Singlet Nitrene Research Articles

RNA-tethered phenyl azide photocrosslinking via a short-lived indiscriminant electrophile.

Arylazide mediated photocrosslinking has been widely used to obtain structural constraints in biological systems, even though the reactive species generated upon photolysis in aqueous solution have not been well characterized. We establish a mechanistic framework for formation of adducts between photoactivated 3-hydroxyphenyl azide and RNA. Tethered to an internal site in an RNA duplex via a 2'-amido linkage, photolysis of the aryl azide yields a cross-strand cross-link. Analysis of the ability of reagents with diagnostic reactivities to intercept formation of this cross-strand cross-link supports the assignment that the photoactivated intermediate is the ketenimine or a ketenimine-derived ring expansion product. Neither the initially produced singlet nitrene nor the subsequently formed triplet nitrene contribute to cross-link formation. Argon matrix and time-resolved solution experiments show that photolysis of free 3-hydroxyphenyl azide releases (in <or=20 ns) either a ketenimine or azepinone intermediate that reacts with nucleophiles. Adenosine, uridine, and guanosine monophosphate nucleotides have approximately equivalent abilities to quench the cross-strand cross-link, indicating that the photoactivated intermediate reacts broadly with functional groups in RNA. The reactive intermediate forms an adduct with adenosine monophosphate when tethered to both an RNA duplex or unstructured single strand; thus, cross-link formation is independent of the local RNA environment. The lifetime of the reactive intermediate generated upon photolysis of free 3-hydroxyphenyl azide in 50 mM Hepes diamine buffer is found to be 60-160 micros or significantly shorter than large scale RNA folding events. RNA-tethered 3-hydroxyphenyl azide cross-linking in aqueous buffer can thus be used with confidence to map structural neighbors, including most dynamic interactions, in RNA.

Study of the chemistry of ortho- and para-biphenylnitrenes by laser flash photolysis and time-resolved IR experiments and by B3LYP and CASPT2 calculations.

The photochemistry of ortho-biphenyl azide (1a) has been studied by laser flash photolysis (LFP), with UV-vis and IR detection of the transient intermediates formed. LFP (266 nm) of 1a in glassy 3-methylpentane at 77 K releases singlet ortho-biphenylnitrene (1b) (lambda(max) = 410 nm, tau = 59 +/- 6 ns), which under these conditions decays cleanly to the lower energy triplet state. In fluid solution at 298 K, 1b rapidly (tau < 10 ns) partitions between formation of isocarbazole (4) (lambda(max) = 430 nm, tau = 70 ns) and benzazirine (1e) (lambda(max) = 305 nm, tau = 12 ns). Isocarbazole 4 undergoes a 1,5-hydrogen shift, with k(H)/k(D) = 3.4 at 298 K to form carbazole 9 and smaller amounts of two other isocarbazoles (7 and 8). Benzazirine 1e ring-opens reversibly to azacycloheptatetraene (1f), which serves as a reservoir for singlet nitrene 1b. Azacycloheptatetraene 1f ultimately forms carbazole 9 on the millisecond time scale by the pathway 1f --> 1e --> 1b --> 4 --> 9. The energies of the transient intermediates and of the transition structures connecting them were successfully predicted by CASPT2/6-31G calculations. The electronic and vibrational spectra of the intermediates, computed by density functional theory, support the assignment of the transient spectra, observed in the formation of 9 from 1a.

A Laser Flash Photolysis Study of Diphenylphosphoryl Azide. Kinetics of Singlet and Triplet Nitrene Processes

Laser flash photolysis (266 nm) of diphenylphosphoryl azide 1 produces singlet diphenylphosphorylnitrene 2s (not observed), which can either react with solvent or relax to form the lower energy triplet nitrene 2t. Triplet 2t absorbs at 345 nm in chloroform, cyclohexane, 1,2-dichloroethane, dichloromethane, ethyl acetate, 1,1,2-trichlorotrifluoroethane, and tetrahydrofuran, but the intensity and shape of the absorption band is solvent-dependent. The triplet lifetime is several tens of microseconds in the aforementioned solvents. The magnitude of 1/τ is linearly dependent on the concentration of diphenylphosphoryl azide 1 ( = 1.2 × 106 M-1 s-1) in methylene chloride. The extrapolated lifetime of 2t in the absence of precursor is 500 μs in methylene chloride at ambient temperature. Thus, the long triplet lifetime in the aforementioned solvents is controlled by nitrene reaction with precursor. The one exception is methanol as solvent for which the triplet lifetime is only 6 μs. The reciprocal of the lifetime of 2t is linearly dependent on the concentration of tris-trimethylsilylsilane ((Me3Si)3SiH), and the absolute rate constants to hydrogen transfer ( ) are 3.4 × 105 M-1 s-1 in 1,2-dichloroethane and 3.1 × 105 M-1 s-1 in 1,1,2-trifluorotrichloroethane. A polar effect on increases the rate constant to reaction with the silane in methanol and shortens the lifetime of 2t in this solvent. (MeSi)3SiH reduces the yield of triplet 2t (φ) by the trapping of singlet nitrene 2s. Stern−Volmer analyses reveal that the singlet lifetime 2s is 1, 1, and 4 ns in 1,2-dichloroethane, methanol, and 1,1,2-trifluorotrichloroethane, respectively, assuming that is 5 × 109 M-1 s-1. The rapid rate of nitrene intersystem crossing is attributed to a N−O bonding interaction in the singlet nitrene, which results in a closed-shell electronic structure of the singlet.

Photolysis of ortho -Azidobenzoic Acid in Solutions and a Solid State

The photolysis of o-azidobenzoic acid in solutions, adsorbed on silica gel, and in a crystalline state was studied by IR and UV spectroscopy and thin-layer chromatography. It was found that the photolysis resulted in the formation of 2,1-benzisoxazolone (the product of intramolecular cyclization of singlet nitrenes) and anthranilic acid and o,o"-dicarboxyazobenzene (the reaction products of triplet nitrenes). The formation of 2,1-benzisoxazolone is a reversible reaction because of the secondary photolysis to singlet nitrenes, which leads to an increase in their concentration in the system.

A laser flash photolysis and quantum chemical study of the fluorinated derivatives of singlet phenylnitrene.

Laser flash photolysis (LFP, Nd:YAG laser, 35 ps, 266 nm, 10 mJ or KrF excimer laser, 10 ns, 249 nm, 50 mJ) of 2-fluoro, 4-fluoro, 3,5-difluoro, 2,6-difluoro, and 2,3,4,5,6-pentafluorophenyl azides produces the corresponding singlet nitrenes. The singlet nitrenes were detected by transient absorption spectroscopy, and their spectra are characterized by sharp absorption bands with maxima in the range of 300-365 nm. The kinetics of their decay were analyzed as a function of temperature to yield observed decay rate constants, k(OBS). The observed rate constant in inert solvents is the sum of k(R) + k(ISC) where k(R) is the absolute rate constant of rearrangement of singlet nitrene to an azirine and k(ISC) is the absolute rate constant of nitrene intersystem crossing (ISC). Values of k(R) and k(ISC) were deduced after assuming that k(ISC) is independent of temperature. Barriers to cyclization of 4-fluoro-, 3,5-difluoro-, 2-fluoro-, 2,6-difluoro-, and 2,3,4,5,6-pentafluorophenylnitrene in inert solvents are 5.3 +/- 0.3, 5.5 +/- 0.3, 6.7 +/- 0.3, 8.0 +/- 1.5, and 8.8 +/- 0.4 kcal/mol, respectively. The barrier to cyclization of parent singlet phenylnitrene is 5.6 +/- 0.3 kcal/mol. All of these values are in good quantitative agreement with CASPT2 calculations of the relative barrier heights for the conversion of fluoro-substituted singlet aryl nitrenes to benzazirines (Karney, W. L. and Borden, W. T. J. Am. Chem. Soc. 1997, 119, 3347). A single ortho-fluorine substituent exerts a small but significant bystander effect on remote cyclization that is not steric in origin. The influence of two ortho-fluorine substituents on the cyclization is pronounced. In the case of the singlet 2-fluorophenylnitrene system, evidence is presented that the benzazirine is an intermediate and that the corresponding singlet nitrene and benzazirine interconvert. Ab initio calculations at different levels of theory on a series of benzazirines, their isomeric ketenimines, and the transition states converting the benzazirines to ketenimines were performed. The computational results are in good qualitative and quantitative agreement with the experimental findings.

On the Stabilisation of a Singlet Nitrene by the Phosphaniminato and Related Imine-Type Substituents, a Quantum Chemical Investigation

The substituent effects on the singlet−triplet energy separations are explored for phosphanylnitrenes and related congeners from the Group 14 to Group 16 elements. Imine-type substituents (e.g. phosphaniminato, methyleneimine etc.) are more effective than amino groups in lowering the energy of a singlet below that of a triplet state. It is due to an effective stabilisation of the singlet and a destabilisation of the triplet.

Chemiluminescence upon Photooxidation of 4,4"-Diazidodiphenyl with Molecular Oxygen

It was found that irradiation of the solution of 4,4"-diazidodiphenyl in ethyl alcohol with UV-light at a wavelength longer than 280 nm in the presence of dissolved oxygen resulted in appearance of post-luminescence. The luminescence intensity increases with increasing the oxygen concentration; the luminescence virtually disappears after purging the solution with argon. The observed emission of light was attributed to chemiluminescence of the products of photooxidation of 4,4"-diazidodiphenyl. The rate dependence of the afterglow shows two maxima. The first is observed immediately after cessation of the UV irradiation of the solution and its transfer to a photometric cell. The intensity of the corresponding chemiluminescence decreases by an exponential law with τe= 5 s. The second maximum appears after a certain time interval after the first one. Addition of a triplet sensitizer (Michler's ketone) to the reaction mixture results in quenching of the chemiluminescence from the photooxidation products, whereas the addition of substances that stabilize electrophilic species in the singlet state leads to an increase in the chemiluminescence intensity. It was suggested that the chemiluminescence resulted from reactions involving the singlet nitrene adduct with oxygen.

Facile and efficient synthesis of 4-azidotetrafluoroaniline: a new photoaffinity reagent.

p-Azidotetrafluoroaniline (1) was synthesized in 65-73% yield by two different methods employing a stable carbamate intermediate. The first method trapped the intermediate isocyanate generated via a modified Curtius rearrangement with 2-methyl-2-propanol or 2-(trimethylsilyl)ethanol to form the stable carbamates 2d and 2e, respectively. Benzoic acid 2c was first converted to its acid chloride with PCl(5). Displacement of the chloride by NaN(3) in acetone/water formed the acyl azide. Thermal rearrangement followed by the addition of the appropriate alcohols provided the carbamates. The acid labile carbamate 2d was deprotected with HCl/AcOH to provide 1, while trifluoroacetic acid was required to deprotect 2e and afford 1. In the second path, 1 was synthesized in five steps from pentafluoronitrobenzene (3a) in 65% overall yield. Compound 3a was converted into 4-azidotetrafluoronitrobenzene (3b) with NaN(3) in 93% yield and was used without further purification to form 1, 4-diaminotetrafluorobenzene (3c) by Sn/HCl reduction in 85% yield. The mono-9-fluorenylmethoxycarbonyl (FMOC) derivative 3d was formed from 3c with FMOC-Cl and pyridine in EtOAc in 92% yield. Diazotization of 3d under anhydrous conditions with TFA/NaNO(2) and NaN(3) gave 3e in 87% yield. The aryl azide was formed with concurrent nitration of the 2-position of the fluorenyl system. The protecting group was removed with piperidine to afford 1 in 93% yield. Irradiation of 1 with 254 nm light in cyclohexane gave cyclohexylamine 11, diamine 3c, and azobenzene 12 as the primary products. The formation of C-H insertion product 11 indicates that 1 forms a singlet nitrene upon photolysis. Two heterobifunctional photoaffinity reagents iodoacetamide 9 and dansyl derivative 10 were prepared.

The [2+1] Cycloaddition of Singlet Oxycarbonylnitrenes to C 60

Semiempirical and density functional calculations have been carried out to discuss the origin of the closed [5,6]-aza-bridged adduct obtained as a minor product in the reaction of singlet nitrenes with C60. The results indicated that the most likely source is the direct addition of singlet nitrenes to a [5,6]-bond of C60, in contradiction to the common belief that the [5,6]-bonds are not attacked in cycloaddition reactions to C60.

A Laser Flash Photolysis Study of Some Simple Para-Substituted Derivatives of Singlet Phenyl Nitrene

The photochemistry of several para-substituted aryl azides was studied by laser flash photolysis (LFP) techniques in pentane. Para F, Cl, Br, I, CH3, CF3, COCH3, OCH3, and NO2 substituted aryl azides were studied. LFP of aryl azides generates singlet aryl nitrenes which were detected in absorption with maxima between 300 and 365 nm in pentane. The nitrene decay can be fit to an exponential function and analyzed to yield observed rate constant, kobs, which was measured as a function of temperature. The value of kobs = kR + kISC where kR and kISC are the rate constants of nitrene rearrangement to azirine intermediates and intersystem crossing to the lower energy triplet states, respectively. Values of kobs decrease as the temperature is reduced and reach a limiting value attributed to kISC. Assuming that kISC is temperature independent allows values of kR to be deduced along with the Arrhenius parameters to cyclization for para CH3, CF3, COCH3, F, Cl, and Br singlet phenyl nitrenes. The Arrhenius parameters to rearrangement closely resemble those of parent singlet phenyl nitrene with the exception of the para bromo compound. For para I and OCH3, kISC is large and prevents measurement of kR. The increased rate of intersystem crossing in these two singlet nitrenes is due to heavy-atom and to electron-donation effects, respectively. No transient absorptions were detected upon LFP of p-nitrophenyl azide.

Laser Flash Photolysis Study of Methyl Derivatives of Phenyl Azide

Laser flash photolysis (Nd:YAG, 35 ps, 266 nm, 10 mJ; KrF excimer, 249 nm, 12 ns, 70 mJ; XeCl excimer, 308 nm, 17 ns, 50 mJ) of methyl substituted phenyl azides produces the corresponding singlet nitrenes. The singlet nitrenes were detected directly, and their decay was analyzed to yield the observed rate constant kOBS. The observed rate constant is the sum of kR + kISC where kR is the absolute rate constant of rearrangement to an azirine and kISC is the absolute rate constant of intersystem crossing. Values of kOBS were measured as a function of temperature and dissected assuming that kISC is temperature-independent. It was shown that kISC is independent of temperature for 2,6-dimethyl- and 2,4,6-trimethylphenyl singlet nitrenes. The barriers to rearrangement of singlet phenylnitrene, p-methylphenylnitrene, o-methylphenylnitrene, 2,6-dimethylphenylnitrene, and 2,4,6-trimethylphenylnitrene in hydrocarbon solvents are found to be 5.6, 5.8, 5.3, 7.0, and 7.3 ± 0.4 kcal/mol, respectively. The data demonstrate that two ortho methyl substituents retard cyclization but that a single ortho or para substituent does not. It is concluded that the rate of retardation provided by the methyl groups has a steric origin, as predicted by Karney and Borden (J. Am. Chem. Soc. 1997, 119, 3347). These authors predict that ortho methylation raises the barrier to cyclization by 1−2 kcal/mol, in excellent agreement with our results. Our results are also consistent with the work of Sundberg et al. (J. Am. Chem. Soc. 1972, 94, 513), which demonstrated that singlet 2-methylphenylnitrene cyclizes away from the ortho methyl substituent. Methyl substitution is found to increase the absolute rate constant of intersystem crossing.

Photodecomposition of Some Para-Substituted 2-Pyrazolylphenyl Azides. Substituents Affect the Phenylnitrene S−T Gap More Than the Barrier to Ring Expansion

A series of para-substituted (H, Me, Cl, F, CF3, OMe, NMe2) phenyl azides bearing a dimethylpyrazolyl group in position 2 allowing intramolecular trapping of singlet nitrene have been photolyzed at both 295 and 90 K in ethanol. For three significant models (H, CF3, NMe2), the reaction has been further studied in the presence of diethylamine (DEA) and of oxygen. With all substituents but NMe2, singlet nitrene (trapped intramolecularly to give pyrazolobenzotriazoles) and didehydroazepine (trapped with DEA to give 5H-azepines and then rearranging to 3H-azepines) are in equilibrium. With the NMe2 derivative, the nonelectrophilic singlet is not trapped, while DEA adds to the benzoazirine, the precursor of the didehydroazepine. Thus, electronic effects do not hinder the equilibrium between singlet nitrene and its cyclic isomers, while determining which of the above intermediates decays to a stable end product. The electron-donating group NMe2 has a second important effect, causing a drastic enhancement of the triplet nitrene energy and reduction of the S−T gap, so that triplet nitrene is also in equilibrium with the singlet and the benzoazirine. As for triplet nitrenes, these have been characterized in matrix at 90 K, and the competition between dimerization (to give azo compounds, as typical of such stabilized species) and hydrogen abstraction from the solvent (involving a sizable barrier) has been studied. The energetic p-dimethylamino triplet undergoes hydrogen abstraction exclusively. When present, oxygen adds efficiently to all of the nitrenes, giving a nitroso oxide, likewise characterized in the matrix, which then converts to the nitroso and nitro derivatives in good yields. Photochemical excitation of the triplet in matrix leads to intramolecular hydrogen abstraction.

Irradiation of 5-azido-8-methoxypsoralen † in water–acetonitrile gives nitrenium ion and triplet nitrene transients, but only nitrenium ion products

Irradiation of 5-azido-8-methoxypsoralen 10 in water–acetonitrile mixtures gives essentially quantitative yields of 5-imino-5,8-dihydropsoralen-8-one 17 regardless of the composition. This quinone imine is derived from the reaction of water with the nitrenium ion that results from protonation of the initially-formed singlet nitrene. Laser flash photolysis (LFP) in water and 90∶10 water–acetonitrile reveals a transient intermediate with λmax at 500–520 nm with the characteristics of a nitrenium ion, in particular a very effective quenching by azide ion. The immediate product of the reaction of water and the nitrenium ion is a hemiacetal; the breakdown of this species is also observed. In acetonitrile-rich solutions, the transient is a triplet nitrene (λmax at 410 nm), and at intermediate compositions, signals for both intermediates can be seen. Since the products are derived from the nitrenium ion, a mechanism is required where the triplet nitrene decays by way of this intermediate. Evidence that this actually happens is seen in an LFP experiment in water–2,2,2-trifluoroethanol (TFE). The decay of the nitrenium ion is slowed by the TFE, and the signal at 510 nm can be observed to grow at the same time as the signal for the triplet nitrene decays at 410 nm. Two mechanisms for the triplet nitrene→nitrenium conversion can be proposed, direct protonation or reversion to the singlet nitrene. The latter is favored because 0.02 mol dm–3 H+ has no effect on the rate constant for the decay of the triplet. This implies that the proton transfer step is already very fast with water as the acid, more consistent with the singlet nitrene as the species being protonated.

The effect of the p-nitro group on the chemistry of phenylnitrene. A study via intramolecular trapping

The photodecomposition of a pyrazolyl substituted p-nitrophenyl azide has been studied as an intramolecular model for the reactivity of the parent azide, largely used for photochemical labelling. The singlet nitrene is trapped by intramolecular cyclization onto the pyrazole nitrogen as well as by the low yield addition of intermolecular nucleophiles (EtOH, Et2NH). Ring expansion to a didehydroazepine is absent. The triplet nitrene abstracts hydrogen (intermolecularly) only slightly more efficiently than the non-nitrated derivative, while it is rather efficiently reduced via electron transfer in the presence of amines. Hydrogen abstraction is efficient for the excited triplet nitrenes, as revealed by an intramolecular reaction.

Chemistry of Bifunctional Photoprobes.1 3. Correlation between the Efficiency of CH Insertion by Photolabile Chelating Agents and Lifetimes of Singlet Nitrenes by Flash Photolysis: First Example of Photochemical Attachment of 99mTc−Complex with Human Serum Albumin

Systematic functionalization of perfluoroaryl azides with chelating agents capable of complexing transition metals produces a new class of bifunctional photolabile chelating agents (BFPCAs). The strategy to shield the azide functionality from the electronic and steric influence of the electron-rich metal Pd through ester and amide bridges raised CH insertion efficiency to unprecedented levels (>92%) in a model solvent (cyclohexane). In contrast, perfluoroaryl azides attached to chelating agents via hydrazones show no significant CH insertion in cyclohexane upon photolysis. Measurements of the lifetimes of the singlet nitrenes derived from these agents by flash photolysis techniques correlate well with the efficiency of CH insertion by demonstrating longer lifetimes (10−50 times) for singlet nitrenes derived from azidotetrafluorinated esters and amides compared with the related hydrazones, which failed to yield significant CH insertion. A representative BFPCA 12 is chelated to diagnostic radionuclide 99mTc...

Reactivity of Singlet and Triplet Arylnitrenes: Temperature-Dependent Photodecomposition of 1-(2-Azidophenyl)-3,5-dimethylpyrazole

At >200 K photolysis of 1-(2-azidophenyl)-3,5-dimethylpyrazole (5) gives 1,3-dimethylpyrazolobenzotriazole (6, by electrophilic cyclization of singlet nitrene 14) or, in the presence of diethylamine, aminoazepine 8 (by addition of the nucleophile and rearrangement). At lower temperatures, the yield of these products decreases and the azo derivative 9 (from the dimerization of triplet nitrene 34) as well as products from intramolecular radical cyclization (again via 34) is obtained, to become the only products at <100 K. Differential thermodynamic parameters for the reactions of 14 and 34 are determined by analysis of the temperature dependence of products distribution (ΔΔH⧧ = −10 kJ mol-1 and ΔΔS⧧ = 34 J mol-1 K-1 in ethanol). Addition of the amine may require previous ring enlargement to give the dehydroazepine 12; there is no indication that this is an intermediate of any stability, however, and if formed, this is in equilibrium with 14. Triplet nitrene 34 is characterized in matrix by UV spectroscopy, ...

Photochemical Reactions of Mesityl Azide with Tetracyanoethylene: Competitive Trapping of Singlet Nitrene and Didehydroazepine.

Irradiation of the title azide 4 in the presence of TCNE gives a mixture of two stable adducts. One of them is identified as the azomethine ylide 5, the structure of which is strictly determined by X-ray crystallography. The other is spectroscopically assigned to the spiroazepine 6. The effect of wavelength of the light employed in the photolysis reveals that the TCNE-4 charge-transfer complex (lambda(max) 454 and 550 nm in dichloromethane) does not participate in the adduct formation. The ratio of the adducts obtained in the photolysis is dependent linearly upon the initial concentration of TCNE, which strongly suggests that the adducts 5 and 6 are produced by competitive trapping of singlet mesitylnitrene (8S) and trimethyldidehydroazepine (9), respectively. The rate constant for the reaction of 8S with TCNE is estimated to be on the order of 10(9) M(-)(1) s(-)(1) or greater. The PM3 calculation indicates that the azomethine ylide 5 is thermodynamically more stable than the aziridine 7, which is thought to be initially formed by the reaction of 8S with TCNE. Thus, we propose that these findings make the first example of competitive trapping of singlet arylnitrene and its ring-expanded isomer with an alkene, which definitely reveals the intervention of singlet nitrene in the photolysis of an aryl azide.

Spectroscopy and Kinetics of Singlet Perfluoro-4-biphenylnitrene and Singlet Perfluorophenylnitrene

Laser flash photolysis (LFP) of perfluorophenyl azide and perfluoro-4-biphenyl azide produces the corresponding singlet nitrenes which were detected by their transient absorptions at 330 and 350 nm, respectively. The absolute rate constants of the fundamental processes that consume the singlet nitrenes (intersystem crossing, kisc, rearrangement, kR; reaction with pyridine, kpyr) were determined by monitoring the decay of the singlet nitrene and by the growth of its reaction products (ketenimine, triplet nitrene, or pyridine ylide). In the case of singlet 4-perfluorobiphenylnitrene in CH2Cl2 kisc = (2.2 ± 0.1) × 106 s-1, kR = 1013.2±0.2 exp[−(9400 ± 400)/RT] s-1, and kpyr = 109.06±0.15 exp[−(2400 ± 200)/RT] M-1 s-1. In the case of singlet perfluorophenylnitrene in CH2Cl2 kisc = (1.05 ± 0.05) × 107 s-1, kR = 1013.8±0.3 exp[−(8800 ± 400)/RT] s-1, and kpyr = 109.00±0.13 exp[−(1600 ± 160)/RT] M-1 s-1.

Why Doeso-Fluorine Substitution Raise the Barrier to Ring Expansion of Phenylnitrene?

In an attempt to understand the dramatic difference in reactivity between phenylnitrene (1a) and pentafluorophenylnitrene (1b), the ring expansion reactions of several fluorinated arylnitrenes have been studied computationally at the CASPT2N/cc-pVDZ//CASSCF(8,8)/6-31G* + ZPE level of theory. The nitrenes considered include 2,6-difluorophenylnitrene (1c), 3,5-difluorophenylnitrene (1d), 4-fluorophenylnitrene (1e), and 2-fluorophenylnitrene (1f). In all cases ring expansion of the open-shell singlet nitrenes (1) to the ketenimines (3) was calculated to occur via the same two-step mechanism as that predicted for the parent system (1a), with the first stepcyclization to the azirines (2)being rate-determining. The calculated barrier of 13.4 kcal/mol for cyclization of 1c is 3.5−4.5 kcal/mol higher than the corresponding barriers for nitrenes 1e and 1f, and for 1a. For nitrene 1f, the calculated barrier of 13.0 kcal/mol for cyclization toward fluorine is 3 kcal/mol higher than the barrier for cyclization away f...

Acid−Base Properties of Arylnitrenium Ions

This study uses a combination of laser flash photolysis (LFP) and product analysis to show that singlet nitrenes from the irradiation of phenyl, 4-biphenylyl, and 2-fluorenyl azide can be trapped by protonation in aqueous solutions forming nitrenium ions. With phenyl azide, the phenylnitrenium ion is indicated by the formation of ring-substituted anilines in yields of up to 50% in 1 M acids. The acidity dependence furnishes the ratio kH:kexp = 1.1, where kH refers to H+-trapping of singlet phenylnitrene and kexp to ring expansion of this species. With kH expected to be 2−4 × 1010 M-1 s-1, kexp is therefore estimated as 2−4 × 1010 s-1. Protonation by solvent water also occurs, but even though the rate constant is of the order of 109 s-1, it constitutes a minor pathway in competition with the ring expansion. LFP studies in acids reveal a transient that is assigned the structure of N-protonated 4-hydroxy-2,5-cyclohexadienone imine, the intermediate formed by water addition to the para position of the phenyln...