Synthesis and Transformations of 2-Hydroxy-2-(benzotriazol-1-yl)-1,4-naphthoquinone

2-Hydroxy-3-(benzotriazol-1-yl)-1,4-naphthoquinone reacts with o-phenylenediamine and 4-chloro-2-aminophenol to give cyclization products: 5-oxo-6-(benzotriazol-1-yl)-5,6H-benzo[a]phenazine and 5-oxo-6-(benzotriazol-1-yl)-10-chlorobenzo[a]phenoxazine; the reaction with aniline yields the quaternary anilinium salt, and benzoyl chloride and benzenesulfonyl chloride acylate the nitrogen atom of the benzotriazolyl moiety.     

Novel routes to 1-aryl-1,4-dihydro-3(2H)-isoquinolinones and 2-substituted or 2,3-disubstituted benzofurans by intramolecular cyclizations

N-(α-Benzotriazolylalkyl)arylacetamides, readily available from an arylacetamide, an aldehyde and benzotriazole, undergo intramolecular cyclization under acidic conditions to give 1-aryl-1,4-dihydro-3(2H)-isoquinolinones in good to excellent yields. Similarly, 2-(benzotriazol-1-yl)-2-(o-hydroxyphenyl)ethanols, obtained by lithiation of 2-(benzotriazol-1-ylmethyl)phenols followed by quenching with aldehydes or ketones, eliminate a molecule of water and a molecule of benzotriazole yielding 2-substituted and 2,3-disubstituted benzofurans.     

Synthesis of 1-(benzotriazol-1-yl)alkyldiphenylphosphine oxides and their transformations to novel benzotriazol-1-yl-substituted cyclopropanes

Diphenylphosphinous anion reacted with chloromethylbenzotriazole to give (benzotriazol-1-yl)methyldiphenylphosphine oxide, which, after lithiation, was alkylated to give 1-(benzotriazol-1-yl)alkyldiphenylphosphine oxides in good yield. Treatment of 1-(benzotriazol-1-yl)alkyldiphenylphosphine oxides with n-butyllithium followed by condensation with epoxides, afforded benzotriazol-1-yl-substituted cyclopropanes, which underwent further lithiation and subsequent reaction with numerous electrophiles to provide a variety of novel benzotriazol-1-yl-substituted cyclopropane derivatives.     

Synthesis of benzotriazolylsuccinimides in melt

N-Phenyl-3-(benzotriazol-1-yl)pyrrolidine-2,5-dione was synthesized by condensation of N-phenylmaleimide with benzotriazole in melt. The adducts of 2 moles of benzotriazole to different bismaleimides, namely, bis[3-(benzotriazol-1-yl)pyrrolidine-2,5-diones] were obtained under analogous conditions. These adducts, according to the data from ¹H and ¹³C NMR spectroscopy, contain also (benzotriazol-2-yl)succinimide and residual maleimide fragments.     

A novel synthesis of 5-acylaminooxazoles

1,2-Diacylamino-1,2-di(benzotriazol-1-yl)ethanes 2 , easily prepared from the condensation of 1,2-di(benzotriazol-1-yl)ethane-1,2-diol (1) and primary amides, were converted to 5-acylaminooxazoles in good to moderate yields via intramolecular cyclization upon treatment with sodium hydride.     

Kinetics,catalysis, and mechanism of isomerization of N-[(benzotriazol-1-yl)methyl]anilines into the benzotriazol-2-yl derivatives

The ¹H NMR technique was applied for the measurement of the isomerization rates of N-ethyl-N-[(benzotriazol-1-yl)methyl]aniline ( 4 ) and 4-butyl-N-[(benzotriazol-1-yl)methyl]aniline ( 7 ) to the corresponding benzotriazol-2-yl isomers in dioxane-d₈ at 35°C. The rate constants obtained for pure dioxane-d₈ were 1.62 and 0.28 h^?1 for 4 and 7 , respectively. For both compounds, addition to acetic acid to the dioxane solutions accelerated the isomerizations whereas addition of triethylamine retarded it strongly. Addition of water slowed the isomerization of 4 but accelerated that of 7 : the different effects operating in the two cases are discussed and rationalized. © 1995 John Wiley & Sons, Inc.     

Methyl β-(Benzotriazol-l-yl) vinyl Ketone: A New p-Acetylvinyl Cation Equivalent

A simple and efficient two-step approach to methyl β-(benzotriazol-1-yl)vinyl ketone 7 is described. The synthetic utility of compound 7 has been demonstrated by nucleophilic substitutions of the benzotriazolyl group with a range of nucleophiles. Thus, methyl β-(benzotriazol-1-yl)vinyl ketone provides a new β-acetylvinyl cation equivalent.     

Facile Synthesis of Benzotriazines and Indoles by Ring-Scissions of α-Benzotriazol-1-yl Hydrazones

Abstract: α-(Benzotriazol-1-yl)hydrazones 2a-d and 13a-c were prepared by refluxing the corresponding α-(benzotriazol-1-yl)ketones with p-tosyl hydrazide or benzenesulfonyl hydrazide. Treatment of 2a-b with n-butyllithium in the presence of TMEDA gave benzotriazines 6a-b, while lithiation of 13a-c resulted in indole derivatives 16a-c, depending on the structure of the hydrazones.     

Homophtalonitrile for Multicomponent Reactions: Syntheses and Optical Properties of o-Cyanophenyl- or Indol-3-yl-Substituted Chromeno[2,3-c]isoquinolin-5-Amines

Malononitrile is a useful reagent for multicomponent reactions with hundreds of methods developed. In this paper, we suggest α-(cyano)-o-tolunitrile (homophtalonitrile) to work as a vinylogous malononitrile. Thus, a organocatalytic pseudo-three-component reaction of homopthalonitrile (2 equiv) and o-hydroxybenzaldehyde, leading to the diastereoselective formation of 5-amino-12H-chromeno[2,3-c]isoquinolin-12-yl)(cyano)methyl)benzonitriles, was discovered. The possibility to employ other nucleophiles was demonstrated for indoles, and a sequential three-component reaction of homophtalonitrile, o-hydroxybenzaldehyde, and (aza)indole, giving 12-(1H-Indol-3-yl)-12H-chromeno[2,3-c]isoquinolin-5-amines, was developed. The photophysical properties of the synthesized compounds have been studied, revealing high fluorescence quantum yields (42–70 %) for indol-3-yl substituted 12H-chromeno[2,3-c]isoquinolin-5-amines and reversible fluorescence quenching under acidic conditions.     

Syntheses,structures, and fluorescent properties of two new d10-metal coordination polymers containing 1-((benzotriazol-1-yl)methyl)-1-H-1,2,4-triazole ligand

Two new coordination polymers formulated as {[Zn(bdic)(bmt)H₂O]?·?0.5H₂O} _n (1) and {[Cd(bdic)(bmt)(H₂O)₂]?·?2H₂O} _n (2) (H₂bdic?=?1,3-benzenedicarboxylic acid, bmt?=?1-((benzotriazol-1-yl)methyl)-1-H-1,2,4-triazole) have been synthesized and characterized by elemental analysis, IR, and single-crystal X-ray diffraction. Both coordination polymers exhibit 1-D chain structure where bmt is unidentate and bdic^2? bridging. In 1, bmt hangs at two sides of the main chain, whereas bmt hangs at one side of the main chain in 2. Fluorescent properties have also been determined.     

1,3-Dipolar cycloadditions of electron-rich benzotriazol-1-ylpropenes

The preparation of trans-3-benzotriazol-1-yl-1-(N-rnorpholino)prop-1-ene ( 1 ), trans-3-benzotriazol-1-yl-1-ethoxyprop-1-ene ( 2 ) and trans-1,3-bis-(benzotriazol-1-yl)propene ( 3 ) and their reactions with a benzonitrile oxide ( 4 ), N-(2,4-dibromophenyl)-1-phenylnitrilimine ( 5 ), and p-nitrophenyl azide ( 6 ) are described.     

Preparation of MBHA resin by benzotriazole-mediated amidoalkylation

MBHA (4-methylbenzhydrylamine) resin is widely used as a solid support for the synthesis of carboxamides or peptide C-terminal amides. Herein, we report a new method for synthesizing MBHA resin by benzotriazole-mediated amidoalkylation. MBHA resin was efficiently prepared with N-[(benzotriazol-1-yl)(p-tolyl)methyl]formamide or N-[formamido(p-tolyl)methyl]formamide, and it showed excellent properties as a solid support.     

Generation and reactivity of N,N-dimethylaminobenzotriazolylcarbene a new nucleophilic carbene

N,N-Dimethylaminobenzotriazolylcarbene ( 5 ) reacted with phenyl isocyanate in a [1+2+2] cycloaddition and then with nucleophiles to generate various hydantoins 10 in a one-pot procedure. It was also found that this novel carbene reacted with trans-dibenzoylethylene ( 11 ) in a [1+4] cycloaddition, generating 2-dimethylamino-3-benzoyl-5-phenylfuran ( 13 ) and 2-phenyl-3-[benzotriazol-1-yl]-4-benzoylfuran ( 14 ) whose structures were confirmed by ¹H-¹³C long range correlations as well as the structure of furan 14 being confirmed by X-ray crystallography.     

Synthesis and anticonvulsant activity of 3-[3-[(dimethylamino)-methyl]-5-methyl-4H-1,2,4-triazol-4-yl]-4-(o-chlorobenzoyl)pyridine

Wolff-Kishner reduction of 3-amino-4-(o-chlorobenzoyl)pyridine ( 3 ) afforded 3-amino-4-(o-chlorobenzyl)pyridine ( 5 ), which on subsequent reaction with triethyl orthoformate and then acetyl hydrazide yielded 1-acetyl-2-[N-[4-(o-chlorobenzyl)pyridin-3-yl]formimidoyl]hydrazone ( 7 ). Cyclization of hydrazone 7 gave 3-(3-methyl-4H-1,2,4-triazol-4-yl)-4-(o-chlorobenzyl)pyridine ( 8 ), which on Jones oxidation yielded 3-(3-methyl-4H-1,2,4-triazol-4-yl)-4-(o-chlorobenzyl)pyridine ( 9 ). The Mannick reaction of 3-(3-methyl-4H-l,2,4-triazol-4-yl)-4-(o-chlorobenzyl)pyridine ( 9 ) with aqueous formalin and dimethylamine hydrochloride afforded 3-[3-[(dimethylamino)methyl]-5-methyl-4H-1,2,4-triazol-4-yl]-4-(o-chlorobenzoyl)-pyridine ( 10 ). 3-[3-[(Dimethylamino)methyl]-5-methyl-4H-1,2,4-triazol-4-yl]-4-(o-chlorobenzoyl)pyridine ( 10 ) exhibited good anticonvulsant activity in the subcutaneous pentylenetetrazole anticonvulsant screen indi cating that an appropriately substituted-pyridine ring moiety can serve as a bioisostere of a chlorobenzene ring with respect to anticonvulsant activity.     

Synthesis of new amides of the <Emphasis Type="Italic">N</Emphasis>-methylpiperazine series

New carboxylic acid amides containing an N-methylpiperazine fragment were synthesized by reactions of 1-methylpiperazine or 3- and 4-(4-methylpiperazin-1-ylmethyl)aniline with 4-chlorobenzoyl chloride and of 4-methyl-3-nitroaniline with 4-(4-methylpiperazin-1-ylmethyl)benzoyl chloride or benzotriazol-1-yl 4-(4-methylpiperazin-1-ylmethyl)benzoate. 4-Chloro-N-[4-(4-methylpiperazin-1-ylmethyl)phenyl]benzamide reacted with imidazole, quinolin-5-amine, and 2-methylquinolin-5-amine to give substituted 4-amino-N-[4-(4-methylpiperazin-1-ylmethyl)phenyl]benzamides. 4-Methyl-3-nitrophenyl-4-methylpiperazin-1-yl-substituted benzamides were reduced with hydrazine hydrate over Raney nickel to obtain N-(3-amino-4-methylphenyl)-4-(4-methylpiperazin-1-ylmethyl)benzamide as key intermediate in the synthesis of antileukemic agent imatinib and its isomer with alternative position of the amide group, 4-[(3-amino-4-methylphenylamino)methyl]phenyl-(4-methylpiperazin-1-yl)methanone.     

Synthesis of α-Benzotriazole Sulfides Promoted by Samarium Diiodide

1-(Benzotriazol-1-yl) unsymmetrical diorganyl sulfides were synthesized via replacement of chlorine atom in 1-(benzotriazol-1-yl)-1-chloromethane with thiolate anions promoted by SmI₂.     

Preparation,characterization and reactions of novel vicinal dibenzotriazol-1-yl derivatives of benzotriazole and glyoxal

A variety of novel 1,2-disubstituted-1,2-di(benzotriazol-1-yl)ethane and 1,2-di(benzotriazol-1-yl)ethylene derivatives were prepared from the adduct of benzotriazole and glyoxal.     

N-[1-(Benzotriazol-1-yl)alkyl]amides from N-acyl-α-amino acids or N-alkylamides

A variety of N-(1-methoxyalkyl)amides react with benzotriazole in the presence of PPh₃·HBF₄ and organic bases (Hünig's base, DBU or DABCO) or solid-state-supported bases (SiO₂-Pip or IRA-67) in CHCl₃ to give N-[1-(benzotriazol-1-yl)alkyl]amides in good yields. The most convenient and efficient procedure for obtaining N-[1-(benzotriazol-1-yl)alkyl]amides consists, however, of the addition of benzotriazole sodium salt to a solution of crude 1-(N-acylamino)alkyltriphenylphosphonium salt, obtained in situ from N-(1-methoxyalkyl)amides and PPh₃·HBF₄. A combination of these reactions with the recently described electrochemical decarboxylative α-methoxylation of N-acyl-α-amino acids in the presence of SiO₂-Pip enables an effective two-pot transformation of N-acyl-α-amino acids to N-[1-(benzotriazol-1-yl)alkyl]amides.     

A new synthesis of novel 1-aryl-3-heteroaryl-1H-pyrazolo[3,4-b]quinoxalines via a Key Intermediate

The chlorination of the α-hydrazonoester 4 with phosphoryl chloride/pyridine gave 3-[α-(o-chlorophenylhydrazono)methoxycarbonylmethyl]-2-chloroquinoxaline 5 , whose cyclization with 1,8-diazabicyclo[5,4,0]-7-undecene afforded 3-methoxycarbonyl-1-(o-chlorophenyl)-1H-pyrazolo[3,4-b]quinoxaline 6 . The reaction of 6 with hydrazine hydrate provided 3-hydrazinocarbonyl-1-(o-chlorophenyl)-1H-pyrazolo[3,4-b]quinoxaline 7 , whose reactions with methyl and allyl isothiocyanates furnished 3-(2,3-dihydro-4-methyl-3-thioxo-4H-1,2,4-triazol-5-yl)-1-(o-chlorophenyl)-1H-pyrazolo[3,4-b]quinoxaline 2 and 3-(4-allyl-2,3-dihydro-3-thioxo-4H-1,2,4-triazol-5-yl)-1-(o-chloropheny)-1H-pyrazolo[3,4-b]quinoxaline 8 , respectively. Moreover, the reactions of 7 with triethyl orthoformate and orthoacetate gave 1-(o-chlorophenyl)-3-(1,3,4-oxadiazol-5-yl)-1H-pyrazolo-[3,4-b]quinoxaline 9a and 1(o-chlorophenyl)-3-(2-methyl-1,3,4-oxadiazol-5-yl)-1H-pyrazolo[3,4-b]quinoxaline 9b , respectively.     

Unusual deoxygenation and reactivity studies related to O6-(benzotriazol-1-yl)inosine derivatives

New and unusual developments related to the chemistry of O6-(benzotriazol-1-yl)inosine derivatives are reported. First, a simple, scalable method for their syntheses via the use of PPh3/I2/HOBt has been developed and has been mechanistically investigated by 31P(1H) NMR. Studies were then conducted into a unique oxygen transfer reaction between O6-(benzotriazol-1-yl)inosine nucleosides and bis(pinacolato)diboron (pinB-Bpin) leading to the formation of C-6 (benzotriazol-1-yl)purine nucleoside derivatives and pinB-O-Bpin. This reaction has been investigated by 11B(1H) NMR and compared to pinB-O-Bpin obtained by oxidation of pinB-Bpin. The structures of the C-6 (benzotriazol-1-yl)purine nucleosides have been unequivocally established via Pd-mediated C-N bond formation between bromo purine nucleosides and 1H-benzotriazole. Finally, short and extremely simple synthesis of 1,N6-ethano- and 1,N6-propano-2'-deoxyadenosine are reported in order to demonstrate the synthetic versatility of the O6-(benzotriazol-1-yl)inosine nucleoside derivatives for the assembly of relatively complex compounds.