Chemistry of indole

The condensation of salts of 1-methyl-2-aminoindole with aldehydes in excess alkali gives Schiff bases, while salts of 1-methyl-3-arylidene-2-iminoindolines are obtained in the absence of alkali. The latter may give 12-aryl-5,7-dimethylindolo[2,3-b]--carbolines (I) on reaction with excess 1-methyl-2-aminoindole. Dihydro compounds (II) are formed as intermediates.See [1] for communication XXXI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1368–1373, October, 1972.     

Steric effects in the synthesis of pyrroloindoles from 5-aminoindols

The formation of angular pyrroindoles from 5-aminoindole substitued in the pyrrole ring depends both on the steric requirements of the substituent at the-position of the pyrrole ring, and on the structure of the -hydroxyketone. Significant amounts of the angular pyrroloindole are only formed together with the linear pyrroindole in the reaction of 2-methyl-5-aminoindole with benzoin. In the remaining cases, the linear ring closure of the pyrrole ring predominates.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 55–57, January, 1995.     

Reaction of phenylhydrazides of N-acyl-β-phenyl-β-alanine with phosphorus oxychloride

The reaction of N-methyl-N-phenylhydrazides of N-acyl--phenyl--alanine with phosphorus oxychloride is accompanied by cleavage of the C-N bond in the intermediately formed 2-aminoindole derivative and, after splitting out of an amide fragment, leads to 1-methyl-3-benzylidene-2-iminoindoline and nitriles. Pyrimido [4,5-b] indoles — products of cyclization of the corresponding intermediate 2-aminoindole derivatives — were isolated from the reaction mixtures in low yields. The structure of 1-methyl-3-benzylidene-2-iminoindoline was proved by alternative synthesis.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1356–1359, October, 1980.     

Formation of 3,4-dihydro-α-carbolines from 2-aminoindole

In the condensation of 2-aminoindole with ,-unsaturated oxo compounds, in contrast to ordinary aromatic amines and a number of heterocyclic amines, the direction of cyclization is reversed. The general scheme of the reaction includes the reaction of the position of 2-aminoindole with the activated double bond of the oxo compound via a mechanism of the Michael type and condensation of the carbonyl group of the unsaturated carboline structure, which subsequently undergoes aromatization. The intermediate 3,4-dihydro--carbolines were produced and isolated; this made it possible in a number of cases to establish the structures of the final -carbolines. The structures of the 3,4-dihydro compounds were confirmed by the set of spectral characteristics. Data from the UV, IR, PMR, and mass spectra are presented.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 945–951, pp. 945–951, July, 1977.     

The chemistry of indole

The reaction of 2-aminoindole with ,-unsaturated aldehydes and ketones leads to -carbolines, the -carbon atom of the oxo compound attacking C₃ of the indole. In a number of cases, reactions with bifunctional derivatives take place with the cleavage of a carbon-carbon bond and the formation of the pentacyclic system of indolo[2,3-b]--carboline. The same substances are obtained from 2-amino-3-(arylmethylene)indoles and 3-(arylmethylene)-oxindoles. The replacement of one molecule of 2-aminoindole by other acceptors did not lead to the formation of unsymmetrical structures.For Communication XXXVII, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1273–1278, September, 1973.     

Reaction of 3-aminoindole-2-carboxylic acids with diethyl acetylenedicarboxylate

-Carboline and indolo--carboline derivatives were obtained by reaction of the potassium salts of 3-aminoindole-2-carboxylic acids with diethyl acetylenedicarboxylate. A difference in the behavior of 3-aminoindole derivatives in the Michael reaction due to the nature of the substituent in the 5 position of the indole ring was established.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 82–84, January, 1977.     

Spectrophotometric study of the effect of substitution on the thermodynamic stability of the 1∶1 complexes of the dioxouranium(II) ion with mono-substituted salicylic acids in aqueous media

Summary A systematic study of the effect of substitution on the thermodynamic stability of the 11 complexes which the UO ₂ ^II ion forms in aqueous media with salicylic acid and ten monosubstituted salicylic acids has been carried out using a new spectrophotometric method. The new features of the method as well as a thermodynamic treatment for the effect of substitution is discussed.     

Chemistry of indole

,-Unsaturated ketones form pyrimido[1,2-a]indoles with 2-aminoindole, while 1-alkyl-2-aminoindoles under these conditions are converted to the corresponding -carbolines. The structures of the compounds obtained were confirmed by alternative synthesis.See [1] for communication XIX.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 61–64, January, 1971.     

Untersuchungen im System Nb—Mo—N

The system Nb–Mo–N has been investigated by X-ray techniques in an isothermal section at 1100C and at nitrogen pressures ranging from 1 to 300 bar. In the binary phase-Mo₂N up to 23% of the Mo-atoms can be replaced by Nb-atoms at a nitrogen pressure of 300 bar, while only a small amount of molybdenum nitride is soluble in the binary nitrides of niobium even under high nitrogen pressures. The composition range of the ternary phase NbMoN has been investigated with respect to nitrogen content as well as metal composition. The possibility of substitution of Mo-atoms by W-atoms within theZ-phase has been checked.

     

Enthalpies of solution,partial molal heat capacities and apparent molal volumes of sugars and polyols in water

Integral enthalpies of solution of some sugars and polyols in water at low concentrations have been determined calorimetrically at 25 and 35°C. These data have been used to derive heat capacities of solution C°_p at 30°C. Partial molal heat capacities C°_p,2 have been obtained by combining C°_p with C _p,2 ^* , the heat capacity of pure solid compounds. Apparent molal volumes have been obtained from density data. The sugars as well as polyols show significantly high positive C°_p and C°_p,2 values. The results have been explained in terms of a specific hydration model. The effect of substitution of-OH by glycosidic-OCH₃ and of-CHOH by deoxy-CH₂ are also discussed.     

Intramolecular cyclization of N-phthalyl-β-aryl-β-alanine phenylhydrazide

The reaction of N-phthalyl--aryl--alanine N-methyl-N-phenylhydrazides with phosphorus oxychloride (at80 °C) is accompanied by further transformations of the initially formed 2-aminoindole derivatives and leads to isoindolo[1,22,3]-pyrimido[5,6-b]indole derivatives. Intermediate 2-aminoindoles were isolated at lower reaction temperatures. The hydrolysis of the isoindolo[1,22,3]pyrimido [5, 6-b]indole derivatives was studied. The structures of the compounds obtained were established on the basis of the PMR, IR, and UV spectra and the results of elementary analysis.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 926–929, July, 1982.     

Ring closure reactions of 2,6-diazaheptatrienyl metal compounds: synthesis of 3-aminoindole derivatives and 14-membered macrocyclic dimers

2,6-Diazaheptatrienyl metal compounds 6(-)K(+) are easily accessible from the corresponding diimines 6 by deprotonation using KO-t-Bu as base. According to quantum chemical calculations, they are, in comparison to other isomeric species with nitrogen atoms in other positions, highly reactive intermediates, which undergo in dilute solution at 50 °C ring closure reactions to form 3-aminoindole derivatives 8/10. In contrast, in more concentrated solution at room temperature, the formation of 14-membered macrocyclces 13 as a result of formal dimerization is observed. The 3-aminoindole derivatives obtained in this work possess rare substitution patterns, and the macrocyclic compounds are essentially unknown. Two-fold vinylogous derivatives 7 give rise to tricyclic systems with δ-carboline backbone 12. The experimental results are interpreted using high-level DFT calculations with regard to the possible reaction mechanism and the nature of the transition state of the five-membered ring formation. The molecular structures in the solid state of all types of compounds were elucidated by X-ray diffraction.     

Conformational analysis of thiopeptides: (ϕ,ψ) maps of thio‐substituted dipeptides

Noncoded amino acids such as isobutyric acid have been used extensively in the process of drug design and protein engineering. This article focuses on a noncoded amino acid where the oxygen in the peptide unit is replaced with a sp² sulfur. It was hypothesized that the conformational space as well as the conformational preferences of thiopeptides will be more restricted and altered by the bulkier atom with different electrostatic properties. In vacuo conformational minima as well as associated energies for the thio‐substituted alanine dipeptides were calculated at the ab initio HF/6‐31G* level. When the bulkier sulfur atom acts as a hydrogen bond acceptor in the C₅ conformation or in the C$^{\mathrm{axial}}_{7}$ and C$^{\mathrm{equatorial}}_{7}$ conformations, the hydrogen bond lengths are much longer than that of normal peptides. Consequently, the ?, ψ dihedral angles of the C₅, C$^{\mathrm{axial}}_{7}$, and C$^{\mathrm{equatorial}}_{7}$ conformations change to accommodate the longer hydrogen bonds. The thiopeptide group is a poorer hydrogen bond acceptor and a better hydrogen bond donor than the normal peptide group. Therefore, thio‐substitution at the amino terminal leads to disfavoring of the C₇ conformations relative to the C₅ conformations and thio‐substitution at the carboxyl terminal leads to favoring of the C₇ conformations relative to the C₅ conformation. To simulate the conformations in solution, (?,ψ) conformational energy maps were calculated for the glycine and alanine dipeptides at various dielectric constants using the CFF91 force field with our previously derived parameters for the thioamide group. The results show that thio‐substitution does restrict the conformations available to amino acids residues in peptides. Thio substitution at the amino terminal introduces unfavorable interactions near ?=?120 and 120, where there are increased overlaps between S_n?1?H_β, and S_n?1?C_β atoms, respectively. Thio substitution at the carboxyl terminal restricts the conformations near ψ=60, ?60, and 180, which correspond with increase overlaps between S_n?C_β, S_n?H_β′ and S_n?N_n atoms, respectively. The effects of dithio substitutions of either the alanine or the glycine dipeptides are similar to the combined effects of the two single thio substitutions. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1026–1037, 2001     

Oxazepines and thiazepines,XXVIII Circular dichroism of optically active 2,3-dihydro-2-methyl-1,5-benzoxazepin-4(5H)-ones

Summary Chiroptical properties of the title compounds have been studied. The influence of the substitution pattern of the aromatic moiety and the consequence of the amide thioamide conversion are discussed as well.Dedicated to Prof. Dr. W. Wiegrebe on the occasion of his 60th birthday     

Amphiphilic Cholic‐Acid‐Modified Dextran Sulfate and its Application for the Controlled Delivery of Superoxide Dismutase

A novel amphiphilic and biodegradable polyelectrolyte DS‐CA is prepared by the esterification of DS with CA. DS‐CA can self‐assemble into stable nanoparticles in water. SOD can effectively associate with DS‐CA at pH = 5.0 by virtue of electrostatic and hydrophobic interactions. SOD release from the complex nanoparticles is slow at pH = 1.2. The release at pH = 7.4 PBS shows an extended behavior and is tunable by changing the weight ratio of SOD to DS‐CA as well as the CA substitution degree. Increasing the CA substitution degree of DS‐CA can significantly enhance the cellular uptake of the loaded SOD. This study demonstrates that the amphiphilic DS‐CA provides a promising strategy for oral delivery of protein/peptide drugs.

     

Formation of Tc(III)-EDTA complex

Tc(III)-EDTA complex has been synthesized by the ligand substitution reaction of hexakis-(thiourea) technetium(III) ion with EDTA. The complex exhibits absorption maxima at 368 and 470 nm. The formation reaction proceeds predominantly as follows:

An expedient, regioselective synthesis of 2-alkylamino- and 2-alkylthiothiazolo[5,4-e]indoles

1-Benzenesulfonyl-5-aminoindole 5, prepared from 5-nitroindole 3, was condensed with alkyl isothiocyanates and separately with carbon disulfide and alkyl bromides/iodides to furnish efficiently the corresponding N-alkyl-thioureidoindoles 6a-c and the alkyl N-(indol-5′-yl)dithiocarbamates 9a-e, respectively. Their cyclisation using N-bromosuccinimide (NBS) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), in the cold, followed by indolic N-deprotection, furnished regioselectively the 2-alkylamino- and the 2-alkylthiothiazolo[5,4-e]indoles 8a-c and 11a-e, respectively, in good overall yields.     

The Hydrolysis/Condensation Behaviour of Methacryloyloxyalkylfunctional Alkoxysilanes: Structure-Reactivity Relations

Various methacryloyloxymethylalkoxysilanes have been synthesized by nucleophilic substitution reactions starting from chloromethylalkoxysilanes under phase transfer catalysis conditions. The compounds thus obtained show an exceptionally high degree of reactivity with regard to hydrolysis and condensation both under acidic as well as under basic conditions compared to the established 3-methacryloyloxypropyltrimethoxysilane. A mechanistic model for this high reactivity by intramolecular activation is discussed.     

Kinetics and mechanism of substitution of bis(tptz)iron(II) by 2,2′-bipyridine and 1,10-phenanthroline

The kinetics of substitution of Fe(tptz)²+₂ by 2,2-bipyridine and 1,10-phenanthroline have been investigated in acetate buffers in the 3.6–5.6pH range employing stopped-flow spectrophotometry. These reactions are very fast and complete within 5s. The rate of substitution is linearly dependent on [phen] and [bpy]², and increases with the increase in pH. Suitable mechanisms have been proposed involving the unprotonated form of the entering ligand, viz. bipyridine/phenanthroline as the reactive species. The pK_a values of bipyridine and phenanthroline, determined from the kinetic data, are in agreement with the literature values. It is concluded that the substitutions of iron(II)-diimine complexes also occur by an associative mechanism.     

Synthesis and reactions oe 2-chlorohexafluorocyclopentene- and 2-chlorooctafluorocyclohexene-1-carbonitriles

2-Chlorohexafluorocyclopentene- and 2-chlorooctafluorocyclohexene-1-carbonitriles were synthesized. Products of substitution of the chlorine atoms by a phenylamino group and the fluorine atoms in the position by a phenylimino group were obtained by reaction of the products with aniline. The reactions with amidines of trifluoro- and trichloroacetic acids, as well as with 2-aminopyridine, lead to pyrimidine derivatives with condensed perfluorinated five- and six-membered rings.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1407–1409, October, 1982.