Radical Nucleophilic Substitution Research Articles

Competitive Reaction Pathways foro-Anilide Aryl Radicals: 1,5- or 1,6-Hydrogen Transfer versus Nucleophilic Coupling Reactions. A Novel Rearrangement to Afford an Amidyl Radical

The photoinduced reactions of o-iodoanilides (o-IC6H4N(Me)COR, 4a-d) with sulfur nucleophiles such as thiourea anion (1, -SCNH(NH2)), thioacetate anion (2, MeCOS-), and sulfide anion (3, S(2-)) follow different reaction channels, giving the sulfides by a radical nucleophilic substitution or the dehalogenated products by hydrogen atom transfer pathways. After an initial photoinduced electron transfer (PET) from 1 to iodide 4, the o-amide aryl radicals 12 are generated. These aryl radicals 12 afford alternative reaction pathways depending on the structure of the alpha-carbonyl moiety: (a) 12b (R = Me) adds to 1 to render the methylthio-substituted compounds by quenching the thiolate anion intermediate with MeI after irradiation; (b) 12c (R = -CH2Ph) follows a 1,5-hydrogen transfer to give a stabilized alpha-carbonyl radical (17); and (c) 12d (R = t-Bu) affords 1,6-hydrogen transfer, followed by a 1,4-aryl migration to render an amidyl radical (20), which is reduced to the N-benzyl-N,2-dimethylpropanamide (10). Together with this last rearranged product, the ipso substitution derivative was also observed. Similar results were obtained in the PET reactions of 4d (R = t-Bu) with anions 2 and 3 under entrainment conditions with the enolate anion from cyclohexenone (5) or the tert-butoxide anion (6). From this novel rearrangement, and only under reductive conditions by PET reaction with anion 5, iodide 4d (R = t-Bu) affords quantitatively the propanamide 10. The energetic of the intramolecular rearrangements followed by radicals 12b-d were rationalized by B3LYP/6-31+G* calculations.

Radical Nucleophilic Substitution of 2-(4-Halophenyl)-2-methyl-1-chloropropane with Enolate Ions of Ketones

The photoinitiated reaction of 2-(4-halophenyl)-2-methyl-1-chloropropane 2a,b (halogen=Br, I, respectively) with the anions of pinacolone (3a) and acetophenone (3b) either in DMSO or in liquid ammonia are reported. In DMSO, the main reaction is the SRN1 nucleophilic substitution at the aromatic (Csp2-halogen) center with substitution or reduction at the aliphatic (Csp3-Cl) one. In liquid ammonia, the main reaction is substitution at the aromatic C-halogen site. This difference in product distribution is ascribed to modifications in the rate constant of Csp3-Cl dissociation of the radical anions proposed as intermediates in going from DMSO (rt) to liquid NH3 (-33 degrees C).

Some Synthetic Applications of the Aromatic Radical Nucleophilic Substitution Reactions

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of 7-Acyl-2,4-disubstituted Pteridines by Radical Nucleophilic Substitution and Displacement Reactions

Abstract 2,4-Disubstituted pteridine derivatives (1-3) react with acyl radicals very selectively in position 7 by a nucleophilic Substitution mechanism (4-10). Oxidation of the 2-methylthio group proceeds with m-chloroperbenzoic acid in good yields to the corresponding 7-acyl-2-methylsulfonyl-4-aminopteridines (11-16). The methylsulfonyl group can easily been displaced by nucleophiles such as aliphatic amines (27, 29, 32-42, 45), cyclic amines (56- 61), aromatic amines (30, 31) and amino acids (43-54). Oxygen nucleophiles lead to 7-acyl-isopterin derivatives (62-66). The acyl side-chain is also prone to structural modifications leading to the corresponding secondary alcohols on NaBH4 reduction (74-77) or to imino derivatives on reactions with amines (67-73) which can analogously been reduced to 2,4-disubstituted 7-( l-aminoalkyl)pteridines (80-85). An interesting H-shift was observed during heating of 32, 78 and 79 with benzylamine leading not to the benzylimines but the isomeric benzylideneamino derivatives 86-88. Various acetylations by acetic anhydride (AC2O) gave 89-93 and reduction of the pyrazine moiety to the 5,6,7,8-tetrahydro-pteridine derivatives 94-96 proceeded in the expected manner. The characterization of ther newly synthesized pteridine derivatives was performed by 1H-NMR spectra, UV-spectra and elemental analyses. Measurements of the basic pKa values of a selection of 2,4,7-trisubstituted pteridines were pteridines to characterize the dication, monocation and the neutral species by their UV-spectra.

Photochemical preparation of 1,3,5,7-tetracyanoadamantane and its conversion to 1,3,5,7-tetrakis(aminomethyl)adamantane.

New adamantane derivatives 1 and 2 that bear functionalized one-carbon extensions at all four bridgehead positions have been prepared. Radical nucleophilic substitution (S(RN)1) reaction of 1,3,5,7-tetrabromoadamantane with cyanide produces 1,3,5,7-tetracyanoadamantane (1), which was reduced with borane reagents to 1,3,5,7-tetrakis(aminomethyl)adamantane (2). Improvements in the preparation of 1,3,5,7-tetrahaloadamantanes (halogen = Br, Cl, I) are also reported. [structure--see text]

Recent Advances on Radical Nucleophilic Substitution Reactions

The radical nucleophilic substitution mechanism or SRN1 is a chain process, in which radicals and radical anions are intermediates. This process has been extensively used to effect substitution on a wide variety of substrates. The SRN1 reaction has been studied from both mechanistic and synthetic standpoints. The SRN1 mechanism requires an initiation step. Spontaneous electron transfer (ET) from the nucleophile to the substrate has been observed in a few systems; light stimulation, electrodes, alkali metals or inorganic salt-mediation is used otherwise. There are systems that are totally inert or undergo rather slow substitutions by classical polar mechanisms. Their lack of reactivity is usually due to strain (cycloalkyl and polycycloalkyl halides), steric (cycloalkyl, polycycloalkyl and neopentyl halides), or electronic factors (unactivated aromatic, vinyl halides and perfluoroalkyl halides). For these families of compounds, the nucleophilic substitution can be accomplished by the SRN1 mechanism. Conversely, there is a class of substrates, for which substitution can be achieved through both polar and ET mechanisms; however, the ET pathway is favored in some systems (i.e.: alkyl halides with EWG). We propose to undertake a compilation and critical review on SRN1 reactions dealing with substitutions on aromatic substrates, cycloalkyl, bridgehead, neopentyl, vinyl halides, perfluoroalkyl iodides, aliphatic substrates with EWG in the _ position and N,N-Dialkyl-p-toluenesulfonamides. With this aim in mind, we expect to cover recent SRN1 substitutions, with an emphasis on the scope of the process in terms of synthetic capability and target applications.

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.

The electrodeless discharge lamp: a prospective tool for photochemistry: Part 2. Scope and limitation

We have previously reported results from the study of an original photochemical reactor consisting of an electrodeless discharge lamp (MWL) placed into the reactor vessel of a microwave oven [P. Klán, J. Literák, M. Hájek, J. Photochem. Photobiol. A: Chemistry 128 (1999) 145]. The microwave field generates ultraviolet irradiation in the lamp at the same time as it interacts with the studied sample, which is therefore affected by a simultaneous UV/VIS and MW irradiation. Here, five different common photoreactions have been investigated in the reactor: Norrish type II reaction of valerophenone and its p-methyl derivative, photo-Fries reaction, photoreduction of acetophenone, photolysis of a phenacyl ester, and a radical nucleophilic substitution of chlorobenzene in methanol. The reaction conversions and product distributions have been studied in terms of the MWL quality and the scale of the experiment. In addition, MW experiments were compared to those using a conventional UV lamp. The electrodeless lamp is presented as a very simple, economic, and efficient tool for photochemistry.

Reactivity of aminyl radicals in radical nucleophilic substitution reactions with diphenylphosphide anion

The photostimulated reactions of N-cyclopropyl-N-ethyl p-toluensulfonamide (4) with diphenylphosphide ions (2) in liquid ammonia gave 1,3-bis(diphenylphosphinyl)-1-(N-ethyl)propylamine, isolated as the oxide 5, and 1,3-bis(diphenylphosphinyl)-1-propanol, isolated as the oxide 6, all of them corresponding to the aperture of the cyclopropylaminyl radical intermediate. The reaction of 4 with 2 in excess and longer reaction times gave only 5 (73% yield). The photostimulated reactions of N-(n-butyl)-N-cyclobutyl p-toluensulfonamide (13) with 2 in liquid ammonia gave, after oxidation, N-(n-butyl)-N-cyclobutyl diphenylphosphonamide (14) in 94% yield. All these reactions occur by the radical nucleophilic substitution in which aminyl radicals are intermediates. The order of the magnitude of the rate constant for the coupling reaction of a dialkylaminyl radical with 2 could be intermediate between those of the rearrangements of the cyclopropyl and cyclobutylaminyl radicals.Key words: aminyl radicals, SRN1 reactions, radical clocks, photochemistry.

Reactivity of aminyl radicals in radical nucleophilic substitution reactions with diphenylphosphide anion

The photostimulated reactions of N-cyclopropyl-N-ethyl p-toluensulfonamide (4) with diphenylphosphide ions (2) in liquid ammonia gave 1,3-bis(diphenylphosphinyl)-1-(N-ethyl)propylamine, isolated as the oxide 5, and 1,3- bis(diphenylphosphinyl)-1-propanol, isolated as the oxide 6, all of them corresponding to the aperture of the cyclopropylaminyl radical intermediate. The reaction of 4 with 2 in excess and longer reaction times gave only 5 (73% yield). The photostimulated reactions of N-(n-butyl)-N-cyclobutyl p-toluensulfonamide (13) with 2 in liquid ammonia gave, after oxidation, N-(n-butyl)-N-cyclobutyl diphenylphosphonamide (14) in 94% yield. All these reactions occur by the radical nucleophilic substitution in which aminyl radicals are intermediates. The order of the magnitude of the rate constant for the coupling reaction of a dialkylaminyl radical with 2 could be intermediate between those of the rearrangements of the cyclopropyl and cyclobutylaminyl radicals.

Kinetic and mechanistic studies of the nonchain radical nucleophilic substitution reactions

The kinetics of the radical nucleophilic substitution reaction of p-nitrochlorobenzene with the sodium salt of the ethyl α-cyanoacetate carbanion in dimethyl sulfoxide (DMSO) solution at 335.9, 340.1, 343.9, 347.7, and 351.4 K were determined by observing the increase of the UV-visible absorbance of the product, the ethyl α-cyano-α-(p-nitrophenyl)acetate carbanion. The activation energies and entropies for the single electron transfer (k 1 ) and for the p-nitrochlorobenzene radical anion dissociation (k 2 ) were obtained. These results strongly support the previous conclusion that the thermal nucleophilic substitution reactions of o- and p-nitrohalobenzenes with the sodium salt of ethyl α-cyanoacetate carbanion in DMSO solution proceed exclusively via a nonchain radical mechanism (Scheme II)

Effects of electron acceptors and radical scavengers on nonchain radical nucleophilic substitution reactions

The yields of reaction products from thermal nucleophilic substitution reactions in dimethyl sulfoxide (DMSO) of six o- and p-nitrohalobenzenes with the sodium salt of ethyl [alpha]-cyanoacetate carbanion [Na[sup +][sup [minus]]CH(CN)CO[sub 2]Et] were found to be markedly diminished by addition of small amounts of strong electron acceptors (p-dinitrobenzene, m-dinitrobenzene, and o-dinitrobenzene), but little or no diminished effects on the yields of reaction products were observed by addition of radical scavengers (such as galvinoxyl, nitroxyl, etc.). The results are consistent with the conclusion that these reactions proceed via a nonchain radical nucleophilic substitution mechanism. 28 refs., 3 tabs.

Homolytic bond dissociation energies of the carbon–halogen bonds in the benzyl halide radical anion intermediates formed in radical nucleophilic substitution reactions

A simple method has been devised for estimating the homolytic bond dissociation energies (Ebd) for cleavage of the C–X bonds in the radical anion intermediates formed in radical nucleophilic substitution reactions of benzyl chloride, benzyl bromide, and m- and p-substituted benzyl bromides. The method consists of combining values for: (a) the Ebd of the C–X bond in PhCH2X; (b) the redox potential of PhCH2X; and (c) the redox potential of the ionic fragment (X––). Methods of obtaining these quantities are presented. The estimates indicate: (a) that the C–Cl bond in the PhCH2Cl˙– radical anion is thermodynamically unstable by about 6.5 kcal mor–1 toward cleavage to the PhCH2˙ radical and Cl– ion; and (b) that the C–Br bond in the PhCH2Br˙– radical anion is endoenergetic toward a comparable cleavage by only about 3 kcal mol–1. On the other hand, the bond dissociation energies of the C–X bonds in these radical anions estimated for the cleavage to form a PhCH2– ions and X˙ atoms are not much less than those for the corresponding homolytic cleavage in the neutral parent benzyl halides. These thermodynamic estimates are consistent with various kinetic and EPR experimental results which reveal that cleavage of the C–X bonds in benzyl chloride and bromide is concerted with the addition of an electron.

ChemInform Abstract: Aromatic Radical Nucleophilic Substitution Reactions Initiated by Sodium Amalgam in Liquid Ammonia.

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.

Aromatic radical nucleophilic substitution reactions initiated by sodium amalgam in liquid ammonia

Aromatic radical nucleophilic substitution reactions initiated by sodium amalgam in liquid ammonia

Arylation of heterocyclic ketene aminals with 2,4-dinitrohalobenzenes by a radical nucleophilic substitution mechanism

The anions of heterocyclic ketene aminals reacted with 2,4-dinitrohalobenzenes to give arylated products by a radical nucleophilic substitution mechanism. The SRN1 mechanism was confirmed by EPR spectroscopy, EPR spin trapping, and by depression of the reaction rate by the addition of an inhibitor.

Kinetics and mechanism of the reactions of o- and p-nitrohalobeszenes with the sodium salt of ethyl cyanoacetate carbanion: a non-chain radical nucleophilic substitution mechanism

The nucleophilic substitution reactions of o-nitroehlorobenzene (1a), o-nitrobromobenzene (lb), p-nitrofluorobenzene (1c), p-nitrochlorobenzene (1d), p-nitrobromobenzene (1e), and p-nitroiodobenzene (1f) with the sodium salt of ethyl cyanoaceaate carbanion (2) in DMSO all gave the corresponding substitution producss in almost quantitative yields. With the exception of the reaction of 1c with 2, the ESR spectra for the corresponding reactive intermediates, the radical anions of nitrophenyl halides were recorded. The relative intensity of ESR absorption versus time curves at various temperatures for the o-nitrochlorobenzene radical anion (3a), p-nitrochlorobenzene radical anion(3d), and p-nitrobromobenzene radical anion (3e) formed in the reactions of 1a, 1d, and 1e with 2 respectively in DMSO were measured by means of an ESR F/F lock technique. The kinetic curves obtained are consistent with the successive pseudo first-order reaction, and the rate constanss for the single electron transfer reactions of 1a, 1d, and 1e with 2 respectively and for the dissociation reactions of 3a, 3d, and 3e and the corresponding activaiion parameters were calculated. The results provide conclusive evidence that the thermal reactions of o- and p-nitrohalobenzeses (with the possible exception of 1c) with 2 proceed via a non-chann radical nucleophilic substitution mechanism.

Radical-nucleophilic substitution (S RN1) reactions. Part 6. N-anions of diazoles in S RN1 and oxidative additions

The anions of imidazole, benzimidazole, 5(6)-nitrobenzimidazole, and 5(and 6)-nitro-1H-and -2H-indazoles have been shown to undergo oxidative addition to the anion of 2-nitropropane (using potassium ferricyanide and sodium persulphate), and SRN1 reactions with Me2C(X)NO2(X = Cl, Br, and NO2) to yield the corresponding 1-(1-methyl-1-nitroethyl) derivatives. The anions of 5(6)-nitrobenzimidazole and 5(6)-nitro-1H- and -2H-indazoles underwent reaction with p-nitrobenzyl chloride by a SRN1 and/or SN2 mechanism to yield the corresponding 1-(p-nitrobenzyl) derivatives. The ambident anions of 5- and 6-nitrobenzimidazole, 5-nitro-1H- and -2H-indazoles, and 6-nitro-1H- and -2H-indazoles gave ca. 50 : 50 mixtures of the N-1 alkylation products resulting from respective pairs of ambident anions. The 1-(1-methyl-1-nitroethyl) derivatives of benzimidazole and 5- and 6-nitro-1H-indazole underwent further substitution of the aliphatic nitro group with the respective diazole to yield 2,2-di(benzimidazol-1-yl)-, 2,2-di[5(and 6)-nitro-1H-indazol-1-yl]-propanes.

ChemInform Abstract: Radical‐Nucleophilic Substitution (SRN1) Reactions. Part 5. Anions of Nitroimidazoles in SRN1 and Oxidative Addition Reactions

ChemInformVolume 19, Issue 14 Heterocyclic Compounds ChemInform Abstract: Radical-Nucleophilic Substitution (SRN1) Reactions. Part 5. Anions of Nitroimidazoles in SRN1 and Oxidative Addition Reactions A. T. O. M. ADEBAYO, A. T. O. M. ADEBAYO Dep. Chem., Univ. Technol., Loughborough, Leicestershire LE11 3TU, UKSearch for more papers by this authorW. R. BOWMAN, W. R. BOWMAN Dep. Chem., Univ. Technol., Loughborough, Leicestershire LE11 3TU, UKSearch for more papers by this authorW. G. SALT, W. G. SALT Dep. Chem., Univ. Technol., Loughborough, Leicestershire LE11 3TU, UKSearch for more papers by this author A. T. O. M. ADEBAYO, A. T. O. M. ADEBAYO Dep. Chem., Univ. Technol., Loughborough, Leicestershire LE11 3TU, UKSearch for more papers by this authorW. R. BOWMAN, W. R. BOWMAN Dep. Chem., Univ. Technol., Loughborough, Leicestershire LE11 3TU, UKSearch for more papers by this authorW. G. SALT, W. G. SALT Dep. Chem., Univ. Technol., Loughborough, Leicestershire LE11 3TU, UKSearch for more papers by this author First published: April 5, 1988 https://doi.org/10.1002/chin.198814191Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume19, Issue14April 5, 1988 RelatedInformation

Radical-nucleophilic (S RN1) reactions: electron spin resonance studies of electron-capture processes. Part 5. p-Nitrobenzyl and p-nitrocumyl systems

Electron spin resonance spectroscopy has been used to probe two of the steps postulated for the radical-nucleophilic substitution (SRN1) mechanism for p-nitrobenzyl and p-nitrocumyl systems. These two steps are electron-capture by p-nitrobenzyl and p-nitrocumyl derivatives to form radical-anions and their dissociation to yield radicals and anions [equations (1) and (2) in Scheme 1]. A range of radical-anions (p-NO2C6H4CH2X)–˙, with X = I, Br, Cl, and SCN and (p-NO2C6H4CMe2X)–˙, with X = Br and NO2 have been unambiguously identified by e.s.r. spectroscopy and shown to be infinitely long-lived at low temperature. Our results indicate that the p-nitrobenzyl radical-anions do not dissociate to give p-nitrobenzyl radicals at the temperatures used (77 K to ca. 160 K). However, dissociation of the p-nitrocumyl radical-anions (p-NO2C6H4CMe2X)–˙, with X = Br and NO2, to p-nitrocumyl radicals (p-NO2C6H4ĊMe2) and bromide and nitrite anions respectively was clearly observed. The results are compared with those obtained for solution SRN1 reactions for which these radical-anions and radicals are postulated as intermediates.