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Photochemical excitation (λ > 350 nm) of chloro[meso-tetrakis(2, 6-dichlorophenyl)porphyrin]iron(III) [FeIII(TDCPP)Cl] and chloro[meso-tetra(α,α,α,α-pivalamidophenyl)porphyrin] -iron(III) [FeIII(TpivPP)Cl] induces the oxidation of coordinated N-(4-chlorophenyl)-N′-hydroxyguanidine (1) by molecular oxygen, to give iminoxyl radicals and the FeII(O2) [or Fe III(O2.)] adduct. This complex can be accumulated in significant amounts using [FeIII(TpivPP)Cl]. The primary photoproducts give rise to secondary reactions that lead to the formation of N-4-chlorophenyl)urea (2) as the main end-product of 1. The conversion of 1 into 2 is accompanied by the formation of NO, as revealed both by an ESR spin-trapping technique and in the form of its stable end-products NO2- and NO3-. The presence of 1-methyl imidazole (1-MeIm) coordinated in axial position has a significant positive effect on the photoinduced production of 2 and NO from the hydroxyguanidine 1. The observation that radical scavengers inhibit the photooxidation process strongly supports the possibility that the reaction pathway resembles a radical-type autoxidation mechanism, where the very fast reaction of O2 with the ferrous porphyrin in the presence of the photo-generated iminoxyl radical should yield an iron-peroxo intermediate as precursor of the urea 2 and NO. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

The iron-mediated efficient multi-component method has been demonstrated for the synthesis of substituted cyanamides from isothiocyanates under mild reaction conditions. Subsequent nucleophilic addition and desulfurization are involved in this proposed synthetic methodology. All the reactions are rapid, facile, and accomplished at room temperature. A variety of substrates readily underwent the optimized reaction conditions to provide their respective target products in good to excellent yields. Furthermore, we have confirmed that no other by-products could be identified during our experimental reaction process. Graphical abstract: Iron-mediated efficient multi-component method has been demonstrated for the synthesis of substituted cyanamides from isothiocyanates under mild reaction conditions. Subsequent nucleophilic addition and desulfurization are involved in this proposed synthetic methodology.[Figure not available: see fulltext.].

An unprecedented electrochemical trifluoromethylation/SO2 insertion/cyclization process has been achieved in an undivided cell in an atom-economic fashion. The protocol relies on tandem cyclization of N-cyanamide alkenes by using Langlois’ reagent as a source of both CF3 and SO2 under direct anodically oxidative conditions, in which two C?C bonds, two C?X bonds (N?S and S?C), and two rings were formed in a single operation. This transformation enabled efficient construction of various trifluoromethylated cyclic N-sulfonylimines from readily accessible materials.

An operationally simple oxidation-cyanation method for the synthesis of cyanamides is described. The procedure utilizes inexpensive and commercially available N-chlorosuccinimide and Zn(CN)2 as reagents to avoid direct handling of toxic cyanogen halides. It is demonstrated to be amenable for the cyanation of a variety of primary and secondary amines and aniline derivatives as well as a complex synthetic intermediate en route to verubecestat (MK-8931). Additionally, kinetic measurements and other control experiments are reported to shed light onto the mechanism of this cyanation reaction.

A simple, mild and practical process for the direct conversion of nitriles to cyanamides was newly discovered and exhibited a wide substrate scope as well as great functional group-tolerability (36 examples). In this efficient strategy, the in situ generated amidoximes obtained from the reaction of nitriles with hydroxylamine subsequently underwent Tiemann rearrangement, producing the corresponding cyanamides with great isolated yields under SO2F2. Additionally, the control experiments reportedly shed light on the tentative mechanism involved in the formation and elimination of the key intermediate: a sulfonyl ester.

The methodology for the preparation of aromatic cyanamides has been demonstrated. The present method involves consecutive desulphurization/C-N cross-coupling reaction. Cheap, readily available and air stable cobalt catalyst has been used for this methodology. In addition, the substrate scope has been explored.

A one pot highly efficient and simple protocol for the construction of aromatic cyanamides from thiourea via desulphurization/C-N cross coupling using a cheap, readily available and air stable copper source as a catalyst has been described. Various iodobenzenes could give their respective C-N cross-coupled products in good to excellent yields under optimized reaction conditions. Further, the substrate scope has been explored.

In the present work, we have designed a novel, heterogeneous and recyclable magnetic Br?nsted acidic ionic liquid based on 5-phenyl-1H-tetrazole. The {Fe3O4@SiO2@CH2)35-phenyl-1H-tetrazole-SO3H/Cl} ([FSTet-SO3H]Cl) was prepared via the immobilization of 5-phenyl-1H-tetrazole-bonded sulfonic acid onto the surface of silica-coated magnetic nanoparticles using 3-chloropropyltriethoxysilane as a linker. The catalyst was characterized by XRD, TEM, FESEM, EDS, TG-DTA, and FT-IR. The ability and high activity of this catalyst were demonstrated in the synthesis of 1-carbamoyl-1-phenylureas with good to excellent yields via a new, simple and one-pot procedure in aqueous media under reflux conditions. This procedure has advantages such as high yields, short reaction times, a simple methodology and work-up process, green reaction conditions, high stability, catalytic activity, and easy preparation, separation and reusability of the catalyst. The synthesis of these compounds was confirmed by FT-IR, 1H NMR, 13C NMR and CHN. In addition, we investigated the biological properties of the 1-carbamoyl-1-phenylureas as newly synthesized compounds. The described catalyst could be easily separated from the reaction mixture by additional magnetic force and reused several times without a remarkable loss of its catalytic activity and any considerable changes in the product yield and the reaction time.

We have developed methodology for the synthesis of aryl/alkyl cyanamides from amines in one-pot four steps reaction using cheap, readily available and air stable copper source as catalyst under mild reaction conditions. We have also studied the application of cyanamides. In this connection, we could construct aryl tetrazolamine from cyanamides using click reaction.

[Figure not available: see fulltext.] The synthesis of cyanamides and tetrazoles from isothiocyanates through tandem reaction using cobalt catalyst has been demonstrated. In the case of tetrazole preparation, the reaction involved addition/desulfurization/nucleophilic addition/electrocyclization, whereas aromatic cyanamides were constructed from isothiocyanates through addition/desulfurization. Cheap cobalt sulfate was used for the synthesis of various cyanamides and tetrazoles. In addition, cobalt catalyst was found to be desulfurization reagent that has not been previously reported. The final products have been obtained from starting precursors in good to high yield.

A highly efficient and simple protocol for the synthesis of isothiocyanates and cyanamides from their respective amines in the presence of a mild, efficient, and non-toxic reagent tetrapropylammonium tribromide is described. High environmental acceptability of the reagents, cost effectiveness and high yields are the important attributes of this methodology.

One-pot synthesis of cyanamides from isoselenocyanates through deselenisation promoted by ionic liquid-supported hypervalent iodine(III) reagent 1-(4-diacetoxyiodobenzyl)-3-methylimidazolium tetrafluoroborate [dibmim BF4 was developed. This approach provided a simple, mild and environmentally benign way to construct cyanamides in good yields. Moreover, powder Se and dibmim + BF4 could be easily recycled. It was the first example of [dibmim] + [BF4- to be used as a deselenising agent.

The cobalt-catalyzed cross-coupling of organozinc bromides with N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS) is described. The same cobalt catalyst, cobalt(II) bromide, was used for both the synthesis of the organozinc species and the cross-coupling reaction. However in this case, a catalytic amount of zinc dust is necessary in the second step to release the low-valent cobalt. Under these mild conditions, moderate to excellent yields of different benzonitriles were obtained.

Water soluble iron(III) porphyrins immobilized in imidazolium ionic liquids serve as an effective catalyst for the H2O2 mediated oxidation of guanidoximes to selectively give corresponding cyanamides in good yields. The use of ionic liquid with non-coordinating counter anion PF6 affords the product in high yield by facilitating the formation of anionic iron peroxo intermediate. [Figure not available: see fulltext.]

Amidoximes, obtained from the reaction of nitriles with hydroxylamine, underwent Tiemann rearrangement in the presence of benzenesulfonyl chlorides (TsCl or o-NsCl) to form the N-substituted cyanamides. Subsequently, acidic hydrolysis of the cyanamides afforded the corresponding N-monosubstituted ureas. The synthesis of N-monosubstituted ureas from nitriles was accomplished by three steps in one pot, which provides a direct access to versatile N-monosubstituted urea derivatives from a wide variety of nitriles.

A facile and general synthesis of various N-substituted cyanamides was accomplished by the Tiemann rearrangement of amidoximes with benzenesulfonyl chlorides (TsCl or o-NsCl) and DIPEA.

An efficient aminocyanation by the direct addition of aryl cyanamides to arynes is described, enabling incorporation of highly useful amino and cyano groups synchronously via cleavage of inert N-CN bonds, affording synthetically useful 1,2-bifunctional aminobenzonitriles. The postsynthetic functionalization of the aminocyanation products allows diverse formation of synthetically important derivatives such as drug molecule Ponstan and fused heterocycles.

An efficient "one-pot" approach to multiple substituted ureas from N-arylcyanamide and diaryliodonium salts has been presented. The two-step procedure involved the weak base-promoted chemoselective arylation of secondary amines with diaryliodonium and Cu-catalyzed nucleophilic addition of N-arylcyanamide with second diaryliodonium. The diverse unsymmetrical arylureas were obtained in up to 91% yield for 29 examples.

An environmentally benign reaction is devised for the synthesis of cyanamides from dithiocarbamate salts using iodine and H2O 2. Taylor & Francis Group, LLC.

A novel and green protocol for the synthesis of N-1 and C-5 substituted 2-iminohydantoins has been developed. Methyl N-cyano-N-alkyl/aryl-aminoacetate reacts with aqueous ammonia at room temperature in 10-30 min. The developed protocol does not require any work-up for the isolation or purification of the products; simple filtration can lead to the pure products in good to excellent yields.

In a one-pot procedure, bromineless brominating reagent 1,1'-(ethane-1,2-diyl)dipyridinium bistribromide (EDPBT) has been used as a desulfurizing agent in the preparation of organic cyanamides and substituted thiazoles starting from dithiocarbamic acid salts. In this approach, alkyl/aryl isothiocyantes were first obtained by the desulfurization of dithiocarbamic acid salts with EDPBT. The in situ-generated isothiocyanates reacts with an aqueous ammonia, forming alkyl or aryl thioureas, which on subsequent oxidative desulfurization with EDPBT led to the formation of corresponding cyanamides in good yields. Alternatively, an efficient one-pot synthesis of substituted thiazoles has been achieved by the condensation of the in situ-generated 1-aryl thioureas with the in situ-generated -bromoketones from ketones, again using EDPBT. The reagent EDPBT can be easily prepared from the readily available reagents. Desulfurizing ability dominates over its brominating ability for substrates amenable to bromination.

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We have developed a ligand-assisted copper(I)-catalyzed two sequential heteroarylation sequence. An intramolecular S-arylation is followed by an intermolecular N-arylation leading to the direct synthesis of N-aryl-2-aminobenzothiazoles. In most cases however, the 2-arylsulfanyl- arylcyanamide was the major product obtained via an intramolecular C-S bond formation, associated with C-S bond breakage, followed by an intermolecular S-arylation. The selectivity of this ligand-assisted reaction is quite different as compared to that of ligand-free reactions and the rates are much faster giving good yields of products. Various cyanamides can be prepared in excellent yields from their corresponding 1-substituted thioureas with or without the assistance of a ligand with a catalytic quantity of copper(I).

In a one-pot strategy we have achieved an efficient method for the synthesis of organic cyanamides starting from dithiocarbamic acid salts/amines. In this strategy the in situ generated alkyl or aryl isothiocyanates, obtained by the desulfurization of dithiocarbamic acid salts with diacetoxyiodobenzene (DIB) react with aqueous ammonia forming alkyl or aryl thiourea which on subsequent oxidative desulfurization with DIB led to the formation of corresponding cyanamide in good yields. Mild reaction conditions, shorter reaction time, an environmentally benign protocol, and easy isolation of the desired product make the present methodology a suitable alternative for the preparation of various organic cyanamides.

An efficient one-pot method for the synthesis of cyanamides from dithiocarbamate salts via a double desulfurization strategy using molecular iodine is disclosed. Dithiocarbamates, by the action of iodine yield isothiocyanates in situ, which on treatment with aqueous NH3 give thioureas. The thioureas so generated undergo further oxidative desulfurization with I2 giving corresponding cyanamides in good yields. Environmental benignity, cost effectiveness and high yields are the important attributes of this one pot procedure. The Royal Society of Chemistry 2009.

Cyanamides were successfully prepared in a 'one-flask' reaction from isocyanates by use of sodium bis(trimethylsilyl)amide as the deoxygenating agents in THF at room temperature. Georg Thieme Verlag Stuttgart.

A palladium mimic of the Curtius rearrangement and a palladium-catalyzed geminal addition of a Si-N bond occurs in the high-yielding synthesis of cyanamides from isocyanides and trimethylsilyl azide in the presence of a palladium catalyst (see scheme). A

The electrochemical properties of a series of N-substituted-N'-hydroxyguanidines were studied. Two oxidation potentials of each compound were obtained by cyclic voltammetry. The E(ox1) values were from 0.51 to 0.62V, while the E(ox2) values were from 1.14 to 1.81V in acetonitrile solution. Next, their enzymatic controlled NO release abilities were evaluated. All N'-hydroxyguanidines exhibited efficient NO release abilities under the oxidation by horseradish peroxidase in the presence of H(2)O(2).

Enzymatic generation of nitric oxide (NO) by nitric oxide synthase (NOS) consists of two oxidation steps. The first step converts L-arginine to N(G)-hydroxy-L-arginine (NOHA), a key intermediate, and the second step converts NOHA to NO and L-citrulline. To fully probe the substrate specificity of the second enzymatic step, an extensive structural screening was carried out using a series of N-alkyl (and N-aryl) substituted-N'-hydroxyguanidines (1-14). Among the eleven N-alkyl-N'-hydroxyguanidines evaluated, N-n-propyl (2), N-iso-propyl (3), N-n-butyl (4), N-s-butyl (5), N-iso-butyl (6), N-pentyl (8) and N-iso-pentyl (9) derivatives were efficiently oxidized by the three isoenzymes of NOS (nNOS, iNOS and eNOS) to generate NO. N-Butyl-N'-hydroxyguanidine (4) was the best substrate for iNOS (K(m)=33 microM) and N-iso-propyl-N'-hydroxyguanidine (3) was the best substrate for nNOS (K(m)=56 microM). When the alkyl substituents were too small (such as ethyl 1) or too large (such as hexyl 10 and cyclohexyl 11), the activity decreased significantly. This suggests that the van der Waals interaction between the alkyl group and the hydrophobic cavity in the NOS active site contributes significantly to the relative reactivity of compounds 3-11. Moreover, five N-aryl-N'-hydroxyguanidines were found to be good substrates for iNOS, but not substrates for eNOS and nNOS. N-phenyl-N'-hydroxyguanidine was the best substrate among them (K(m)=243 microM). This work demonstrates that N-alkyl substituted hydroxyguanidine compounds are novel NOS substrates which 'short-circuit' the first oxidation step of NOS, and N-aryl substituted hydroxyguanidine compounds are isoform selective NOS substrate.

Oxidations of L-arginine 2, homo-L-arginine 1, their Nω-hydroxy derivatives 4 and 3 (NOHA and homo-NOHA, respectively), and four N-hydroxyguanidines, Nω-hydroxynor-L-arginine 5 (nor-NOHA), Nω-hydroxydinor-L-arginine 6 (dinor-NOHA), N-(4-chlorophenyl)-N'-hydroxyguanidine (8), and N-hydroxyguanidine (7) itself, by either NOS II or (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4)-free NOS II, have been studied in a comparative manner. Recombinant BH4-free NOS II catalyzes the oxidation of all N-hydroxyguanidines by NADPH and O2, with formation of NO2- and NO3- at rates between 20 and 80 nmol min-1 (mg of protein)-1. In the case of compound 8, formation of the corresponding urea and cyanamide was also detected besides that of NO2- and NO3-. These BH4-free NOS II-dependent reactions are inhibited by modulators of electron transfer in NOS such as thiocitrulline (TC) or imidazole (ImH), but not by Arg, and are completely suppressed by superoxide dismutase (SOD). They exhibit characteristics very similar to those previously reported for microsomal cytochrome P450-catalyzed oxidation of N-hydroxyguanidines. Both P450 and BH4-free NOS II reactions appear to be mainly performed by O2?- derived from the oxidase function of those heme proteins. In the presence of increasing concentrations of BH4, these nonselective oxidations progressively disappear while a much more selective monooxygenation takes place only with the N-hydroxyguanidines that are recognized well by NOS II, NOHA, homo-NOHA, and 8. These monooxygenations are much more chemoselective (8 being selectively transformed into the corresponding urea and NO) and are inhibited by Arg but not by SOD, as expected for reactions performed by the NOS FeII-O2 species. Altogether, these results provide a further clear illustration of the key role of BH4 in regulating the monooxygenase/oxidase ratio in NOS. They also suggest a possible implication of NOSs in the oxidative metabolism of certain classes of xenobiotics such as N-hydroxyguanidines, not only via their monooxygenase function but also via their oxidase function.

The Staudinger reaction of the N-substituted o-azidobenzamide 1 with triphenylphosphine or diphenylmethylphosphine allows the isolation of the intermediate phosphazides as crystalline solids, which have been characterized by spectroscopic methods. These compounds react in aza Wittig type fashion with isocyanates to give unexpectedly the corresponding 1,2,3- benzotriazinone derivative. Trapping of a Z-phosphazide by intramolecular aza Wittig reaction is reported for the first time. (C) 2000 Elsevier Science Ltd.

Gas-solid reaction techniques allow quantitative cyanations with ClCN and BrCN. Three primary and four secondary cyanamides, a cyanimide, four cyanates, and four thiocyanates were all prepared as solids in 100% yield from solid anilines, benzimidazoles, imides, phenolates, and thiolates, respectively. Intramolecular solid-state reactions of cyanated o-aminophenol and of cyanated hydrazides gave heterocyclic compounds. When comparable reactions were performed in solution the reported product yields were considerably less than 100% in all cases. The reasons for the success of the environmentally benign solid-state syntheses are discussed in terms of phase rebuilding, phase transformation, and crystal disintegration. Atomic force microscopy (AFM) of selected systems indicates the occurrence of long-range molecular movements which are governed by the crystal packing. This is evident from the obvious correlations between the molecular movements and the known crystal packing data. A new type of geometric surface feature, a rectangular and a rhombic depression which resembles a swimming-pool basin, was found in the cyanation of o-aminophenol and benzohydrazide.

Potassium superoxide stoechiometrically reacts with arylamidoximes with the selective formation of the corresponding benzamide and nitrogen oxides (mainly NO2-) in high yield.A similar oxidative cleavage of the C=NOH bond of N-hydroxy-arylguanidines also occurs upon reaction with KO2; the yield of the corresponding urea is lower and large amounts of the corresponding cyanamide are also formed.The significance of this reaction of O2.- with compounds containing a C=NOH bond in the biological formation of nitrogen oxides including NO is discussed.

A process for the preparation of an aryl cyanamide comprising reacting an arylamine of the formula STR1 in which Ar is aryl, R is hydrogen or alkyl, and n is 1, 2 or 3, (excepting 2-nitroaniline, 4-nitroaniline and arylamines having a nucleophilic charact

Several arylformamidine sulphide dihydrochlorides (IIa-f) have been synthesized by the reaction of arylformamidine chlorides with acetylthiocarbamide, and evaluated for their local anaesthetic and antibacterial activities.Only m-tolyl derivative (IId) has been found to be active as local anaesthetic.All the compounds have been found to be inactive against bacteria.

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