may serve as an easy access to alkylhydrazines. The reaction was also used routinely to detect diazirines in mixtures. The diaziridines formed are easily detected by their reaction with iodide. Phenyllithium or ethylzinc iodide also add to (3) with diaziridine formation. 

Photolytic transformation of diazirines to diazoalkanes was observed in some cases. The parent compound (44) on irradiation in the gas phase with light (A = 3200 A) yields diazomethane. The quantum yield is 0.2 (64JA292). 

Thermal conversion of diazirines to linear diazo compounds was postulated occasionally and proved by indirect methods. The existence of a diazo compound isomeric to diazirine (197) was proved spectroscopically on short thermolysis in DMSO (76JA6416). An intermediate diazoalkane was trapped by reaction with acetic acid, yielding the ester (198) (77JCS(P2)1214). 

Methylvinyldiazirine (199) rearranges at room temperature in the course of some days. Formation of the linear isomer is followed by electrocyclic ring closure to give 3-methyl-pyrazole. The linear diazo compound could be trapped by its reaction with acids to form esters, while the starting diazirine (199) is inert towards acids (B-71MI50801). 

A formal ring enlargement of diazirines to five-membered rings is also observed with some hydrazones of ketodiazirines (65CB2509). On attempted preparation of hydrazones (201) from ketodiazirine (200) at 0 C the diazo compounds (202) are plausible intermediates since their transformation to aminotriazoles (203) is known. 

There are some reports on reactions involving complete N—N cleavage in diazirine reactions such as formation of amidine (205) from chlorophenyldiazirine, or on formation of products containing only one nitrogen atom. Betaine (206) was described as a product from difluorodiazirine and triphenylphosphine. Compound (207) is formed from decomposing (204) and cyclohexane (79AHC(24)63). 

Diazirines are in most cases more easily available than linear diazo compounds. Moreover, their decomposition via true carbenes is free of side reactions, whereas linear diazo compounds in presence of H-donors may react by a cationic pathway. Only where reactions of linear diazo compounds are optimized for carbene formation do they give the same products as do decomposing diazirines. 

Photolysis of dlazirines to nitrogen and carbenes is a general reaction and plays a greater role in carbene chemistry than photolysis of linear diazo compounds. Whereas the latter are often obtained only under the conditions of their thermal decomposition from suitable precursors, diazirines are obtainable in a pure state in most cases. Photolysis has the further advantage to permit nitrogen extrusion at atmospheric pressure, even with low-boiling materials. 

The photolysis of chlorodiazirine was investigated in several cases. From chloromethyl-diazirine (232) vinyl chloride was formed as the stable primary product of stabilization of chloromethylcarbene, with acetylene and hydrogen chloride as secondary products. Some 1,1-dichloroethane was assumed to have been formed through a linear diazo compound by reaction with HCl. Added HBr yielded 1-bromo-l-chloroethane (76MI5Q800). 

Syntheses of alkyldiazirines (287) must start from the diazirinotriazolidines (128) formed from an aldehyde, ammonia and (-butyl hypochlorite. Since the three-membered ring in (128) is much more stable towards acids than the five-membered ring (Section 5.08.3.2.2), the diazirines are obtained by acid hydrolysis of compounds (128) in the presence of an oxidant (62CB795). 

Synthesis of steroidal diazirines has led to some biologically active compounds (65JA2665). The observation that diazirines and their parent ketones are identical in smell (B-67MI50800), points to the possibility that a diazirine group may stand for a keto group vis-d-vis a receptor. 

Diazirine, fluoromethoxy-nitrogen extrusion, 7, 224 Diazirine, methylvinyl-rearrangement, 7, 221 Diazirines addition reactions to Grignard compounds, 7, 2 0 as carbene precursors, 7, 236 IR spectra, 7, 203 microwave spectrum, 7, 199 molecular spectra, 7, 202-204 nitrogen extrusion, 7, 223 NMR, 7, 202 photoconversion to diazoalkanes, 7, 234 photoisomerization, 7, 221 photolysis, 7, 225-227 quantum chemical investigations, 7, 197 reactions... 

Acetylenic Compounds Metal Acetyl ides Haloacetylene derivatives Diazirines... 

Diaziridine Syntheses from Diazirines and Grignard Compounds... 

A further synthesis of 1-alkyl-diaziridines is the addition of Grignard compounds to the NN double bond of diazirines [Eq. (35) ]. The... 

In the discussion on the structure of the aliphatic diazo compounds, the question of the existence of isomeric diazo compounds with three-membered rings was never considered. It wms therefore a surprise when the cyclic diazo compounds, i.e. the diazirines, became known their preparation wms published independently by Paulsen and by Schmitz and Ohme. ... 

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