SRN1 Substitution Research Articles

“Transition-metal-free” synthesis of carbazoles by photostimulated reactions of 2′-halo[1,1′-biphenyl]-2-amines.

An efficient and simple protocol for the preparation of a series of 9H-carbazoles by photostimulated SRN1 substitution reactions is presented. Substituted 9H-carbazoles were synthesized in low to excellent yields (up to 96%) through an intramolecular C–N bond formation of 2′-halo[1,1′-biphenyl]-2-amines by the photoinitiated SRN1 mechanism under mild and “transition-metal-free” conditions. The biphenylamines used as substrates were obtained with isolated yields ranging from 21% to 84% by two approaches: (A) the cross-coupling Suzuki–Miyaura reaction and (B) the radical arylation of anilines. Some key aspects of the proposed mechanism were evaluated at the B3LYP/6-311+G* level.

Arylation of aryl chlorides, a convenient method for the synthesis of new potential triazolic fungicides

We evaluated two alternative routes for the arylation of known chlorinated fungicides. The first pathway involved a SRN1 substitution, followed by Stille reaction, while the second consisted in a one step reaction by the Suzuki coupling. Both methodologies were useful to obtain new products that could be potential fungicides.

Synthesis of 1,1-Bis(trimethylstannyl)cyclopropanes by the SRN1 Mechanism

The reactions of readily available 1,1-dichlorocyclopropanes, obtained by addition of dichlorocarbene to alkenes, with Me3Sn− anions are reported. The process is described in terms of a photoinduced SRN1 substitution. The 1,1-bis(trimethylstannyl)cyclopropanes were obtained in good to excellent isolated yield (71−90%); 7,7-dichloro-2-oxa-bicyclo[4.1.0]heptane gave the 1,1-bis(trimethylstannyl) product in only 40% yield.

Synthesis of 1H-quinazoline-4-ones using intramolecular aromatic nucleophilic substitution

The anions of 1-(2-bromobenzoyl)-3-phenylthiourea 1, 1-(2-chlorobenzoyl)-3-phenylthiourea 2 and 1-(2-bromobenzoyl)-3-phenylurea 8 undergo intramolecular nucleophilic substitution (putative SNAr mechanism), and not intramolecular SRN1 substitution, to yield 1-phenyl-2thioxo-2,3-dihydro-1H-quinazolin-4-one 6 and 1-phenyl-1H-quinazoline-2,4-dione 9 respectively. Under the same reaction conditions with the addition of copper(I) iodide, phenylthioureas 1 and 2 gave a rearrangement to the respective 2-halogeno-N-phenylbenzamides.

Radical-nucleophilic substitution (SRN1) reactions. Part 7. Reactions of aliphatic α-substituted nitro compounds.

α-Nitrothiocyanates R2C(SCN)NO2 have been prepared by oxidative addition of thiocyanate anion to nitronate anions and undergo SRN1 substitution reactions by loss of thiocyanate with nitronate anions, phenylsulfinate, azide and p-nitro- and p-chloro-benzenethiolates in dipolar aprotic solvents. 2-Nitro-2-thiocyanatopropane and other 2-substituted-2-nitropropanes [Me2C(X)NO2 with X = I, Br, Cl, NO2, PhSO2] react with thiolates by SRN1 reactions and/or redox reactions to give disulfides by a polar abstraction or chain SET (SET2) mechanisms. The products are dependent on the nucleophilicity of the thiolates, the polarisability of the α-substituent, the solvent and the presence of light catalysis, radical traps or strong electron acceptors. 2-Substituted-2-nitropropanes [Me2C(X)NO2 with X = N3, NO2, CN, p-NO2–C6H4–NN] undergo SRN1 substitutions with thiolates by loss of nitrite. 2-Substituted-2-nitropropanes Me2C(X)NO2 and thiolates only yield disulfides in methanol due to solvation of the nitro groups.

Preparation of S42- polysulfide from a sacrificial sulfur cathode and its use as a nucleophile in an electrochemically induced SRN1 substitution reaction

Polarization in deaerated acetonitrile of a sacrificial sulfur cathode constituted of a 2:1 mixture of S8 and graphite powder contained in a graphite envelope, at a potential corresponding to the first reduction step of S8, led to the S3- (S62-) polysulfide. After reduction of the total amount of S8, the further reduction of S3- at a potential corresponding to the second reduction step of S8, and using the graphite envelope as a cathode, gave exclusively S42-. Addition of one equivalent of 3-bromoquinoline (BrQ) followed by its mediated reduction by redox catalysis led to a mixture of QS3Q, QS2Q and QSQ in similar yields (22±4%), resulting from SRN1 substitution reactions involving the S42-, QSS- and QS- nucleophiles, respectively. Pre′paration de polysulfures S42- a partir d'une cathode consommable de soufre, et leur utilisation dans une re′action de substitution nucle′ophile SNR1 induite e′lectrochimiquement. Une e′lectrode consommable de soufre, constitue′e d'un me′lange de soufre S8 et de poudre de graphite (2:1) contenu dans une enveloppe de graphite, et polarise′e dans de l'ace′tonitrile a un potentiel correspondant au premier stade de re′duction de S8 conduit a l'anion polysulfure S3- (S62-). Apres re′duction totale de S8, la re′duction de S3– au potentiel correspondant a la seconde vague de re′duction de S8 et en utilisant l'enveloppe de graphite comme cathode, conduit exclusivement a S42-. L'addition d'un e′quivalent de 3-bromoquinole′ine (BrQ) suivie de sa re′duction par l'interme′diaire d'un me′diateur redox conduit a un me′lange de QS3Q, QS2Q et QSQ avec des rendements voisins (22±4%), ces produits re′sultant de re′actions de substitution de type SNR1 mettant respectivement en jeu les nucle′ophiles S42-, QSS- et QS-.

ChemInform Abstract: Electrochemically Induced SRN1 Substitution of Fluorinated Aryl Halides. Application to the Synthesis of Fluorinated‐Aryl Heterocycles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: A Convenient Synthesis of Perfluoroalkylated and Fluorinated‐Aryl Nitrogen Bases by Electrochemically Induced SRN1 Substitution.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Substitution of Bridgehead Halogens by a Free-Radical Electron-Transfer Mechanism

The reactions of 1-bromo-7-nitro- and 1-bromo-6-nitro-1,4-methanonaphthalene (2) and (3), and 9-bromo-2-nitro, 10-bromo-2-nitro-, 9,10-dibromo-2-nitro- and 9,10-diiodo-2-nitro-9,10-ethano-9,10-dihydroanthracene (4)-(7). respectively, with the sodium salt (1) of p-toluenethiol gave substitution products that were shown to be formed by an SRN1 or a related radical chain mechanism. In the relatively slow substitution reactions of the salt (1) with compounds (2)-(5). That contain bromine at bridgehead positions that are either meta- or para-benzylic to an aromatic nitro group, the rates of substitution in the isomers where the leaving group was meta- benzylic to the aromatic nitro group were slightly greater than those for the corresponding para-benzylic isomer. In compounds (6)and (7) the halogens are at bridgehead positions that are either meta- or para-benzylic relative to an aromatic nitro group within the same molecule. In the case of the reaction of the dibromide (6) with the thiolate (1), substitution was slow and occurred more rapidly at the benzylic -bridgehead position meta to the nitro group than at the corresponding para-benzylic position. In contast , the reaction of the diiodide (7) with the thiolate (1) gave substitution products which formed more rapidly than in the corresponding reaction of the dibromide (6) and the regioselectivity was reversed, with substitution occurring more readily at the bridgehead position para-benzylic to the nitro group than at the corresponding meta- benzylic position. The ratio of meta to para substitution products, determined for the reactions of compounds (2)-(6) with the salt (1), were in the range 1.15-2.5:1, while the reaction of (7) with the same nucleophile afforded a meta-to-para ratio of 1:2:3. These ratios contrast not only with each other, but also with the differences in reactivities determined for other nitrobenzylic systems, which are known to undergo SRN1 substitution reactions with the same nucleophile. The differences in first, the regioselectivity of substitution between the bridgehead systems, and secondly, the differences in the observed rates of regioselective substitution are compared with other simple nitrobenzylic halides. These differences are rationalized in terms of the effect of fixing the C-X bond at a bridgehead position to be orthogonal with the plane of the nitroaromatic group; this results in a reduction of the rate constants of intramolecular electron transfer, with significant consequences on the detailed overall mechanism for these reactions.

Electrochemical synthesis in an undivided cell of aromatic mono and dichalcogeno derivatives by SRN1 substitution reactions in MeCN

The two-step electrochemical synthesis of chalcogeno derivatives ArEPh (1) and ArEEAr (3) resulting from the oxidation of ArE− (2) (AR = 4 − NCC6H4, 1-naphthyl, 2-quinolyl; E = S, Se, Te) can be conveniently carried out in MeCN, by reduction of an aryl halide (ArX) in the presence of electrogenerated PhE− or E22− anions (SRN1 substitution reaction). To circumvent the disadvantages connected with the use of a divided cell equipped with degradable membranes, a method based on a beaker-type cell has been developed. Thus, the synthesis of substituted compounds1 and3 can be carried out in an undivided cell equipped with a magnesium anode, if a fluoride salt, such as Et4NF.2H2O is purposely added before electrolysis (for3) or after the first step (for1). Under such conditions, the yields are competitive with those obtained in a divided cell.

ChemInform Abstract: Perfluoroalkylation of Purine and Pyrimidine Bases by Electrochemically Induced SRN1 Substitution.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Acetonitrile is a better solvent than dimethyl sulfoxide for electrochemically induced SRN1 substitution reactions with chalcogenophenoxide anions

Acetonitrile is a better solvent than dimethyl sulfoxide for electrochemically induced SRN1 substitution reactions with chalcogenophenoxide anions

Nature of the reactions involving 4-haloisoquinolines and amide ion in ammonia. Remarkable competition between SRN1 substitution and .sigma. complex formation

4-Bromo- or 4-chloroisoquinoline in refluxing liquid ammonia containing amide and thiomethoxide ions reacts preferentially with the thiolate ion to give 4-(methylthio)isoquinoline in high yield. The bromo substrate was shown to require amide ion in order to react with thiomethoxide ion, no reaction taking place in its absence. Substitution product is believed to form from both halides by an S RN 1 mechanism. By contrast, 3-chloroisoquinoline under the same conditions of mixed anions gives 3-aminoisoquinoline. The role of amide ion and its addition to give σ complexes in these and other reactions of 4-halogenated isoquinolines in ammonia is discussed

ChemInform Abstract: Perfluoroalkylation of Imidazoles by Electrochemically Induced SRN1 Substitution.

Abstract Indirect electrochemical reduction, by means of aromatic anion radical mediators, of perfluoroalkyl halides in the presence of imidazolate or of substituted imidazolate anions yields the corresponding perfluoroalkylated imidazoles along an S RN 1 mechanism.

Imidazol-5-yl radicals as reactive intermediates

Imidazol-5-yl radicals have been generated as reactive intermediates in reduction reactions e.g. the reduction of 5-bromo-1,2-dimethylimidazole with Na/NH3/ButOH and the reduction of 5-iodo- and 5-bromo-imidazole with Bu3SnH, to yield 1,2-dimethylimidazole. The imidazol-5-yl radical resulting from the Na/NH3/ButOH and Bu3SnH reduction of 5-bromo-1 -(but-3-en-1-yl)-2-methylimidazole has been trapped by exo-radical cyclisation to yield the bicyclic imidazole (7). Attempted SRN1 substitution reactions between nucleophiles and 5-bromo- and 5-iodo-1,2-dimethylimidazole were unsuccessful. The radical anions of 5-nitroimidazoles were shown not to dissociate to nitrite anions and the corresponding imidazol-5-yl radicals, thereby disproving a putative explanation for the generation of nitrite anions in the antimicrobial mode of action of 5-nitroimidazoles. A mechanism has been proposed to explain the release of nitrite in the mode of action of nitroimidazoles.13C NMR spectroscopy has been used to distinguish between 4- and 5-bromo- and -iodo-imidazoles.

Synthesis of 4-Highly Branched Imidazole Derivatives via Cine-Substitution and SRN1 Substitution of 5-Nitroimidazoles with Anions of Nitroalkanes

Substitution de dimetridazole par action de 2-nitroporpan-2-ure ou de 1-nitrocyclohexanure: obtention respectivement de 4-[2-nitro-1,1,2-trimethylpropyl]- et 4-isopropenyl-1,2-dimethylimidazoles et de 1-[1,2-dimethylimidazol-4-yl]-1'-nitrobicyclohexyle et 4-cyclohex-1-enyl-1,2-dimethylimidazole

ELECTROCHEMICAL SYNTHESIS OF SELENO AND TELLURO DERIVATIVES IN MeCN

Abstract Large-scale electrolysis with concurrent sonication in MeCN allows for the synthesis of a large variety of seleno and telluro derivatives. Aliphatic chalcogenides REER or RER (E = Se, Te) can be prepared by reduction of E powder to E2 2- or E2-, followed by addition of an alkyl halide RX. Depending upon R, substitution can compete with homogeneous electron or H+ transfers. RE+ can be prepared by anodic oxidation of REER, and trapped by nucleophiles and olefins. The synthesis of aromatic chalcogenides ArEAr' can be carried out by electrochemically induced SRN1 substitution. The yields are improved by redox catalysis. Under such conditions, the synthesis of PhEAr (Ar = NCC6H4, PhCOC6H4) proceeds in good yields. ArEEAr and ArEAr can be prepared by cathodic reduction of PhEAr.

A novel SRN1 substitution: the reaction between the anion of 2-nitropropane and 3-bromo-1-nitrocyclohex-1-ene

X-Ray crystallography has been used to determine the unusual cyclopropyl structure for the product of the S RN l reaction between the anion of 2-nitropropane and 3-bromo-1-nitrocyclohex-1-ene.

The peculiar behaviour of the trifluoromethyl substituent in S RN1 processes

Reaction of the enolate of 3,3-dimethylbutan-2-one with α,α,α-trifluoro-o-iodotoluene in a SRN1 process does not yield the expected substitution product, but a more complex molecule deriving from It. An accurate n.m.r. analysis of the products, along with other evidence, indicates a mechanism for this rearrangement, where an interaction of the trifluoromethyl group with the adjacent enolate moiety occurs, once the ‘normal’SRN1 substitution product has formed. The peculiar effect of the CF3 substituent is not only confined to the ortho position. Even α,α,α-trifluoro-p-iodotoluene shows unusual behaviour and affords a rearranged product. A mechanistic explanation is offered, where some of the key steps are similar to those involved in the case of the ortho isomer.

Radical–nucleophilic substitution (SRN1) reactions. Part 2. Preparation and reactions of α-nitrosulphides

A range of α-nitrosulphides [Me2C(SR)NO2, with R = 2-pyridyl, pyrimidin-2-yl, 1,3-benzothiazol-2-yl, 1-methylimidazol-2-yl, and 4,5-dihydro-1,3-thiazol-2-yl] have been prepared by oxidative addition of thiolate anion to the anion of 2-nitropropane, SN2 attack of the anion of 2-nitropropane on symmetrical disulphides, and SRN1 reaction of 2-substituted-2-nitropropanes with thiolate anions. The α-nitrosulphides undergo SRN1 substitution with the anion of 2-nitropropane, and SRN1 substitution or redox reactions with thiolate anions. The electron spin resonance (e.s.r.) spectrum of the radical-anion of 1-methyl-1-nitroethyl pyrimidin-2-yl sulphide has been observed.