Diamino Derivatives Research Articles

Selective mono- and diamination of some polyhalogenbenzenes in anhydrous ammonia

Abstract Aminodefluorination of polyhalogenbenzenes (chloropentafluoro-, 1,3-dichlorotetrafluoro-, sym -trichlorotrifluoro-, 1,2,3,5-tetrafluoro- and 1,2,4,5-tetrafluoro-3-trifluoromethylbezenes) in anhydrous ammonia was investigated. The optimal conditions for selective preparation of mono- and diamino derivatives, which are ensured by the reaction temperature, were elucidated. In some examples of diamine synthesis, in order to improve the selectivity of second aminodefluorination, it is advisable to separate the isomeric monoamino derivatives produced in the first step of the synthesis.

A novel and efficient synthesis of diamino derivatives of pyrano[3,4-c]pyridines

The new and effective method for the synthesis of diamino substituted pyrano[3,4-c]pyridines was developed, based on recyclization of the pyridine ring. As initial compounds 6-aminopyrano[3,4-c]pyridine-2(1H)-thiones 4а–е were used. The X-ray crystallographic analysis showed the presence of intramolecular and intermolecular hydrogen bonds in the diamino derivative 6k. The synthesized compounds were analyzed for the antimicrobial activity.

On the reactivity of 4-cyano-1,3-dichloro-7-methyl-5,6,7,8-tetrahydro-2,7-naphthyridine with several amines in different experimental conditions: monosubstitution, disubstitution, and a new unexpected rearrangement

The reactivity of 4-cyano-1,3-dichloro-7-methyl-5,6,7,8-tetrahydro-2,7-naphthyridine 1 with nucleophiles has been investigated. The different reactivity of the two chlorine atoms in 1 enabled us to obtain, by using different experimental conditions, the mono- and the di-amino-substituted derivatives of 5,6,7,8-tetrahydro-2,7-naphthyridines 2 and 3, respectively. Thus, by carrying out the reaction in a low-boiling solvent and in the presence of a quasi-stoichiometric amount of amine, the mono-substituted derivatives 2 were obtained, which under harsher conditions was transformed into the diamino derivatives 3 when using an excess of amine. During the synthesis of some diamino derivatives 3 a new rearrangement was observed with formation of 1-oxo derivatives of 3,4-dihydro-2,7-naphthyridines 4. The structure of the unexpected compounds 4 was confirmed by X-ray crystallography. A mechanism for the rearrangement is tentatively suggested.

Synthesis and characterization of hydrogels from template polymerization of acrylic acid on to modified chitosan

A novel hydrogel based on chitosan was prepared by graft copolymerization of acrylic acid on diamino derivative of chitosan, i.e., 6-amino-6-deoxy-chitosan (6a6dC). This diamino chitosan was grafted with acrylic acid in an aqueous solution in contrast to acetic acid in the conventional method. Hydrogen peroxide/l-ascorbic acid redox system was found to be an efficient initiator system for grafting reaction in an aqueous system at room temperature. The synthesized hydrogel, 6a6dC-g-PAA, was characterized by Fourier transform infrared, thermogravimetric analyses and Scanning electron microscopy (SEM). Thermal studies showed that it is more stable than chitosan and 6-amino-6-deoxy-chitosan. This 6a6dC-g-PAA, also showed an appreciable water absorbing capacity which was attributed to the very porous surface as observed from SEM analysis.

Spectroscopy of Protonated Tetraphenylporphyrins with Amino/Carbomethoxy Substituents: Hyperporphyrin Effects and Evidence for a Monoprotonated Porphyrin

Spectrophotometric titrations for a full series of para-amino/carbomethoxy-substituted tetraphenylporphyrins were carried out using methanesulfonic acid in DMSO to study the hyperporphyrin effect across different substitution patterns. The series included zero, one, two (cis and trans), three, and four amino groups, with the remaining para substituents carbomethoxy groups. With increasing numbers of aminophenyl groups, the relative basicity increased and the hyperporphyrin effect increased, marked by a strong red band and a split Soret band. The cis diamino derivative showed a stronger hyperporphyrin effect compared to the trans isomer, which can be explained based on simple resonance forms. For the monoamino derivative, an initial increase in the Soret band upon acid titration along with well-defined isosbestic points provided evidence for a monoprotonated porphyrin, distinct from the diprotonated and triprotonated states. The relative stability of this unusual intermediate is proposed to be due to charge delocalization of the first cation to the single amino group and destabilization of the second protonation by the electron-withdrawing carbomethoxy substituents.

Bis(nitro- and polynitromethyl-ONN-azoxy)azoxyfurazans and some of their derivatives

Reaction of diamino derivative of azoxyfurazan with 2,2-dimethyl-5-nitro-5-nitroso-1,3-dioxane in the presence of dibromoisocyanuric acid afforded bis(2,2-dimethyl-5-nitro-1,3-dioxan-5-yl-ONN-azoxy)azoxyfurazan. The reaction of the latter with AcCl/MeOH and further transformations of the product gave the first representative of substituted (mono- and polynitroalkyl-ONN-azoxy)azoxyfurazans, e.g. bis(nitromethyl-ONN-azoxy)azoxyfurazan, bis(dinitromethyl-ONN-azoxy)azoxyfurazan, bis(trinitromethyl-ONN-azoxy)azoxyfurazan, and some of their derivatives.

The Use of Aminopyridines in Neurological Disorders

Aminopyridines are members of a family of monoamino and diamino derivatives of pyridine, and their principal mechanism of action is dose-dependent blockade of voltage-gated potassium channels, in particular, fast voltage-gated potassium channels. To date, only 2 main broad-spectrum potassium channel blockers, 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP), have been used as investigational new drugs in various neurological diseases. More recently, licensed versions of these compounds including dalfampridine extended release (Fampyra, Biogen Idec) for the improvement of walking in adult patients with multiple sclerosis, and amifampridine (Firdapse, Biomarin Europe Ltd) for the treatment of Lambert-Eaton myasthenic syndrome have been released, and the costs associated with using these new products highlights the importance of evaluating the clinically meaningful treatment effects of these drugs.The current review summarizes the evidence of aminopyridine use in neurological conditions and in particular presents a systematic review of all randomized trials of 3,4-DAP in Lambert-Eaton myasthenic syndrome to determine the efficacy of this treatment using meta-analysis of clinical and electrophysiological end points.

Development and validation of a multiclass method for the determination of veterinary drug residues in chicken by ultra high performance liquid chromatography–tandem mass spectrometry

A multiclass method has been optimized and validated for the simultaneous determination of 20 veterinary drug residues belonging to several classes, as quinolones, sulfonamides, macrolides, anthelmintics, avermectins and diamino derivatives, and benzathine, used as a marker of the presence of penicillin, in muscle chicken. It has been based on QuEChERS methodology (quick, easy, cheap, effective, rugged and safe) and ultra high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry (UHPLC–MS/MS). Several chromatographic conditions were optimized, obtaining a running time <8.5min. The developed method was validated on the basis of international guidelines. Mean recoveries ranged from 70 to 120%, except for benzathine (65.6% at 20μgkg−1) and sulfadimidine (69.0% at 100μgkg−1). Repeatability was lower than 20.0% except for sulfachlorpyridazine (22.1% at 20μgkg−1) and tylosin (20.5% and 20.6% at 30 and 50μgkg−1, respectively), whereas reproducibility was lower than 25% except for flumequine (27.4% at 20μgkg−1) and benzathine (37.8% and 27% at 20 and 50μgkg−1, respectively). Limits of detection (LODs) and quantification (LOQs) ranged from 3.0 to 6.0μgkg−1 and 10.0 to 20.0μgkg−1, respectively, except for tylosin that showed a LOD and LOQ of 9.0 and 30.0μgkg−1. Decision limit (CCα) and detection capability (CCβ) were calculated and CCβ ranged from 24.1μgkg−1 (mebendazole) to 423.6μgkg−1 (flumequine). Finally, the method was applied to real samples and traces of some compounds were found in eight samples of chicken and benzathine was detected in one sample at 29.9μgkg−1.

Synthesis, biological activity and HPLC validation of 1,2,3,4-tetrahydroacridine derivatives as acetylcholinesterase inhibitors

The synthesis and biochemical evaluation of new hybrids of tacrine (THA) and 4-fluorobenzoic acid (4-FBA) possessing activity towards acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition are presented. The compounds of interest were obtained from the reaction of activated 4-FBA and diamino derivatives of 1,2,3,4-tetrahydroacridine. The compounds C6-2KW/HCl, C6-4KW/HCl and C6-3KW/HCl have four-fold higher antiacetylcholinesterase activity than THA. All of the acquired compounds present higher selectivity towards AChE than THA and lower selectivity towards BuChE. In addition, a rapid, selective and stability-indicating HPLC method was developed and validated for the determination of C6-2KW/HCl, C6-3KW/HCl and C6-4KW/HCl. THA and 4-FBA were found to be the main impurities. Chromatographic separation was achieved isocratically on a Waters Symmetry C18 150 × 3.9 mm, 4 μm column with a mobile phase of acetonitrile/buffer (17 mM sodium dodecyl sulphate and 8.3 mM sodium dihydrogen phosphate, 50:50 v/v) (overall pH 4). A 1.5 ml/min flow rate and a 247 nm wavelength were chosen for this method. C6-2KW/HCl, C6-3KW/HCl and C6-4KW/HCl were subjected to acidic and basic hydrolysis, chemical oxidation, thermal exposition at 60 °C and intense UV light. The limits of detection (LOD) and quantification (LOQ) were less than 2 μg/ml and 6 μg/ml for C6-2KW/HCl, C6-3KW/HCl and C6-4KW/HCl, 0.04 μg/ml and 0.12 μg/ml for THA, 0.42 μg/ml and 1.41 μg/ml for 4-FBA, respectively.

The structure of mono- and di-amino derivatives of cyclohexane: Energetic and Natural Bond Orbital approaches

A full exploration of the conformational space of mono and di-amino derivatives of cyclohexane have been performed using the second-order Møller-Plesset approximation method (MP2) and the aug-cc-pVDZ basis set. These data were further complemented by the application of the Natural Bond Orbital (NBO) theory. The population of the equatorial conformers was found to be 84% in cyclohexylamine (CHA), varying from 94% to 99% in the cyclohexyldiamine isomers (CHDA). Based on the weighed mean energies computed for the different CHDA isomers, the following energetic sequence has been established: t12<c12<t14≈c13<c14≈t13. The results given by the MP2 calculations were discussed in terms of pairwise steric repulsions between filled orbitals and electron delocalization from filled to vacant orbitals provided by the NBO analysis. With the exception of the vicinal isomers, the former interactions were found to be the most important factor for the conformers/isomers stabilization. Attention was also given to the role played by the syn-1,3-di-axial repulsions in the destabilization of the axial conformers of CHA. An intramolecular hydrogen bond was found to stabilize the di-axial conformers of c13CHDA.

Influence of an additional amino group on the potency of aminoadamantanes against influenza virus A. II – Synthesis of spiropiperazines and in vitro activity against influenza A H3N2 virus

Spiro[piperidine-2,2′-adamantane] 4 is one of the most potent synthetic anti-influenza A aminoadamantanes or other cage structure amines tested so far. Based on previous results Tataridis et al. (2007) [5h] which demonstrate the boost of in vitro potency by the presence of an additional amino group, we examined whether the incorporation of a second amino group into this heterocycle would increase the anti-influenza A virus activity. The new synthetic molecules 5– 7 are capable of forming two hydrogen bonds within the receptor. We identified the diamino derivatives 5 and 6, which are active against influenza A H3N2 virus although less potent than amantadine and its equipotent spiropiperidine 4.

ChemInform Abstract: Synthesis of 3,3′‐Diaryl‐Substituted 2,2′‐Diamino‐1,1′‐binaphthyl and Its Derivatives.

AbstractEach step affords the product with &lt; 90% yield.

ChemInform Abstract: 8-Azaguanine 2′,3′Dideoxyribonucleosides: Glycosylation of the 5-Amino- 7-methoxy-3H-1,2,3-triazolo(4,5-d)pyrimidinyl Anion with 2,3-Dideoxy-D- glycero-pentofuranosyl Chloride.

The synthesis of the regioisomeric 8-azaguanine N7-, N8-, and N9-(β-D-2′,3′-dideoxyribonucleosides) (1, 2, and 3, respectively) and of the diamino derivative 13 is described. The anion of 5-amino-7-methoxy-3H-1,2,3-triazolo[4,5-d]pyrimidine (5) was glycosylated with 5-O-[(tert-butyl)dimethylsilyl]-2,3-dideoxy-D-glycero-pentofuranosyl chloride (6; anomeric mixture), yielding the regioisomeric 2′,3′-dideoxyribofuranosides as anomeric mixtures 7a/10a, 8a/11a, and 9a/12a. They were desilylated with Bu4NF in THF affording the 5-amino-7-methoxy-nucleosides 7b–12b. Treatment with aqueous NaOH gave the 8-azaguanine β-D-2′,3′-dideoxynucleosides 1–3 and their α-D-anomers 14–16. The reaction of 7b with NH3/MeOH yielded the diamino compound 13. The N-glycosylic bond of 8-aza-2′,3′-dideoxyguanosine (1) is four-times more stable against acid than that of 2′,3′-dideoxyguanosine. Compounds 1, 2, and 13 were converted to their 5′-triphosphates 17–19 which showed only modest inhibitory activity against HIV-reverse transcriptase.

Synthesis of 3,3′-Diaryl-Substituted 2,2′-Diamino-1,1′-binaphthyl and Its Derivatives

Substitution at the 3 and/or 3' position of a binaphthyl skeleton sometimes enhances stereoselectivity during asymmetric reactions. High-yield and stepwise introduction of aryl groups into the 2,2'-diamino derivative has been established for the first time via an ortho-lithiation/iodization/Suzuki-Miyaura coupling protocol. The results described herein will facilitate the synthesis of a variety of 3,3'-substituted 2,2'-diamino-1,1'-binaphthyl compounds, which are key intermediates for obtaining valuable related ligands and organocatalysts.

Crystal Structures of SomeN-substituted 2,5-Dimethylpyrrole Derivatives

The crystal and molecular structures of five di-(2,5-dimethylpyrrole) and one tri-(2,5-dimethylpyrrole) derivatives have been determined. These compounds were synthesized from the respective diamino derivatives and hexane-2,5-dione in direct and simple reactions. The molecular packings are largely based on C-H...π interactions.

Effective double-ended chelating agents: crystal structures of N,N,N′,N′-tetraacetyl diamino derivatives and their chelates

Crystal structure determinations of six N,N,N′,N′-tetraacetyl diamino derivatives, N,N,N′,N′-tetraacetyl m-xylylenediamine 1, N,N,N′,N′-tetraacetyl p-xylylenediamine 2, N,N,N′,N′-tetraacetyl 1,5-diaminonaphthalene 3, N,N,N′,N′-tetraacetyl 1,4-diaminocyclohexane 4, N,N,N′,N′-tetraacetyl 1,4-diaminobutane 5 and N,N,N′,N′-tetraacetyl 1,8-diaminooctane 6 have been carried out. In all these compounds the anti–syn configuration, in each DAA group, is preferred and the two DAA groups, at each end of the extended ligand, are coplanar with respect to one another. Further, the syntheses and crystal structures of two metal complexes [Cu(N,N,N′,N′-tetraacetyl 1,4-diaminobutane)2(H2O)2](ClO4)25a and [Zn(N,N,N′,N′-tetraacetyl 1,6-diaminohexane)2(H2O)2](ClO4)27 are also reported. Single crystal analysis confirmed that the N,N,N′,N′-tetraacetyl diamino derivatives act as bis-chelating, double-ended ligands. In an unbound state all the tetraacetyl derivatives adopt the expected anti–syn configuration but on complex formation this configuration of the ligand changes to anti–anti resulting in the formation of chelate complexes.

Synthesis and Characterization of Banana-Shaped Mesogens Derived From a Benzophenone Moiety

A homologous series of Schiff's bases consisting of a benzophenone moiety as the central core has been synthesized. Schiff's bases were prepared starting from benzophenone by a sequence of reactions, viz., nitration followed by reduction and heating the resulting diamino derivative with 4-formyl-3-hydroxyphenyl 4-(alkyloxy)benzoate. Higher homologues of this series exhibit mesomorphism, but the lower homologues do not seem to possess any liquid crystalline property. The B2 mesophase was characterized by DFT study for orientation of dipole moment. Dipolar interaction and intramolecular H-bonding (N–H) have been considered to discuss the origin of the B2 phase in this homologous series of benzophenone moiety derived systems.

New diamino derivatives of p-tert-butylcalix[4]arene for oxyanion recognition: synthesis and complexation studies

We have prepared new diamino derivatives of p-tert-butylcalix[4]arene from the reduction of corresponding amide derivatives. The examination of their recognition abilities towards some selected oxyanions shows that the new calix[4]arene amines are mostly more effective receptors than their amide derivatives for dichromate anions and nitrite, and capable of extracting these anions in yields as high as 95%. However, neither the calix[4]arene amines nor their corresponding amides were capable of extracting phosphate or nitrate at pH 1.5.

A new synthesis of the linearly fused [1,2,4]triazolo[1,5- b]isoquinoline ring. Observation of an unexpected Dimroth rearrangement

A new and general synthesis of the linearly fused [1,2,4]triazolo[1,5- b]isoquinoline ring system starting from 2,3-diaminoisoquinolinium salts has been elaborated. Starting compounds bearing an alkyl group in position 4 easily reacted with aldehydes to yield the cyclized products. In the case of a lack of electron donating group in position 4 (e.g., unsubstituted or 4-cyano substituted diamino derivatives) a Dimroth rearrangement took place under the same reaction conditions to yield 3-isoquinolylhydrazones. The mechanism of this unexpected transformation has been verified by isotope labelling experiments. Clarification of the reaction mechanism allowed finding proper reaction conditions to eliminate the rearrangement route, and thus, to perfect successful ring closure to the fused triazoles.

Electrochemical synthesis of 1,3-dimethyl-4-amino-5-formyluracyl in the presence of ammonium chloride

The synthesis of 1,3-dimethyl-4-amino-5-formyluracyl, an intermediate of theophylline synthesis, was studied in an ammonium chloride medium using the electroreduction of 1,3-dimethyl-4-amino-5-nitrosouracyl to a diamino derivative with its further formylation. The electrolysis and formylation conditions were optimized. The reduction of 1,3-dimethyl-4-amino-5-nitrosouracyl was performed under the following conditions: its concentration was 12.0–13.5 %, the cathode was a Kh18N10T stainless steel gauze, the electrolysis was performed in the presence of ammonium chloride, the current density was 7.5–8.0 A/dm2, the electrolysis temperature was 40–45°C, and the formylation temperature was 71–72°C. The substance yield of overall formylaminouracyl was 81.2–83.3% and the current efficiency was 62.0–64.5%. The developed process of 1,3-dymethyl-4-amino-5-formyluracyl synthesis was evaluated at a scaled-up laboratory setup with a filter-press cell.