A new synthesis of 1,3-difunctionalized 2-sulfonamidopropane derivatives via regioselective ring opening reactions of 2-(bromomethyl)-1-sulfonylaziridines by substituted arylsulfonamides

The novel functionalized N,N′-[2-(arylsulfonamido)propane-1,3-diyl]bis(N-allylarylsulfonamide) and N,N′-[2-(methylsulfonamido)propane-1,3-diyl]bis(N-benzylarylsulfonamide) derivatives have been prepared from 2-(bromomethyl)-1-sulfonylaziridines for the first time using substituted arylsulfonamides in the presence of sodium methoxide under catalyst-free condition in good yields.     

Synthesis of Ethyl (2RS,3SR)-1-Tosyl-3-Vinylazetidine-2-carboxylate and ethyl (2RS,E)-3-ethylidene-1-tosylazetidine-2-carboxylate (=rac-ethyl N-tosylpolyximate)

The synthesis of 3-ethylideneazetidine-2-carboxylic acid (=polyoximic acid; 3 ) is a approached in two different ways leading to potential precursors of 3 . The first way involved a ring closure to a vinyl-subsatituted azetidin. Thus, Ireland-Claisen rearrangement of the Boc-glycinates 6 and 10 of (Z)- and (E)-2-butene-1,4-diol afforded, after exchange of the N-protecting groups, the isomeric 2-(tosylamino)-3-vinylbutanolides 13 and 14 with high stereoselectivity. Only the cis-isomer 14 could be further transformed to 3-(bromomethyl)-2-(tosylamino)-4-pentenoate 17 , and in a smoth cyclization with K₂CO₃, to trans-3-vinylazetidtene-2-carboxylaze 18 (Scheme 2). In the second approach, the 3-ethylidene isomer 19 of 18 was obtained more directly by a [2+2] cycloaddition, together with the two isomers 23 and 24 , from methlallene 20 and (tosyliminno)acetate 21 (Scheme 3). The main product of this reaction was, however, 2-(tosylamino)-4-hexinoate 22 , the product of an ene reaction.     

从2-(2-吡啶)-1,3-丙二醇衍生出的一些新的吡啶化合物

本文报道了2-(2-吡啶)-1,3-丙二醇及其衍生物的一些新的反应,以此得到了一系列新的1,3-二取代2-(2-吡啶)丙烷和3-取代2-(2-吡啶)丙烯-1化合物,并讨论了这些化合物的光谱数据。     

Gold-catalyzed cycloisomerizations of 1-(2-(tosylamino)phenyl)prop-2-yn-1-ols to 1H-indole-2-carbaldehydes and (E)-2-(iodomethylene)indolin-3-ols

A method to prepare 1H-indole-2-carbaldehydes and (E)-2-(iodomethylene)indolin-3-ols by gold(I)-catalyzed cycloisomerization of 1-(2-(tosylamino)phenyl)prop-2-yn-1-ols with N-iodosuccinimide (NIS) is reported. The reactions were shown to be operationally simplistic and proceed efficiently for a wide variety of substrates, affording the corresponding products in good to excellent yields (70-99%). The mechanism is suggested to involve activation of the alkyne moiety of the substrate by the gold(I) catalyst. This triggers intramolecular addition of the tethered aniline moiety to give a vinyl gold intermediate, which undergoes iododeauration with NIS to give the (E)-2-(iodomethylene)indolin-3-ol adduct. Subsequent 1,3-allylic alcohol isomerization (1,3-AAI) followed by formylation of this vinyl iodide intermediate then gives the 1H-indole-2-carbaldehyde.     

Structure and Conformational Analysis of 5,5-Bis(bromomethyl)-2-methyl-2-phenyl-1,3-dioxane

Russian Journal of General Chemistry - The structure of 5,5-bis(bromomethyl)-2-methyl-2-phenyl-1,3-dioxane 1 has been studied by means of 1H and 13C NMR spectroscopy as well as X-ray diffraction...     

A novel entry toward 2-imino-1,3-thiazolidines and 2-imino-1,3-thiazolines by ring transformation of 2-(thiocyanomethyl)aziridines

A new, efficient, and straightforward synthesis of 3-arylmethyl-4-chloromethyl-2-imino-1,3-thiazolidines and 2-(N-acylimino)-3-arylmethyl-4-chloromethyl-1,3-thiazolidines has been developed by ring transformation of 1-arylmethyl-2-(thiocyanomethyl)aziridines upon treatment with a catalytic amount of titanium(IV) chloride in dichloromethane. The latter 2-(thiocyanomethyl)aziridines were prepared in high yields from 1-arylmethyl-2-(bromomethyl)aziridines by reaction with potassium thiocyanate in DMF. The 2-imino-1,3-thiazolidines and 2-(N-acylimino)-1,3-thiazolidines thus obtained can be easily interconverted, either by treatment with an acid chloride and a base in ether toward 2-(N-acylimino)thiazolidines or by treatment with potassium carbonate in methanol toward N-deprotected 2-iminothiazolidines. Dehydrohalogenation of 2-(N-acylimino)-3-arylmethyl-4-chloromethyl-1,3-thiazolidines by means of potassium tert-butoxide in DMSO afforded 2-(N-acylimino)-4-methyl-2,3-dihydro-1,3-thiazolines in good yields.     

Unexpected Regioselective Reactions of 2-(Bromomethyl)-1,3-thiaselenole with 1-Methyl-1H-imidazol-2-thiol,Accompanied by Rearrangements

Russian Journal of Organic Chemistry - The previously unknown regioselective reactions of 2-(bromomethyl)-1,3-thiaselenole with 1-methyl-1H-imidazol-2-thiol were used to develop efficient synthetic...     

Synthesis of 1-arylmethyl-2-(cyanomethyl)aziridines and their ring transformation into methyl N-(2-cyanocyclopropyl)benzimidates

1-Arylmethyl-2-(cyanomethyl)aziridines were prepared in high yields from the corresponding 2-(bromomethyl)aziridines upon treatment with potassium cyanide in DMSO. Ring opening of the aziridine moiety with N-chlorosuccinimide in CCl4 and subsequent treatment of the thus formed 4-chloro-3-(N-chloro-N-(alpha,alpha-dichlorobenzyl)amino)butanenitriles with sodium methoxide in methanol resulted in novel methyl N-(2-chloro-1-(cyanomethyl)ethyl)benzimidates, although in low yields. The latter gamma-chloro nitriles were smoothly converted into methyl N-(2-cyanocyclopropyl)benzimidates as precursors of biologically relevant beta-ACC derivatives through a 1,3-cyclization protocol by reaction with potassium tert-butoxide in THF.     

(4-甲基-1,3-二噻烷-2-亚甲基)-1,7-二芳基-1,6-二烯-3,5-二酮的合成

从2,4-戊二酮和1,2,3-三溴丙烷出发合成了一类新的α-羰基二硫缩烯酮类化合物,并以其为底物合成了(4-甲基-1,3-二噻烷-2-亚甲基)-1,7-二芳基-1,6-二烯-3,5-二酮类化合物,通过IR和1H NMR方法对其进行了表征.     

Expanding the scope of the indium-promoted allylation reaction: 4-(bromomethyl)-1,3-dioxol-2-one as a synthetic equivalent of a 3-arylhydroxyacetone enolate

Cyclic enol carbonates of type 2, obtained via the indium-promoted allylation of aldehydes with 4-(bromomethyl)-1,3-dioxol-2-one, undergo Heck reaction with aryl iodides in the presence of silver trifluoroacetate, to give the corresponding arylated products. Thus, 4-(bromomethyl)-1,3-dioxol-2-one can be considered as a synthetic equivalent of 3-arylhydroxyacetone enolate.     

Structure and Conformational Analysis of 5,5-Bis(bromomethyl)-2-[4-(dimethylamino)phenyl]-1,3-dioxane

Russian Journal of Organic Chemistry - The structure of 5,5-bis(bromomethyl)-2-[4-(dimethylamino)phenyl]-1,3-dioxane, a promising reagent for fine organic synthesis and a potential bactericidal...     

Novel synthesis of 2-aminopentanedinitriles from 2-(bromomethyl)aziridines and their transformation into 2-imino-5-methoxypyrrolidines and 5-methoxypyrrolidin-2-ones

1-Arylmethyl-2-(bromomethyl)aziridines were transformed into 2-[N-(arylmethyl)amino]pentanedinitriles upon treatment with an excess of potassium cyanide in DMSO through an unprecedented and peculiar reaction mechanism, involving base-induced ring opening of intermediate 2-(cyanomethyl)aziridines into allylamines, followed by migration of the double bond out of the conjugation towards aldimines via enamine intermediates. The resulting aminopentanedinitriles served as substrates for the synthesis of novel 2-imino-5-methoxypyrrolidines upon treatment with sodium methoxide in methanol, which were either acetylated at the free imino group to afford the more stable N-acetylimino derivatives or hydrolyzed towards the corresponding synthetically relevant 5-methoxypyrrolidin-2-ones.     

Reduction of 5-(bromomethyl)-1-pyrrolinium bromides to 2-(bromomethyl)pyrrolidines and their transformation into piperidin-3-ones through an unprecedented ring expansion-oxidation protocol

3,3-Dialkyl-5-(bromomethyl)-1-pyrrolinium bromides, prepared via bromocyclization of N-(2,2-dialkyl-4-pentenylidene)amines by means of bromine in dichloromethane, were reduced to 4,4-dialkyl-2-(bromomethyl)pyrrolidines for the first time using borane dimethyl sulfide in dichloromethane. Furthermore, the latter 2-(bromomethyl)pyrrolidines were transformed into the corresponding piperidin-3-ones through an unprecedented ring expansion-oxidation protocol in dimethylsulfoxide in the presence of potassium carbonate. Reduction of 5,5-dialkylpiperidin-3-ones by means of sodium borohydride in methanol afforded 5,5-dialkyl-3-hydroxypiperidines in good yields.     

A new approach towards 2-amino-1-aryloxy-3-methoxypropanes from 1-arylmethyl-2-(bromomethyl)aziridines

1-Arylmethyl-2-(bromomethyl)azirdines were converted into the corresponding 2-(aryloxymethyl)aziridines upon treatment with the appropriate potassium phenoxides in DMF/acetone in excellent yields, followed by regioselective ring opening towards N,N-di(arylmethyl)-N-(2-bromo-3-aryloxypropyl)amines using benzyl bromide in acetonitrile. Treatment of the latter β-bromoamines with sodium methoxide afforded the desired 2-amino-1-aryloxy-3-methoxypropanes as the major compounds (49-58%) besides the isomeric 3-amino-1-aryloxy-2-methoxypropanes in minor quantities (9-15%).     

Convenient synthesis of （2S,3R,4R,5S,6R）-2-（3-（4-ethylbenzyl）-4- chlorophenyl）-6-（hydroxymethyl）-tetrahydro- 2H-pyran-3,4,5-triol

A convenient approach for the preparation of （2S,3R,4R,5S,6R）-2-（3-（4-ethylbenzyl）-4-chlorophenyl）-6-（hydroxymethyl）- tetrahydro-2H-pyran-3,4,5-triol I is developed. The target compound via four steps is synthesized from 4-bromo-2-（bromomethyl）- 1-chlorobenzene and the isomers of undesired ortho-products were avoided during the preparation.     

Nouvelles applications du bis (bromomethyl)-2,3 butadiene-1,3: acces a des bis (methylene)-1,2 cyclopentanes,a des 2H-isoindoles et a des dithia-2,3 naphtalenes

2,3-Bis (bromomethyl)-1,3 butadiene 1 was found to be a good reagent for C-dialkylation by phase transfer reaction. Adducts of 1 with propiolic acid are versatile precursors of 2H-isoindoles and of 2,3-dithianaphtelenes.     

Synthesis of 1-arylmethyl-2-(2-cyanoethyl)aziridines and their rearrangement into novel 2-(aminomethyl)cyclopropanecarbonitriles

1-Arylmethyl-2-(bromomethyl)aziridines were transformed into novel 2-(2-cyanoethyl)aziridines upon treatment with alpha-lithiated trimethylsilylacetonitrile in THF in an efficient and straightforward approach. The latter aziridines underwent ring opening by reaction with benzyl bromide in acetonitrile, affording 5-amino-4-bromopentanenitriles through a regiospecific ring opening of intermediate aziridinium salts by bromide. Further elaboration of these gamma-bromonitriles resulted in the synthesis of novel 2-[N,N-bis(arylmethyl)aminomethyl]cyclopropanecarbonitriles in high yields by means of a 1,3-cyclization protocol upon treatment with KOtBu in THF.     

2-,3-和4-溴甲基吡啶的水解反应的动力学研究

用HPLC测定了2-、3-和4-溴甲基吡啶在60℃、离子强度μ为0.15、pH 0.9～9.9的缓冲溶液中水解成相应的羟甲基吡啶的反应速度.通过数学处理,求得溴甲基吡啶的一级和二级反应速度常数以及溴甲基吡啶共轭酸的一级反应速度常数.水解反应的可能机理是S_N1和S_N2.     

The Use of 4-(Bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one as “Masked” α-Bromo-α'-Hydroxy Ketone in the Synthesis of Heterocyclic Systems

4-(Bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one was obtained on the basis of the readily obtainable 4-methylene-5,5-dimethyl-1,3-dioxolan-2-one. It forms 2-imidazo[1,2-a]pyridin-2-yl-2-propanol with 2-aminopyridine, 11a-hydroxy-1,1-dimethyl-3-oxo-1,5,11,11a-tetrahydro[1,3]oxazolo[3,4-a]pyrido[1,2-d]-10-pyrazinium bromide with 2-(aminomethyl)pyridine, and the corresponding derivative of 4-hydroxyoxazolidin-2-one with 2-(3,4-dimethoxyphenyl)ethylamine. The last product was converted by intramolecular amidoalkylation without isolation into 10b-(bromomethyl)-8,9-dimethoxy-1,1-dimethyl-1,5,6,10b-tetrahydro[1,3]oxazolo[3,4-a]isoquinolin-3-one.     

Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with respect to sodium methoxide: a combined computational and experimental study

The difference in reactivity between the activated 2-bromomethyl-1-tosylaziridine and the nonactivated 1-benzyl-2-(bromomethyl)aziridine with respect to sodium methoxide was analyzed by means of DFT calculations within the supermolecule approach, taking into account explicit solvent molecules. In addition, the reactivity of epibromohydrin with regard to sodium methoxide was assessed as well. The barriers for direct displacement of bromide by methoxide in methanol are comparable for all three heterocyclic species under study. However, ring opening was found to be only feasible for the epoxide and the activated aziridine, and not for the nonactivated aziridine. According to these computational analyses, the synthesis of chiral 2-substituted 1-tosylaziridines can take place with inversion (through ring opening/ring closure) or retention (through direct bromide displacement) of configuration upon treatment of the corresponding 2-(bromomethyl)aziridines with 1 equiv of a nucleophile, whereas chiral 2-substituted 1-benzylaziridines are selectively obtained with retention of configuration (via direct bromide displacement). Furthermore, the computational results showed that explicit accounting for solvent molecules is required to describe the free energy profile correctly. To verify the computational findings experimentally, chiral 1-benzyl-2-(bromomethyl)aziridines and 2-bromomethyl-1-tosylaziridines were treated with sodium methoxide in methanol. The presented work concerning the reactivity of 2-bromomethyl-1-tosylaziridine stands in contrast to the behavior of the corresponding 1-tosyl-2-(tosyloxymethyl)aziridine with respect to nucleophiles, which undergoes a clean ring-opening/ring-closure process with inversion of configuration at the asymmetric aziridine carbon atom.