Ketones diazirine

Diaziridines (156) unsubstituted on both nitrogens decompose at 125 °C by a redox reaction yielding one mole of a diazirine (157) together with two moles of ammonia and one mole of ketone from two moles of (156). The reaction proceeds below 60 °C when copper salts are present (64AG(E)229). 

By similar procedures diazirines were prepared not only from simple aliphatic ketones but also from hydroxyketones and )3-aminoketones (B-67MI50800), and so were a large number of diazirines from steroidal ketones (65JA2665). Permanganate, bromine, chlorine and hypochlorite were used as oxidants. A one-step preparation of diazirines from ketones like 3-nonanone, ammonia and chlorine has been claimed in a patent (66USP3290289). 3,3-Diazirinedicarboxylic acid derivatives like (286) were obtained directly from oxime tosylates by the action of two moles of O-ethoxyamine (81AG(E)200). 

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. 

The photolysis of cyclic diazo ketones in hydroxylic solvents leads to ring contracted carboxylic acid derivatives via this ketocarbene -> ketene rearrangement. Examples of such reactions are given in (2.24)239) and (2.25) 240). In this last example a photoequilibrium between the diazo ketone and its valence isomer, a diazirine, has been observed, both products then eliminating nitrogen to afford the cyclobutane carboxylic acid. 

Diaminourea, c9 Diamylamine, d737 Diamyl ether, d738 Diamyl ketone, ull Diazirine, d63... 

The synthetic scheme often applied for the preparation of 3-aryl-3-(trifluoromethyl)-3//-diazirine nowadays is shown in Scheme 5a [60]. It starts by lithiation of an aryl bromide (38), which subsequently reacts with /V-ftrifluoroacetyl)piperidine 39 (easily prepared from trifluoroacetic anhydride and piperidine) under the formation of trifluoroacetophenone 40. Next, the ketone is converted into the corresponding oxime 41, after which the hydroxyl group is converted into its tosylate (42). Reaction with liquid ammonia (usually under pressure) allows the installment of the diaziridine group (43). Subsequent oxidation with iodine finally results in the diazirine (44). This five-step reaction sequence is especially compatible with acid-labile protective groups, which are often used to protect and/or install functionalities at the R position. 

Only a few years have elapsed since the first synthesis of the diazirines. In this short time considerable effort has been expended on trying to elucidate the photochemical reactions of these compounds. These reactions are of intrinsic interest not only because they represent a new field of investigation for gas-phase photochemists (providing an escape from the well-worked ketone field) but because they provide another... 

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. ... 

Whereas the diazirine group survives almost all chemical operations going on at suitable distances from it, it is very sensitive to all operations producing a partial positive charge at a carbon atom adjacent to the three-membered ring. The oxidation of a-hydroxydiazirines, e.g., 153, succeeds only under very mild conditions and leads to ketones very sensitive toward acids. ° Dilute acid transforms 154 at room temperature with nitrogen elimination to a mixture of cyclopentane carboxylic acid and methylene-cyclopentanone. 

So far, however, the attractive potentialities of diazirines to act as carbene precursors have not been exploited to the full. In the steroid field, ketones have been transformed to olefins via diazirines 172 yielded the A -compound preferentially. Pyrolysis of spirodiazirine 173 at 320°C yielded 96% dehydroadamantane 174. ... 

Diaziridines and diazirines [1,483]. A Lederle group13 investigated the reaction of hydroxylamine-O-sulfonic acid with steroid ketones and found that only noncon-jugated 2(5a)-ketones and 3(5a or 5/3)-ketones react. A4-3-Ketosteroids, 17-keto-steroids, and 20-ketosteroids were found unreactive. A solution of 502 mg. of 17a-methyl-5a-androstane-17/3-ol-3-one (1) in methanol was saturated with ammonia at 2° and treated with 236 mg. of hydroxylamine-O-sulfonic acid, added in small portions. The diaziridine (2) was oxidized with silver oxide in ether in practically quantitative yield to the diazirine (3). 

Three-membered rings with two heteroatoms are usually encountered only as reagents. Diazirines are nsefnl carbene precnrsors" - they are generally more stable than the equivalent isomeric diazo compounds, thongh they are sometimes explosive in the pure state. They can be prepared by oxidation of diaziridines that, in tnm, are available via the condensation of a ketone or aldehyde with ammonia and chloramine. Chloro-diazirines, from the reaction of amidines with hypochlorite, wiU undergo Sn2 or Sn2 displacement reactions."" ... 

In 1960, however, Paulsen and, in the following years, Schmitz and Ohme (1961 a-c), and Graham (1962) achieved the first synthesis of diazirine. As Scheme (5-14) shows, they used methods that are completely independent of diazomethane. With ammonia and hydroxylamine-O-sulfonic acid (or NH2CI with an oxidant such as tert-h xiy hypochlorite, -C4H90C1), formaldehyde (for mono-and disubstituted diazirines other aldehydes and ketones, respectively) forms diaziridine (5.61, originally called an isohydrazone), which is then dehydrogenated to diazirine with silver oxide or bichromate (5-14). 

Valence isomerizations of a-diazo ketones and the corresponding diazirines are also known. A particularly instructive case is the system 3-diazoindolin-2-one (5.71a) spiro[diazirine-3,3 -indoline]-2 -one (5.72a), and A -methyl derivatives, which were investigated by Voigt and Meier (1975). 

Most of the work concerning the modification of carbene reactivity has been performed on cyclodextrins (CD) with reactive alkyl carbenes. Diazirines have proven to be the most convenient precursors due to the small size of the three-membered ring and the volatility of the leaving group, molecular nitrogen. Diazirines are usually obtained from the corresponding ketone in two steps in a methanolic solution of ammonia, hydroxylamine-0-sulfonic acid (HOSA) is added yielding a diaziridine which then is oxidized to the diazirine, most conveniently with iodine. 

Diaziridines unsubstituted on the N-atoms can be oxidized to give 3H-diazirines. Diaziridines are prepared by the action of ammonia and chlorine on ketones. Primarily, chloramine is formed ... 

Disregarding inconsistencies in the natural fluorescence rate constants, it is important to note that aliphatic ketones (biacetyl and acetone) as well as several cis-azoalkanes show fluorescence in solution [81], This includes not only the examples of DBH-T [47,98] and DBO [56,103,138] (see Structnre 3.1), but also the smaller derivatives (see Structure 3.2) 2,3-diazabicyclo[2.1.1]hex-2-ene [139], diazirines, e.g., adamantyldiazirine [140], and even some sterically hindered azobenzenes [141], In contrast, DBH is not flnorescent with the exception of a report in siliceous zeohtes [66] it undergoes denitrogenation with unit quantum efficiency from the... 

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