Ranitidine hydro­chloride,a polymorphic crystal form

In the title compound, di­methyl­({5‐[2‐(1‐methyl­amino‐2‐nitro­eth­enyl­amino)­ethyl­thio­methyl]‐2‐furyl}­methyl)­ammon­ium chloride, C₁₃H₂₃N₄O₃S⁺·­Cl^?, protonation occurs at the di­methyl­amino N atom. The ranitidine mol­ecule adopts an eclipsed conformation. Bond lengths indicate extensive electron delocalization in the N,N′‐di­methyl‐2‐nitro‐1,1‐ethenedi­amine system of the mol­ecule. The nitro and methyl­amino groups are trans across the side chain C=C double bond, while the ethyl­amino and nitro groups are cis. The Cl^? ions link mol­ecules through hydrogen bonds.     

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.     

13C NMR chemical shifts of N-unsubstituted- and N-methyl-pyrazole derivatives

¹³C shielding data for 100 derivatives of pyrazole are reported. These include methyl, ethyl, n-propyl, tert-butyl, phenyl, hydroxymethyl, carboxyl, ethoxycarbonyl, cyano, amino, hydrazino, nitro, azido, chloro, bromo and iodo groups as substituents on the ring carbon atoms.     

Cyano–cyano and chloro–cyano interactions in two imidazole derivatives

In two closely related 1‐aryl‐2‐methyl‐4‐nitro‐5‐cyano­imid­azoles, namely 2‐methyl‐4‐nitro‐1‐phenyl‐1H‐imidazole‐5‐carbo­nitrile, C₁₁H₈N₄O₂, and 1‐(4‐chloro­phenyl)‐2‐methyl‐4‐nitro‐1H‐imidazole‐5‐carbo­nitrile, C₁₁H₇ClN₄O₂, different weak intermolecular interactions determine the crystal packing. In the 1‐phenyl derivative, dipole–dipole interactions between antiparallel cyano groups connect mol­ecules into centrosymmetric dimers, while in the 1‐(4‐chloro­phenyl) derivative, the dimers are connected by C≡N⋯Cl—C halogen bonds. These interactions, together with weak C—H⋯O(N) hydrogen bonds, connect mol­ecules related by subsequent centres of inversion into infinite tapes.     

5‐Nitro‐2‐nitromethyl‐2H‐1,2,3,4‐tetrazole

The mol­ecule of the title compound, C₂H₂N₆O₄, consists of three planar fragments, namely a tetrazole ring, a nitro­methyl group and a nitro group. The nitro group and the tetrazole cycle are arranged in the same plane, but the planar nitro­methyl group is located nearly orthogonal to this plane. The mol­ecules are packed in the crystal via van der Waals interactions.     

2‐[2‐Methyl‐5‐nitro‐4‐(phenyl­sulfonyl­methyl)­imidazol‐1‐yl]­ethanol and 2‐methyl‐5‐nitro‐4‐phenyl­sulfonyl­methyl‐1,3‐thia­zole

The title compounds, C₁₃H₁₅N₃O₅S and C₁₁H₁₀N₂O₄S₂, respectively, both contain a phenyl­sulfonyl group connected, through a methyl­ene bridge, to either a substituted nitro­imidazole or nitro‐1,3‐thia­zole ring. In the imidazole‐containing mol­ecule, the nitro and sulfonyl groups are trans relative to the sulfonyl–methyl bond, while in the thia­zole‐containing mol­ecule, these substituents are cis. The stabilizing interactions within the crystals are also different between the two compounds.     

Mass spectrometry of imidazole-4(5)-carboxaldehyde and some 1-methyl and nitro derivatives

The mass spectra of imidazole-4(5)-carboxaldehyde, its two 1-methyl derivatives, 4(5)-nitroimidazole, 5(4)-nitroimidazole-4(5)-carboxaldehyde and 1-methyl-5-nitroimidazole-4-carboxaldehyde are presented and discussed in comparison with those of other imidazole-carboxaldehydes and nitroimidazoles earlier reported. The imidazole-carboxaldehydes and their 1-methyl derivatives exhibit the characteristic fragmentation of aromatic aldehydes, and differences between the isomers can be observed. The nitroimidazoles show the fragmentation typical of aromatic nitrocompounds. In the o-nitroimidazole-carboxaldehydes, the typical losses of aldehydes do not occur, but primary ortho effects between the formyl and nitro groups give rise to important fragmentation routes. In their 1-methyl derivatives, the presence of the methyl group adjacent to the nitro group originates additional double and secondary ortho effects. For some of these transformations, fragmentation mechanisms are proposed.     

Acid Catalyzed tert‐Butylation and Tritylation of 4‐Nitro‐1,2,3‐triazole: Selective Synthesis of 1‐Methyl‐5‐nitro‐1,2,3‐triazole via 1‐tert‐Butyl‐4‐nitro‐1,2,3‐triazole

4‐Nitro‐1,2,3‐triazole was found to react with tert‐butanol in concentrated sulfuric acid to yield 1‐tert‐butyl‐4‐nitro‐1,2,3‐triazole as the only reaction product, whereas tert‐butylation and tritylation of 4‐nitro‐1,2,3‐triazole in presence of catalytic amount of sulfuric acid in benzene was found to provide mixtures of isomeric 1‐ and 2‐alkyl‐4‐nitro‐1,2,3‐triazoles with predominance of N2‐alkylated products. A new methodology for preparation of 1‐alkyl‐5‐nitro‐1,2,3‐triazoles from 1‐tert‐butyl‐4‐nitro‐1,2,3‐triazole via exhaustive alkylation followed by removal of tert‐butyl group from intermediate triazolium salts was demonstrated by the example of preparation of 1‐methyl‐5‐nitro‐1,2,3‐triazole.     

Synthesis of Poly(arylene ether amide)s Containing CF3 Groups by Nitro Displacement Reaction of AB‐Type Monomers

New poly(arylene ether amide)s with trifluoromethyl pendent groups were prepared via nucleophilic nitro displacement reaction of AB‐type monomers. 4‐Nitro‐3‐trifluoromethyl‐[N‐(4‐hydroxyphenyl)]benzamide ( 3 ) and 4‐nitro‐3‐trifluoro‐methyl‐[N‐(3‐hydroxyphenyl)]benzamide ( 4 ) gave polymers with weight‐average molecular weights over 42 000 g/mol and glass transition temperatures of 269°C and 213°C, respectively. Both polymers were soluble in common organic solvents including THF, and formed transparent films upon casting.     

Methylated Phenylarsenical Metabolites Discovered in Chicken Liver

We report the discovery of three toxicologically relevant methylated phenylarsenical metabolites in the liver of chickens fed 3‐nitro‐4‐hydroxyphenylarsonic acid (ROX), a feed additive in poultry production that is still in use in several countries. Methyl‐3‐nitro‐4‐hydroxyphenylarsonic acid (methyl‐ROX), methyl‐3‐amino‐4‐hydroxyphenylarsonic acid (methyl‐3‐AHPAA), and methyl‐3‐acetamido‐4‐hydroxyphenylarsonic acid (or methyl‐N ‐acetyl‐ROX, methyl‐N ‐AHPAA) were identified in such chicken livers, and the concentration of methyl‐ROX was as high as 90 μg kg⁻¹, even after a five‐day clearance period. The formation of these newly discovered methylated metabolites from reactions involving trivalent phenylarsonous acid substrates, S‐adenosylmethionine, and the arsenic (+3 oxidation state) methyltransferase enzyme As3MT suggests that these compounds are formed by addition of a methyl group to a trivalent phenylarsenical substrate in an enzymatic process. The IC₅₀ values of the trivalent phenylarsenical compounds were 300–30 000 times lower than those of the pentavalent phenylarsenicals.     

Silica‐tethered cuprous acetophenone thiosemicarbazone (STCATSC) as a novel hybrid nano‐catalyst for highly efficient synthesis of new 1,2,3‐triazolyl‐based metronidazole hybrid analogues having potent antigiardial activity

The preparation, characterization and application of silica‐tethered cuprous acetophenone thiosemicarbazone (STCATSC) as a novel hybrid nano catalyst for synthesis of new 1,2,3‐triazolyl‐based metronidazole hybrid analogues is described. STCATSC is fully characterized by different microscopic, spectroscopic and physical techniques, including scanning electron microscopy (SEM), transmission, X‐ray diffraction (XRD), Energy‐dispersive X‐ray spectroscopy (EDS), thermogravimetric analysis (TGA), FT‐IR and inductively coupled plasma (ICP) analysis. This catalyst is used to prepare the new 1,2,3‐triazolyl‐based metronidazole hybrid analogues. The ‘Click’ Huisgen cycloaddition reaction of 2‐methyl‐5‐nitro‐1‐prop‐2‐ynyl‐1H‐imidazole with diverse β‐azidoalcohols in a THF‐water media at R.T. provides the products in good to excellent yields using STCATSC. STCATSC is proved to be a stable, low cost, reusable and environmentally benign hybrid catalyst. Products are in vitro tested against Giardia lamblia (G. lamblia) in which determined that all compounds exhibit varied promising antigiardial activity compare to metronidazole as a reference drug. Among the products, 1‐(4‐((2‐methyl‐5‐nitro‐1H‐imidazol‐1‐yl)methyl)‐1H‐1,2,3‐triazol‐1‐yl)‐3‐phenethoxypropan‐2‐ol and 1‐(4‐((2‐methyl‐5‐nitro‐1H‐imidazol‐1‐yl)methyl)‐1H‐1,2,3‐triazol‐1‐yl)‐3‐(3‐phenylpropoxy)propan‐2‐ol are demonstrated to exhibit the potent antigiardial activity even stronger than metronidazole.     

A theoretical study of the structure and vibrations of 2,4,6-trinitrotolune

Theoretical calculations of the structure, internal rotations and vibrations of 2,4,6-trinitrotolune, TNT, in the gas phase were performed at the B3LYP/6-31G* and B3LYP/6-311+G** levels of theory. Two genuine energy minimum structures were found. In both structures the 4-nitro group is planar to the phenyl ring, while the 2,6-nitro groups are slightly out of plane with the phenyl ring due to steric interaction with the methyl group. The two structures are related by internal rotations of the methyl and 2, or 6-nitro group. The lowest energy route for interconversion between them is a concerted motion of the methyl group and 2 or 6 nitro group in a ‘cog wheel’ type of mechanism. The geometry of the low energy structure A is closest to that observed in the crystal structures of TNT, where all three nitro groups are out of plane with the phenyl ring. FTIR and Raman spectra of solid TNT and ¹³C, ¹⁵N enriched TNT are presented and assigned with the help of the B3LYP/6-311+G** calculations on A. The lower level B3LYP/6-31G* calculation fails to predict the correct vibrational coupling between the nitro and phenyl groups. The B3LYP/6-311+G** calculation gives a good prediction of the nitro vibrations and the isotopic shifts observed for TNT isotopomers.     

3,5‐Bis[(N,N‐di­methyl­amino)­methyl­ene­amino]‐1‐methyl‐4‐nitro­pyrazole from X‐ray powder diffraction data

The structure of the title compound, C₁₀H₁₇N₇O₂, was determined using a bond‐restrained Rietveld refinement which gave bond lengths and angles within the expected ranges. Although the two nearly planar (N,N‐dimethylamino)methyleneamino groups are inclined at approximately 46° to the pyrazole ring, the conformations of the two amino chains are different, owing to either a repulsion effect of the pyrazole‐methyl group or a short interatomic contact with the nitro group in one of the chains.     

Synthesis of D‐Desosamine and Analogs by Rapid Assembly of 3‐Amino Sugars

D ‐Desosamine is synthesized in 4 steps from methyl vinyl ketone and sodium nitrite. The key step in this chromatography‐free synthesis is the coupling of (R)‐4‐nitro‐2‐butanol and glyoxal (trimeric form) mediated by cesium carbonate, which affords in crystalline form 3‐nitro‐3,4,6‐trideoxy‐α‐D ‐glucose, a nitro sugar stereochemically homologous to D ‐desosamine. This strategy has enabled the syntheses of an array of analogous 3‐nitro sugars. In each case the 3‐nitro sugars are obtained in pure form by crystallization.     

Studies of the Synthesis of Rubranitrose and Crystal Structure of Methyl 2,3,6-Trideoxy-3-C-Methyl-3-Nitro-α-D-Ribo-Hexopyranoside

Abstract

The branched-chain nitro sugar methyl 2,3,6-trideoxy-3-C-methyl-3-nitro-α-D-ribo-hexopyranoside 4 was investigated as a precursor to D-rubranitrose, a nitro sugar found in the antibiotic rubradirin. X-ray cyrstallographic analysis of 4 shows that the pyranose ring adopts the ⁴ C ₁ conformation with the methoxy group at C-1 and the nitro group at C-3 in a 1,3-diaxial relationship. There is an intermolecular hydrogen bond involving a nitro group oxygen of one monosaccharide residue and the C-4 hydroxyl group of the adjacent residue in the crystal lattice. This interaction results in a helical crystal packing. A series of nucleophilic displacement reactions was carried out on the triflate derivative of 4 in an attempt to introduce an axial carbon-oxygen bond at C-4 required for rubranitrose. Displacements with acetate and propionate gave as products the monosaccharide esters with the desired D-xylo configuration.     

Weak C–H⋯O and C–H⋯N ­interactions in nitro­pyrazoles

The structures of 1‐methyl‐3‐nitro­pyrazole and 1‐methyl‐4‐nitro­pyrazole, C₄H₅N₃O₂, have been determined. The 3‐nitro derivative has crystallographic m‐symmetry while the 4‐nitro compound has no imposed symmetry. The significant differences in bond distances and angles between the structures are ascribable to the electron‐withdrawing effects of the nitro group attached to C3 or C4, respectively. In both structures, the mol­ecules are organized into layers by an extensive network of C—H?O or C—H?N hydrogen interactions. Within a layer, the mol­ecules are arranged in a similar way, although differences of up to 0.3 Å in the analogous H?O or H?N intermolecular distances are observed. The cohesion of the layers is due to van der Waals and C—H?O contacts.     

Use of some aryl and heteroaryl nitrilimines and nitrones in the synthesis of spiroheterocycles

1,3‐Dipolar cycloadditions of C‐(5‐nitro‐2‐furyl)‐N‐methyl nitrilimine (2a) , C‐(5‐nitro‐2‐furyl)‐N‐phenyl nitrilimine (2b) , C‐4‐nitrophenyl‐N‐methyl nitrilimine (2c) and C,N‐diphenyl nitrilimine (2d) with 1‐R‐substituted 3,3‐methylene‐5,5‐dimethylpyrrolidin‐2‐ones (1a‐d) where R is H, acetyl, 1,1‐dimethylethoxycarbonyl and 1‐methylethenyl proceed with complete regioselectivity in good yields to afford 1,3,7‐trisubstituted‐6‐oxo‐8,8‐dimethyl‐1,2,7‐triazaspiro[4,4]non‐2‐enes (5a‐g) exclusively. Cycloaddition of C‐(5‐nitro‐2‐furyl)‐N‐phenylnitrone (3b) to the exocyclic double bond of the dipolarophile 1a proceeds to 2‐phenyl‐3‐(5‐nitro‐2‐furyl)‐6‐oxo‐8,8‐dimethyl‐1‐oxa‐2,7‐diazaspiro[4,4]nonane (7) with complete regio‐ and stereoselectivity.     

Nitroradical Anion Formation from some Iodo‐Substituted Nitroimidazoles

The electrochemical behavior of iodo nitroimidazole derivatives such as 1‐methyl‐4‐iodo‐5‐nitroimidazole (M‐I‐NIm) and 1‐methyl‐2,4‐diiodo‐5‐nitroimidazole (M‐I₂‐NIm) and the parent compound 1‐methyl‐5‐nitroimidazole (M‐NIm), was studied in protic, mixed and non‐aqueous media. The electrochemical study was carried out using Differential Pulse Polarography (DPP), Cyclic Voltammetry (CV), Differential Pulse Voltammetry (DPV) and coulometry and as working electrodes mercury and glassy carbon were used. As can be expected, in all media, the effect of introduce iodo as substituent in the nitroimidazole ring produced a decrease of the energy requirements of the nitro group reduction. Certainly, this fact can be explained by the electron withdrawing character of the iodo substituent that acts diminishing the electronic density on the nitro group thus facilitating their reduction. In all the studied media the reduction of M‐NIm produced a detectable signal for a nitro radical anion derivative. In the case of M‐I‐NIm the nitro radical anion was only detectable in both mixed and non‐aqueous media. On the other hand the nitro radical anion for the M‐I₂‐NIm was detected only in non‐aqueous medium. When glassy carbon electrode was used as the working electrode in a mixed medium a detectable nitro radical anion derivative appeared for all compounds, thus permitting an adequate comparison between them. The obtained values of k₂ for M‐NIm, M‐I‐NIm and M‐I₂‐NIm in non‐aqueous medium were 5.81×10², 132×10² and 1100×10² M^?1 s^?1, respectively. From the obtained k₂ and t_1/2 values in this medium, it is concluded that there is a direct dependence between the presence of iodo substitution in the nitroimidazole ring with the stability of the nitro radical anion.     

2‐Nitro‐1,4‐diaminobenzene‐Functionalized Poly(vinyl amine)s as Water‐Soluble UV‐Vis‐Sensitive pH Sensors

Summary: Nucleophilic aromatic substitution of 2,6‐O‐dimethyl‐β‐cyclodextrin (β‐DMCD)‐complexed 4‐fluoro‐3‐nitroaniline derivatives with poly(vinyl amine) (PVAm) in water results in 2‐nitro‐1,4‐benzenediamine‐functionalized water‐soluble PVAms in one step. The 2‐nitro‐1,4‐benzenediamine moiety linked to the polymer is solvatochromic and undergoes protonation and deprotonation as function of pH as shown by UV‐Vis spectroscopy. The occurrence of an isosbestic point in the UV‐Vis spectrum is suitable to directly determine the pK_a value using the Henderson‐Hasselbalch equation. The influence of the methyl group substitution of the polymer and the 2‐nitro‐1,4‐benzenediamine moiety on the pK_a is discussed.

Structure of the 4‐N,N‐dimethyl‐2‐nitro‐1,4‐benzenediamine‐functionalized PVAm and its solution in water at varying pH.