Diamino Derivatives Research Articles

Synthesis of 5,5′-Dinitro- and 5,5′-Diaminobis(cyclopenta[<i>b</i>]indoles) Bound at <i>N</i><sup>4</sup>,<i>N</i><sup>4′</sup> Atoms with a Dioxoalkane Spacer

Upon condensation of 2 equiv. of 3R*,3aR*,8bS*-3-iodo-7-methyl-1,2,3,3а,4,8b-hexahydrocyclopenta[b]indole with 1 equiv. of glutaric or decanedicarboxylic acid dichloranhydride [N4,N4′-di-(3R*,3aR*,8bS*,3′R*,3a′R*,8b′S*)- and N4,N4′-di-(3aR*,3aR*,8bS*,3′S*,3a′S*,8b′R*)-3-iodo-7-methyl-1,2,3,3а,4,8b-hexahydrocyclopenta[b]indolyl]alkanediamides were synthesized. Their didehydrohalogenation to 3aR*,8bR*,3a′R*,8b′R*- and 3aS*,8bS*,3a′R*,8b′R*-1,3a,4,8b-tetrahydroanalogues was carried out by boiling these diiodides in piperidine. The presence of rotamerism in the products of dehydrohalogenation was shown, which is manifested by doubling the signals in the NMR spectra in different ratios. Nitration with trifluoroacetyl nitrate in CH2Cl2 yielded their 5,5′-dinitro analogs, which, when reacted with freshly prepared Fe(OH)2, along with 5,5′-diamino derivatives, also formed 5-amino-5′-nitro-substituted products of incomplete reduction. When a nitro group or an amino group appears at the C5 and C5′ carbon atoms of the cyclopenta[b]indole fragments, the doubling of the signals in the NMR spectra disappears. The interaction of a 5,5′-diamino derivative (n = 8) with decanedicarboxylic acid dichloride yielded a compound with 30 atoms in the macrocyclic ring.

How is the Observation of High-Order Overtones and Combinations Elucidated by the Charge-Transfer Mechanism in SERS?

The charge-transfer chemical mechanism is responsible for altering the molecular spectral pattern and providing valuable insights into the properties of adsorbates. The impact of charge transfer becomes more pronounced in SERS spectra when CT states can gain intensity through vibronic coupling with high-intensity excitations. Experimental SERS spectra of diamino molecules, such as 4,4'-diaminostilbene (DAS) and 4,4'-diaminotolane (DAT), featuring bright CT transitions, have been compared to dipyridyl compounds, such as 1,2-bis(4-pyridyl) ethylene (BPE) and 1,2-di(4-pyridyl) acetylene (DPA), characterized by nearly dark CT excitations. This comparison aims to elucidate the effect of CT transitions on the presence of overtones and combination bands. We explain this distinction using Albrecht's formalism for resonance Raman spectroscopy within the framework of path integral time-dependent density functional theory considering the Herzberg-Teller corrections. It is worth noting that the energy gap between the highest occupied metallic orbital and the lowest unoccupied molecular orbital in diamino derivatives is noticeably smaller than in compounds featuring two pyridyl rings. The high-intensity SERS-CT spectra for diamino derivatives, primarily driven by the Albrecht A term, were acquired and used to elucidate the experimental observation of high-order modes with a significant Huang-Rhys factor. Conversely, the absolute intensity of SERS-CT for dipyridyl compounds is at least 106 times smaller than that for diamines, and the C term makes a significant contribution, explaining the silent overtones.

Simple and Efficient Synthesis of Diamino Derivatives of bis-1,2,4-oxadiazole via Tandem Staudinger/aza-Wittig Reaction.

Two convenient and efficient routes for synthesizing diamino derivatives of bis-1,2,4- oxadiazoles were described. This study provides a simple protocol for the synthesis of bis-1,2,4-oxadiazoles. The two procedures were based on a tandem Staudinger/aza-Wittig reaction from the same starting material of diaziglyoxime, isocyanates and triphenylphosphonium. In synthesis method I, diaziglyoxime 1 was treated with various aromatic or aliphatic isocyanates to give diazioxalimides 2 a high yield. Diazioxalimides 2 reacted with Ph3P to produce the iminophosphoranes 4; the reaction was directly heated from room temperature to 115 ℃ to get the desired diamino derivatives of bis-1,2,4-oxadiazole 4 in 72-92% yields. In synthesis method II, the same target compounds 4 were synthesized in a one-pot reaction by Ph3P and aromatic or aliphatic isocyanates in toluene for 10 h under 115 ℃ in 53-71% yields. The two procedures provide proficient methods of making nitrogen-containing heterocyclic rings. The structures of target compounds 4 were identified by IR, 1HNMR, 13CNMR and HRMS.

Manufacturing of Corrosion Inhibitors and Flow Improvers from Recycling of Waste at Hail City, Saudi Arabia: Physicochemical and Electrochemical Studies on Steel in Petroleum Industries.

The aim of the present research paper is to convert daily waste materials generated by human activity at Hail city into useful petroleum additives. In this respect, novel multifunctional corrosion inhibitors working as inhibitors and flow improvers for crude oil were prepared. Polyethylene terephthalate (PET) plastic waste is used in the production of corrosion inhibitors and flow improvers for petroleum crude oil. A multifunctional corrosion inhibitor for the SABIC carbon steel in corrosive seawater for application in the petroleum industry was manufactured using PET waste that was gathered, cleaned, and used as starting materials. The PET green recycling method takes place via the Abdel-Hameed green recycling reported method. In the first step, PET waste was reacted without a solvent with a diamine to form the diamino derivative of phthalic acid amide (PETAA), which was characterized by FT-IR, 1HNMR, and elemental analysis. In the presence of a catalyst, the used recycling method is a solvent-free green recycling process that is environmentally friendly. Chemical and electrochemical measurements were performed, and the effects of concentration and temperature were studied. The inhibition efficiency was found to increase with concentration. A maximum inhibition of 97% was obtained using 4000 ppm from the prepared PETAA inhibitor, while the efficiency decreased with temperature. Potentiodynamic polarization (PDP) data indicates the mixed-type nature of the used inhibitor. According to potentiodynamic polarization data, the inhibitor boosts polarization resistance and inhibition performance by adsorbing on the metal/electrolyte interface. The data from electrochemical impedance spectroscopy (EIS) show that the charge-transfer mechanism is the primary governing factor in the steel dissolution process. The size of the semicircle grows in direct proportion to the concentration of the inhibitor. The prepared additive acts as a flow improver (viscosity improvers and pour point depressants) for waxy crude oil, indicating that it can be used in the manufacturing of multifunctional inhibitors in the petroleum industry. The depression in the pour point temperatures depended on the concentration and composition of the additive prepared from the plastic waste collected from Hail city.

Synthesis, antimicrobial and docking studies of some novel (N1E, N2E)-N1, N2-bis(2-amino-3,5-dibromobenzylidene)-aryl-1,2-diamines

The diamino derivative is utilized to synthesize various substituted derivatives, which are characterized by IR and NMR. The antibacterial properties of synthesized compounds have been explored. Novel (E)-4,6-dibromo-N1- (4-substitutedbenzylidene)benzene-1,2-diamine derivatives ( 1-6 ) have been obtained in good yields from 2-amino-3,5-dibromobenzaldehyde and 4-substituted benzene-1,2 diamines in a single pot synthesis. The antimicrobial activity of the synthesized compounds have been screened against different strains such as Staphylococcus aureus , Bacillus subtilis , Streptococcus pyogenes , Klebsiella pneumoniae , Escherichia coli and compared with Ciprofloxacin as a standard and compound 6 shows significant activity against Staphylococcus aureus . The docking study results also support the antimicrobial activity data.

Synthesis and anticancer activity of bis-benzo[d][1,3]dioxol-5-yl thiourea derivatives with molecular docking study

New thiourea derivatives incorporating two benzo[d][1,3]dioxol-5-yl moieties have been synthesized through the reaction of two molecules of benzo[d][1,3]dioxol-5-yl isothiocyanate with one molecule of various diamino derivatives. The synthesized compounds were examined for their cytotoxic effects using SRB assay on three cancer cell lines HepG2, HCT116 and MCF-7. Most of compounds showed significant antitumor activity and some compounds showed strong results greater than the reference drug. As example, IC50 values of 1,1′-(1,4-phenylene)bis(3-(benzo[d][1,3]dioxol-5-yl)thiourea) 5 were 2.38 µM for HepG2, 1.54 µM for HCT116 and 4.52 µM for MCF7, while the IC50 values of standard drug doxorubicin were 7.46, 8.29 and 4.56 µM, respectively. Interestingly, these compounds were non cytotoxic toward the tested normal cell line (IC50 value > 150 µM). The anticancer mechanisms were studied via EGFR inhibition assessment, annexin V-FITC apoptosis assessment, cell cycle analysis and study the effect on mitochondrial apoptosis pathway proteins Bax and Bcl-2 as well as molecular docking studies.

Tetrahydro-4 H-(pyrrolo[3,4- d]isoxazol-3-yl)methanamine: A Bicyclic Diamino Scaffold Stabilizing Parallel Turn Conformations.

A tetrahydro-4 H-(pyrrolo[3,4- d]isoxazol-3-yl)methanamine scaffold was designed as a diamino derivative to stabilize parallel turn conformations. Its synthesis took advantage of a [1,3]-dipolar cycloaddition reaction between the nitrile oxide derived from the inexpensive enantiopure l -phenylalanine and N-benzyl-3-pyrroline. Two diastereoisomers were formed, whose distribution depends on the selected base. 3a R,6a S-Isomer is favored in organic bases, which formation is driven by π-interactions. However, the above interactions were significantly prevented using an inorganic base due to the chaotropic effect of the cation, decreasing the amount of the above isomer. Finally, we demonstrated that this isomer is able to stabilize parallel turn conformations when inserted in short peptide sequences.

3,4-Epoxyperfluorooxolane in the synthesis of new fluorine-containing furo[3,4-b]quinoxaline derivatives

The reaction between equimolar amounts of 3,4-epoxyperfluorooxolane and 3,3′,4,4′-tetraaminobiphenyl provided a new fluorine-containing diamino derivative of furoquinoxaline, namely, 6-(3,4-diaminophenyl)-1,1,3,3-tetrafluoro-1,3-dihydro-furo[3,4-b]quinoxaline. Its reactions with 3,4-epoxyperfluorooxolane, 1,2-diphenylethanedione, or di(2-thienyl)ethanedione yielded new quinoxaline fluorine-containing polycyclic compounds whose structures were confirmed by X-ray diffraction.

Synthesis of Isomeric Dinitro and Diamino Derivatives of Polycyclic Crown Ethers: Dibenzo-18-crown-6 and Dibenzo-24-crown-8

Specific features of the synthesis of polycyclic crown ethers dibenzo-18-crown-6 and dibenzo-24-crown-8 and their dinitro and diamino derivatives have been studied. A mixture of isomers of dibenzocrown ether derivatives was obtained and separated. The spectral and thermal characteristics of the synthesized compounds and the kinetics of synthesis of dibenzo-24-crown-8 by the two-component condensation of pyrocatechol with 1-chloro-2-[2-(2-chloroethoxy)ethoxy]ethane in an alcoholic medium in the presence of a KOH template agent were studied.

Synthesis and structure of diamino derivatives of pyrano-[3,4-c]pyridines and 5,6,7,8-tetrahydroisoquinolines

A new and effective method was developed for obtaining diamino derivatives of pyrano[3,4-c]pyridines and 5,6,7,8-tetrahydro-isoquinolines from 3-cyanopyridin-2(1H)-ones by Smiles rearrangement of the respective oxyacetamides. The structures of the synthesized compounds were studied by NMR spectroscopy and X-ray diffraction analysis. The results of X-ray diffraction studies revealed the presence of intermolecular hydrogen bonds in 6-(benzylamino)-3,3-dimethyl-8-(pyrrolidin-1-yl)-3,4-dihydro-1H-pyrano-[3,4-c]pyridine-5-carbonitrile. The obtained compounds were also tested for antimicrobial activity.

Two new alkaline earth metal organic frameworks with the diamino derivative of biphenyl-4,4′-dicarboxylate as bridging ligand: Structures, fluorescence and quenching by gas phase aldehydes

Alkaline earth metal ion organic frameworks (AEMOFs) represent a relatively underexplored subcategory of MOFs. Two new MOFs [Ca6(bpdc-(NH2)2)5(μ3-HCO2)2(H2O)2.5(DMF)0.5]·0.5H2O·2.5DMF (1) and [Sr4(bpdc-(NH2)4)(μ2-DMF)2(DMF)1/3]·2/3(DMF) (2) [H2bpdc-(NH2)2 = 2,2′-diamino-[1,1′-biphenyl]-4,4′-dicarboxylic acid); DMF = N,N-dimethylformamide] are presented here. These MOFs display structural variety with diverse topologies and new structural features. Luminescence studies revealed that both MOFs display ligand based fluorescence with small differences in emission profiles possibly attributable to the difference in charge density of the metal ions combined with the different conformation adopted by the ligand in the crystal structures of 1 and 2. Furthermore, initial sensing studies reveal that both MOFs can potentially function as fluorescent sensors for gas phase aldehydes.

Derivatives of 4, 4’‐Oxydianiline Show Distinct In Vitro Cytotoxicity, Apoptosis Induction, and Selectivity against HepG2 Cancer Cells

AbstractGathering of number of pharmacophore on a single molecular platform evidently lead to improved therapeutic efficiencies and reduced side effects of conventional chemotherapy drugs. Three diamino precursors 4,4’‐bis(2‐(alkylamino)acetamido)diphenylether (L1‐L3) was selected to derive new series of metallomacrocyclic dithiocarbamate complexes [M2‐μ2‐bis‐{(κ2S,S‐S2CN(R)CH2CONHC6H4)2O}] {R=Cy, M=NiII1a, CuII 1 b, ZnII1c; R=iPr, M=NiII2a, CuII 2 b, ZnII2c; R=nBu, M=NiII3a, CuII 3 b, ZnII3c}. These were characterized by standard spectroscopic and thermogravimetric methods. MTT assay was carried out on these compounds to explore their in vitro cytotoxicity against HepG2 (hepatoma) cell line. The diamino derivatives (L1‐L3) in their metal‐free form and metallomacrocyclic complexes, 1 a, 1 c, 2 a, 2 b, 2 c, 3 a, 3 b and 3 c exhibit improved cytotoxicity than Cisplatin and selectivity against HepG2 over normal cells. Remarkably, complexes 2 c (3.55 ± 0.06 μM) and 3 c (2.19 ± 0.04 μM) demonstrate 21 folds to 34 folds better cytotoxic activity whereas L3 (5.49 ± 0.04 μM), 1 a (7.27 ± 0.16 μM) and 3 a (4.42 ± 0.06 μM) showed more than 10 fold better cytotoxic activity against HepG2 cell line as compared to the reference drug Cisplatin. Morphological evidences like shrinking of cells indicates the induction of apoptosis as part of the mechanism of action of these compounds which is further supported by the distinct staining of the cells by acridine orange/ethidium bromide (AO/EB).

Synthesis of diacetylamino and diamino derivatives of adamantane series

1,3-Diacetylamino derivatives were synthesized directly from adamantane series hydrocarbons or from adamantan-1-ylacetic acids by a one-pot method with a succession of an oxidation stage and Ritter’s reaction in nitric acid and in a mixture of sulfuric and nitric acids. The hydrolysis of 1,3-diacetylamino derivatives in an acidic medium leads to scaffold diamines and diaminoacids.

Selective one-pot synthesis of aminopolyhalobenzonitriles from polyhalobenzotrichlorides in anhydrous ammonia

Polyhalogenated benzotrichlorides (pentafluoro-, chlorotetrafluoro-, chlorotrifluoro-, and tetrafluorobenzotrichlorides) undergo one-pot ammonolysis+aminodefluorination by the action of anhydrous ammonia to form mono- and diamino derivatives of polyhalobenzonitriles. For the substrates comprising halogen at the para-position, the ammonolysis of the CCl3 group and the first aminodefluorination occur simultaneously in the temperature range from −33 to 5°C. The temperature of introducing the second NH2 group is higher by 60–100°C, whereby conditions were found for the selective synthesis of mono- and diaminopolyhalobenzonitriles. The use of anhydrous ammonia as a reagent and a solvent minimizes side reactions and simplifies an isolation of the high purity products.

Reactivity in 7-benzyl-2,7-naphthyridine Derivatives: Nucleophilic Substitutions, Rearrangements, Heterocyclizations and Related Reactions

Background and Objective: Continuing our studies in the field of a new rearrangement in the 2,7- naphthyridine series, the synthesis and rearrangement of mono- 2 and di-amino derivatives 3 of 2,7- naphthyridine was carried out. Taking into account the wide range of pharmacological activities of pyrazole derivatives the synthesis of some 3-amino-1-(3,5-dimethyl-1H-pyrazol-1-yl)-2,7-naphthyridines 8 and of pyrazolo[3,4-c]-2,7-naphthyridine 12 was described. Keywords: Amidines, heterocycles, 5, 6, 7, 8-tetrahydro-2, 7-naphthyridine, pyrazolo[3, 4-c]-2, 7-naphthyridine, nucleophilic substitution, rearrangement.

19F-nuclear magnetic resonance spectroscopy as a tool to investigate host-guest complexation of some antidepressant drugs with natural and modified cyclodextrins

Purpose: 19 F-Nuclear magnetic resonance spectroscopy ( 19 F-NMR) was used to study host-guest complexation of three fluorine containing antidepressant drugs, viz, fluoxetine hydrochloride, citalopram hydrobromide and fluvoxamine maleate, with various cyclodextrins (CD), including α-, β-cyclodextrin, methylated α-cyclodextrin (M-α-CD), diamino derivative of methylated α-cyclodextrin, (DAM-α-CD) and tetramino derivative of methylated α-cyclodextrin (TAM-α-CD). Methods: Using the mole ratio method, a 1:1 stoichiometry was determined for the resulting inclusion complexes. 19 F chemical shifts were used to determine the formation constant of the complexes. Experiments were performed with solutions containing 0.001 M drug and various concentrations of CDs. NMR data were plotted as 19 F chemical shift versus CD/drug mole ratio, and fitted using the nonlinear least-squares curve fitting program, KINFIT, to obtain the formation constant of CD-drug complex. Molecular modeling (MM) calculations were used to predict the geometry of the complex of fluvoxamine and β-CD. Molecular modeling studies were performed in vacuum phase, employing empirical force fields and semi-empirical quantum theory using AM1 Hamiltonian. Results: Complex formation caused separation of the fluorine peaks that can be assigned to the two enantiomers of fluoxetine hydrochloride. Molecular modeling data suggest that fluvoxamine/β-CD inclusion complexes have a 1:1 stoichiometry and that the CF3-substituted ring of fluvoxamine is embedded in the cavity of β-CD, indicating a good agreement between molecular modeling calculation and experimental data (NMR data). Conclusion: One-dimensional 19 F-NMR is a fast and convenient method for the determination of complex stoichiometry and complexation constants of natural and modified CDs and fluorinated drugs. Keywords: Antidepressant drugs, Cyclodextrins, Complexation, Inclusion complex, Formation constant, 19 F-NMR

Continuous Flow Synthesis of a Key 1,4-Benzoxazinone Intermediate via a Nitration/Hydrogenation/Cyclization Sequence

The preparation of a functionalized 4H-benzo-[1,4]-oxazin-3-one was completed via a three-step nitration/hydrogenation/cyclization sequence. The unstable nature of the nitro and amino intermediates, in addition to the hazards associated with the nitration of organic compounds in general, makes this procedure exceedingly difficult to perform on industrial scale. To overcome these limitations, we have developed a fully integrated continuous protocol in which the aromatic starting material (2,2-difluoro-2-(3-fluorophenoxy)-N,N-dimethylacetamide) is subjected to an initial continuous flow dinitration using 20% oleum in combination with 100% HNO3 (2.5 equiv) using a microstructured device heated to 60 °C. This was followed directly by continuous flow hydrogenation of the dinitrointermediate over a Pd/C fixed bed catalyst at 45 °C. The resulting air-sensitive diamino derivative was then directly cyclized to the desired 6-amino-2,2,7-trifluoro-4H-benzo-[1,4]-oxazin-3-one target compound via an acid-catalyzed cyc...

Synthesis and neurotropic activity of 6,8-diamino derivatives of pyrano[3,4-c]pyridines

New diamino derivatives of pyrano[3,4-c]pyridines were synthesized by the pyridine ring recyclization. The presence of the intramolecular hydrogen bond in 6-[(4-methoxyphenyl)amino]-3,3-dimethyl8-methylamino-3,4-dihydro-1H-pyrano[3,4-c]pyridin-5-carbonitrile was identified by X-ray diffraction. A pharmacological study of the synthesized compounds was carried out in known tests, such as assay for antagonism induced by corazole subcutaneous injection and the open field test. The method of rotating rod was used to evaluate neurotoxicity. The diamino derivatives of pyrano[3,4-c]pyridines were found to possess neutrotropic properties. The synthesized compounds, as well as diazepam, prevent the occurrence of clonic seizures and clonic corazoleinduced convulsions in animals; however, they cause a behavior-depressing sedative effect.

Synthesis and characterization of new polyamides containing symmetrical and unsymmetrical thiadiazole rings

Diamino derivatives of thiadiazole namely, 2,5-diamino-1,3,4-thiadiazole and 3,5-diamino-1,2,4-thiadiazole were synthesized and characterized. Polyamides were synthesized by condensation of the two diamino derivatives with diacide chlorides. The structures of polyamides were verified by elemental analysis, FTIR, 1H-NMR, 13C-NMR and mass spectroscopy. The polyamides possess good solubility in aprotic organic solvents such as DMF, DMAC, DMSO and NMP at room temperature. Intrinsic viscosity measurements indicate that the polyamides synthesized have moderate molecular weights. The thermal stability of these polyamides in nitrogen atmosphere is relatively good, especially for those polyamides containing phenylene ring in the backbone. Compared to the structurally related Kevlar aramide, using 2,5-diamino-1,3,4-thiadiazole and 3,5-diamino-1,2,4-thiadiazole instead of p-phenylene diamine results in reducing the melting points of polyamides to below 350 °C.

Preparation and Biodistribution of Technetium-99m-Labeled Bis- Misonidazole (MISO) as an Imaging Agent for Tumour Hypoxia.

Diagnosis of tumour hypoxia is an important aspect in determining the course of tumour therapy. In this study, we developed a novel imaging agent, (99m)Tc-ethylenedicysteine-bis-misonidazole ((99m)Tc-EC-MISO), for diagnosing tumour hypoxia. We used 2-nitroimidazole as a reactant to synthesize the amino derivative of misonidazole (MISO) in the first step and then conjugated the di-amino derivative of MISO to the chelating agent ethylenedicysteine (EC) for labelling (99m)Tc in the second step. (99m)Tc-pertechnetate ((99m)TcO4-) was reduced by tin chloride (SnCl2) for radiolabeling. The radiochemical purity was up to 94%. Tissue biodistribution and SPECT/CT imaging studies were conducted on subcutaneous gliomal tumour-bearing mice. The tumour-to-muscle ratio in the (99m)Tc-EC-MISO group increased with time, up to 4.6 at 4 h after injection. SPECT/CT imaging confirmed that the tumours could be visualized clearly with (99m)Tc-EC-MISO at 2 h. By introducing a second 2-nitroimidazole redox centre, an apparent hypoxic accumulation of this novel (99m)Tc-labeled imaging agent in the tumour was observed.