(Anthracen-9-yl)methyl sulfides as a mechanistic probe for chemical as well as photochemical electron-transfer reactions

We have examined the intermediacy of sulfur-centred radical cations in the one-electron oxidation of (anthracen-9-yl)methyl sulfides. Reaction of (anthracen-9-yl)methyl sulfides with ceric ammonium nitrate (CAN) gave predominantly nitration and oxidation products along with products arising through sulfur-centred radical cations in minor amounts. Upon irradiation, (anthracen-9-yl)methyl sulfides underwent efficient intramolecular single electron transfer leading to a variety of products arising through the intermediacy of sulfur-centred radical cations.


Introduction
Electron-transfer reactions in solution have been thoroughly investigated in chemical reaction dynamics and major progress has been made in the field of the dependence of electron-transfer rates on the free energy of reaction, on donor-acceptor distances as well as on the static properties of the solvents. 1,2Organic sulfides undergo fast one-electron oxidation reactions, owing to their relatively low ionization potentials.][5][6][7][8][9][10][11] One of the most frequently used reagents for the oxidative generation of radicals is the strong one-electron oxidant cerium(IV) ammonium nitrate (CAN).CAN has been widely used in organic reactions which include oxidation, [12][13][14][15][16] oxidative addition, [17][18][19][20][21] photooxidation, 22 nitration, [23][24][25] deprotection, 26,27 graft polymerization, 28,29 etc. Intermediates formed in these reactions may undergo oxidative fragmentation, 30,31 rearrangement, [32][33][34] or C-H, C-C and C-S bond [35][36][37][38] cleavages.Organic sulfides can be oxidized with catalytic amounts of Ce(IV) salts rapidly and selectively to sulfoxides. 39,40nthracene undergoes oxidation with cerium(IV) ammonium nitrate to form the anthracene radical cation which undergoes nitration followed by O-N fragmentation and dimerization to give 9,10-anthraquinone, bianthrone etc. 41 There are also reports on the radical oxidation and addition reactions of some anthracene derivatives with dimethyl malonate in the presence of CAN. 42,43In the presence of acetic acid and polyethylene glycol, anthracene reacted with CAN and sodium bromate to give 1-nitro-9,10-anthracenedione. 442][53][54] Organic sulfides undergo fast one-electron oxidation reactions because of their relatively low ionization potentials.These sulfide radical cations decay through competitive pathways involving deprotonation at C α -H bond, C-S fragmentation, oxidation, aromatic substitution and dimerization by photoinduced electron-transfer reaction. 55,56(Anthracen-9yl)methyl sulfides with in-built sulfide and arene units are potent candidates for intramolecular electron-transfer reactions leading to intramolecular radical anion/radical cation pairs.In the present study, we examined the reaction of several (anthracen-9-yl)methyl sulfides with CAN in acetonitrile-water and compared these results with photochemical reactions of (anthracen-9yl)methyl sulfides.

Results and Discussion
Anthracenemethyl sulfides are conveniently synthesized via a one-pot reaction of 9anthracenemethanol, thiourea and the corresponding alkyl halide and also by base promoted onepot reductive coupling of tosylhydrazones with thiols. 57,58For the present investigation, we selected six (anthracen-9-yl)methyl sulfides 1a-f (Chart 1) having different steric and electronic environments around the sulfur atom.

CAN-mediated transformations
When a 1:1 mixture of CAN and (anthracen-9-yl)methyl sulfides 1a-f in 5:1 acetonitrile-water mixture was refluxed for three hours, a variety of products were formed (Scheme 1).Compounds 6 and 7 were formed in major amounts whereas compounds 2-5, 8 and 9 were obtained in low yields.
Generation of products 2-9 is explicable on the basis of two distinct reaction pathways.Disulfides 2 and 9-anthracenecarboxaldehyde (3) are generated by sulfur-to-CAN single electron transfer followed by further transformations as detailed in Scheme 2. On the other hand, nitration and oxidation products such as 4-9 are formed by the reaction of CAN with the anthracene component in 1a-f.[44][59][60][61] Interestingly, formation of 7 and 8 in the CAN-mediated transformation of anthracene and its derivatives has not been reported earlier.A logical conclusion here is that the 9-(2-alkylthiomethyl) substituent plays a persuasive role in the generation of 7 and 8.In order to test this hypothesis, we reexamined the reaction of 9methylanthracene with CAN under identical conditions.Products such as 4-8 were generated in comparable yields in these reactions ruling out any significant role for the 9-(2-alkylthiomethyl) substituent in the generation of 7 and 8.In order to verify the involvement of the 9-substituent in the formation of 7 and 8, we repeated the reaction of anthracene with CAN under identical conditions.In contrast to previous reports, products such as 7 and 8 were formed in substantial amounts in this reaction as well.These results indicated that reactivity of (anthracen-9-yl)methyl sulfides is similar to that of other anthracenes under the conditions employed by us.A major difference here is the concomitant sulfur-to-CAN single electron transfer that takes place as a minor competing pathway for (anthracen-9-yl)methyl sulfides.The nature of the S-substituent does not play a significant role in the reaction of (anthracen-9-yl)methyl sulfides with CAN.Scheme 3.All reaction products for the photochemical reactions of (anthracen-9-yl)methyl sulfides 1a-f.
Mechanism for the photochemical reaction of (anthracen-9-yl)methyl sulfides 1a-f can be explained on the basis of intramolecular one-electron transfer which takes place in (anthracen-9yl)methyl sulfides in the excited state to form intramolecular sulfide radical cation-anthracene radical anion pair 27.This leads to the destabilization and cleavage of a C-S bond to form the anthracenemethyl radical (28) and sulfide radical 29.Sulfide radical (29) undergoes a series of reactions to form products such as alcohols, thiols, thioethers, disulfides, and even trisulfides in some cases.The chemistry of the anthracenemethyl radical ( 28) is well documented. 62,67,73It can be represented as a resonance hybrid of 28(p) and 28(α) forms.Hydrogen atom abstraction by 28 leads to the formation of 9-methylanthracene (12).Lepidopterene ( 14) is formed by the α/p dimerization of 28 followed by intramolecular [4+2] cycloaddition.This is a thermal intramolecular [4+2] cycloaddition, a facile process even at room temperature. 791,2-Bis(9anthracenyl)ethane ( 13) is the α/α dimerization product of 28.Biplanene ( 15) is formed by intramolecular [4+4] cycloaddition of 13 initiated by stray light.Generation of 9-anthraldehyde (3) is explained on the basis of initial intramolecular excited-state electron transfer leading intermediate 27 followed by α-H atom loss and bond reorganization to sulfonium cation 30.Hydrolysis of 30 gives 9-anthraldehyde (3).9,10-Anthraquinone ( 6) is formed through the bond homolysis followed by β-scission of the endoperoxide 31 generated from 1a-f 80 by the reaction with singlet oxygen 81 (Scheme 4).Scheme 4. Proposed mechanistic sequences for the photochemical reactions of (anthracen-9yl)methyl sulfides 1a-f.

Conclusion
We have illustrated the single electron-transfer oxidation reaction of (anthracen-9-yl)methyl sulfides via chemical electron transfer as well as intramolecular excited-state electron-transfer methods.We have established that multiple pathways operate in the CAN-mediated and photochemical transformations of anthracenemethyl sulfides.These include single electrontransfer mediated transformations, C-S bond fragmentation, nitration and oxidation as major pathways.

Experimental Section
General.All reactions were carried out in oven-dried glassware.All experiments used distilled and dried solvents by using standard protocols.All starting materials were purchased from either Sigma-Aldrich or Spectrochem Chemicals and were used without further purification.All the reactions and chromatographic separations were monitored by thin layer chromatography (TLC).Aluminium sheets coated with silica gel (Merck) were used for thin layer chromatography.Separation and purification of compounds was achieved by column chromatography using silica gel (Spectrochem Chemicals, 60-120 mesh).The products were further purified by recrystallization from suitable solvent systems.Melting points are uncorrected and were determined on a Neolab melting point apparatus.Infrared spectra were recorded using Jasco 4100 and ABB Bomem (MB Series) FT-IR spectrometers.The 1 H and 13 C NMR spectra were recorded at 400 MHz on a Bruker Avance III FT-NMR spectrometer with tetramethylsilane (TMS) as internal standard.Chemical shifts (δ) are reported in parts per million (ppm) downfield of TMS.Elemental analysis was performed using Elementar Systeme (Vario EL III).Molecular mass was determined by electrospray ionization (ESI) using GC-MS (Agilent GC-7890A, Mass-5975C) and fast atom bombardment (FAB) using JMS 600 JEOL mass spectrometers.All new compounds were identified on the basis of spectroscopic and analytical data.Relevant references are cited for known compounds.

Synthesis of (anthracen-9-yl)methyl sulfides.
(Anthracen-9-yl)methyl sulfides 1a-f were prepared by adaptation of known procedures. 57,58,82,83eneral experimental procedure for the chemical electron-transfer reactions of (anthracen-9-yl)methyl sulfides 1a-f with CAN.To a solution of (anthracen-9-yl)methyl sulfide 1a-f (0.38g,1 equiv.) in MeCN-H 2 O (5:1, 6 mL), CAN (2.1 equiv.) was added and the mixture was refluxed for 3 h.After completion of the reaction, the reaction mixture was poured into H 2 O and extracted with CH 2 Cl 2 .The organic layer was separated, washed with H 2 O and dried over anhydrous Na 2 SO 4 .Solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel.Elution with a mixture of hexane and CH 2 Cl 2 separated twelve products such as compounds 2-9.Compounds 2b-f were obtained by the elution using hexane.Compounds 3-6 were obtained by elution using a mixture of hexane and CH 2 Cl 2 (3:2).Elution using hexane and CH 2 Cl 2 (3:7) yielded 7 and 8. Elution using hexane and CH 2 Cl 2 (1:4) yielded the compound 9.