Iminyl Radicals Research Articles

Gas-phase cyclisation reactions of 1-(2-arylthiophenyl)alkaniminyl and 2-(aryliminomethyl)thiophenoxyl radicals

Flash vacuum pyrolysis (FVP) of the oxime ethers 12–14 and of the sulfides 18–20 at 650 °C (10−2–10−3 Torr) gave products derived from the corresponding iminyl and thiophenoxyl radicals. In all cases, benz[d]isothiazoles (e.g., 26) are formed as major products viaSHi mechanisms though the yields are greatest with the iminyl precursors. Alternative pathways observed from the thiophenoxyls in specific cases include the formation of the anilinobenzothiophene 36 and of dibenzothiophene 23, via an SHi process and a spirodienyl rearrangement, respectively. There is no evidence for significant interconversion of the iminyl and thiophenoxyl species.

ChemInform Abstract: Photolytic and Radical Induced Decompositions of O-Alkyl Aldoxime Ethers.

Direct photolytic and radical induced homolyses of O-alkyl arylaldoxime ethers (ArCHNOR) were studied by EPR spectroscopy and by end product analyses. Initiating radicals (X˙), including t-BuO˙, t-BuS˙, alkyl and Me3Sn˙, added rapidly to the CN double bond to give adduct oxyaminyl radicals (ArCHXN˙OR) that could be observed and characterised by EPR spectroscopy. For O-alkyl arylaldoxime ethers containing H-atoms attached to the carbon adjacent to the ether oxygen (OR = OCHR12), t-BuO˙ radicals also abstracted this hydrogen to yield oxyalkyl radicals that underwent rapid β-scission to afford iminyl radicals (ArCHN˙) and an aldehyde or ketone (R12CO). As judged by the relative importance of ROH and ArCN amongst the products, abstraction of the iminyl hydrogen atom also took place to yield oximidoyl radicals (ArC˙NOR), although this could not be confirmed by EPR spectroscopic observation of these radicals. Thus, homolysis induced by t-BuO˙ radicals took place comparatively unselectively. Addition of the t-BuO˙ radical to the CN double bond of oxime ethers was very fast, the rate constant being comparable to that for addition of the same radical to nitrones. Direct and photosensitised UV photolysis of O-alkyl arylaldoxime ethers gave alkoxyl and aryliminyl radicals in very low yields. Although traces of 2-methyltetrahydrofuran were detected from cyclisation of the pent-4-enyloxyl radical generated by direct photolysis of O-pent-4-enyl benzaldoxime, yields were too low for preparative purposes.

Radical cyclisation onto nitriles

Iminyl radicals, generated by 5- exo cyclisation of alkyl, vinyl and aryl C-centred radicals onto nitriles, undergo β-scission (nitrile translocation), reduction or tandem cyclisation onto alkenes depending on the nature of the α-substituent. 5- exo Cyclisations of aryl radicals onto nitriles undergo nitrile translocation when the α-substituent is CN, CO 2R, SO 2Ph or CONMe 2. The rate of translocation is faster than 5- or 6- exo cyclisation onto alkenes or 1,5-hydrogen abstraction of allylic hydrogens. When the α-substituents are alkyl, the intermediate iminyl radicals do not undergo nitrile translocation.

On the Regioselectivity of Imidoyl Radical Cyclisations

The previously reported tandem cyclisation of N-aryl α-(2-cyanophenyl)sulfanyl imidoyl radicals affords one quinoxaline derivative arising from exclusive 1,6-cyclisation of the final iminyl radical onto the N-aryl ring. When the imidoyl radicals are generated by addition of photolytically generated (2-cyanophenyl)sulfanyl radicals to isocyanides, the reaction also gives small amounts of a by-product that is formed by an analogous route and whose X-ray crystallographic data are reported here. The formation of this product entails a rare ortho-selective photo-Fries rearrangement of the starting disulfide, followed by addition to the isocyanide and regioselective 1,5-cyclisation of the resulting imidoyl onto only one of the two available radical acceptors, i.e. the cyano group and the sulfide moiety. Semiempirical MNDO-d calculations were performed in order to throw some light on the factors affecting these competitive cyclisations.

Exploitation of aldoxime esters as radical precursors in preparative and EPR spectroscopic roles

Photolyses of aldoxime esters, containing a considerable range of alkyl groups, lead to cleavage of their N–O bonds and formation of aryliminyl and alkyl radicals. The process was found to be favoured by 4-methoxyacetophenone as a photosensitiser and by methoxy substituents in the aryl rings. 4-Nitro- and pentafluoro-substitutions of the aryl rings were, on the other hand, deleterious. The intermediate iminyl radicals, together with primary, secondary and tertiary alkyl radicals were characterised by 9 GHz EPR spectroscopy. Cyclopropyl, CF3, and CCl3 radicals were probably also formed, but were too reactive for direct EPR spectroscopic detection. Photosensitised reaction of benzophenone oxime O-nonanoyl ester produced the diphenylmethaniminoxyl, as well as the expected n-octyl and iminyl radicals. This indicated that O–C bond scission accompanied O–N scission for this ketoxime ester. At higher temperatures the C-centred radicals added to the starting oxime esters to produce alkoxyaminyl radicals that were also spectroscopically detected in some cases. No evidence for abstraction of the iminyl hydrogen by tert-butoxyl radicals was obtained. Instead, the t-BuO˙ radicals added to the CN double bonds of the oxime esters. Similarly, chlorine abstraction from alkylbenzohydroximoyl chlorides by trimethyltin radicals did not take place. Preparative scale experiments with oxime esters containing suitably unsaturated alkyl groups showed that good yields of cyclised products could be obtained in the presence of the photosensitiser. This process constitutes a general method by which carboxylic acids or acid chlorides can be converted into alkyl radicals and hence to cyclised derivatives. p

Photolytic and radical induced decompositions of O-alkyl aldoxime ethers

Direct photolytic and radical induced homolyses of O-alkyl arylaldoxime ethers (ArCHNOR) were studied by EPR spectroscopy and by end product analyses. Initiating radicals (X˙), including t-BuO˙, t-BuS˙, alkyl and Me3Sn˙, added rapidly to the CN double bond to give adduct oxyaminyl radicals (ArCHXN˙OR) that could be observed and characterised by EPR spectroscopy. For O-alkyl arylaldoxime ethers containing H-atoms attached to the carbon adjacent to the ether oxygen (OR = OCHR12), t-BuO˙ radicals also abstracted this hydrogen to yield oxyalkyl radicals that underwent rapid β-scission to afford iminyl radicals (ArCHN˙) and an aldehyde or ketone (R12CO). As judged by the relative importance of ROH and ArCN amongst the products, abstraction of the iminyl hydrogen atom also took place to yield oximidoyl radicals (ArC˙NOR), although this could not be confirmed by EPR spectroscopic observation of these radicals. Thus, homolysis induced by t-BuO˙ radicals took place comparatively unselectively. Addition of the t-BuO˙ radical to the CN double bond of oxime ethers was very fast, the rate constant being comparable to that for addition of the same radical to nitrones. Direct and photosensitised UV photolysis of O-alkyl arylaldoxime ethers gave alkoxyl and aryliminyl radicals in very low yields. Although traces of 2-methyltetrahydrofuran were detected from cyclisation of the pent-4-enyloxyl radical generated by direct photolysis of O-pent-4-enyl benzaldoxime, yields were too low for preparative purposes.

Tin-Mediated Free-Radical Cyclization of β-Allenylbenzoyloximes

A set of allene-tethered benzoyloximes (5) has been treated with nBu3SnH. Depending on their substitution pattern, a wide range of compounds has been obtained. If the stannyl radical adds on the allene, the C-centred radical thus formed undergoes either a 5-exo ring closure to give the cyclopentene derivatives 7 or a 6-endo ring closure onto the N atom to give the dihydropyridines 8. If the stannyl radical adds on the benzoyl moiety, an iminyl radical is formed which leads to the 3H-pyrroles 9 and the alkylidene-pyrrolines 10. Steric effects as well as polar effects are the factors governing the reaction course.

ChemInform Abstract: A New Method for the Generation and Cyclization of Iminyl Radicals via the Hudson Reaction.

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.

Generation and Capture of Iminyl Radicals from Ketoxime Xanthates

Generation and Capture of Iminyl Radicals from Ketoxime Xanthates

ChemInform Abstract: A New Method for the Generation and Capture of Iminyl Radicals.

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.

Photolysis reaction mechanism of dibenzophenoneoxime hexamethylenediurethane, a new type of photobase generator

The photochemical and photophysical phenomena of dibenzophenoneoxime hexamethylenediurethane have been investigated with laser flash photolysis to understand its participating mechanism in polymer curing reactions. Owing to the extremely short lifetimes of the first excited singlet (22 ps) and triplet (10 ns) (n, π *) states, that the molecules undergo, with a small quantum efficiency of 10 −4, decarboxylation at the lowest triplet state with the rate constant of 10 6 s −1, forming dehydrogenated iminyl and aminyl radicals. Abstracting a hydrogen atom in the time scale of 270 μs, the iminyl radical converts mainly into diphenyl-1-imine which, with being irradiated, dehydrogenates and dimerizes to yield benzophenone azine. Meanwhile, the aminyl radical abstracts H to generate benzophenoneoxime-urethanyl hexamethyleneamine, which, as a photobase, raises solution pH.

A new method for the generation and cyclization of iminyl radicals via the Hudson reaction.

[formula: see text] A mild new synthetic procedure has been developed for in situ generation and cyclization of iminyl radicals onto pendant alkenes, followed by functionalization of the resulting carbon radical by one of a variety of trapping reagents. The key process in the method involves production of the iminyl radical via treatment of an aldoxime or ketoxime with readily available 2,6-dimethylbenzenesulfinyl chloride at -50 degrees C to room temperature (Hudson reaction).

A new method for the generation and capture of iminylradicals

Iminyl radicals can be generated from ketoxime esters and captured by an internal olefin; the sequencemay be terminated in a variety of ways depending on the nature of the ensuing carbon radical and the added external trap.

The Cp(2)TiPh-Mediated Reductive Radical Cyclization of Cyanoketones and Related Reactions. Efficient Trapping of Ketyl Radicals by Cp(2)TiPh-Coordinated Polar Multiple Bonds.

The reductive radical cyclization of cyanoketones was achieved using Cp(2)TiPh. The Ti(III) reagent was prepared by the sequential addition of i-PrMgCl and PhMgBr to commercial Cp(2)TiCl(2) in this order and used effectively without isolation. The cyclization of the gamma- and delta-cyanoketones was performed in toluene at ambient temperature for several hours to give alpha-hydroxycyclopentanones and hexanones in moderate to good yields, respectively. The titanium reagent independently coordinates to both the carbonyl and cyano termini. As a result of lowering the LUMO of the cyano group upon coordination of the Ti(III) species, the irreversible cyclization successfully proceeds without formation of the unstable iminyl radical intermediate. The ester group can also be activated by the coordination of Cp(2)TiPh, and aromatic ketones with an ester group at the gamma position are cyclized to give the corresponding alpha-hydroxyketones.

Cyclizations in the homolytic reactions of unsaturated nitriles withtert-butylmercury halides in the presence of proton donors

Cyclizations are observed in the homolytic reactions of t-BuHgI with CH2CHCH2YCH2CN [Y = CH2, O, CMe2, C(CO2Et)2, NCH2CN] and CH2CHCH2CH2YCH2CN [Y = CH2, O, C(CO2Et)2] in Me2SO in the presence of hydriodic acid. Only with Y = C(CO2Et)2 does the adduct radical, t-BuCH2ĊHCH2YCH2CN, undergo facile 5-exo cyclization in the absence of a proton donor. The other 5-exo and all 6-exo cyclizations require substrate protonation to yield t-BuCH2ĊH(CH2)nYCH2CNH+ (n = 1, 2), which cyclizes readily to the iminium radical cation followed by electron transfer with I− or t-BuHgI2− to form the imine as a precursor to the cyclopentanone or cyclohexanone upon hydrolysis. For CH2CHCH2C(CO2Et)2CH2CN the formation of the cyclopentanone is dramatically promoted by NH4I in the dark in the absence of any other acid. In this case, where cyclization of the adduct radical occurs readily without substrate activation, protonation of the cyclized iminyl radical allows the electron transfer with I− or t-BuHgI2− to occur with regeneration of t-Buċ. A similar effect is observed with CH2CHCH2C(CO2Et)2CH2N3 where only a slow reaction is observed upon photolysis with t-BuHgI in the absence of NH4I, although apparently cyclization of t-BuCH2ĊHCH2C(CO2Et)2CH2N3 (with loss of N2) occurs readily. In the presence of NH4I the cyclized aminyl radical can be protonated and the resulting amine radical cation readily reduced by I− or t-BuHgI2− to continue a chain process. With the thioesters CH2CHCH2YCH2C(O)SPh [Y = O, CH2, CMe2, C(CO2Et)2], significant cyclization upon photolysis with t-BuHgX occurred only for Y = C(CO2Et)2. © 1998 John Wiley & Sons, Ltd.

Cyclizations in the homolytic reactions of unsaturated nitriles with tert‐butylmercury halides in the presence of proton donors

Cyclizations are observed in the homolytic reactions of t-BuHgI with CH2CHCH2YCH2CN [Y = CH2, O, CMe2, C(CO2Et)2, NCH2CN] and CH2CHCH2CH2YCH2CN [Y = CH2, O, C(CO2Et)2] in Me2SO in the presence of hydriodic acid. Only with Y = C(CO2Et)2 does the adduct radical, t-BuCH2ĊHCH2YCH2CN, undergo facile 5-exo cyclization in the absence of a proton donor. The other 5-exo and all 6-exo cyclizations require substrate protonation to yield t-BuCH2ĊH(CH2)nYCH2CNH+ (n = 1, 2), which cyclizes readily to the iminium radical cation followed by electron transfer with I− or t-BuHgI2− to form the imine as a precursor to the cyclopentanone or cyclohexanone upon hydrolysis. For CH2CHCH2C(CO2Et)2CH2CN the formation of the cyclopentanone is dramatically promoted by NH4I in the dark in the absence of any other acid. In this case, where cyclization of the adduct radical occurs readily without substrate activation, protonation of the cyclized iminyl radical allows the electron transfer with I− or t-BuHgI2− to occur with regeneration of t-Buċ. A similar effect is observed with CH2CHCH2C(CO2Et)2CH2N3 where only a slow reaction is observed upon photolysis with t-BuHgI in the absence of NH4I, although apparently cyclization of t-BuCH2ĊHCH2C(CO2Et)2CH2N3 (with loss of N2) occurs readily. In the presence of NH4I the cyclized aminyl radical can be protonated and the resulting amine radical cation readily reduced by I− or t-BuHgI2− to continue a chain process. With the thioesters CH2CHCH2YCH2C(O)SPh [Y = O, CH2, CMe2, C(CO2Et)2], significant cyclization upon photolysis with t-BuHgX occurred only for Y = C(CO2Et)2. © 1998 John Wiley & Sons, Ltd.

Radical annulations with nitriles: Novel cascade reactions of cyano-substituted alkyl and sulfanyl radicals with isonitriles

New radical annulation reactions are described involving addition of cyano-substituted alkyl and sulfanyl radicals to aromatic isonitriles. The tandem cyclisation of the resulting imidoyl radicals onto the cyano group affords cyclopenta- and thienoquinoxalines, respectively. The intervention of the isonitriles in the aromatisation process of the cyclohexadienyl radicals is discussed, as well as the regiochemistry of the cyclisation of the iminyl radicals obtained by addition of the imidoyls to the nitrile moiety. The hypothesis of an exclusive 6-membered ring closure onto the aromatic ring is also supported by the results of semiempirical AM1 calculations.

Novel [3+2] radical annulations of cyano-substituted aryl radicals with alkynes

Abstract New radical annulation reactions are described involving addition of ortho -cyano-substituted aryl radicals to alkynes. Addition of the aryl radical to the CC triple bond gives rise to a vinyl radical, whose cyclisation onto the carbon atom of the nitrile moiety produces an iminyl radical. The final reaction products derive from the iminyl by hydrogen abstraction — followed by hydrolysis — dimerisation, or cyclisation onto another aromatic ring. In the last case, new nitrogen heterocycles are formed through a novel application of the radical addition, tandem cyclisation strategy. New radical annulations are described involving addition of ortho -cyano aryl radicals to alkynes. The final iminyl radical, obtained by cyclisation of the resulting vinyl radical onto the nitrile triple bond, gives the reaction products through hydrogen abstraction, dimerisation, or cyclisation onto another aromatic ring.

Cp2TiPh-coordinated cyano and ester groups as efficient ketyl radical acceptors in the reductive radical cyclization of γ- and δ-cyano ketones and δ-keto esters

Cp2TiPh promotes the reductive radical cyclization of γ- and δ-cyano ketones and δ-keto esters to give α-hydroxycycloalkanones in moderate to good yields; the titanium reagent coordinates to both the ketone and the cyano or ester terminus, the LUMO of the cyano or ester group is thus lowered, and cyclization proceeds irreversibly without formation of the unstable iminyl or alkoxy radical intermediates.

Gas-phase cyclisation reactions of 1-(2-arylaminophenyl)alkaniminyl radicals

Flash vacuum pyrolysis (FVP) of the oxime ethers 9–11 at 650 °C (10–2–10–3 Torr) gives products such as the nitrile 17, carbazoles 19 and 20 and acridines 18 and 21 derived from the corresponding iminyl radicals 13–15. The mechanism proposed for the formation of the acridines involves a key hydrogen abstraction by the iminyl of the adjacent N–H atom. When this route is blocked by an N-methyl group, as in 12, alternative cyclisations ensue, yielding the dihydroquinazoline 26 (via another hydrogen abstraction process) and the benzimidazole 25 (via an iminyl–imidoyl interconversion).