The synthesis and transformations of 2‐[2‐ethoxycarbonyl‐2‐(2‐pyridinyl)ethenyl]amino‐3‐dimethylaminopropenoates. the synthesis of substituted β‐amino‐α,β‐didehydro‐a‐amino acid derivatives

Alkyl (Z)‐2‐[(E)‐2‐ethoxycarbonyl‐2‐(2‐pyridinyl)ethenyl]amino‐3‐dimethylaminopropenoates 7 and 8 were prepared from ethyl 2‐pyridinylacetate (1) in two steps. Substitution of the dimethylamino group with alkyl‐, aryl‐, or heteroarylamines afforded the corresponding β‐alkyl‐ 22–24 , β‐aryl‐ 25–35 , and β‐herteroaryl‐amino‐α,β‐didehydro‐α‐amino acid 36 and 37 derivatives, intermediates for further preparation of various heterocyclic systems. The orientation around both double bonds were determined by various nmr techniques.     

Synthesis of 3‐Ω‐amino‐2‐thiohydantoins

In the reaction of ethyl isothiocyanatoacetate with diamines, followed by cyclization of the intermediate product, 3‐monosubstituted thiohydantoins have been obtained. It was found that the reaction course depends on the purity of the isothiocyanate used and also, in the case of dialkylaminoamines, the self‐cyclization occurs. Besides the dialkylamino derivatives of 3‐monosubstituted 2‐thiohydantoins also new monoalkylamino, amino and heterocyclic derivatives were synthesized. The aryldiazonium derivative of 3‐monosubstituted 2‐thiohydantoin yielded both respective phenol derivative after hydrolysis and the product of coupling with 2‐naphthol.     

An amino–imino resonance study of 2‐amino‐4‐methylpyridinium nitrate and 2‐amino‐5‐methylpyridinium nitrate

The contributions of the amino and imino resonance forms to the ground‐state structures of 2‐amino‐4‐methylpyridinium nitrate, C₆H₉N₂⁺·NO₃⁻, and the previously reported 2‐amino‐5‐methylpyridinium nitrate [Yan, Fan, Bi, Zuo & Zhang (2012). Acta Cryst. E 68 , o2084], were studied using a combination of IR spectroscopy, X‐ray crystallography and density functional theory (DFT). The results show that the structures of 2‐amino‐4‐methylpyridine and 2‐amino‐5‐methylpyridine obtained upon protonation are best described as existing largely in the imino resonance forms.     

4‐Dimethyl­amino‐β‐nitro­styrene and 4‐dimethyl­amino‐β‐ethyl‐β‐nitro­styrene at 100 K

The structures of 4‐dimethyl­amino‐β‐nitro­styrene (DANS), C₁₀H₁₂N₂O₂, and 4‐dimethyl­amino‐β‐ethyl‐β‐nitro­styrene (DAENS), C₁₂H₁₆N₂O₂, have been solved at T = 100 K. The structure solution for DANS was complicated by the presence of a static disorder, characterized by a misorientation of 17% of the mol­ecules. The mol­ecule of DANS is almost planar, indicating significant conjugation, with a push–pull effect through the styrene skeleton extending up to the terminal substituents and enhancing the dipole moment. As a consequence of this conjugation, the hexa­gonal ring displays a quinoidal character; the lengths of the C—N [1.3595 (15) Å] and C—C [1.448 (2) Å] bonds adjacent to the benzene ring are shorter than single bonds. The mol­ecules are stacked in dimers with anti­parallel dipoles. In contrast, the mol­ecule of DAENS is not planar. The ethyl substituent pushes the nitro­propene group out of the benzene plane, with a torsion angle of −21.9 (3). Nevertheless, the mol­ecule remains conjugated, with a shortening of the same bonds as in DANS.     

Improved Synthesis of 2‐Chloro‐3‐amino‐4‐methylpyridine

2‐Chloro‐3‐amino‐4‐methylpyridine ( 1 ), a key intermediate in the synthesis of nervirapine, was prepared from 2‐cyanoacetamide and 4,4‐dimethoxyl‐2‐butanone via condensation, cyclization, one‐pot reaction of chlorination and hydrolysis, and Hofmann reaction. Utilization of the quadratic orthogonal test resulted in a high yield (62.1%) of the whole process.     

Polar aspects of intramolecular interactions in 2‐amino‐5‐nitro‐4‐methylpyridines and 2‐amino‐3‐nitro‐4‐methylpyridines

The dipole moments of twelve 2‐N‐substituted amino‐5‐nitro‐4‐methylpyridines ( I‐XII ) and three 2‐N‐substituted amino‐3‐nitro‐4‐methylpyridines ( XIII‐XV ) were determined in benzene. The polar aspects of intramolecular charge‐transfer and intramolecular hydrogen bonding were discussed. The interaction dipole moments, μ_int, were calculated for 2‐N‐alkyl(or aryl)amino‐5‐nitro‐4‐methylpyridines. Increased alkylation of amino nitrogen brought about an intensified push‐pull interaction between the amino and nitro groups. The solvent effects on the dipole moments of 2‐N‐methylamino‐5‐nitro‐4‐methyl‐( I ), 2‐N,N‐dimethylamino‐5‐nitro‐4‐methyl‐ ( II ) and 2‐N‐methylamino‐3‐nitro‐4‐methylpyridines ( XIII ) were different. Specific hydrogen bond solute‐solvent interactions increased the charge‐transfer effect in I , but it did not disrupt the intramolecular hydrogen bond in XIII.     

Z and E isomers of butenedioic acid with 2‐amino‐1,3‐thiazole: 2‐amino‐1,3‐thiazolium hydrogen maleate and 2‐amino‐1,3‐thiazolium hydrogen fumarate

Maleic acid and fumaric acid, the Z and E isomers of butenedioic acid, form 1:1 adducts with 2‐amino‐1,3‐thiazole, namely 2‐amino‐1,3‐thiazolium hydrogen maleate (2ATHM), C₃H₅N₂S⁺·C₄H₃O₄⁻, and 2‐amino‐1,3‐thiazolium hydrogen fumarate (2ATHF), C₃H₅N₂S⁺·C₄H₃O₄⁻, respectively. In both compounds, protonation of the ring N atom of the 2‐amino‐1,3‐thiazole and deprotonation of one of the carboxyl groups are observed. The asymmetric unit of 2ATHF contains three independent ion pairs. The hydrogen maleate ion of 2ATHM shows a short intramolecular O—H...O hydrogen bond with an O...O distance of 2.4663 (19) Å. An extensive hydrogen‐bonded network is observed in both compounds, involving N—H...O and O—H...O hydrogen bonds. 2ATHM forms two‐dimensional sheets parallel to the ab plane, extending as independent parallel sheets along the c axis, whereas 2ATHF forms two‐dimensional zigzag layers parallel to the bc plane, extending as independent parallel layers along the a axis.     

Polymeric (3‐amino‐2‐chloropyridine)nitratosilver(I)

In the title compound {alternative name: poly­[silver(I)‐μ‐(3‐­amino‐2‐chloro­pyridine)‐μ‐nitr­ato]}, [Ag(NO₃)(C₅H₅ClN₂)]_n the Ag^I atom is in an irregular AgN₂O₃ geometry, surrounded by one pyridyl N atom [Ag—N 2.283 (5) Å], one amine N atom [Ag—N 2.364 (6) Å] and three O atoms from different nitrate ions [Ag—O 2.510 (6)–2.707 (6) Å]. The Ag ions are bridged by the 3‐amino‐2‐chloro­pyridine ligands into helical chains. Adjacent uniform chiral chains are further interlinked through the NO₃ bridges into an interesting two‐dimensional coordination network in the solid.     

Halogen,hydrogen and electrostatic interactions in 2‐amino‐5‐chloro‐1,3‐benzoxazol‐3‐ium nitrate and 2‐amino‐5‐chloro‐1,3‐benzoxazol‐3‐ium perchlorate

In the title compounds, C₇H₆ClN₂O⁺·NO₃⁻ and C₇H₆ClN₂O⁺·ClO₄⁻, the ions are connected by N—H...O hydrogen bonds and halogen interactions. Additionally, in the first compound, co‐operative π–π stacking and halogen...π interactions are observed. The energies of the observed interactions range from a value typical for very weak interactions (1.80 kJ mol⁻¹) to one typical for mildly strong interactions (53.01 kJ mol⁻¹). The iminium cations exist in an equilibrium form intermediate between exo‐ and endocyclic. This study provides structural insights relevant to the biochemical activity of 2‐amino‐5‐chloro‐1,3‐benzoxazole compounds.     

Reactions of N‐arylmaleimides with 3‐amino‐1,2,4‐triazole and 2‐aminobenzimidazole

The reaction of 3‐amino‐1,2,4‐triazole ( 1 ) with N‐arylmaleimides leads to azolopyrimidines 4 and 5 . The 2‐aminobenzimidazole ( 2 ) in the reaction with 3 gives the pyrimidobenzimidazoles 6 . In similar conditions, the reaction of amine 2 with maleic anhydride ( 7 ) leads to formation of 2‐oxo‐1,2,3,4‐tetrahydropyrimido[1,2‐a]benzimidazole‐4‐carboxylic acid ( 8 ). The structures of 4 , 5 , 6 , and 8 were proved by X‐Ray and NOE NMR measurements. J. Heterocyclic Chem., (2011)     

Synthesis of 2‐amino‐4,5‐dihydro‐3‐methanesulfonylfurans (and ‐thiophenes)

2‐Amino‐4,5‐dihydro‐3‐methanesulfonylfurans 7 and 2‐amino‐4,5‐dihydro‐3‐methanesulfonylthiophenes 8 were prepared by deamidation of tetrahydro‐2‐imino‐3‐methanesulfonyl‐3‐furancarboxamides 3 and of tetrahydro‐2‐imino‐3‐methanesulfonyl‐3‐thiophenecarboxamides 4 with bases. Compounds 3 and 4 were obtained by reaction of 2‐amino‐4,5‐dihydro‐3‐furancarboxamides 1 and 2‐amino‐4,5‐dihydro‐3‐thio‐phenecarboxamides 2 with methanesulfonyl chloride in the presence of triethylamine.     

5‐Acetyl‐2‐amino‐6‐methyl‐4‐(3‐nitrophenyl)‐4H‐pyran‐3‐carbonitrile and 2‐amino‐5‐ethoxycarbonyl‐6‐methyl‐4‐(3‐nitrophenyl)‐4H‐pyrano‐3‐carbonitrile

The structures of the title compounds, C₁₅H₁₃N₃O₄, (I), and C₁₆H₁₅N₃O₅ [IUPAC name: ethyl 6‐amino‐5‐cyano‐2‐methyl‐4‐(3‐nitro­phenyl)‐4H‐pyrano‐3‐carboxyl­ate], (II), are very similar, with the heterocyclic rings adopting boat conformations. The pseudo‐axial m‐nitro­phenyl substituents are rotated by 84.0 (1) and 98.7 (1)° in (I) and (II), respectively, with respect to the four coplanar atoms of the boat. The dihedral angles between the phenyl rings and nitro groups are 12.1 (2) and 8.4 (2)° in (I) and (II), respectively. The two compounds have similar patterns of intermolecular N—H?O and N—H?N hydrogen bonding, which link mol­ecules into infinite tapes along b .     

Synthesis of novel 2‐amino‐6,8‐dithioxopurine derivatives

The synthesis of novel 2‐amino‐9‐alkoxyalkylpurine derivatives with both identical and different sulfur containing substituents at positions 6 and 8 of the purine cycle has been accomplished. The thionation and alkylation of the key intermediate ‐ 2‐[2‐(acetylamino)‐6,8‐dichloro‐9H‐purin‐9‐yl]methoxyethyl acetate or its reactions with thiolates were used. The structures of compounds obtained were confirmed by spectroscopic data and X‐ray diffraction analysis.     

Synthesis of 1‐amino‐2‐methylindoline by Raschig process: Kinetics of the oxidation of 1‐amino‐2‐methylindoline by chloramine

The synthesis of 1‐amino‐2‐methylindoline by the Raschig process was undertaken in aqueous solution. The principal side reaction that occurs in the medium is the oxidation of 1‐amino‐2‐methylindoline formed by chloramine. To increase the yield of 1‐amino‐2‐methylindoline, its oxidation by chloramine was studied by GC and HPLC at various concentrations of reactants and for a pH interval ranging between 9.9 and 13.5. The reaction is bimolecular and exhibits a specific acid catalysis. In alkaline medium, 1‐amino‐2‐methylindole is the principal product. The enthalpy and entropy of activation were determined at pH 12.89. In unbuffered solution, the interaction was autocatalyzed by the ammonium ions formed, which indicates a competitive oxidation of neutral and ionic forms of 1‐amino‐2‐methylindoline by chloramine. A mathematical treatment based on one implicit equation allows a quantitative interpretation of all the phenomena observed over the above pH interval. It takes both acid–base dissociation equilibrium and alkaline hydrolysis of chloramine into account. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 515–523, 2002     

Complexes of diethyl‐2‐amino‐2‐oxoethylphosphonate with lanthanide nitrates

Lanthanide complexes LnL₂(NO₃)₃ 3a–f are obtained where Ln is La, Ce, Sm, Eu, Er, and Yb and L is the diethyl 2‐amino‐2‐oxoethylphosphonate. They were characterized by elemental analysis, IR, and NMR spectroscopy. Monodentate coordination by the phosphoryl group is suggested for the ligand on the basis of the spectral data. The stabilization is achieved by including a molecule of the solvent in the complexes 3a–d . © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:128–131, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10112     

The reaction of amino‐imidazoles, ‐pyrazoles and ‐triazoles with α,β‐unsaturated nitriles

The reactions of α,β‐unsaturated nitriles ( 1, 9, 12 ) as bielectrophiles with aminoazoles ( 2, 4, 6 ) as binu‐cleophiles were investigated. Acrylonitrile ( 1 ) reacts almost exclusively in a chemoselective Michael‐type addition yielding the substituted azoles 3, 5 and 7 , respectively. Cinnamonitriles 9a,b behave in a similar way, but the free CN group adds a second molecule 4 yielding 10a,b and its cyclocondensation product 11a,b as minor component. The attempted formation of azolopyrimidines is best achieved by the reaction of the benzylidenemalononitriles 12a ‐ f with 2 or 4 . The process is chemo‐ and regioselective. The structure determinations were based on NMR measurements including DEFT, COSY, ROESY, HMQC and HMBC techniques and correct earlier suggestions.     

Ethyl 6‐amino‐2‐methoxypyridine‐3‐carboxyl­ate,interplay of molecular and supramolecular structure

The title compound, C₉H₁₂N₂O₃, crystallizes with two mol­ecules in the asymmetric unit. There is extensive hydrogen bonding which results in the formation of a two‐dimensional corrugated sheet. This supramolecular structure is determined by the formation of hydrogen‐bonded chains resulting from the presence of a 6‐amino group and an ethoxy­carbonyl group as substituents on a pyridine ring in relative para positions which constitute a π‐electron `push–pull' system.     

Synthesis of N‐amino‐3‐hydroxy‐2‐phenyl‐4(1H)‐quinolinone

2‐[(Disubstituted‐methylene)‐hydrazino] benzoic acid phenacylesters 2a‐2d , prepared from anthranilic acid phenacylester 1 , were unsuccesfully tried as starting materials for the synthesis of N‐amino‐3‐hydroxy‐2‐phenyl‐4(1H)‐quinolinone 8 . The desired compound 8 was prepared by cyclization of N‐acetyl as well as N‐benzoyl‐hydrazinobenzoic acid phenacylester 6a or 6b in polyphosphoric acid to afford N‐acylamino‐3‐hydroxy‐2‐phenyl‐4(1H)‐quinolinone 7a or 7b , respectively. Surprisingly, the acyl group was resistant to attack by both hydrochloric acid as well as sodium hydroxide solution. It could be removed by boiling the compounds 7a or 7b respectively in 50% sulphuric acid to afford the the target compound 8 .     

Ethyl 3‐amino‐6‐phenyl‐4‐tolylthieno[2,3‐b]pyridine‐2‐carboxylate

In the title compound, C₂₃H₂₀N₂O₂S, the central thieno­pyridine ring system is essentially planar, the dihedral angle between the planes of the two rings being 0.3 (2)°. The terminal ethyl carboxyl­ate group is twisted by 26.7 (3)° away from the central ring system. A short intramolecular hydrogen bond involving the amino N atom and the carbonyl O atom [N⋯O = 2.806 (4) Å] forms a pseudo‐six‐membered ring. Significant intermolecular C—H⋯N, C—H⋯O and C—H⋯π interactions contribute strongly to the stability of the structure, along with weak π–π‐stacking interactions.