Acetamidine Hydrochloride Research Articles

A Novel Bis-Trifluoromethylated Compound Demonstrates High Efficacy as a Nematicide Against Root-Knot Nematodes on Pistachio, Supported by Docking Studies.

Three novel trifluoromethylated compounds were designed and synthesized by reacting trifluoroacetimidoyl chloride derivatives with acetamidine hydrochloride or thiourea in the presence of potassium carbonate or sodium hydrogen carbonate as a base. In vitro and in vivo assays demonstrated the efficacy of the tested compounds in controlling root-knot nematode disease on pistachio rootstocks caused by Meloidogyne incognita. Bis-trifluoromethylated derivatives, namely N,N''-thiocarbonylbis(N'-(3,4-dimethylphenyl)-2,2,2-trifluoroacetimidamide) (compound A1), showed high efficacy as novel and promising nematicides, achieving up to 78.28% control at a concentration of 0.042 mg/liter. This effect is attributed to four methyl and two trifluoromethyl groups. In the pre-inoculation application of compound A1, all three concentrations (0.033, 0.037, and 0.042 mg/liter, and Velum) exhibited a higher level of control, with 83.79, 87.46, and 80.73% control, respectively. In the microplot trials, compound A1 effectively reduced population levels of M. incognita and enhanced plant growth at a concentration of 0.037 mg/liter. This suggests that compound A1 has the potential to inhibit hedgehog protein and could be utilized to prevent the progression of root-knot disease. Furthermore, the molecular docking results revealed that compounds A1 and A3 interact with specific amino acid residues (Gln60, Asp530, Glu70, Arg520, and Thr510) located in the active site of hedgehog protein. Based on the experimental findings of this study, compound A1 shows promise as a lead compound for future investigations.

A straightforward trifluoromethylation at the C6 position of morphinane alkaloids, their modification and evaluation of inhibition of the SARS-CoV-2 main protease

A catalytic trifluoromethylation of stereoisomeric 6-ketomorphinans using Ruppert–Prakash reagent and tetrabutylammonium fluoride (TBAF) was studied. 14β-Hydroxycodeinone, 4-O-methylsinomenine and 1-iodo-4-O-methylsinomenine provided good to excellent yields of the corresponding 6-trifluoromethylated compounds. The new morphinan derivative (6-deoxo-1-iodo-6α-(trifluoromethyl)-4-O-methylsinomenin-6β-ol) was involved in some catalytic transformations for introduction of additional substituent on C-1 position of the morphinan core. The palladium-catalyzed carbonylation–cross coupling reaction of 1-iodo-derivative with phenylacetylene in the presence of PdCl2-(1-Ad)2PBn catalytic system and Mo(CO)6 as a source of carbon monoxide in MeCN proceeds with high selectivity with the formation of alkynyl ketone as the main product. The cyclocondensation with acetamidine hydrochloride afforded the arylpyrimidine – 6α-(trifluoromethyl)-4-O-methylsinomenin-6β-ol hybrid compound. The action of the dehydration system (SOCl2-Py-DMAP) on 6-deoxo-6α-(trifluoromethyl)-4-O-methylsinomenin-6β-ol have led to the formation оf 8β‑chloro-6,7-didehydro-6-(trifluoromethyl)morphinan which showed inhibition the main viral protease (3CLpro) of SARS-CoV-2 at IC50 value of 25 μM.

Comparative Study of Guanidine-, Acetamidine- and Urea-Based Chloroaluminate Electrolytes for an Aluminum Battery.

Aluminum-based batteries are a promising alternative to lithium-ion as they are considered to be low-cost and more friendly to the environment. In addition, aluminum is abundant and evenly distributed across the globe. Many studies and Al battery prototypes use imidazolium chloroaluminate electrolytes because of their good rheological and electrochemical performance. However, these electrolytes are very expensive, and so cost is a barrier to industrial scale-up. A urea-based electrolyte, AlCl3:Urea, has been proposed as an alternative, but its performance is relatively poor because of its high viscosity and low conductivity. This type of electrolyte has become known as an ionic liquid analogue (ILA). In this contribution, we proposed two Lewis base salt precursors, namely, guanidine hydrochloride and acetamidine hydrochloride, as alternatives to the urea-based ILA. We present the study of three ILAs, AlCl3:Guanidine, AlCl3:Acetamidine, and AlCl3:Urea, examining their rheology, electrochemistry, NMR spectra, and coin-cell performance. The room temperature viscosities of both AlCl3:Guanidine (52.9 cP) and AlCl3:Acetamidine (76.0 cP) were significantly lower than those of the urea-based liquid (240.9 cP), and their conductivities were correspondingly higher. Cyclic voltammetry (CV) and linear sweep voltammetry (LSV) showed that all three electrolytes exhibit reversible deposition/dissolution of Al, but LSV indicated that AlCl3:Guanidine and AlCl3:Acetamidine ILAs have superior anodic stability compared to the AlCl3:Urea electrolyte, as evidenced by anodic potential limits of +2.23 V for both AlCl3:Guanidine and AlCl3:Acetamidine and +2.12 V for AlCl3:Urea. Coin-cell tests showed that both AlCl3:Guanidine and AlCl3:Acetamidine ILA exhibit a higher Coulombic efficiency (98 and 97%, respectively) than the AlCl3:Urea electrolyte system, which has an efficiency of 88% after 100 cycles at 60 mA g-1. Overall, we show that AlCl3:Guanidine and AlCl3:Acetamidine have superior performance when compared to AlCl3:Urea, while maintaining low economic cost. We consider these to be valuable alternative materials for Al-based battery systems, especially for commercial production.

Intermolecular interaction energies and molecular conformations in N-substituted 4-aryl-2-methylimidazoles with promising in vitro antifungal activity.

A convenient one-pot synthesis of 4-aryl-2-methyl-N-phenacylimidazoles (4) through a microwave-assisted pseudo-tricomponent reaction of α-bromoacetophenones (1) with acetamidine hydrochloride (2) is reported. Ketones (4) were successfully used as substrates for the preparation of the respective N-(2-hydroxyethyl)imidazoles (5) with yields up to 87%. The synthesized compounds were characterized by NMR and high-resolution mass spectrometry analyses, and several structures were confirmed and studied by single-crystal X-ray diffraction. The analysis of the whole-of-molecule interactions shows that, despite the difference in the atom-atom contacts forming the crystals, dispersion energies make the largest contribution to the formation of the solids, giving an isotropic tendency in the topology of the energy framework diagrams for pairs of molecules. In addition, the in vitro antifungal activity of both families of compounds [ketones (4) and alcohols (5)] against Candida albicans and Cryptococcus neoformans was evaluated, where the 2,4-dichlorophenyl-substituted alcohol (5f), an isomer of the drug miconazole, showed the highest activity (IC50 = 7.8 µg ml-1 against C. neoformans).

Synthesis and in vitro Antifungal Evaluation of Novel N‐Substituted 4‐Aryl‐2‐methylimidazoles

AbstractAn efficient and regioselective synthesis of novel 4‐aryl‐2‐methyl‐N‐phenacylimidazoles 5 by a microwave‐assisted pseudo‐tricomponent reaction between acetamidine hydrochloride (3) and α‐bromoacetophenones 2 has been developed. The reduction of the carbonyl group of the ketones 5 offered the corresponding N‐(2‐hydroxyethyl)imidazoles 6 in good yields. Novel N‐substituted imidazoles 5 and 6 were tested for antifungal activity against two clinically important fungi Candida albicans and Cryptococcus neoformans. The results showed that all compounds displayed very low activity against C. albicans. In contrast, compounds 5 and 6 were active against C. neoformans. Among them, ketones 5 showed better activity than alcohols 6, with IC50 values as low as 15.6 μg/mL for some of them. The difluorinated compound 5 e showed the best activity against C. neoformans, followed by the dichlorinated derivative 5 b. The difluorinated compound 5 e showed the best activity against C. neoformans, followed by the dichlorinated derivative 5 b.

Transition-metal-free access to 2-aminopyridine derivatives from 2-fluoropyridine and acetamidine hydrochloride.

Under catalyst-free conditions, an efficient method for the synthesis of 2-aminopyridine derivatives through the nucleophilic substitution and hydrolysis of 2-fluoropyridine and acetamidine hydrochloride has been developed. This amination uses inexpensive acetamidine hydrochloride as the ammonia source and has the advantages of a high yield, high chemoselectivity and wide substrate adaptability. The results suggest that other N-heterocycles containing fluorine substituents can also complete the reaction via these reaction conditions and yield the target products.

A highly efficient heterogeneous copper-catalysed cascade reaction of aryl iodides with acetamidine hydrochloride leading to primary arylamines

A highly efficient heterogeneous copper-catalysed cascade reaction of aryl iodides with acetamidine hydrochloride was achieved in DMF in the presence of 10 mol% of an MCM-41-immobilised L-proline-copper(I) complex (MCM-41-L-proline-CuI) with Cs2CO3 as base, yielding a variety of primary arylamines in good to excellent yields. The new heterogeneous copper complex can be easily prepared from commercially readily available and inexpensive reagents, recovered by a simple filtration of the reaction solution and used at least seven more times without any decrease in activity.

A Concise Synthesis of Novel Aryl Pyrimidine C‐Nucleoside Analogs from Sugar Alkynes

AbstractAryl‐ and amino‐substituted pyrimidine C‐nucleoside analogs have been synthesized in good to excellent yields by one‐pot coupling of terminal sugar alkynes, substituted benzoyl chlorides, and amidine salts. The reaction conditions are tolerant of various structurally complex sugars having sterically bulky groups, unprotected hydroxyl groups, and sensitive substituents. The sugar alkynes include structurally diverse pyranosides, acyclic glycosides, and furanosides. The substituted benzoyl chlorides bear electron‐withdrawing and ‐donating substituents with different steric hindrance. The amidine salts include acetamidine hydrochloride, benzamidine hydrochloride, and guanidine hydrochloride.

An efficient synthesis of 3,4-dihydropyrimidin-2(1H)-one and 5,6-diphenylpyrimidine derivatives under solvent-free and base conditions

An efficient and convenient Biginelli-like reaction one-pot synthesis of a series of 4-aryl-5,6-diphenyl-3,4-dihydropyrimidin-2(1H)-one and 4-aryl-5,6-diphenylpyrimidine derivatives under solvent-free conditions from the reaction of aromatic aldehydes, 1,2-diphenylethanone, urea, guanidine carbonate or acetamidine hydrochloride has been reported. This methodology has the advantages of short reaction time, mild reaction conditions, easy work-up and environmental friendliness. Moreover, 4-aryl-5,6-diphenylpyrimidine derivatives were first reported in this process. The structures of the title compounds were further determined by X-ray diffraction. More importantly, different from general Biginelli reaction, this reported method was carried out under base conditions.

A highly efficient heterogeneous copper-catalysed cascade reaction of aryl iodides with acetamidine hydrochloride leading to primary arylamines_esi

A highly efficient heterogeneous copper-catalysed cascade reaction of aryl iodides with acetamidine hydrochloride leading to primary arylamines_esi

Comparative theoretical kinetics and thermodynamics study on high-energy insensitive explosive 1,1-diamino-2,2-dinitroethene synthesis.

Two synthesis methods were investigated in this study in order to explore feasible reaction pathways to obtain the target DADNE product: (1) the nitration of tetrahalogen ethene and (2) the reaction of acetamidine hydrochloride with dicarbonyl dichloride. Through theoretical simulation, the findings revealed that synthesis was possible, starting from acetamidine hydrochloride in a hydrated environment, followed by subsequent reaction routes via cyclization of the methoxy-substituted acetamidine anion intermediate with oxalyl chloride to form 2-methoxy-2-methyl-imidazolan-4,5-dione, acid-catalyzed synthesis of 2-methylene-imidazolan-4,5-dione, nitration using nitric acid to obtain 2-dinitromethylene-imidazolan-4,5-dione, and hydrolysis to produce 1,1-diamino-2,2-dinitroethene. A total energy of 1048.4kJ mol(-1) was needed to carry out the reaction according to calculation of the energy barriers at each stage, as shown by the reaction profiles.

ChemInform Abstract: Regioselective Synthesis of Pyrazolo[3,4‐d]pyrimidine Based Carbocyclic Nucleosides as Possible Antiviral Agent.

Carbocyclic nucleosides are considered as nucleoside mimetic having high therapeutic potentials, however diverse exploration is still limited due to their synthetic difficulties. The major challenges are associated with the preparation of new base and carbocyclic sugar key intermediates. The modified base may provide conformational advantage to achieve better nucleoside mimetics and may also help in increasing the drug-like properties. In this manuscript, we report the use of acetamidine hydrochloride to synthesize 6-methyl-4-amino-pyrazolo[3,4-d]pyrimidine base and regioselective synthesis of six new carbocyclic nucleosides (6a-f) for antiviral evaluation. Theoretical investigations were carried out on the basis of thermodynamic and kinetic stability using MM based energy optimizations and QM based transition state search for the significant regioselectivity, which was further experimentally analyzed by NOE and UV spectroscopy.

Regioselective Synthesis of Pyrazolo[3,4-D]Pyrimidine Based Carbocyclic Nucleosides as Possible Antiviral Agent

ABSTRACTCarbocyclic nucleosides are considered as nucleoside mimetic having high therapeutic potentials, however diverse exploration is still limited due to their synthetic difficulties. The major challenges are associated with the preparation of new base and carbocyclic sugar key intermediates. The modified base may provide conformational advantage to achieve better nucleoside mimetics and may also help in increasing the drug-like properties. In this manuscript, we report the use of acetamidine hydrochloride to synthesize 6-methyl-4-amino-pyrazolo[3,4-d]pyrimidine base and regioselective synthesis of six new carbocyclic nucleosides (6a-f) for antiviral evaluation. Theoretical investigations were carried out on the basis of thermodynamic and kinetic stability using MM based energy optimizations and QM based transition state search for the significant regioselectivity, which was further experimentally analyzed by NOE and UV spectroscopy.

One-pot synthesis and in vivo biological evaluation of new pyrimidine privileged scaffolds as potent anti-inflammatory agents

A simple methodology has been developed for the synthesis of diverse members of multifunctionalized 4-hydroxy-2-methyl-6-(phenyl)pyrimidine-5-carbonitrile derivatives via multicomponent reaction of aromatic aldehydes, ethyl cyanoacetate, and acetamidine hydrochloride using a quantitative amount of NaOH in dry DMF at 80 °C in a single procedural step. The carbon skeleton of synthesized compounds resembles the bacimethrin, an antibiotic active against several yeast and bacteria. The anti-inflammatory activities of all the synthesized compounds were assessed on Wistar rats using diclofenac sodium as a standard reference. The compound AC1, 2, 5, 9, and AC10 showed promising anti-inflammatory activity (80–83 %) in comparison with diclofenac sodium (85 %) in the carrageenan-induced rat paw edema assay, which is the key finding of this article. The synthesized 4-hydroxy-2-methyl-6-(phenyl)pyrimidine-5-carbonitrile derivatives shown promising anti-inflammatory activity (80–83 %) in comparison with diclofenac sodium (85 %) in the carrageenan-induced rat paw edema assay.

Synthesis of Indeno[1,2‐d]pyrimidin‐5‐Ones and Their Fluorescence in Solid State

New fluorescent compounds, 2‐substituted indeno[1,2‐d]pyrimidin‐5‐ones (3a, 3b, 3c, 3d) were synthesized in good yield by the reaction of 2‐[bis(methylsulfanyl)methylene]indan‐1,3‐dione (1) with the respective amidine derivatives [guanidine carbonate (2a), acetamidine hydrochloride (2b), S‐methylisothiourea sulfate (2c), and S‐benzylisothiourea sulfate (2d)]. 4‐Substituted amino‐2‐aminoindeno[1,2‐d]pyrimidin‐5‐ones (7b, 7c, 7d) were synthesized by a one‐pot reaction of 1, 2a and the respective amine compounds (4b, 4c, 4d) in pyridine. These fused pyrimidine derivatives showed fluorescence in the solid state.

An Efficient One Pot Protocol to the Annulation of Face “d” of Benzazepinone Ring with Pyrazole, Isoxazole, and Pyrimidine Nucleus through the Corresponding Oxoketene Dithioacetal Derivative

A highly facile single step approach to the annulation of face “d” of benzazepinone nucleus with pyrazole, isoxazole, and pyrimidine ring has been described. The annulation proceeded smoothly on the reaction of oxoketene dithioacetal derivative 3 with (i) NH2–NH2·H2O, (ii) NH2OH·HCl, (iii) acetamidine hydrochloride, (iv) guanidine nitrate, (v) urea, and (vi) thiourea which yielded the pyrazolo, isoxazolo, and pyrimido annulated analogues of benzazepinone 4–9, respectively, in acceptable yields. The 4-ketene dithioacetal analogue of 7-fluorobenzo[b]azepine-2,5-dione (3) was in turn obtained from the reaction of 7-fluoro-3,4-dihydro-1H-benzo[b]azepine-2,5-dione (2) (with CS2 + CH3I in presence of t-BuOK). 7-Fluoro-3,4-dihydro-1H-benzo[b]azepine-2,5-dione (2) resulted from the acylation of p-fluoroaniline with succinyl chloride followed by cyclocondensation of the later with polyphosphoric acid (PPA).

Three-Component Reaction of Tautomeric Amidines with 3-Ferrocenylmethylidene-2,4-pentanedione. Formation of Polymeric Coordination Complexes of Potassium Ferrocenyl-(hexahydro)pyrimidoxides

Acetamidine hydrochloride and p-aminobenzamidine dihydrochloride interact with 3-ferrocenylmethylidene-2,4-pentanedione at 80–82 °C in the presence of K2CO3 in the water–alcohol medium in two tautomeric forms (the amidoimine and enediamine ones) with formation of mixtures of pyrimidine and piperidone derivatives and polymeric coordination complexes of potassium ferrocenyl(hexahydro)pyrimidoxides. The structure of the resultant compounds is elucidated on the basis of IR, 1H- and 13C-NMR spectroscopy, mass spectrometry and elemental analysis data. The crystal structures of 6-ferrocenyl-4-hydroxy-4-methyl-2-piperidone, potassium 6-ferrocenyl-4-methyl-2-methylidene(hexahydro)pyrimidin-4-oxide and 2-(4-aminophenyl)-4-ferrocenyl-6-methyl-pyrimidine were determined by X-ray analysis of suitable single crystals.

Development of Two Scalable Syntheses of 4-Amino-5-aminomethyl-2-methylpyrimidine: Key Intermediate for Vitamin B1

Two scalable processes for the synthesis of 4-amino-5-aminomethyl-2-methylpyrimidine (2) are described. In the first approach, the less expensive 2-cyanoacetamide was reacted with Vilsmeier reagent to afford enamine 18, followed by the condensation with acetamidine to produce the 4-amino-2-methylpyrimidine-5-carbonitrile (6); subsequent hydrogenation gave 2 in 65% overall yield. In the second approach, malononitrile was treated with the ionic salt 21, prepared in situ from DMF and dimethyl sulfate, to give 18, which, without isolation was reacted with acetamidine hydrochloride to afford the common intermediate 6. Overall yield of this approach was 70%. Both methods are performed in a convenient manner suitable for industrial use.

ChemInform Abstract: A Mild Liquid Reduction Route Toward Uniform Blue‐Emitting EuCl2 Nanoprisms and Nanorods.

AbstractUniform EuCl2 nanoprisms and nanorods are synthesized by a new reduction route from mixtures of Eu(OOC‐CCl3)3 for nanoprisms or Eu(OAc)3 for nanorods and acetamidine hydrochloride (or picolinamidine hydrochloride) as the reductant in oleylamine (300 °C, 1 h).

Antitumor Actions of Ruthenium(III)-Based Nitric Oxide Scavengers and Nitric Oxide Synthase Inhibitors

The role of endogenous nitric oxide (NO) in the growth and vascularization of a rat carcinosarcoma (P22) has been investigated. Tumor-bearing animals were treated with (i) nitric oxide synthase (NOS) inhibitors, administered via the drinking water, including N(G)-nitro-l-arginine methyl ester (L-NAME), a nonisoform-selective inhibitor, and 2 others that target the inducible (NOS II) enzyme preferentially, namely 1-amino-2-hydroxyguanidine or N-[3-(aminomethyl)benzyl]acetamidine hydrochloride; or (ii) daily injections (intraperitoneally) of 2 Ru(III) polyaminocarboxylates, AMD6221 and AMD6245, both of which are effective NO scavengers. L-NAME, AMD6221, and AMD6245 reduced tumor growth by approximately 60% to 75% of control rates. Tumor sections stained with abs to CD-31/platelet endothelial cell adhesion molecule-1 or NOS III showed that this was associated with a marked reduction (60%-77%) of tumor microvascular densitiy (MVD). Tumors resumed growing promptly when treatment was discontinued, accompanied by partial or complete restoration of MVDs. In contrast, NOS-II selective inhibitors had no effect on tumor growth or vascularization, indicating that both responses require complete blockade of NO production. The results corroborate the view that endogenous NO facilitates tumor development. We suggest that NO deprivation causes tumor feeder vessels to constrict, reducing tumor blood flow. The delivery of oxygen and essential nutrients to the developing tumor is impaired as a consequence, hampering further growth. Normalizing NO levels by withholding treatment causes tumor feeder vessels to dilate, increasing tumor perfusion and reestablishing conditions that allow tumors to begin growing again.