Ground and excited-state electron-transfer reactions of a few (anthracen-9-yl)methanamines: a comparative study

Comparative study of chemical and light induced electron-transfer reactions of some (anthracen-9-yl)methanamines is reported. Ceric ammonium nitrate was used to initiate chemically-induced electron-transfer reactions of anthracenemethanamines. Nitration at the 2-position followed by oxidation was the major pathway observed in the reaction with CAN while electron-transfer mediated C-N bond cleavage followed by dimerization was the major pathway in photochemical reactions.


Introduction
Ceric ammonium nitrate (CAN) is widely employed in organic synthesis.Most of its applications are based on its potential to act as either a single-or two-electron acceptor and low affinity towards oxygen.2][3][4] Reaction of anthracene and its derivatives with CAN has attracted considerable attention. 5,6The radical cation of anthracene arising through single electron-transfer to CAN is an important intermediate in these reactions.Subsequently, both nitration and oxidation products are formed in the reaction between anthracenes and CAN.][9][10][11][12][13][14] The efficiency of such debenzylations is a sensitive function of the nature of the N-substituents. 7Initial single electron transfer to CAN is invoked to account for the debenzylation process.Interestingly, secondary amines are inert towards CAN.Based on these observations, a viable protection/deprotection strategy for secondary amines has emerged: Nbenzylation followed by CAN-mediated debenzylation completes the protection-deprotection sequence.
Recently, we unravelled an interesting single electron-transfer reaction between anthracenemethanamines and electron deficient acetylenes. 15Similar electron-transfer reactions were observed between anthracenemethyl sulfides and electron-deficient acetylenes. 16Single electron-transfer reactions between amines and electron acceptors such as Cu(II) perchlorate are well documented in the literature. 17The reduction potential for Cu(II) to Cu(I) is 0.15 V while that for Ce(IV) to Ce(III) is 1.61 V. So, it is reasonable to assume that CAN can also initiate single electron-transfer mediated reactions with anthracenemethanamines 18 and anthracenemethyl sulfides. 19Furthermore, anthracenemethanamines are benzylamine analogs that are likely to undergo C-N bond cleavage in the presence of CAN as well as reactions characteristic of the anthracene component.
In the present investigation, we examined both CAN-mediated and photochemical transformations of several structurally diverse (anthracen-9-yl)methanamines.These systems are designed to unravel the effect of structure on both chemical electron transfer (CET) and photochemical electron transfer (PET).

Results and Discussion
(Anthracen-9-yl)methanamines 1a-k having diverse steric and electronic environments around the nitrogen atom were accessed through Leukart reactions between 9-anthraldehyde and appropriate secondary amines (Chart 1). 15,35CAN and light induced transformations of 1a-k were examined by product analysis.A general outline of our investigations and findings is provided in Chart 2.

Reaction of (anthracen-9-yl)methanamines with CAN.
Reaction between 9-(N,N-dimethylaminomethyl)anthracene (1a) and CAN was carried out in a (5:1) mixture of acetonitrile and water and under reflux for four hours.Several products arising through a variety of reactions including single electron transfer from nitrogen (2), nitration (3, 4), oxidation (5) and nitration followed by oxidation (6, 7) were formed (Chart 3).To examine the effects of N-substituents in controlling the reaction between anthracenemethanamines and CAN, we repeated the reaction with (anthracen-9-yl)methanamines 1b-k.With 1b-k, we obtained identical products and the product distribution was virtually the same as obtained from 1a.In all reactions, C-N bond cleavage resulting in the formation of 9-anthraldehyde (2) and the corresponding secondary amine was observed as a minor reaction pathway.In reactions between 1a-g and CAN, we could not establish the generation of the corresponding secondary amine components.However, in the reaction of (anthracen-9-yl)methanamines 1h-k having a significant amine component with CAN, corresponding secondary amines 8-11 could be isolated 7 (Chart 4).In contrast to reported reactions between anthracenes and CAN, 5,[36][37][38][39] reaction of anthracenmethanamines with CAN resulted in regioselective nitration at the 2-position leading to products such as 6 and 7, suggesting a posssible role for the 9-methylamino group in controlling orientation in the reaction between anthracenemethanamines and CAN.To test this possibility, we reexamined the reaction between 9-methylanthracene and CAN. 5 In contrast to previous reports, products 3-7 were exclusively generated as with 1a-k indicating an insignificant role for 9-methylamino group in controlling orientation of nitration.This experiment also indicated that the presence of a 9-methylamino substituent, is required for the formation of 9-anthraldehyde (2) through a mechanism unavailable for 9-methylanthracene.In continuation, we reexamined the reaction between anthracene and CAN. 6In this case also, in contrast to earlier reports, products such as 3-7 along with bianthronyl (12) were formed as with 1a-k revealing that even in the absence of a 9-substituent, for anthracenes, nitration at the 2-position is favored.In yet another control experiment, we observed that reaction between anthracene and a nitrating mixture (HNO 3 /H 2 SO 4 ) also gave products such as 3-7 in yields comparable to those obtained in the reaction with CAN.Thus it appears that a common mechanism is operating for these reactions.Single electron transfer from the anthracene component to the nitrating medium is possibly the first step in such reactions.However, in the case of anthracenemethanamines, concomitant electron transfer from the amine component to CAN followed by further transformation also occurs as a minor side reaction.The nature of N-substituents is insignificant in controlling reactivity of (anthracen-9-yl)methanamines towards CAN.
The structure of 7 was assigned on the basis of rigorous analysis of its 13 C NMR spectrum.In the 13 C NMR spectrum of 7, the two carbonyl carbons are not chemical shift equivalent ruling out a 2,6-dinitro substitution pattern.In order to check the intermediacy of 6 in the generation of 7, we treated 6 with excess CAN in a 5:1 mixture of acetonitrile and water.Unchanged 6 was recovered in quantitative amounts even after prolonged exposure to CAN.This experiment convincingly rules out the intermediacy of 6 in the formation of 7 in favor of species such as 13 and 15 respectively (Scheme 1).Oxidation of 13 and 15 to 6 and 7 may follow two distinct mechanisms.In a previous report, Rindone et al. 6 proposed a mechanism involving a 9anthracenoxy radical to account for the generation of anthraquinone in the anthracene-CAN reaction.Similarly, anthraceneoxy radical 19 may be involved in the CAN-mediated oxidation of 1 (Scheme 1).In a control experiment, when a solution of 1 in 5:1 acetonitrile-water mixture was refluxed for four hours, anthraquinone was formed in trace amounts (<2%).Based on this experiment, we conclude that formation of products such as 5, 6 and 7 is mostly by direct oxidation with CAN and, to an insignificant part, by direct oxidation of anthracenemethanamines with molecular oxygen.[42][43] Scheme 1. Reaction between (anthracen-9-yl)methanamines and CAN.
Based on products obtained from the photoreaction, we conclude that the anthracenemethyl radical is involved as an intermediate in the photochemical transformations of (anthracen-9yl)methanamines. 15Products such as 20, 21, 22 and 23 share common parentage of anthracenemethyl radical generated through intramolecular electron-transfer processes. 15,16If this is true, the rate of the photoreaction may depend on the electronic and steric environment around the nitrogen atom of (anthracen-9-yl)methanamines.In electron-transfer reactions, the rate of reaction is primarily decided by two processes viz.forward and back electron transfer.In the case of anthracenemethanamines electron availability on nitrogen and stabilization of incipient radical cation centre on nitrogen are crucial factors in controlling forward and back electron transfer, and hence, overall reaction rates.An attractive proposal is that the electronic and steric environment around nitrogen could control the efficiency of both forward and back electron transfer.In systems where electron availability on nitrogen is high and/or back electron transfer is inefficient, a faster reaction is anticipated.
To analyse the effect of steric and electronic environment around the nitrogen atom on the photoinduced electron-transfer reactions of (anthracen-9-yl)methanamines, we carefully studied the photoreactions of 1b-k by supplying the same conditions as in the reaction of 1a.Upon exhaustive irradiation, 1b-k gave the same products in near-identical yields as in the case of 1a (Chart 4).However, reaction times varied from substrate to substrate.As with the case of CAN mediated reactions, we could not establish the fate of the amine component in the photolysis of the (anthracen-9-yl)methanamines 1a-g presumably due to their loss as volatile fractions.Fortunately, in the irradiation of (anthracen-9-yl)methanamines having significant amine component such as 1h-k, corresponding secondary amines 8-11 were formed in isolable amounts (Chart 4).
Remarkable differences in reaction times were observed with 1a-k.Normally, starting material was totally consumed in 6-7 hours.For 1g and 1j, the reaction was comparatively faster and starting material was totally consumed in two hours.On the other hand, prolonged irradiation (15 hours) was required in the case of 1h.On the basis of electron availability on nitrogen, one would expect lower efficiency for electron transfer in the case of 1h and 1j thanks to efficient delocalization of the nitrogen lone pair of electrons.The effect of electron deficiency is reflected in the slow reaction exhibited by 1h.It may be noted that electron transfer in 1h destroys the aromaticity of the imidazole ring and hence is disfavoured.However, in the case of 1j, it may be noted that a radical cation centre on nitrogen once generated is stabilized by resonance and hence back electron transfer in this case is not exigent.Similarly, suppression of back electron transfer in 1g having a morpholine component may account for fast photochemical reaction exhibited by it.Transannular electron hopping between ring oxygen and radical cation centre on nitrogen is a distinct possibility here.In other words, anthracenemethanamines where back electron transfer is suppressed are the ones that react faster.Notably, the steric environment around nitrogen appears insignificant in controlling the reaction rates.

Conclusions
Based on experimental results, it may be concluded that anthracenemethanamines exhibit dual reactivity towards CAN in the ground state: 1) intermolecular electron-transfer reactions from nitrogen to CAN (minor) and 2) nitration and oxidation like any other anthracene (major).Single electron transfer from anthracene to CAN is a distinct possibility here.For anthracenemethanamines, at lower concentrations, intramolecular electron transfer predominates in the excited state.Anthracenemethyl radical derived products dominate in the excited state reactions.9-Anthraldehyde is a common product in CAN-mediated and light-induced reactions.Nature of electron transfer depends on reaction conditions.In the reaction between anthracenemethanamines and CAN, intermolecular single electron-transfer pathway is operating.On the other hand, under the influence of light, for anthracenementhanamines, intramolecular electron-transfer pathway is operating.

Experimental Section
General.All reactions were carried out using oven-dried glasswares.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.Progress of the reaction and chromatographic separations were monitored by dried and activated silica gel TLC plates (Aluminium sheets coated with silica gel, E. Merck).Visualisation of TLC plates was acquired by exposure to iodine vapours or UV lamp.Separation and purification of compounds were achieved by column chromatography using either silica gel (Spectrochem Chemicals, 60-120 mesh) or neutral alumina (Spectrochem Chemicals).The products were further purified by recrystallization from suitable solvent systems.Eluates from column chromatography were concentrated using Heidolph rotary evaporator.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 NMR spectra were recorded on a 400 MHz 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 electron impact (EI) method using GC-MS (Agilent GC-7890A, Mass-5975C) and fast atom bombardment (FAB) using JMS 600 JEOL mass spectrometer.Here we give only the spectral and analytical data for novel compounds; the corresponding reference is cited for known compounds.
General procedure for the reaction of (anthracen-9-yl)methanamines with CAN.Ceric ammonium nitrate (8.04 mmol) and (anthracen-9-yl)methanamines (1a-k, 3.80 mmol) were added to a mixture (5:1) of MeCN and H 2 O (15 mL) and the mixture and was refluxed for 4 h.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 (4:1) gave compounds 2, 3 55 and 4. 56  ) and the mixture and was refluxed for 4 h, providing the same conditions as in the above reactions.Work-up of the reaction mixture yielded anthraquinone 5 (<2%) along with unreacted anthracenemethanamines.General procedure for exhaustive irradiation of (anthracen-9-yl)methanamines.

Chart 4 .
Secondary amines isolated from the reactions of 1h-k with CAN.