Kinetic study of the addition of trihalides to unsaturated compounds in ionic liquids. Evidence of a remarkable solvent effect in the reaction of ICl2-

The kinetic constants and activation parameters for the reactions of Br(3)(-) and ICl(2)(-) with some alkenes and alkynes have been determined in the ionic liquids [bmim][PF(6)], [emim][Tf(2)N], [bmim][Tf(2)N], [hmim][TF(2)N], [bm(2)im][Tf(2)N], and [bpy][TF(2)N] (where emim = 1-ethyl-3-methylimidazolium, bmim = 1-butyl-3-methylimidazolium, hmim = 1-hexyl-3-methylimidazolium, bm(2)im = 1-butyl-2,3-dimethylimidazolium, bpy = butylpyridinium, PF(6) = hexafluorophosphate, and Tf(2)N = bis(trifluoromethylsulfonyl)imide) and in 1,2-dichloroethane. The rates of both reactions increase on going from 1,2-dichloroethane to ILs. Evidence suggests that, while the hydrogen bonding ability of the imidazolium cation is probably the main factor able to increase the rate of the addition of ICl(2)(-) to double and triple bonds, this property has no effect on the electrophilic addition of Br(3)(-) to alkenes and alkynes. Furthermore, in the case of the ICl(2)(-) reaction, the hydrogen bonding ability of ILs can be exploited to suppress the unwanted nucleophilic substitution reaction on the products by the Cl(-) anion.     

Synthesis of naphthalenes and 2-naphthols by the electrophilic cyclization of alkynes

[reactions: see text] A wide variety of substituted naphthalenes are readily prepared regioselectively under mild reaction conditions by the 6-endo-dig electrophilic cyclization of appropriate arene-containing propargylic alcohols by ICl, I2, Br2, NBS, and PhSeBr. 3-Iodo-2-naphthols have also been prepared in excellent yields by the cyclization of analogous 1-aryl-3-alkyn-2-ones. This methodology readily accommodates various functional groups and has been successfully extended to the synthesis of substituted carbazoles and dibenzothiophenes.     

Bromination of aromatic molecules with polymer supported reagents

Crosslinked co-poly/styrene-4-vinyl(N-hexylpyridinium bromide) was converted with bromine or chlorine to insoluble polymer supported complexes or respectively, and their reactivity studied in reactions with various aromatic molecules. Reagent was found in all cases to be milder than reagent and regiospecifically transformed alkoxy and amino substituted benzenes ( ) into 4-bromo derivatives, while corresponding reactions with resulted in dibromo derivatives. Several benzoheterocyclic molecules were converted with to substitution or addition products, i.e. 2,3-dibromo-N-methylpyrrole, 3-bromobenzo/b/thiophene, and 2,3-dibromo-2,3-dihydrobenzofuran. In the series of ortho-alkyl disubstituted benzene derivatives, i.e. o-xylene, indane, and tetraline, where the Mills-Nixon effect was established with various electrophilic reagents, bromination reactions with showed higher β-selectivity than the corresponding reactions with bromine. The rate of bromination in various alkyl substituted benzenes with reagent depended on the magnitude of the alkyl group, as well as the para/ortho regioselectivity, amounting to 100% in the case of tert-butylbenzene.     

Electrophilic fluorination of organosilanes

The fluorination of organosilanes with the silyl groups directly attached or adjacent to an aryl or alkenyl group has been only very recently examined despite the fact that the corresponding fluorinated products are synthetically useful building blocks. In these reactions, the silyl group enhances the reactivity of the pi-nucleophile and controls the sense of regiochemistry upon addition of the electrophilic source of fluorine. These reactions take advantage of the beta effect of the silicon-carbon bond and recent results from the literature revealed that this chemistry allows for the preparation of a variety of novel fluorinated building blocks including enantio-enriched derivatives.     

Studies on the synthesis of heterocyclic compounds. XI. Cleavage of 1,3-benzodioxoles by magnesium bromide-acetic anhydride

The cleavage reaction of some 1,3-benzodioxole derivatives with magnesium bromide and acetic anhydride has been studied. The reactions have been carried out in acetonitrile solution at room temperature. In all of the 1,3-benzodioxoles studied, the opening of the heterocyclic ring with formation of bromides, alkenes and their corresponding products of hydrolysis have been observed. The competitive electrophilic substitution on the benzene ring was very limited and was insignificant when a large excess of the cleavage reagent was used. The structures of newly prepared compounds have been determined by elemental analysis, spectroscopic data and comparison with authentic samples.     

Synthesis of 2(3H)-furanones via electrophilic cyclization

A variety of highly substituted 2(3H)-furanones are readily prepared from 3-alkynoate esters and the corresponding acids via electrophilic cyclization. Successful electrophiles in this process include I2, ICl, and PhSeCl. This highly efficient process proceeds under mild conditions, tolerates various functional groups, and generally provides substituted 2(3H)-furanones in good to excellent yields.     

Catalytic Friedel–Crafts C−H Borylation of Electron‐Rich Arenes: Dramatic Rate Acceleration by Added Alkenes

In the electrophilic C−H borylation of electron‐rich aromatic compounds with catecholborane, the catalytic generation of the boron electrophile is initiated by heterolysis of the B−H bond by various Lewis and Brønsted acids, with a boronium ion formed exclusively. After ligand dissociation, the corresponding borenium ion undergoes regioselective electrophilic aromatic substitution on aniline derivatives as well as nitrogen‐containing heterocycles. The catalysis is optimized using B(C₆F₅)₃ as the initiator and proceeds without the addition of an external base or dihydrogen acceptor. Temperatures above 80 °C are generally required to secure efficient turnover in these Friedel–Crafts‐type reactions. Mechanistic experiments reveal that regeneration of the boronium/borenium ion with dihydrogen release is rate‐determining. This finding finally led to the discovery that, with added alkenes, catalytic C−H borylations can, for the first time, be carried out at room temperature.     

Electrophilic cyclization of (Z)-selenoenynes: synthesis and reactivity of 3-iodoselenophenes

We present here our results of the electrophilic cyclization reaction of (Z)-selenoenynes with different electrophiles such as I(2), ICl, PhSeBr, and PhSeCl. The cyclization reaction proceeded cleanly under mild reaction conditions, and 3-substituted selenophenes were formed in moderate to excellent yields. We observed that the nature of solvent and structure of (Z)-selenoenyne were important to the cyclization reaction. In addition, the obtained 3-iodoselenophenes were readily transformed to more complex products using a metal-halogen exchange reaction with n-BuLi and trapping the intermediate formed with aldehydes, furnishing the desired secondary alcohols in good yields. Conversely, using the palladium or copper catalyzed cross-coupling reactions with terminal alkynes or alkyl alcohols, we were able to convert 3-iodoselenophene to Sonogashira or Ullmann type products, respectively, in good yields.     

Synthesis and reactions of pyrido[3,2,1‐jk]carbazole‐4,6‐diones

Pyrido[3,2,1‐jk]carbazoles 1 , synthesized from carbazoles and alkyl‐ or arylmalonates, gave regioselective electrophilic substitution reactions at position 5 such as chlorination to 5‐chloro derivatives 2 , nitration to 5‐nitro compounds 3 , or hydroxylation to 5‐hydroxy derivatives 4 . 5‐Hydroxy compounds 4 gave on treatment with strong bases ring contraction to 5 , 6 or the ring opening product 7 . Exchange of the chloro group in 2 with azide or amines gave the corresponding azides 8 and the 5‐amino derivatives 9 and 10 . Alkylation of 1 with benzyl chloride or allyl bromide resulted in the formation of 5‐C‐alkylated products 11 together with 4‐alkyloxy derivatives 12 . J. Heterocyclic Chem., 48, 1039 (2011).     

1,3-benzoxathioles. Electrophilic aromatic substitution

Some electrophilic substitution reactions on 1,3-benzoxathiole derivatives are described. Bromination and acylation reactions take place in position 5, i.e., para to the oxygen atom. 1,3-Benzoxathiole nitration yields a mixture of the corresponding sulfoxide and of the 6-nitro derivative when performed with 33% nitric acid, while, using a mixture of 40% nitric acid and acetic acid or acetyl nitrate, the 6-nitroderivative is obtained together with large amounts of gummy products. 2,2-Dimethyl-1,3-benzoxathiole nitration with 33% nitric acid yields disulfide XI, while with 33% nitric acid and acetic acid or with acetyl nitrate a mixture of disulfide XI and XII is obtained. The structure of the products have been determined by spectroscopic methods.     

Conversions of methyl esters of (6-methyl-2-methylthio-4-pyrimidinyloxy)- and (3,4-dihydro-6-methyl-2-methylthio-4-oxo-3-pyrimidinyl)acetic acids

A study has been made of nucleophilic reactions (hydrolysis, hydrazinolysis, ammonolysis, reduction) and electrophilic reactions (bromination, nitration) of isomeric methyl esters of (6-methyl-2-methylthio-4-pyrimidinyloxy) acetic acid and (3,4-dihydro-6-methyl-2-methylthio-4-oxo-3-pyrimidinyl)acetic acid. Carboxyl-group derivatives and also derivatives with substituents in position 5 of the pyrimidine ring have been synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1655–1659, December 1992.     

A study of the atmospherically important reactions of dimethylsulfide (DMS) with I2 and ICl using infrared matrix isolation spectroscopy and electronic structure calculations

The reactions of dimethylsulfide (DMS) with molecular iodine (I(2)) and iodine monochloride (ICl) have been studied by infrared matrix isolation spectroscopy by co-condensation of the reagents in an inert gas matrix. Molecular adducts of DMS + I(2) and DMS + ICl have also been prepared using standard synthetic methods. The vapour above each of these adducts trapped in an inert gas matrix gave the same infrared spectrum as that recorded for the corresponding co-condensation reaction. In each case, the infrared spectrum has been interpreted in terms of a van der Waals adduct, DMS?:?I(2) and DMS?:?ICl, with the aid of infrared spectra computed for their minimum energy structures at the MP2 level. Computed relative energies of minima and transition states on the potential energy surfaces of these reactions were used to understand why they do not proceed further than the reactant complexes DMS?:?I(2) and DMS?:?ICl. The main findings of this research are compared with results obtained earlier for the DMS + Cl(2) and DMS + Br(2) reactions, and the atmospheric implications of the conclusions are also considered.     

Synthesis and antibacterial activities of novel 2,5-diphenylindolo[2,3-e] pyrazolo[1',5':3",4"]pyrimido[2",1"-c] [1,2,4]triazines

The formation of (E)-3-{2-(2,5-diphenylpyrazolo[1,5-c]pyrimidin-7-yl)hydrazono}indolin-2-ones 3 has been achieved by condensation of equimolar amounts of 7-hydrazino-2,5-diphenylpyrazolo[1,5-c]pyrimidine (1) and isatin (or isatin derivatives) 2 at room temperature. The (E)-products could be isomerized into corresponding the (Z)-3 isomers. Reactions of the latter fused heterocyclic hydrazones towards different electro-philic reagents yielded the corresponding 3-substituted derivatives 4-7. Dehydrative cyclisation of the hydrazones 3 using phosphorus oxychloride afforded the 2,5-diphenyl- indolo[2,3-e]pyrazolo[1',5':3",4"]pyrimido[2",1"-c][1,2,4] triazines 13. The polyfused heterocyclic ring system 13 underwent electrophilic substitution reactions at position 4 rather than at position 3. The 3-bromo isomer of 17 was prepared by a sequence of reactions starting from 2,5-diphenylpyrazolo[1,5-c]pyrimidine-7(6H)-thione (11). The orientation of the electrophilic attack was supported by spectroscopic and chemical evidence. Some of the synthesized compounds were found to possess slight to moderate activity against the microorganisms Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa.     

Naphthoindoles. 8. Electrophilic substitution reactions of 4,11-dimethyxynaphtho[2,3-f]indole-5,10-dione

Some electrophilic substitution reactions characteristic of indole derivatives have been investigated for 4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione. The corresponding 3 derivatives were obtained as a result of Vilsmeier, Mannich, and acylation reactions.See [1] for Part 7.Russian Chemico-Technological University, Moscow 125190. Center for Drug Chemistry, All-Russian Chemical and Pharmaceutical Research Institute, Moscow 119815. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 939–941, July, 1998.     

Reaction of 5-hydroxyindole derivatives with o-nitrobenzenesulfenyl chloride

In the reaction of o-nitrobenzenesulfenyl chloride with 5-hydroxyindole derivatives, electrophilic substitution occurs in the 3 position. When there is a carbethoxy group in the 3 position, the o-nitrobenzenesulfenyl residue enters the 6 position. The corresponding 5-hydroxy derivatives, the aminomethylation of which leads to 4-dimethylaminomethyl derivatives, were obtained by hydrolysis of the 5-acetoxy derivatives of o-nitrophenyl 3-indolyl sulfides.     

2,3-联烯醇及其衍生物的反应

2,3-联烯醇是一类含1,2-二烯官能团和羟基的化合物, 具有很高的反应活性, 它及其衍生物是一类重要的联烯化合物. 概述了2,3-联烯醇及其衍生物的反应, 包括2,3-联烯醇在过渡金属催化下的自身异构环化反应、钯催化的偶联反应、钌催化的环羰基化反应、不同条件下不同方式的扩环反应、亲电试剂参与的反应、分子内环加成反应、自由基反应等和2,3-联烯醇衍生物在零价钯催化下基于亚甲基-π-烯丙基钯中间体生成联烯或1,3-共轭二烯的区域选择性反应, S_N2'类型的加成-消除反应, 二价钯催化下的分子内环化反应以及重排反应等.     

Highly regio- and stereoselective synthesis of indene derivatives via electrophilic cyclization

[reaction: see text] Indene or naphthalene derivatives are readily prepared in moderate to excellent yields with high regio- and stereoselectivity under very mild reaction conditions by the reaction of acetylenic malonates and ketones with I2, ICl, or NIS. The resulting iodides can be further elaborated using palladium-catalyzed coupling reactions.     

Synthesis and anticancer evaluation of some novel N,O,S heterocyclic compounds pendant to 3-methyl-5-cyano-6-(3,4-dimethoxyphenyl)pyrimidine and other related fused pyrimidines

The key starting compound 5-cyano-6-(3,4-dimethoxyphenyl)-2-thiouracil ( 1 ) was synthesized and allowed to undergo electrophilic substitution with methyl iodide to give the corresponding 6-(3,4-dimethoxyphenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile ( 2 ). Nucleophilic substitution on compound 2 with hydrazine hydrate led to the corresponding 2-hyrazinopyrimidone intermediate 3 . Compound 3 underwent several substitution and cyclization reactions with β-ketoester, β-ketone, alkyl halides, arylisothiocyanate, or aromatic aldehydes followed by cyclization reactions to give the corresponding N,O,S heterocyclic compounds incorporated into pyrimidine moiety and/or the related S-triazino[3,4-b]pyrimidine derivatives 4 - 18 . Anticancer evaluation of some representative examples of newly synthesized compounds was carried out against MCF-7, HCT116 cell lines. Some of the newly synthesized compounds showed significant activity.     

Reactivity of pyrido[4,3,2-kl]acridines: regioselective formation of 6-substituted derivatives

Pyrido[4,3,2-kl]acridines represent a new class of heterocycles, isomers of marine alkaloids. The 7H-pyrido[4,3,2-kl]acridine reacts as an electron rich heterocycle, and in particular via electrophilic substitution such as H/D exchange and the Vilsmeier-Haack reaction. The reaction is fully regioselective and gives the corresponding 6-substituted derivatives. The pyrido[4,3,2-kl]acridin-4-one reacts with amines and thiol, via 1,4-Michael addition to give the 6-amino or 6-thio analogues in a very efficient way. Molecular calculations account for the observed regioselectivity.     

Synthesis and substitution reactions of β-alkoxyvinyl bromodifluoromethyl ketones

β-Alkoxyvinyl bromodifluoromethyl ketones 1a, 1b and 1c were synthesized by the reaction of bromodifluoroacetic anhydride with appropriate vinyl ethers in high yields. The acyclic enone 1a reacted with amines to give the corresponding β-aminovinyl bromodifluoromethyl ketones 2 in good yields. The reaction of 1a with electrophilic reagent ICl yielded α-iodoenone 4. The substitution reaction of the cyclic enones 1b and 1c with thio-nucleophiles gave the corresponding difluoromethylene thioethers 6. The three-component reactions of 2 with primary amines and formaldehyde gave multifunctional 1,2,3,4-tetrahydropyrimidine 3 in moderate yields.