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.     

Azaindoles. 69. Some reactions of 5-cyano-6-chloro-7-azaindoles and lactam-lactim tautomerism in 5-cyano-6-hydroxy-7-azaindolines

Electrophilic substitution in the 3-position of 1-benzyl-4-methyl-5-cyano-6-chloro-7-azaindole requires more severe conditions than in 7-azaindoles without the 5-cyano-substituent. Increased ease of nucleophilic replacement of the chlorine atom by the methoxy group has been observed in 1-benzyl- (and 1-butyl)-4-methyl-5-cyano-6-chloro-7-azaindoles, and the cyano-group in these compounds has been found to be resistant to hydrolysis and alcoholysis. The introduction into 1-benzyl- (and 1-butyl)-4-methyl-6-hydroxy-7-azaindoles of a 5-cyano-substituent results in a shift of the lactam-lactim tautomeric equilibrium towards the lactim forms.For communication 68, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 100–106, January, 1987.     

Azaindole derivatives

It is shown that it is possible to synthesize 1-acyl-4-methyl-7-azatryptamines from ethyl (4-methyl-7-aza-3-indolyl)acetate through 3-(-chloroethyl)-4-methyl-7-azaindole with subsequent acylation by replacement of halogen by a nitro group and reduction. The N-acetyl group is cleaved in the reaction of 1-acetyl-3-(-chloroethyl)-4-methyl-7-azaindole with ammonia, bis (dimethylmethoxysilyl)amide potassium salt, and potassium phthalimide (with subsequent removal of the phthalimide protective group).See [1] for communication XLII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1370–1373, October, 1973.     

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.     

Azaindole derivatives

A mechanism for the polarographic oxidation of azaindolines that includes electrochemical and chemical steps is proposed. The preparative electrolysis of 1-phenyl-4-methyl-6-morpholino-7-azaindoline, which gives the corresponding 7-azaindole and (7-aza-5-indolinyl)-7-azaindoline, was accomplished.See [1] for communication XLVIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1277–1283, September, 1975.     

7-Azaindole derivatives

A study is made of new synthetic routes, based on accessible 3-formyl-7-azaindoles, to 3-substituted 7-azaindole. 2-Phenyl-4-(1-phenyl-4-methyl-7-azaindolyl-3-rnethylene)-1, 3-oxazol-5-one is synthesized, and it is converted to 1-phenyl-4-methyl-7-azatryptophane, 1-phenyl-4-methyl-7-azaindolyl-3-acetic acid,1-phenyl-3-(,-dihydroxypropyl)-4-methyl-7-azaindole, and 1-phenyl-4-methyl-7-azaindolyl-3-pyrotartaric acid.For Part XVIII see [1].     

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.     

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.     

Synthesis and reactivity of N-heterocycle-B(C6F5)3 complexes. 4. Competition between pyridine- and pyrrole-type substrates toward B(C6F5)3: structure and dynamics of 7-B(C6F5)3-7-azaindole and [7-Azaindolium]+[HOB(C6F5)3]-

Reaction between 7-azaindole and B(C6F5)3 quantitatively yields 7-(C6F5)3B-7-azaindole (4), in which B(C6F5)3 coordinates to the pyridine nitrogen of 7-azaindole, leaving the pyrrole ring unreacted even in the presence of a second equivalent of B(C6F5)3. Reaction of 7-azaindole with H2O-B(C6F5)3 initially produces [7-azaindolium]+[HOB(C6F5)3]- (5) which slowly converts to 4 releasing a H2O molecule. Pyridine removes the borane from the known complexes (C6F5)3B-pyrrole (1) and (C6F5)3B-indole (2), with formation of free pyrrole or indole, giving the more stable adduct (C6F5)3B-pyridine (3). The competition between pyridine and 7-azaindole for the coordination with B(C6F5)3 again yields 3. The molecular structures of compounds 4 and 5 have been determined both in the solid state and in solution and compared to the structures of other (C6F5)3B-N-heterocycle complexes. Two dynamic processes have been found in compound 4. Their activation parameters (DeltaH = 66 (3) kJ/mol, DeltaS = -18 (10) J/mol K and DeltaH = 76 (5) kJ/mol, DeltaS = -5 (18) J/mol K) are comparable with those of other (C6F5)3B-based adducts. The nature of the intramolecular interactions that result in such energetic barriers is discussed.     

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.     

Etude cinétique comparée de la substitution nucléophile de quelques chloro-2 pyridines condensées

A comparatie kinetic study of nucleophilic substitution of some condensted 2-chloropyridines by piperidine was carried out and an “autocatalytic effect” was observed in the case of 1-methyl-4-chloro-5-azaindole. The rate constants of such substitutions were determined for 1-methyl-4-chloro-5-azaindole, 4-chlorofuro[3,2-c]pyridine, 1-phenyl- and 1-benzy;(1H)pyrazolo[4,3-c]pyridines, 4-chloro-6,7-dimethylpyrrolo[2,3-d]pyrimidine, and a classification of reactivity of these compounds, as compared to 2-chloropyridine, was established.     

Heterogeneous-catalytic fischer reaction

The catalytic synthesis of 7-azaindole and its 2-methyl derivative has been accomplished for the first time by cyclization of acetaldehyde and acetone 2-pyridylhydrazones in the presence of -Al₂O₃ and fluorinated aluminum oxide. The temperature dependence of the yields of reaction products — azaindoles and 2-aminopyridine — was studied. The cyclization of acetaldehyde 2-pyridylhydrazone proceeds under more severe conditions. The maximum yield of 7-azaindole is 15% at 450° on fluorinated aluminum oxide. The yield of 2-methyl-7-azaindole reaches 50% at 315°. Fluorinated aluminum oxide displays higher catalytic activity.See [1] for communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 656–658, May, 1972.     

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 functionalized 7-azaindoles via directed ortho-metalations

Functionalization at C-5 of 4-fluoro- and 4-chloro-1-triisopropylsilyl-7-azaindole, 1 and 2, respectively, leads to a variety of new substituted 7-azaindole derivatives. We also describe two approaches to introduce functionality at C-6.     

7-azaindole derivatives

A new method for synthesizing 5- and 7-azaindoles is given, -Chlorobutyronitrile and malonyl chloride give 2, 4, 6-trichloro-3-(ß-chloroethyl) pyridine, which is cyclized with ammonia to 4, 6-dichloro-7-azaindoline and 4, 6-dichloro-5-azaindoline. 6-Chloro derivatives of 7-azaindolines are not dehydrogenated by chlorainil, but 2, 3-dichloro-S, 6-dicyanobenzoquinone converts them to 6-chloro-7-azaindoles. It is shown that sodium in liquid ammonia is an effective means of dehydrogenating the 5-azaindoline to 5-azaindole. In this case, dehydrogenation of 4, 6-dichloro-7-azaindoline is followed by dehalogenation.For Part IX see [1].     

Reaction of Aminobenzimidazoles with 4-Hydroxy-6-methyl-2-pyrone and 4-Hydroxycoumarine

6- and 7-(4-hydroxy-6-methyl-2-oxo-1-pyridyl)benzimidazoles and 1-(6- and 7-benzimidazolyl)-4-hydroxy-2-oxoquinolines were synthesized by reaction of aminobenzimidazoles with 4-hydroxy-6-methyl-2-pyrone and 4-hydroxycoumarine.     

Cyclization of 2-methoxy-6-(substituted benzyloxy)acetophenone hydrazones in the presence of polyphosphoric acid(PPA)

Cyclization of 2-methoxy-6-benzyloxy acetophenone hydrazone gave 3-methyl-4-meth-oxy indazole and 3-methyl-4-methoxy-7-benzyl indazole in the presence of polyphosphoric acid(PPA).The hydrazone was probably converted to 2-hydroxy-6-methoxy acetophenone hydra-zone and 2-hydroxy-3-benzyl-6-methoxy acetophenone hydrazone followed by cyclization to thecorresponding indazoles in acidic conditions.Cyelization of 2-methoxy-6-(halo or alkyl or arylbenzyloxy)acetophenone hydrazones gave similar products.Cyclization of 2-methoxy-6-(p-nitrobenzyloxy)acetophenone hydrazone gave 2-(p-nitrophenyl)-3-methyl-4-methoxy benzo-furan and 3-methyl-4-methoxy indazole while 2-methoxy-6-(m-nitrobenzyloxy)acetophenonehydrazone gave 3-methyl-4-methoxy indazole,3-methyl-4-methoxy-7-(m-nitrophenyl)indazole and3-methyl-4-(m-nitrobenzyloxy)indazole.     

Synthesis of 4-(cyclic dialkylamino)-7-azaindoles by microwave heating of 4-halo-7-azaindoles and cyclic secondary amines

Nucleophilic aromatic substitution of 4-chloro- and 4-fluoro-7-azaindoles with cyclic secondary amines under microwave heating gave a straightforward and rapid synthesis of 4-(cyclic dialkylamino)-7-azaindoles. 4-Fluoro-7-azaindoles showed a greater reactivity towards S_NAr reactions under these conditions than 4-chloro-7-azaindole.     

Synthesis of 2-Substituted 7-Methyl-6-(nitroimidazolyl)thiopurines

2-Substituted 7-methyl-6-(nitroimidazolyl)thiopurines have been synthesized by the reaction of 2-chloro(phenylamino, cycloalkylamino)-7-methyl-6-thiopurines with 5(4)-halo-4(5)-nitroimidazoles and the reaction of 2,6-dichloro-(6-chloro-2-dimethylamino)-7-methylpurines with sodium or ammonium salts of 5(4)-mercapto-4(5)-nitroimidazoles.     

Correlations of the physicochemical parameters of azaindoles with their reactions

Using the AM1 semiempirical quantum method the enthalpies of formation, ionization energies, electron affinities, energy differences between highest occupied and lowest unoccupied orbitals, atomic charges, bond orders, and dipole moments have been calculated for 4-, 5-, 6-, and 7-azaindoles. A correlation has been built up between the calculated physicochemical parameters and the Hammett para-substituent and inductive constants. The 1H to 7H proton transfer in 7-azaindole has been quantitatively described. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1062–1072, July, 2006.