Remir G. Kostyanovsky

Asymmetrical nonbridgehead nitrogen-XXVI: Synthesis, configurational stability, and resolution of N,N-dialkoxyamines into antipodes

Abstract Alkoxyamines with tertiary N-alkyl substituents were chlorinated to N-chloro-N-alkoxyamines whose reaction with alcohols enabled synthesis of N,N-dialkoxyamines. The DNMR method was used to determine the barriers of inversion of these compounds. Alkaline hydrolysis ( 13 ) followed by subsequent reactions with R -(+)- and S -(−)-α-phenylethylamine yielded diastereomeric salts (+ 29 and − 29 ) whose crystallization and subsequent esterification resulted in optically active acyclic amines (− 13 and + 13 ) with the asymmetric center only at the N atom in the open chain.

Asymmetric nitrogen—41: Stereochemistry of bicyclic 1,2-cis-diaziridines

Abstract The twisting of 5- and 6-membered rings in bicyclic cis-diaziridines—1,5-diazabicyclo [3.1.0]hexanes 12–17 and l,6-diazabicyclo[4.1.0]heptane 18—is a rapid process in the time scale of 1H- and 13C-NMR even at -80°. According to the 1H- and 13C-NMR spectra, 1,5-diazabicyclo [3.1.0]hexanes 12,13,15a,15b and 16a,16b do, exist mostly in the boat form ; only the introduction of endo substituents into position 3 or 6 leads to the population of the chair, as is the case with 14 and 17. 2,4-Dialkyl substituted 1,5-diaza- and 1,3,5-triazabicyclo[3.1.0]hexanes are formed via a transition cyclization state similar in its geometry to the initial chair-shaped N-chlorodi(tri)azanes.

Asymmetric nitrogen−35 : Structure and properties of l(s)-α-carboxyethyl-3, 3-bis(trifluoromethyl)diaziridine and its derivatives

Abstract A second-kind asymmetric transformation involving N-atom inversion has been observed at 20° for 1(S) - α - carboxyethyl - 3,3 - bis(trifluoromethyl)diaziridine 1 and its methyl ester 2. X-Ray data for the diastereomer (1S, 2S, α-S), 1A (which is thermodynamically preferred in the crystalline phase), 1H NMR spectra of ethyl ester 3-15N(1) and 3-15N(2), CD spectra of 1A,B, 2A,B, potassium salt 4A,B and semiempirical calculations (MINDO/3 and INDO) for 1A, show that the stereospecificity of crystallization of the diastereomer A is due to the higher energy of the crystal lattice of the diastereomer (1R, 2R, α-S), 1B because of hindered charge compensation as well as to the hindrance by the CF3, groups to intermolecular H-bonds. According to semiempirical calculations, the stability of 3,3 - bis(trifluoromethyl) - diaziridines (TFD) to the action ofel w-orbital energies and depolarization of the C-N bonds due to hyperconjugation and the inductive effect of the CF3,-groups. The steric effect of these groups is the reason of the low configurational stability of TFD compared with the 3,3-dimethyl analogues.

Asymmetrical nonbridgehead nitrogen—30 geminal systems—21: The influence of vicinal n — σ* interaction on the pyramidal stability of tricoordinated nitrogen atom in the geminal system

Abstract The vicinal n - σ* interaction stabilizes the pyramidal state of the nitrogen geminal system where X and Y are electronegative substituents with high-lying levels of nonbonding n orbitals. A approximate value for the energy of n - σ* stabilization of pyramidal state in N , N -dialkoxyamines, equal to ∼5.7 kcal/mol, has been found by comparing the average experimental value of the inversion barrier for these compounds with the one calculated according to the additive scheme. The influence of the vicinal n - σ* interaction on the structural peculiarities of N -alkoxyisoxazolidines manifests itself in the conformations with the greatest overlapping of n and σ* orbitals being predominantly populated and in a change in NO bond lengths and valence angles. The combination of a ligand having the highest-lying level of n orbital with a ligand, which forms the σ bond with a N atom, having the lowest-lying antibonding level results in the dissociation of a nitrogen geminal system into an ionic planar form of the type. From this is inferred the dual nature of the influence exerted by the vicinal n - σ* interaction upon the inversion barrier of the geminal system.

Self-assembly of cage structures. Paper 12: The synthesis and crystal structures of 2,5-diazabicyclo[2.2.2]octane-3,6-dione-1,4-dicarboxylic acids and their diesters ☆

Abstract Synthesis of racemic and enantiomeric 2,5-diazabicyclo[2.2.2]octane-3,6-dione-dicarboxylic acids and their diesters, as functionalized building blocks for supramolecular chemistry, is described. It is shown that heterochiral H-bonded zigzag tape with R22(8) graph and molecular ‘brick wall’ with a non-polar coating are persistent and stable motifs in the crystal structures of the racemic dialkyl 2,5-diazabicyclo[2.2.2]octane-3,6-dione-1,4-dicarboxylates ( 1 , 5 , 11 ). This stability was confirmed by quasi-racemate [CD(−)230]-1 · 4 formation and crystal structure determination. Packing of the diacids (±)-2 and (−)-2 dihydrates differed from that of esters, with H2O molecules linking homochiral spirals, into corrugated homochiral layers, observed in both structures. The crystal structure of enantiomeric diester (−)-1 contained spirals similar to those observed in diacids with participation of the ester carbonyl groups in H-bonding.

ASYMMETRICAL NITROGEN - 40; GEMINAL SYSTEMS - 26. N-CHLOROHYDRAZINES

Abstract The factors determining the kinetic and thermodynamic stabilities of N-chlorohydrazines are discussed. Acyclic N-chlorohydrazines exist only as trialkyldiazenium chlorides 3a,b. Chlorination of 2-acyl-1, 1-dimethylhydrazines 6a,b gave 1,4-diacyl-2,3-dimethylhexahydro-1,2,4,5-tetrazines 7a,b via hydrazyl radical intermediates, and chlorination of a 1-phenylpyrazolidin-5-one 8 gave phenylazoisovaleric esters 9a,b. Stable N-chlorohydrazines were obtained from bicyclic hydrazines; viz. the 2-chloro-1,2-diazabicyclo [2.2.2]octan-3-one 12 and 7-chloro-1,7-diazabicyclo[2.2.1]heptane 16. The restricted inversion of N(7) in 16 and its 1-methyl quaternary salt 21 were observed in the 13C-NMR spectra. The acyclic N-chloro-hydrazinium salt 25 was isolated.

Asymmetrical nonbridgehead nitrogen—XXIV: Complete separation into antipodes and absolute configuration of chiralic N-alkoxyaziridines

Optically active derivatives of 1 - methoxyaziridine - 2,2 - dicarboxylic acid have been obtained: the diethyl ester S-(− 1a) by kinetic enrichment under the action of 1-ephedrine; the diamines R-(+2d) and S-(−2f) by crystallization from 1-methyllactate; the diamide S-(−2g) by asymmetric inversion reaction at the N atom while heating in 1-methyllacetate. The basic possibility of 1-alkoxyaziridine reactions with retention of optical activity (ammonolysis and reduction with LAH4) has been demonstrated for S-(−1a) and R-(+1). 1-Methoxy - aziridine - 2,2 - dicarboxylic acid cis-ethyl ester 4 has been completely separated into antipodes 1R, 2S-(+4) and 1S, 2R-(−4) which under the effect of diazoethane afford diethyl esters R-(+1) and S-(−1) with optical purity of 96.2 and 93.8% (determined by PMR using a chiralic shift-reagent). On the basis of X-ray analysis of monoamides of 1 - methoxyaziridine - 2,2 - dicarboxylic acid ethyl ester and of salt +7 the trans-specificity of ammonolysis and hydrolysis of 1 and the absolute configurations of all the optically active derivatives obtained were established.

Asymmetric nitrogen - 70. geminal systems - 44. trialkoxy-amines(orthonitrites). Synthesis and properties

Abstract The chlorination of acyclic N,N-dialkoxyamines under the action of tert-BuOCl results in the formation of unstable N-chloro-N,N-dialkoxyamines which in situ react with sodium methoxide to give previously unknown trialkoxyamines (orthonitrites). The properties of the N-chloro-N,N-dialkoxy-and trialkoxyamines have been demonstrated to be similar to those of their carbon analogues: dialkoxyalkylchlorides and orthoesters, respectively.

Temperature-dependent racemic compound-conglomerate crystallization of 2,3 :6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-dione

Abstract 2,3:6,7-dibenzobicyclo[3.3.1]nona-2,6-diene-4,8-dione 1 is a new example of a compound capable of temperature-dependent racemate-conglomerate crystallization: at temperatures below 90°C crystals of the racemic compound (space group P 1, Z =4) can be obtained, whereas above 100°C a conglomerate of (+)- and (−)-homochiral crystals (space group P 2 1 2 1 2 1 , Z =4) forms and therefore it undergoes spontaneous resolution upon crystallization. Enantioselective analytical gas chromatography on a single crystal has been proposed as a simple method for detection of conglomerate formation. The 1 H and 13 C NMR spectra of 1 are analyzed in detail and the crystal structures of both species (racemic compound and single enantiomer) have been solved by X-ray structural analysis.

The chiral drug Albicar: resolution of its racemate via complexation with BINOL

Both enantiomers of the title drug (2,6-diethyl-4,8-dimethylglycoluril; 1) were prepared from their complexes with (R)- and (S)-BINOL in 59% ((+)-1) and 43% ((−)-1) yield from its racemate. The absolute configuration of (1R,5R)-(+)-1 was determined by an XRD study of the (R)-(+)-BINOL-(+)-1·H2O complex.