Diazirine Fragmentation

An investigation of the thermal fragmentation of aryldiazirines inside hemicarcerands showed that the walls of hemicarcerands stabilize transition states, if bond breaking 

In an extended study, Sanchez Carrera et al. explored the influence of hanicarcerand shape on the thermolysis of phenyldiazirines. All inner phase transition states were slightly accelerated. Rate constants increase in the order 9049 12049 10049 4049 13049 and vary overall by a factor of 3.2. Again, inner phase transition states where stabilized enthalpically by about 2kcalmor and moderately destabilized entropi-cally. Furthermore, faster rates were observed for hemicarceplexes whose fourth shorter bridge induces a slight kink in the host structure. This was interpreted with an induced flt model and a better ability of the latter hemicarcerands to accommodate the slightly bend transition state. 

---

Figure 9.14 (A) Products and mechanism of diazirine fragmentation. (B) Inner phase...

Further examples and a mechanistic discussion may be found in reference 7. Borrevang10 has reported a closely related fragmentation involving diazirine derivatives of cyclic a,/ epoxyketones. 

Aryl halodiazarines 119 when reduced with potassium ethyl xanthate are reported to give 3-aryl-5-ethoxy-1,2,4-thiadiazoles 120 (13%) along with the expected product benzonitrile (87%) (Equation 31). A mechanism involving fragmentation of the diazirine 119 is proposed <1999TL29>. 

In addition, 18-19% of isobutene and chloroacetylene formed via fragmentation. Photolysis of the diazirine in up to 9 M trimethylethylene in pentane led to a sharp decrease in 27 and 28 (to 32% and 8.5%), along with 40% of cyclopropanes formed via the capture of 19. However, the yield of isobutene and chloroacetylene was unchanged, indicating that these products did not stem from the carbene, but arose directly by fragmentation of its excited diazirine precursor.45... 

When the diazirine was decomposed thermally, avoiding its electronically excited state, the yield of fragmentation products dropped to 1-2%. Further analysis revealed that, under photolytic conditions, cyclobutenes 27 and 28 were formed from both the carbene (63%) and directly from the excited diazirine (17%) fragmentation accounted for the remainder of the material balance. LFP studies by the pyridine ylide method gave rate constants for 19 —> 27 (1.3 x 106 s-1) and 19 — 28 (2.5 x 105 s-1), with the 5-fold preference for CH2 migration to 27 over CMe2 migration to 28 attributed to differential steric effects.45... 

Related observations were reported for frans-r-butylcyclopropylcarbene, 20.46 Photolysis of diazirine 29 in freon-113 gave f-butylcyclobutene, 30 (46-49%), as well as 20% of f-butylethene (and ethene) fragmentation products Scheme 5. 

The great majority of matrix isolation studies of carbenes and nitrenes have employed their formal adducts with molecular nitrogen, that is, diazo compounds or diazirines in the case of carbenes, azides in the case of nitrenes, as precursors for their in situ generation. Usually, these compounds will readily release N2 on irradiation with a low-pressure mercury lamp (254 nm), and this fragment has the advantage that it will usually not react with or perturb the targeted reactive intermediate (see Scheme 17.2). 

Further examples are the synthesis of 5-cyclodecynone [52][53] and the fragmentation of l,2-epoxy-3-diazirine-5a-androstan-17/ -ol by treatment with sodium iodide and acetic acid. (The A ring is opened between C(2) and C(3) to give the l-oxo-2,3-alkyne derivative) [54],... 

The pyrolysis of tetramethylenediazirine in the gas phase is a first-order reaction yielding only cyclopentene and nitrogen. Similarly, the treatment of the tosylhydrazone of cyclopentanone with base under aprotic conditions yields cyclopentene as the only hydrocarbon product. Photolysis of this diazirine yields cyclopentene as the principal hydrocarbon product (99.2%), but very small quantities of bicyclo[2,1,0]-pentane (0.3%) and methylenecyclobutane (0.1%) are also formed. In addition, about 0.5% of another hydrocarbon was detected but not identified. Its early position of the chromatogram indicates that it may be a fragmentation product. 

Borrevang, P., Hjort, J., Rapala, R. T., Edie, R. Novel ring fragmentation products via diazirines and its conversion to A-nor steroids. Tetrahedron Lett. 1968, 4905 907. 

Recently, diazirine rearrangement in the excited state (RIES) that mimics the result of cyclopropylcarbene fragmentation has been postulated. For examples, see (a) Ref. 128d,e (b) Thamattoor, D.M., Jones Jr., M., Pan, W. and Shevlin, P.B. (1996). Tetrahedron Lett. 37, 8333-8336... 

Thus, diaziridine (5) is also named as a 2-hydrazipropane. A convenient short name for the N-N fragment of the diazirine cycle is azi (not to be confused with the similar abbreviations azy and azo for the residues of aziridine 2-carboxylic acid and azetidine 2-carboxylic acid, respectively <84YGK390>. The chemical structures of diaziridinone (6), diziridinimine (7), as well as fused diaziridine C—N bridged (8) and N—N bridged (9) (usually cis) systems are given. 

A number of diaryloxydiazirines (4 X = Y = H, MeO, Me, Cl X = H, Y = MeO, Cl X = MeO, Y = Cl) (Scheme 2) have been synthesized and their thermolyses and photolyses investigated in various media.Although the thermolysis of (4) afforded products only from the expected carbenes (6), photolysis gave both carbenes (6) and aryloxy radicals by a-scission. The fragmentation of diaryloxycarbenes (6) to aryloxy radicals appears to be unprecedented and, moreover, thermodynamically improbable, as indicated by computations. The authors suggest, therefore, that the a-scission takes place from the excited state of the diazirine, which they depict as the ring-opened diradical (5). 

A mechanism involving nitrene formation by fragmentation of an intermediate N-substituted diazirine has been suggested to account for production of benzonitrile on reaction of aryl halodiazirines with potassium ethyl xanthate. ... 

---