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Cyclic alkoxyguanidines such as 2-methoxyiminoimidazolidine, 2-benzyloxyiminoimidazolidine and 6',7'-dihydro-5' H-spiro(cyclohexane-1,3'-imidazo(2,1-c)(1,2,4)oxadiazole react with isocyanates and isothiocyanates to give the corresponding urea and thiourea derivatives, which under basic reaction conditions undergo an intramolecular SN2σ nucleophilic substitution reaction at the sp 2 nitrogen atom of the alkoxyimine moiety with simultaneous extrusion of the alkoxy anion leading to the formation of imidazo(2,1-c)(1,2,4)triazol-3-one and imidazo(2,1- c)(1,2,4)thiadiazole with new N-N and N-S bonds, respectively. The above extensions of the Boulton-Katritzky rearrangement were studied theoretically with the DFT B3LYP-6-31+G* method and SM8 solvation model.

Background: Cutaneous and invasive fungal infections are constant threats to human health that substantiate the need for the development of new efficacious and safe antimycotics. Methods: A series of N1-alkyl, N1-acyl and N1-sulfonyl derivatives of 4,6- dimethylisoxazolo[3,4-b]pyridin-3(1H)-one (1) were synthesized. The antimicrobial activities of title compounds against 21 pathogenic yeast-like fungal clinical isolates and 5 reference strains were evaluated by means of a broth microdilution method. Results: Among the compounds tested, the newly prepared N1-benzoyl (2m) and N1-(4-fluorobenzoyl) (2n) derivatives of 1 showed 81% and 95% inhibitory efficacy, respectively, against the clinical isolates, which were comparable to that of the reference drug fluconazole. The strains that exhibited the highest susceptibility to the compound 2n included Candida utilis (MIC < 6.2 g/mL), C. parapsilosis (MIC in the range

Two new 1,2,4-triazole-containing alkenoic acid derivatives were obtained from the reaction of N -phenyl-(pyridin-2-yl)carbohydrazonamide with itaconic anhydride, depending on the reaction conditions. The structures of 2-((4-phenyl-5-(pyridin-2-yl)-4 H -1,2,4-triazol-3-yl)methyl)acrylic acid or ( E )-2-methyl-3(4-phenyl-5-(pyridine-2-yl)-4 H -1,2,4-triazol-3-yl)acrylic acid were confirmed by means of 1D and 2D NMR spectroscopic data as well as by single-crystal X-ray diffraction analysis. The experiential 1 H and 13 C chemical shifts were compared with those calculated with B3LYP, EDF1, and EDF2 density functional theories. The theoretical study of the observed terminal-to-internal alkene isomerization was performed with density functional (DFT) B3LYP/6-31+G ∗ method using SM8 water and DMF solvation models. Antimicrobial activities of the newly prepared alkenoic acid derivatives were verified experimentally by a broth microdilution method.

A series of 2-[(heteroaryl)methyl]imidazolines was synthesized and tested for their activities at α(1)- and α(2)-adrenoceptors and imidazoline I(1) and I(2) receptors. The most active 2-[(indazol-1-yl)methyl]imidazolines showed high or moderate affinities for α(1)- and α(2)-adrenoceptors. However, their intrinsic activities at α(2A)-adrenoceptors proved to be negligible. A selected 7-chloro derivative behaved as a potent α(1)-adrenoceptor antagonist and exhibited peripherally mediated hypotensive effects in rats.

A high yielding three-step procedure was applied for the synthesis of N-(imidazolidin-2-ylidene)-1-arylmethanamine oxides 3 (α-aminonitrones) starting from the easily accessible imidazolidin-2-one O-benzyl oxime 1. The α-aminonitrone-α-iminohydroxyloamine tautomerism of these products was studied theoretically and the structures of the synthesised compounds were confirmed by single crystal X-ray crystallographic analysis. The compounds were evaluated in vitro for their binding affinities to α(1) and α(2) adrenoceptors as well as imidazoline I(1) and I(2) receptors. The highest potencies at the α(2) adrenergic receptors were observed for compounds bearing biphenyl (4h, K(i) = 9 nM) and naphthyl (4i, K(i) = 92 nM) moieties. Compounds 4h and 4i were further tested in vivo for their cardiovascular and sedative-hypnotic effects in rats.

Hydroxylamine-O-sulfonic acid (HOSA) was used as an efficient nucleophilic amination reagent for 2-chloropyrimidines, 2-chloroquinolines, and 1-chloroisoquinoline. The newly obtained heteroaromatic hydroxylamine-O-sulfonates subjected to the reaction with acyl isothiocyanates underwent tandem nucleophilic addition–electrophilic 5-endo-trig cyclization. The mechanism of the cyclization was investigated with use of the long-range corrected hybrid density functional ωB97X-D/6-31+G∗ and SM8 (DMF) solvation model. The structures of the heteroaromatic hydroxylamine-O-sulfonates and N-(5-methoxy-2H-[1,2,4]thiadiazolo[2,3-a]pyrimidin-2-ylidene)benzamide were confirmed by single crystal X-ray analysis. N-(2H-[1,2,4]thiadiazolo[3,2-a]isoquinolin-2-ylidene)benzamide exhibited a pronounced in vitro cytostatic activity against human tumor cell lines SISO, LCLC, A-427, DAN-G, and RT-4 (IC50 in the range 1.47–2.97 μM).

The course of reaction of aryl and heteroaryl sulfonamides with diphenylcarbonate (DPC) and 4-dimethylaminopyridine (DMAP) was found to depend on the pKa of the sulfonamide used. Aryl sulfonamides with pKa approximately 10 gave 4-dimethylamino-pyridinium arylsulfonyl-carbamoylides, while the more acidic heteroaryl sulfonamides (pKa approximately 8) furnished 4-dimethylaminopyridinium heteroarylsulfonyl carbamates. Both the carbamoylides and carbamate salts reacted with aliphatic and aromatic amines with the formation of appropriate aryl(heteroaryl)sulfonyl ureas, and therefore, can be regarded as safe and stable substitutes of the hazardous and difficult to handle aryl(heteroaryl)sulfonyl isocyanates. ispartof: Molecules vol:15 issue:3 pages:1113-1126 ispartof: location:Switzerland status: published

The addition reaction of lithium reagents to the 4 position of 2-chloropyrimidine or 2-chloroquinazoline followed by oxidation of the resultant dihydro intermediate product is a powerful tool for the synthesis of 4-substituted 2-chloropyrimidines or 2-chloroquinazolines. 4-Vinyl derivatives undergo a conjugate nucleophilic addition across the vinyl group. A nucleophilic displacement of chloride in 4substituted 2-chloropyrimidines or 2-chloroquinazolines by treatment with 4-methylpiperazine provides compounds that are antagonists of the serotonin 5-HT2A receptor.

A series of variously substituted 2-(4,5-dihydro-1H-imidazol-2-yl)indazoles 3a-j and 2-(4,5-dihydro-1H-imidazol-2-yl)-4,5,6,7-tetrahydroindazole 6 were prepared by the regiospecific heteroalkylation of corresponding indazoles 1a-k with 2-chloro-4,5-dihydroimidazole (2). Their affinity to imidazoline I(2) receptors and alpha(2)-adrenergic receptors was determined by radioligand binding assay carried out on P(2) membrane preparations obtained from rat whole brains. 4-Chloro-2-(4,5-dihydro-1H-imidazol-2-yl)indazole (3f, 4-Cl-indazim) showed a 3076-fold difference in affinity for the [(3)H]2BFI-labeled imidazoline I(2) receptors relative to the [(3)H]RX821001-labeled alpha(2)-adrenergic receptors. This highly selective compound should prove to be useful tool in further understanding the functions of the imidazoline I(2) receptors.

[2950-43-8] H3NO4S (MW 113.11) InChI = 1S/H3NO4S/c1-5-6(2,3)4/h1H2,(H,2,3,4) InChIKey = DQPBABKTKYNPMH-UHFFFAOYSA-N (amination; hydroxymethylation; reduction; conversion of alkenes to primary amines1-3) Alternate Name: HOSA. Physical Data: mp 210 °C (dec); single crystal X-ray diffraction analysis.51 Solubility: sol cold water, methanol; slightly sol ethanol; insol ether, CHCl3. Form Supplied in: white solid; widely available. Analysis of Reagent Purity: quantitative analysis of HOSA can be made by iodometric titration.4, 5 Preparative Methods: by reacting hydroxylamine sulfate with 30% fuming H2SO44 or 60% oleum6 at rt, or by heating a mixture of hydroxylamine sulfate and chlorosulfonic acid at 100 °C for several hours.5 Handling, Storage, and Precautions: hygroscopic; should be stored in tightly sealed bottles in a refrigerator. Aqueous solutions are unstable, decomposing rapidly above 25 °C. It is thus important to use freshly prepared solutions in reactions. Use in a fume hood.

(Pyridinium, 4-(dimethylamino)-1-{[(phenylsulfonyl)amino]carbonyl}-, inner salt) [932744-07-5] C14H15N3O3S (MW 305.35) InChI = 1S/C14H15N3O3S/c1-16(2)12-8-10-17(11-9-12)14(18)15-21(19,20)13-6-4-3-5-7-13/h3-11H,1-2H3 InChIKey = QODGALWZGNTOLI-UHFFFAOYSA-N (carbamoylation; conversion of amines to N-(benzenesulfonyl)ureas; conversion of alcohols to N-(benzenesulfonyl)carbamates,1, 2 tandem nucleophilic addition–electrophilic amination) Alternate Name: 4-dimethylaminopyridinium N-(benzenesulfonyl)carbamoylide. Physical Data: mp 214–217 °C (dec). Solubility: soluble in DMF, DMSO, slightly soluble in acetonitrile, insoluble in ether and CHCl3. Form Supplied in: commercially not available. Analysis of Reagent Purity: IR, NMR. Preparative method: by reacting benzenesulfonamide (1 equiv) with diphenyl carbonate (DPC, 1.1 equiv) and 4-(dimethylamino)pyridine (DMAP, 1.1 equiv) in CH3CN at room temperature for 18 h.1 Handling, Storage, and Precautions: can be stored at ambient temperature in an open vial exposed to air and moisture for several months. Toxicity unknown.

All the title compounds (V) and (VI) show very weak binding affinities to imidazoline I1 receptors, but some of them exhibit good affinity to the imidazoline I2 receptors.

Conjugate addition reaction of various nucleophiles across the vinyl group of 2-chloro-4-vinylpyrimidine, 2-chloro-4-(1-phenylvinyl)pyrimidine and 2-chloro-4-vinyl-quinazoline provides the corresponding 2-chloro-4-(2-substituted ethyl)pyrimidines and 2-chloro-4-(2-substituted ethyl)quinazolines. Treatment of these products, without isolation, with N-methylpiperazine results in nucleophilic displacement of chloride and yields the corresponding 2,4-disubstituted pyrimidines and quinazolines.

Experimental evidence for rearrangement of benzoyl cyanide into corresponding isocyanide is provided by the reaction of benzoyl cyanide with triethylaminium 2-hydroxylaminoimidazolidine-O-sulfonate (2) which affords N-(4-cyano-2-phenyloxazol-5-yl)benzamide (4) as a result of the trimerization of benzoyl isocyanide. Compound 4 was further converted into N-acetyl-N-(4-cyano-2-phenyloxazol-5-yl)acetamide (6) upon heating in acetic acid anhydride. Structure of 6 was confirmed by X-ray crystallographic analysis.

2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate (1) has been prepared by reacting 2-chloro-4,5-dihydroimidazole with hydroxylamine-O-sulfonic acid. Deprotonated compound 1a containing both the nucleophilic endocyclic nitrogen atoms and electrophilic exocyclic nitrogen was used for the syntheses of 3-substituted 6,7-dihydro-5H-imidazo[2,1-c][1,2,4]oxadiazoles 2-9 and 6,7-dihydro-5H-imidazo[2,1-c][1,2,4]thiadiazole-3-thione (10) by tandem nucleophilic addition-electrophilic amination reaction. The method promises utility in the synthesis of a variety of other heterocycles. On the other hand, the convenient routes to 7,8-dihydroimidazo[1,2-c][1,3,5]thiadiazine-2,4(6H)-dithione (16) and 2,6,7,8-tetrahydroimidazo[1,2-a][1,3,5]triazine-4(3H)-thione derivative (17) are reported starting from compound 1. The structures of the compounds prepared were established by elemental analyses, IR, NMR, and MS spectra, and in some instances X-ray analyses.

The reactions of 2-chloro-4, 5-dihydroimidazole 1 with o-substituted anilines and azoles promoted by carbon disulfide have been carried out. Ab initio MO calculations were used to elucidate the mechanism of the reaction of 1 with N-nucleophilic reagents. A facile synthesis of 2-(4, 5-dihydroimidazol-2-yl)-1H-indazole 3e bearing structural resemblances to 2-BFI, a potent and selective agonist of imidazoline I2 receptors, is also described. Structure of 3e was confirmed by NMR spectroscopy and X-ray analysis.

The structure of the title compound, C5H4N3S3−·C3H8N3+·2C3H7NO, has been determined from a non-merohedral twin. The asymmetric unit consists of a heterocyclic anion, a guanidinium-type cation and two dimethyl­formamide solvent mol­ecules. The three C—N bond lengths in the guanidinium fragment range from 1.315 (3) to 1.342 (3) A, the shortest bond being to the exocyclic amino group. The anion and cation are connected via a pair of N—H⋯N hydrogen bonds and the two solvent mol­ecules are linked to this ion pair via N—H⋯O hydrogen bonds.