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An enzyme which is capable of catalyzing C–H amination reactions is considered to be a dream tool for chemists due to its pharmaceutical potential and greener approach. Recently, the Arnold group achieved this feat using an engineered CYP411 enzyme, which further undergoes a random directed evolution which increases its efficiency and selectivity. The present study provides mechanistic insight and the root cause of the success of these mutations to enhance the reactivity and selectivity of the mutant enzyme. This is achieved by means of comprehensive MD simulations and hybrid QM/MM calculations. The study shows that the efficient C–H amination by the engineered CYP411 is a combined outcome of electronic and steric effects. The mutation of the axial cysteine ligand to serine relays electron density to the Fe ion in the heme, and thereby enhances the bonding capability of the heme-iron to the nitrogen atom of the tosyl azide. In comparison, the native cysteine-ligated P450 cannot bind the tosyl azide. Additionally, the A78V and A82L mutations in P411 provide ‘bulk’ to the active site which increases the enantioselectivity via a steric effect. At the same time, the QM/MM calculations elucidate the C–H amination by the iron nitrenoid, revealing a mechanism analogous to Compound I in the native C–H hydroxylation by P450., Computer simulation method reveals the mechanism of C–H amination reaction due to a single site mutation.

Generation of tosyl azide 12 in acetonitrile in flow under water-free conditions using an azide resin and its use in diazo transfer to a series of aryl acetates are described. Successful telescoping with a rhodium acetate-catalyzed O–H insertion has been achieved, thereby transforming the aryl acetate 8 to α-hydroxy ester 10, a key intermediate in the synthesis of clopidogrel 11, without requiring isolation or handling of either tosyl azide 12 or α-aryl-α-diazoacetate 9, or indeed having significant amounts of either present at any point. Significantly, the solution of α-diazo ester 9 was sufficiently clean to progress directly to the rhodium acetate-catalyzed step without any detrimental impact on the efficiency of the O–H insertion. In addition, the rhodium acetate-catalyzed O–H insertion process is cleaner in flow than under traditional batch conditions. Use of the azide resin offers clear safety advantages and, in addition, this approach complements earlier protocols for the generation of tosyl azide 12 in flow; this protocol is especially useful with less acidic substrates.

A new synthesis of tetraazaperopyrenes (TAPPs) starting from a halogenated perylene derivative 3,4,9,10‐ tetrabromo‐1,6,7,12‐tetrachloroperylene (1) gave access to bay‐substituted TAPPs for the first time. Selective lithiation of the bromine‐positions and subsequent addition of tosyl azide led to the formation of the tetraazidotetrachloroperylene (2), which was subsequently reduced by addition of sodium borohydride to the corresponding tetraaminotetrachloroperylene (3). Oxidation to its semiquinoidal form 4 and subsequent cyclization with acid chlorides gave rise to a series of bay‐chlorinated TAPPs. Whereas the aromatic core of the previously studied ortho‐substituted TAPPs was found to be planar, the steric pressure of the two chlorine substituents on each side leads to the twist of the peropyrene core of approximately 30 degrees, a structural feature also observed in other bay‐substituted perylene derivatives. An experimental and computational analysis reveals that introducing chloride substituents at these positions leads to slightly increased electron affinities (EA) enabling the selective generation and characterization of the reduced mono‐anionic radicals and closed shell di‐anionic species. These anions were isolated and characterized by UV/Vis spectroscopy and EPR or NMR, respectively. Processing of the bay‐chlorinated TAPPs in n‐channel organic TFTs revealed electron mobilities of 0.001 to 0.003 cm2 V−1 s−1. These reduced electron mobilities compared to the ortho‐halogenated TAPPs are thought to be rooted in the less densely packed solid‐state structures., First twisted—then TAPPed: Previously inaccessible bay‐substituted tetratazaperopyrenes (TAPPs) were obtained from “twisted” perylene‐containing bay‐substituents. The resulting TAPPs were found to be readily reduced to their radical monoanions and closed shell dianions.

Treatment of N-chlorodimethylamine with sodium azide in dichloromethane does not lead to N-azidodimethylamine, as thought for more than 50 years. Instead, surprisingly, (azidomethyl)dimethylamine is generated with good reproducibility. A plausible reaction mechanism to explain the formation of this product is presented. The reaction of lithium dibenzylhydrazide with tosyl azide does not result in the creation of an N-azidoamine, which can be detected by IR spectroscopy at ambient temperature, as it was claimed previously. Additional experiments with diazo group transfer to lithium hydrazides show that intermediate N-azidoamines are very short-lived or their formation is bypassed by direct generation of 1,1-diazenes via synchronous cleavage of two N-N bonds.

An enzyme which is capable of catalyzing C-H amination reactions, is considered to be a dream tool for chemists due to its pharmaceutical potential and greener approach. Recently, the Arnold group achieved this feat using an engineered CYP411 enzyme, which further undergoes a random directed evolution which increases its efficiency and selectivity. The present study provides the mechanistic insight and the root cause of the success of these mutations to enhance the reactivity and selectivity of the mutant enzyme. This is achieved by means of comprehensive MD simulations and hybrid QM/MM calculations. The study shows that the efficient C-H amination by the so-engineered CYP411 is a combined outcome of electronic and steric effects. The mutation of axial cysteine ligand to serine relays electron density to the Fe ion in the heme, and thereby enhances the bonding capability of the heme-iron to the nitrogen atom of the tosyl azide. By comparison, the native cysteine-ligated P450, cannot bind the tosyl azide. On top, the A78V and A82L mutations in P411 provide ‘bulk’ to the active site which thereby increases the enantioselectivity via steric effect. At the same time, the QM/MM calculations elucidate the C-H amination by the iron nitrenoid, revealing a mechanism analogous to Compound I in the native- C-H hydroxylation by P450.

Here we report a cytochrome P450 variant that catalyzes C(2)-amidation of 1-methylindoles with tosyl azide via nitrene transfer. Before evolutionary optimization the enzyme exhibited two undesired side reactivities resulting in reduction of the putative iron-nitrenoid intermediate or cycloaddition between the two substrates to form triazole products. We speculated that triazole formation was a promiscuous cycloaddition activity of the P450 heme domain, while sulfonamide formation likely arose from surplus electron transfer from the reductase domain. Directed evolution involving mutagenesis of both the heme and reductase domains delivered an enzyme providing the desired indole amidation products with up to 8400 turnovers, 90% yield, and a shift in chemoselectivity from 2:19:1 to 110:12:1 in favor of nitrene transfer over reduction or triazole formation. This work expands the substrate scope of hemoprotein nitrene transferases to heterocycles and highlights the adaptability of the P450 scaffold to solve challenging chemoselectivity problems in non-natural enzymatic catalysis.

The click chemistry reaction between 2, 2-dimethylethynyl carbinol (MBY) and tosyl azide (TA) was used to form triazole films on copper surface. The effect of cuprous ions on the assembled films was investigated by the electrochemical measurements. The assembled films have the best protection efficiency of 93.8%. The attack of chloride ions gives out cuprous ions to catalyze the formation of compact triazole films. It shows that the assembled films have an anodic passivation role, and suppress the anodic corrosion reactions evidently. The role of cuprous ions on the films formation during the assembling process is discussed.

The synthesis of 4-acyl-NH-1,2,3-triazoles has been accomplished with high efficiency through the cycloaddition reactions between N,N-dimethylenaminones and tosyl azide. This method is featured with extraordinary sustainability by employing water as the sole medium, free of any catalyst or additive, authentically mild conditions (40 °C stirring) as well as practical scalability.

A scalable access to functionalized 1,1’- and 1,2-ferrocenyl azides has been realized in flow. By halogen‒lithium exchange of ferrocenyl halides and subsequent reaction with tosyl azide, a variety of functionalized ferrocenyl azides was obtained in high yields. To allow a scalable preparation of these potentially explosive compounds, an efficient flow protocol was developed accelerating the reaction time to minutes and circumventing accumulation of potentially hazardous intermediates. Switching from homogeneous to triphasic flow amidst process was key for handling a heterogeneous reaction mixture formed after a heated reactor section. The corresponding and synthetically versatile ferrocenyl amines were then prepared by a reliable reduction process.

2-Azido-4,6-dimethoxy-1,3,5-triazine (ADT) was reported recently as a new "intrinsically safe" diazo-transfer reagent. This assessment was based on differential scanning calorimetry data indicating that ADT exhibits endothermic decomposition. We present DSC data on ADT that show exothermic decomposition with an initiation temperature ( Tinit) of 159 °C and an enthalpy of decomposition (Δ HD) of -1135 J g-1 (-207 kJ mol-1). We conclude that ADT is potentially explosive and must be treated with caution, being of comparable exothermic magnitude to tosyl azide (TsN3). A maximum recommended process temperature for ADT is 55 °C.

The self-assembled monolayer (SAMs) of 2-(1-tosyl-1H-1,2,3-triazol-4-yl) propan-2-ol (TTP) was in-situ assembled on copper surface via click chemistry reaction between 2, 2-dimethylethynyl carbinol (MBY) and tosyl azide (TA). The electrochemical results indicate that the click-assembled TTP film can strongly suppress the corrosion reaction of copper in 3 wt.% NaCl and its protection efficiency is 93.6%. Polarization curves show that TTP SAMs is an anodic passivation type inhibitor. The adsorption of TTP molecules on Cu2O (0 0 1) surface is in the flat orientation of the nearby triazole ring and O atoms.

Heat and shock sensitive tosyl azide was generated and used on demand in a telescoped diazo transfer process. Small quantities of tosyl azide were accessed in a 'one pot' batch procedure using shelf stable, readily available reagents. For large scale diazo transfer reactions tosyl azide was generated and used in a telescoped flow process, to mitigate the risks associated with handling potentially explosive reagents on scale. The in situ formed tosyl azide was used to rapidly perform diazo transfer to a range of acceptors, including beta-ketoesters, beta-ketoamides, malonate esters and beta-ketosulfones. An effective in-line quench of sulfonyl azides was also developed, whereby a sacrificial acceptor molecule ensured complete consumption of any residual hazardous diazo transfer reagent. The telescoped diazo transfer process with in-line quenching was used to safely prepare over 21 g of an alpha-diazocarbonyl in > 98% purity without any column chromatography.

An attempt to prepare a new triazole series by Cu catalyzed multicomponent reactions of tosyl azide, propargyl bromide and secondary amines led to the synthesis of enamidines. All the synthesized enamidines were evaluated for antiproliferative activities. The four molecules 4a–c and 4h showed higher anticancer activity with GI50 values less than the standard drug doxorubicin against human breast cancer cell line MCF-7. The virtual analysis ascertains the mode of action of these compounds via inhibition of human cell division protein kinase7 (CDK7).

A novel rhodium(II)-catalyzed formal [3 + 2] cycloaddition of N-sulfonyl-1,2,3-triazoles with isoxazoles has been achieved that provides an efficient method for the synthesis of polysubstituted 3-aminopyrrole derivatives. An operationally simple one-pot synthesis of the titled compounds from terminal alkynes, tosyl azide, and isoxazoles was also developed. The presented reaction affords an illustrative example of employing 1,2,3-triazoles as the [2C]-component in relevant cycloaddition reactions.

Oxidation of the rhodium(I) ethylene complex, [(TPA)Rh(h 2 -CH2CH2)] þ (1 ,T PA¼ N,N,N-tris(2pyridylmethyl)amine) with a selection of nitrene precursors led to formation of N-substituted azarhodacyclobutanes. Appropriate choice of oxidant allowed for selective preparation of one isomer. For example, treatment of 1 with tosyl azide provided isomer 3 exclusively for the first time. Variation of the substituent on the ring-nitrogen was possible e.g., by employing nosyl iodinane precursor 8. Substituted carbamates were also screened, providing two rotamers of isomer type 3. In addition, preliminary reactivity studies revealing the increased chemical reactivity of the product complexes 14 and 15 are presented.

One of the greatest challenges in protein design is creating new enzymes, something evolution does all the time, starting from existing ones. Borrowing from nature’s evolutionary strategy, we have engineered a bacterial cytochrome P450 to catalyze highly enantioselective intermolecular aziridination, a synthetically useful reaction that has no natural biological counterpart. The new enzyme is fully genetically encoded, functions in vitro or in whole cells, and can be optimized rapidly to exhibit high enantioselectivity (up to 99% ee) and productivity (up to 1,000 catalytic turnovers) for intermolecular aziridination, demonstrated here with tosyl azide and substituted styrenes. This new aziridination activity highlights the remarkable ability of a natural enzyme to adapt and take on new functions. Once discovered in an evolvable enzyme, this non-natural activity was improved and its selectivity tuned through an evolutionary process of accumulating beneficial mutations., Engineered cytochrome P450 variants take on challenging non-natural reaction, aziridination of olefins, demonstrating the power of evolution to expand biocatalytic reaction space.

An efficient, four-component reaction for the synthesis of hydrazono-sulfonamide adducts via in situ generated ketenimine was discovered. Highly porous copper benzenetricarboxylate [Cu(BTC)], a metal–organic framework (MOF), was used as a heterogeneous catalyst for the four-component coupling reaction involving aldehyde, alkyne, tosyl azide, and phenylhydrazine in a one pot process. For the first time, a copper(II) catalyst was utilized to generate a ketenimine intermediate. The Cu(BTC) catalyst was recycled and reused six times without any substantial loss in the yield. In addition, pyrene adduct (5r) shows remarkable aggregation induced emission enhancement (AIEE) properties, and was studied in detail using THF : water solvent mixtures. Adduct 5r is almost non-emissive in pure THF solution, however, it emits a greenish-yellow colour in the aggregated state. Formation of nano-aggregates was confirmed by TEM analysis. A theoretical DFT study supports the observed photophysical changes.

A simple and effective heterogeneous catalyst based on zeolite-type materials has been developed for the diazo transfer reaction involving 1,3-dicarbonyl compounds and tosyl azide. α-Diazo carbonyl compounds were obtained under mild conditions in good to high yields using commercial molecular sieve 4A or analogues as the catalyst. The best catalyst was found to be 4A-1000, a synthetic potassium-free nepheline obtained by heating molecular sieve 4A at 1000 °C. Characterization of the resulting aluminosilicate by XRD, FTIR and SEM-EDS analysis confirmed the change of the crystal structure. Besides being nontoxic and inexpensive, the heterogeneous catalyst was readily removed by filtration and could be reused at least for four runs without any special treatment.

The synthesis of a novel class of N-(1H-benzo[d]imidazol-2-yl)-2-alkyl-N′-sulfonylacetamidines via a copper-catalyzed, three-component coupling reaction of 1H-benzo[d]imidazol-2-amine, sulfonyl azides, and terminal alkynes is described.

Various β-hydroxy-substituted amidines were obtained starting from methyl serinates, aldehydes or ketones, and tosyl azide. These were converted via Mitsunobu intramolecular cyclization into enantiomerically pure methyl 2-alkyl-l-tosyl-4,5-dihydro-1H-imidazole-4-carboxylates.

In the reactions of cobaltadithiolene complexes [CpCo(S2C2Z2)] (Z=CN, COOMe, Ph, Me) with aryl azides, two types of substitution reactions occurred. One is the replacements of the sulfur of cobaltadithiolene by arylimido groups and the other is the replacements of the SCZCZ moiety of cobaltadithiolene. The product of latter reaction was also formed by the reactions of the metal cluster complex [Cp4Co4S6] with aryl azides. The azides with electron-donating substituents gave these products in higher yields than those with electron-withdrawing substituents. In these reactions, arylnitrenes as intermediates were predictable. The reactions of [CpCo(dmit)] (dmit=C3S5) with phenyl azide and tosyl azide led to the replacements of the terminal sulfur (CS) of the dmit ligand by imido groups to give novel imine complexes [CpCo(S2C2S2CNR)] (R=Ph, Ts).

The Lewis base adducts of imidovanadium(V) compounds 5a,b undergo chemoselective cyclooligomerization reactions with the kinetically stabilized phosphaalkynes 4a-e to furnish the azatetraphosphaquadricyclanes 6a-f with incorporation of the imido fragment. The reactivity of this novel class of heteropolycyclic compounds has been examined exemplarily for compound 6a. Complexation of one and two phosphorus atoms was achieved by reaction with nonacarbonyldiiron or the tungsten pentacarbonyl-THF complex resulting in the formation of the transition metal compounds 17-20. Reactions of 6a with the sulfonyl azides 21ac furnished the Staudinger products 22a-c. The reaction of 6a with two equivalents of tosyl azide gave a surprising result. No double complexation leading to a symmetrical product was achieved, and compound 23 was obtained instead in which the two phosphorus atoms of one diphosphirane ring are functionalized. Oxidative cleavage of a P/P bond in 6a to furnish product 24 is observed in the reaction of 6a with the Lewis base-free imidovanadium(V) species 15a.

Simple total syntheses of two Leucetta -derived marine alkaloids have been developed using position-specific halogen-metal exchange of polyhaloimidazoles to introduce the benzyl substituted sidechains. Introduction of the C2 amine group by lithiation and trapping with tosyl azide provides amines on catalytic hydrogenation, which can be converted to naamidine G and 14-methoxynaamidine G using a procedure described in the literature.

Treatment of the lithiated cymantrene [C 5 Cl 4 Li]Mn(CO) 3 ( 1a ) with tetrachlorodiazocyclopentadiene yields, after work-up, the organometallic hydrazone (OC) 3 Mn[η 5 -C 5 Cl 4 NHNC 5 Cl 4 ] ( 2 ). The reaction of tosyl azide with 1a or the in situ generated [C 5 X 5− n Li n ]Mn(CO) 3 (X=Cl, n =2: 1b ; X=Br, n =1: 1c ; X=Br, n =2: 1d ) and [C 5 H 3 X(Li)]Mn(CO) 3 (X=Cl: 1e , X=H: 1f ) gave the corresponding azidocymantrenes [C 5 X 5− n (N 3 ) n ]Mn(CO) 3 ( 3a , c , d ), [C 5 Cl 3 H(N 3 )]Mn(CO) 3 ( 3b′ ), and [C 5 H 3 X(N 3 )]Mn(CO) 3 ( 3e , f ), respectively. Reduction of 3a and 3e with NaBH 4 led to the formation of the aminocymantrenes [C 5 Cl 4− n H n (NH 2 )]Mn(CO) 3 ( n =0: 4a ; n =1: 4b′ , n =3: 4e ) in high yield. The molecular structures of 2 and 4e in the crystal were determined by X-ray diffraction.

Sodium tetraisopropylcyclopentadienide (2) is attacked selectively in 5-position by tosyl azide with formation of 5-diazo-1,2,3,4-tetraisopropylcyclopentadiene (1) and also by the iminium salt [Me2NC(H)OMe]+ MeOSO3- to yield 1,2,3,4-tetraisopropyl-6-dimethylamino-pentafulvene (3) with concomitant methanol elimination. In a one pot reaction 3 adds methyllithium to form a cyclopentadienide intermediate (4) which is converted in situ to 1,2,3,4- tetraisopropyl-6-methyl-pentafulvene (5) with dimethylchlorosilane. By the same procedure with 1,4-dilithiobutane instead of methyllithium two tetraisoproylfulvene moieties are linked to the bis-fulvene 8 with a -(CH2)4- backbone. 3 can be converted directly to 1,2,3,4- tetraisopropylpentafulvene (7) with diisobutylaluminum hydride. 5 again adds methyllithium to give lithium pentaisopropylcyclopentadienide (6) or can be deprotonated at the 6-methyl group with potassium hydride. The intermediate potassium salt gives 1,2,3,4-tetraisopropyl- 6-trimethylsilylmethyl-pentafulvene (9) with trimethylchlorosilane. The fulvene 7 could be η6-coordinated to the tricarbonyl chromium complex 10 with [Cr(CO)3(NCEt)3], 5 and 7 yield the molybdenum analogues 11 and 12 with [Mo(CO)3(NCEt)3].

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An efficient general strategy was developed for the synthesis of previously unknown 3-C-linked glycosyl iminocoumarins. The strategy involves a copper-catalyzed multicomponent reaction of sugar-derived alkynes with tosyl azide and salicylaldehyde to give a diverse array of glycosyl iminocoumarins in good yields. These compounds can serve as appropriate precursors for the synthesis of the corresponding coumarin 3-C-glycosides.

International audience; A practical protocol for the large-scale preparation of 2-diazo-1,3-dicarbonyl compounds is described by diazo-transfer reactions with tosyl azide followed by efficient chromatographic purifications on silica gel and/or alumina.

The exothermic decompositions of the tosyl azide 1, five substituted aryl monoazides 2 – 6 and two diazides: 1-azido-4-(4-azidophenoxy)benzene 7 and 1-azido-4-[(4-azidophenyl)sulfanyl]benzene 8 were studied experimentally using DSC, weight loss TGA-FTIR and C80-FTIR techniques, and theoretically using the CHETAH software. Numerical modelling and electron impact mass spectrometry (EI-MS) were also performed to investigate the nature of the intrinsic molecular reactivity of the azides 1 — 8, and the possible early stages rate-controlling of an oxidative self-heating process. Significant data were obtained in the instances of 4-methyl-benzenesulfonyl azide 1, 4-azido-1,1’-biphenyl 2, 2-azido-1,1’-biphenyl 3 and 1-azido-2-(trifluoromethyl)benzene 6. The most likely decomposition pathways of the azides are proposed to explain the observed thermal behavior.

1-Hydroxypyrazolo[3,4-c]quinoline (22), 1-hydroxypyrazolo[4, 3-c]quinoline (21), 1-hydroxypyrazolo[3,4-c]isoquinoline (20), and 1-hydroxypyrazolo[4,3-c]isoquinoline (19) were prepared from 1-benzyloxypyrazole (6), establishing the pyridine B-ring in the terminal step. The pyridine ring of pyrazoloquinolines 14 and 18 was formed via cyclization of a formyl group at C-4 or C-5 and an amino group of a 2-aminophenyl substituent at C-5 or C-4 in 1-benzyloxypyrazole. The pyridine ring of pyrazoloisoquinolines 5 and 9 was created via cyclization of a formyl group in a 2-formylphenyl substituent at C-4 or C-5 with an iminophosphorane group installed at C-5 or C-4 of 1-benzyloxypyrazole by lithiation followed by reaction with tosyl azide and then with tributylphoshine utilizing the Staudinger/aza-Wittig protocol. The 2-aminophenyl and the 2-formylphenyl substituent were introduced at C-5 or C-4 by regioselective metalation followed by transmetalation to the pyrazolylzinc halide and subsequent palladium-catalyzed cross-coupling with 2-iodoaniline or 2-bromobenzaldehyde. The order of reactions and use of protecting groups in the individual sequences have been optimized. The 1-benzyloxy-substituted pyrazoloquinolines and isoquinolines thus obtained were debenzylated by strong acid to the corresponding 1-hydroxy-substituted pyrazoloquinolines and isoquinolines 19-22.

2-(Diazobenzyl)-p-naphthoquinone was synthesized from 2-benzyl-1,4-dimethoxynaphthalene by cerric ammonium nitrate oxidation to 2-benzyl-p-naphthoquinone followed by diazo transfer with tosyl azide. 1,7-Dideoxy-3-demethylprekinamycin was prepared from 1,4-dimethoxynaphthalene by bromination, lithiation, and condensation with acetanthranil to give 2-(2‘-N-acetaminobenzoyl)-1,4-dimethoxynaphthalene, which, following deacylation, was subjected to Pschorr cyclization to give 1,3,7-trihydro-O,O-dimethylkinafluorenone. This was then demethylated, subjected to hydrazinolysis, and then oxidized with Fetizon's reagent to complete the synthesis. 1-Deoxy-3-demethylprekinamycin was synthesized from 3-bromo-1,5-dimethoxy-4-naphthol by an identical route.

The photochemical and thermal reactions of 3-diazothiochroman-4-one (2a), 3-diazochroman-4-one (2b), 3-diazo-1-methyl-1, 2, 3, 4-tetrahydroquinolin-4-one (2c), and 2-diazo-1-tetralone (2d) were investigated. Wolff rearrangement was observed with 2a, 2c, and 2d only under photolytic conditions. In the case of 2a, migration of the thioether group competed with the above reaction.

Since the discovery of the sulfonimidoyl function in 1949, sulfoximines and related derivatives of sulfonimidic acid have received considerable attenti0n.l A key feature is the variety of substitutions available to the sulfur-attached imino group. Unfortunately, direct methods for obtaining sulfoximines unsubstituted a t nitrogen have serious limitations. The standard procedure involves the reaction of a sulfoxide with hydrazoic acid in a mixture of sulfuric acid and chloroform2 (Scheme I, method A). In addition to the use of a potentially hazardous reagent: this method is limited to compounds having sulfur substituents that are incapable of forming stable carbonium ions; under the acidic reaction conditions heterolysis of a carbon+ulfur bond usually occurs in cases where the alkyl group is tertiary and to some extent in secondary c a ~ e s . ~ , ~ Treatment of a sulfoxide with 0-(mesitylsulfony1)hydroxylamine5 (MSH, method B) provides a general and mild alternate route. The method is limited since MSH is quite difficult to prepare and to handle.6 A useful indirect method is the cleavage of the tosyl (p-tolylsulfonyl) group of a N-tosylsulfoximine (1). These compounds are readily available by treatment of a sulfoxide with tosyl azide (or Chloramine-T in the case of dimethyl sulfoxide) in the presence of a copper(I1) salt4 (route 1). They may also be prepared by oxidation of N-t~sylsulfilimines~ with alkaline hydrogen peroxide? m-chloroperbenzoic acid (mCPBA) anion,g or sodium periodate-catalytic ruthenium dioxidelo (route 2). N-Tosylsulfoximines have been obtained by reaction of a sul

The one-pot reaction of phenylacetaldehyde with a primary amine followed by tosyl azide yields the corresponding benzamidine 1 along with the N-monosubstituted-N-tosylformamidine 2. The participation of α-amino acid esters as reactants permitted the base-promoted intramolecular condensations of benzamidines 1d, 1e, 1f and 1i to give the corresponding 1,2-dihydropyrol-3ones 6a-6d, respectively. The combination of phenylacetaldehyde, a pair of heterocyclic secondary amines, and 4-nitrophenyl azide in turn led to the two dihydrotriazole derivatives, 4b and 4c. Loss of nitrogen from 4 in refluxing toluene afforded trisubstituted benzamidines 5b and 5c, that also undergo base-promoted intramolecular condensation, forming 1,2-dihydropyrrol-3ones 7a and 7b in turn.