Diazirines synthesis

An extension of the Graham method of diazirine synthesis has enabled the first synthesis of 3-carboalkoxy-3-halodiazirines (e.g., 76) <2004JOC7359>. Conversion of the amidines 74a and 74b into the corresponding N,N,N -trichloroamidines 75a and 75b was achieved through successive chlorination steps reductive dechlorination with bromide or chloride gave the diazirines 76a and 76b (Scheme 26). 

Work on diazirine synthesis during the last 10 years has not led to fundamentally new ways either of diaziridine formation or of diaziridine dehydrogenation, in spite of the remarkable volume of synthetic activity, for example, in the search for biologically active diazirines. 

Besides the dehydrogenation agents silver oxide and bichromate, described in the first papers on diazirine synthesis, there has been application of bromine, iodine, and t-butyl hypochlorite. Chloramine, which is used as aminating agent in diaziridine synthesis, may act as a dehydrogenating agent when applied in excess, e.g., in reactions of simple aliphatic ketones or steroid ketones. ... 

The synthetic activity in the steroid field was followed by extensive investigations on diazirine synthesis in other classes of compounds. For example, diazirines of type 152 were prepared, where X stands for the hydroxy group, a carboxyl group or derivatives of amino groups, ... 

It is interesting to note that the existence of an isomer of diazomethane with a diazirine structure was never discussed, so the report on its synthesis 61TL612) simultaneously started and ended the discussion on its existence. 

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). 

The chemical inertness of the three-membered ring permitted many conversions of functional groups in diazirines. Esterifications, cleavage of esters and acetals, synthesis of acid chlorides, oxidation of hydroxy groups to carboxyl groups as well as Hofmann alkenation all left the three-membered ring intact (79AHC(24)63). 

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. 

ESR spectra, 7, 19 Diaziridinyl radicals ESR, 7, 202 reactions, 7, 19 Diazirine, alkyl-photolysis, 7, 225-226 synthesis... 

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

Graham recently reported a second synthesis of diazirine [Eq, (57)]. The yield reached 62%. 

One example of a naturally occurring diazirine, duazomycin A (137 Scheme 11.20), has been reported, isolated in 1985 from a Streptomyces species during a screen for herbicidal compounds [196], It was fotind to inhibit de novo starch synthesis and it was suggested that this is due to direct inhibition of protein synthesis. Duazomycin A is structurally related to 6-diazo-5-oxo-L-norleucine (138), also reported as a natural product from Streptomyces [197], which acts as a glutamine antagonist and inhibits purine biosynthesis [198],... 

Chen, F.-Q., et al. (1994). Synthesis and preliminary chemi- and bioluminescence studies of a novel photolabile coelenterazine analogue with a trifluoromethyl diazirine group. Chem. Commun. 2405-2406. 

It has been found that the catalytic activity of PKC is enhanced by a lipid component of the cell membrane, namely phosphatidylserine. This activity is further stimulated by sn-1,2-diacylglycerol. Oleic acid also activates the enzyme in the presence of 1,2-diacylglycerol, and thus it is presumed to mimic phosphatidylserine. In order to identify that modulating binding site for oleic acid on PKC, a photoaffinity analogue was devised. A carbene generating photophore, diazirine was placed in the apolar terminus of the unsaturated fatty acid ligand (30, Fig. 12). The synthesis and the photochemical activation properties were reported by Ruhmann and Wentrup [113]. 

Vasella et al. introduced an approach to glycoside synthesis using the glycosylidene carbene generated from the diazirine sugar as a novel type of glycosyl donor. The... 

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],... 

Diazirines are the cyclic isomers of the alphatic diazo compounds. Both the diaziridines and the diazirines are starting materials for the synthesis of alkyl hydrazines. 3,3-Pentamethyl-enediaziridine can be hydrolyzed quantitatively to hydrazine. Methylamine may be substituted for ammonia in the procedure resulting in l-methyl-3,3-pentamethylenediaziridine (m.p. 35-36°, yield 62% of theoretical) and then methyl hydrazine. Use of ethylenediamine leads to ethylene bis-hydrazine via a bifunctional diaziridine (m.p. 143-144°, yield 48% of theoretical). Ammonia can also be replaced by w-propylamine or cydo-hexylamine cyclohexanone by acetone. 

Thermolysis of aryl chloro diazirine (18) in the presence of acetone and a trapping agent such as A -phenylmaleimide gave rise to cycloadducts such as 41. The unstable adduct hydrolyzed during purification resulting in synthesis of bicyclic hemiacetals 42 and 43 as a mixture of endo and exo adducts in 37 and 8% yield, respectively. The exclusive generation of the singlet carbene was confirmed by low-temperature electron spin resonance (ESR) study of the irradiated diazirine. 

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