Photoaddition of ketones to imidazoles,thiazoles, isothiazoles and isoxazoles. Synthesis of their oxetanes

Imidazole itself did not undergo photoaddition reactions with ketones. However, irradiation of 1-acetyl and 1-benzoylimidazole, and 1,1-carbonyldiimidazole with benzophenone yielded oxetanes. On irradiation with carbonyl compounds, 1,2-dimethylimidazole and 1-benzylimidazole did not give oxetanes but a hydroxyaryl or hydroxyalkyl derivative. Thiazole itself did not yield any photoaddition product, but 2,4-dimethylthiazole afforded oxetanes on irradiation with benzophenone and with 3-benzoylpyridine. Irradiation of 2,4-dimethylthiazole with acetophenone led to the formation of a dimeric material. On irradiation with benzophenone, 4-methylisothiazole did not yield an oxetane but rather a hydroxyphenyl derivative. 3,5-Dimethylisoxazole on irradiation with benzophenone and with 3-benzoylpyridine gave oxetanes. Irradiation of 4,5-dimethylisoxazole yielded similarly an oxetane with benzophenone     

Photopolymerization via the Paterno-Büchi reaction. I. Reaction of aromatic diketones with tetramethylallene

Aromatic diketones of the benzophenone type undergo photopolymerization on irradiation at 350 nm with tetramethylallene in benzene solution. The polymers produced contain oxetane units in the main chain, and spectroscopic analysis demonstrates that the distribution of structural units parallels that found in the reaction between benzophenone and tetramethylallene. The polymers are rapidly degraded thermally and by mineral acids.     

Photopolymerization via the Paterno-Büchi reaction. II. Reaction of aromatic diketones with furans

Attempts to photopolymerize 1:1 mixtures of furan and aromatic diketones of the benzophenone type by irradiation of benzene solutions at 350 nm were unsuccessful. An alternative route via furan-diketone 2:1 adducts was more successful but was complicated by the intervention of hydrogen abstraction reactions in competition with oxetane formation, leading to crosslinking and insolubilization in some cases.     

Notable temperature effect on the stereoselectivity in the photochemical [2+2] cycloaddition reaction (Paternò-Büchi reaction) of 2,3-dihydrofuran-3-ol derivatives with benzophenone

A notable temperature effect (nonlinear Eyring plot) on stereoselectivity, trans-configured oxetane 2 versus cis-configured oxetane 2, is reported in the photochemical [2+2] cycloaddition reaction (Paternò-Büchi reaction) of 2,3-dihydrofuran-3-ol derivatives 1 with benzophenone.     

Synthesis of oxetanes by photoaddition of carbonyl compounds to thiophene derivatives

2,3-Dimethyl, 3,4-dimethyl and 2,3,5-trimethylthiophene were synthesized and subjected to interaction with excited benzophenone. 2,3-Dimethylthiophene affords an oxetane in good yield. These experiments were carried out in order to generalize this reaction which thus far has only been successful with 2,5-dimethylthiophene.     

Reactivity of 1H-pyrrolo[2,3-b]pyridine. I. Synthesis of 3-acetyl-7- azaindole and related compounds

The behaviour of 1H-pyrrolo[2,3-b)pyridine (7-azaindole) towards several acylating reagents are reported. The preparation of 3-acetyl-7-azaindole, 3-chloroacetyl-7-azaindole and 3-(2-hydroxiethyl)-7-azaindole are described.     

Synthesis of pyrrolopyridines (azaindoles)

Improved, convenient, and reliable routes for the synthesis of 4-, 5-, 6-, and 7-azaindole, 7-methyl-4-azaindole, 7-methyl-6-azaindole, and the hitherto unreported 7-amino-4-azaindole are described. The syntheses have been accomplished either by significant modifications to established procedures or by new methods which afford the compounds in improved yields.     

Azaindole derivatives

The reaction of 6-chloro-7-azaindolines with naphthyllithium and subsequent treatment with benzophenone give (7-aza-6-indolinyl)diphenylcarbinol and 6-unsubstituted 7-azaindolines, the ratios of the amounts of which are determined by the character of the substituent attached to the nitrogen atom in the 1 position of the azaindoline molecules. In the presence of acidic catalysts (1-butyl-4-methyl-7-aza-6-indolinyl)diphenylcarbinol undergoes dehydration to 1-butyl-4-methyl-6-diphenylmethyl-7-azaindole. Ideas regarding the mechanism of this reaction are expressed.See [1] for communication L.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1527–1530, November, 1977.The authors thank Yu. N. Sheinker, K. F. Turchin, L. F. Linberg, E. M. Peresleni, and T. Ya. Filipenko for conducting the spectral investigations.     

1H and 13C NMR studies of 7-azaindole and related compounds

The ¹H and ¹³C chemical shifts, proton-proton coupling constants, and one-bond carbon-hydrogen coupling constants have been obtained for 7-azaindole, 1-methyl-7-azaindole, their corresponding methyl iodide salts, and the related compound 7-methyl-7H-pyrrolo [2,3-b]pyridine. are different from those of either 7-azaindole or 1-methyl-7-azaindole.     

EXCITED STATE INTERACTIONS OF 7-AZAINDOLE WITH ALCOHOL AND WATER

Abstract— The fluorescence spectrum of 7-azaindole in alcohol is composed of two fluorescence bands. Effects of pH, temperature and solvent deuteration on the fluorescence spectra and quantum yields of 7-azaindole and other model compounds in ethanol and in water are reported. The long wavelength band arises from a tautomeric species formed in an adiabatic photoreaction involving double proton transfer between one molecule of 7-azaindole and one molecule of alcohol.
The fluorescence spectrum of 7-azaindole in water is composed of only one band, but the emission is weak and shows a large solvent isotope effect. The possibility of a double proton transfer reaction between 7-azaindole and water is discussed.     

Surprising selectivity in the transformation of dimethoxy azaindoles

Transformation of 4,7-dimethoxy-6-azaindole into 4-hydroxy-7-methoxy-6-azaindole or 7-hydroxy-4-methoxy-6-azaindole can be readily controlled by careful selection of a reagent. Treatment with concentrated HCl results in hydrolysis at the 4-position exclusively, while TMS-I provides demethylation at the 7-position only. Products were unambiguously identified by single crystal X-ray crystallography.     

Intermolecular vibrational modes and orientational dynamics of cooperative hydrogen-bonding dimer of 7-azaindole in solution

We observed the low-frequency Raman-active intermolecular vibrational modes of 7-azaindole in CCl(4) by femtosecond Raman-induced Kerr effect spectroscopy. To understand the dynamical aspects and vibrational modes of 7-azaindole in the solution, the ultrafast dynamics of 1-benzofuran in CCl(4) was also examined as a reference and ab initio quantum chemistry calculations were performed for 7-azaindole and 1-benzofuran. The cooperative hydrogen-bonding vibrational bands of 7-azaindole dimer in CCl(4) appeared at 89 cm(-1) and 105 cm(-1) represent the overlap of stagger and wheeling modes and the intermolecular stretching mode, respectively. They are almost independent of the concentration in the solution. We further found from the low-frequency differential Kerr spectra of the solutions with neat CCl(4) that the intermolecular motion in the low frequency region below 20 cm(-1) was less active in the case of 7-azaindole/CCl(4) than in the case of 1-benzofuran/CCl(4). The slow orientational relaxation time in 7-azaindole/CCl(4) is ~3.5 times that in 1-benzofuran/CCl(4) because of the nature of the dimerization of 7-azaindole.     

Intramolecular interactions in the triplet excited states of benzophenone-thymine dyads

Time-resolved and product studies on the synthesized dyads 1 and 2 have provided evidence that the benzophenone-to-thymine orientation strongly influences intramolecular photophysical and photochemical processes. The prevailing reaction mechanism has been established as a Paterno-Büchi cycloaddition to give oxetanes 3-6; however, the ability of benzophenone to achieve a formal hydrogen abstraction from the methyl group of thymidine has also been evidenced by the formation of photoproducts 7 and 8. These processes have been observed only in the case of the cisoid dyad 1. Adiabatic photochemical cycloreversion of the oxetane ring is achieved upon direct photolysis to give the starting dyad 1 in its excited triplet state. The photobiological implications of the above results are discussed with respect to benzophenone-photosensitized damage of thymidine.     

Excited state proton transfer in 3-methyl-7-azaindole dimer. Symmetry control

The concerted double proton transfer undergone by the C(2)(h) dimer of 7-azaindole upon electronic excitation has also been reported to occur in 3-methyl-7-azaindole monocrystals and in dimers of this compound under free-jet conditions. However, the results obtained in this work for the 3-methyl-7-azaindole dimer formed in a 10(-4) M solution of the compound in 2-methylbutane suggest that the dimer produces no fluorescent signal consistent with a double proton transfer in the liquid phase or in a matrix. In this paper, the spectroscopic behavior of the doubly hydrogen bonded dimer of 3-methyl-7-azaindole is shown to provide a prominent example of molecular symmetry control over the spectroscopy of a substance. This interpretation opens up a new, interesting research avenue for exploring the ability of molecular symmetry to switch between proton-transfer mechanisms. It should be noted that symmetry changes in the 3-methyl-7-azaindole dimer are caused by an out-of-phase internal rotation of the two methyl groups.     

The Reaction of Triplet State Benzophenone with Acetylacetone

Irradiation of benzophenone in acetic acid containing acetylacetone resulted in regiospecific addition to form cis-2,2-dihpenyl-3-hydroxy-3-methyl-4-acetyloxetane and the rearrangement products therefrom. In the co-presence of copper ions, the regiospecificity is scrambled to give these products and a small amount of 1,1-diphenyl-1-buten-3-one, the secondary decomposition product of the other oxetane arising from the alternative orientation of the addition.     

A theoretical and optical spectroscopic study of the mechanism of a tautomeric transformation in the 7-azaindole dimer and the 7-azaindole complex with a water molecule

Electronic, vibrational, and electronic vibrational spectra of the 7-azaindole dimer, the 7-azaindole complex with a water molecule, and their tautomers are calculated. Transition states are considered based on the analysis of frequencies and shapes of low-frequency vibrations and the Mulliken charge redistribution. The performed quantum chemical calculation of chemical reactions enabled the determination of the structure of transition states and proton transfer conditions. It is shown that in the 7-AzI dimer the proton transfer has a character consistent with the formation of a zwitterionic form. The structure of excited states is calculated and the fluorescence spectra of the first electronic transitions that can be used as a criterion of the formation of 7-AzI tautomers as a result of chemical reactions proceeding through a proton transfer in the 7-azaindole dimer and the 7-azaindole complex with a water molecule, are interpreted.     

Efficient photochemical oxetane formation from 1-methyl-2,4,5-triphenylimidazole and benzophenones

In contrast to simple imidazoles, 1-methy1–2,4,5-triphenylimidazole ($\text{1}$) produced stable oxetane photoadducts $\text{3b}$ - $\text{e}$ with good efficiency upon irradiation in the presence of benzophenone derivatives $\text{2b}$ - $\text{e}$ in acetonitrile solution. Irradiation in the solid-phase was also studied. The oxetanes $\text{3b}$ - $\text{e}$ readily underwent cycloreversion by acid catalysis or by heating.     

Observation of singlet cycloreversion of thymine oxetanes by direct photolysis

An ultrafast broadband transient absorption spectroscopic study of the direct photolysis of oxetane DMT-BP [which is the oxetane adduct of 1,3-dimethylthymine (DMT) with benzophenone (BP)] is presented. Previous nanosecond time-resolved absorption studies by other researchers observed that direct photolysis of such oxetanes results in a rare, adiabatic photochemical reaction to produce a triplet excited-state carbonyl species. However, the mechanism for this adiabatic photochemical reaction remained unclear for the reaction sequence of the bond scission and the intersystem crossing (ISC) because of the time resolution for the experiments, and this prompted us to further study its mechanism with ultrafast time-resolution. The ultrafast time-resolved spectra presented here indicate that the cycloreversion reaction occurs in a stepwise manner on a singlet excited-state, and then intersystem crossing (ISC) occurs to produce the triplet carbonyl product observed in the previously reported nanosecond time-resolved experiments.     

Nonexponential Fluorescence Decay of 7-Azatryptophan Induced in a Peptide Environment

7-Azatryptophan is an alternative to tryptophan as an optical probe of protein structure and dynamics. 7-Azatryptophan is synthetically incorporated into an octapeptide (NAc-Lys-Ala-Cys-Pro-7-azatryptophan-Asn-Cys-Asp-NH₂) that mimics the active site of potato chymotrypsin inhibitor II, which is known to be a strong inhibitor of α-chymotrypsin. The synthetic octapeptide retains some of this inhibitory activity. This is the first compound containing the 7-azaindole chromophore to display a nonexponential fluorescence decay (well fit to two exponentials) in water when fluorescence is collected over the entire emission band. The effect of external quenchers on the fluorescence decay is monitored and seen to differ markedly for the two components. These results are discussed in terms of the solvation of the 7-azaindole chromophore itself, which promotes or impedes excited-state tautomerization. The fluorescence quenching of free indole and 7-azaindole are compared. The fluorescence quenching of octapeptides containing both chromophores is also compared. It is the thesis of this article that the nonexponential fluorescence decay of the 7-azatryptophan-containing octapeptide is a consequence of excited-state tautomerization of the 7-azaindole chromophore. This tautomerization is suggested to be promoted by solvent reorganization induced by the peptide backbone or by direct interactions of the 7-azaindole with neighboring amino acid side chains.     

Synthesis of oxetanes by photoaddition of carbonyl compounds to pyrrole derivatives

Several electron attracting groups have been substituted on the nitrogen atom to decrease the electron density of the pyrrole ring in order to make it more suitable for photoaddition reactions. Once it was found that N-benzoylpyrrole is the only compound of the series studied, capable of undergoing oxetane formation, other carbonyl compounds in addition to benzophenone were tested as possible addends to the ring. Successful additions were observed when 3- and 4-benzoyl-pyridine were used.