Competition Between Cα-S and Cα-Cβ Bond Cleavage in β-Hydroxysulfoxides Cation Radicals Generated by Photoinduced Electron Transfer?

DR. ANDREA LAPI (Orcid ID : 0000-0001-9728-8132)

Article type : Special Issue Research Article

SPECIAL ISSUE RESEARCH ARTICLE

Competition Between C -S and C -C Bond Cleavage in β-

α

β

Hydroxysulfoxides Cation Radicals Generated by Photoinduced

Electron Transfer^†

Andrea Lapi* , Claudio D’Alfonso, Tiziana Del Giacco, Osvaldo Lanzalunga,¹^,²

1

, 2

1‡

3, 4

¹.

Dipartimento di Chimica, Universita` degli Studi di Roma “La Sapienza” P.le A. Moro 5, I-00185

2

Rome, Italy, . Istituto per i Sistemi Biologici (ISB-CNR), Sede Secondaria di Roma-Meccanismi di

Reazione, c/o Dipartimento di Chimica, Universita` degli Studi di Roma “La Sapienza”, P.le A. Moro

3

5

, I-00185 Rome, Italy, . Dipartimento di Chimica, Biologia e Biotecnologie, Università di Perugia,

4

Via Elce di Sotto 8, 06123, Perugia, Italy, . Centro di Eccellenza Materiali Innovativi Nanostrutturati

(CEMIN), Università di Perugia, Via Elce di Sotto 8, 06123, Perugia, Italy

†

This article is part of a Special Issue dedicated to celebrating the career of Dr. Edward Clennan

This article has been accepted for publication and undergone full peer review but has not been through

the copyediting, typesetting, pagination and proofreading process, which may lead to differences

between this version and the Version of Record. Please cite this article as doi: 10.1111/PHP.13455

‡

Current address: Department of Public Security, Central Anticrime Directorate of Italian National

Police, Forensic Science Police Service (DAC-SPS), Psychotropic and Narcotic Substances Section,

Rome, Italy

*

Corresponding author e-mail: andrea.lapi@uniroma1.it (Andrea Lapi)

ABSTRACT

A kinetic and product study of the 3-cyano-N-methylquinolinium photoinduced monoelectronic

oxidation of a series of β-hydroxysulfoxides has been carried out to investigate the competition

between C -S and C -C bond cleavage within the corresponding cation radicals. Laser flash

α

β

photolysis experiments unequivocally established the formation of sulfoxide cation radicals showing

•

their absorption band (λ_m_a_x≈ 520 nm) and that of 3-CN-NMQ (λ

≈ 390 nm). Steady-state

max

photolysis experiments suggest that, in contrast to what previously observed for alkyl phenyl sulfoxide

cation radicals that exclusively undergo C -S bond cleavage, the presence of a β-hydroxy group

α

makes, in some cases, the C -C scission competitive. The factors governing this competition seem to

α

β

depend on the relative stability of the fragments formed from the two bond scissions. Substitution of

the β-OH group with -OMe did not dramatically change the reactivity pattern of the cation radicals

thus suggesting that the observed favorable effect of the hydroxy group on the C -C bond cleavage

α

β

mainly resides on its capability to stabilize the carbocation formed upon this scission.

INTRODUCTION

It is a great honor for us for having been invited to contribute to the Special Issue of Photochemistry &

Photobiology dedicated to celebrating the career of Dr. Edward Clennan. Because of Ed’s

fundamental contribution to the photochemistry of sulfur-containing compounds, it is a pleasure to

present here our work concerning the one-electron photooxidation of β-hydroxysulfoxides promoted

by 3-cyano-N-methylquinolinium.

It is well known that electron transfer (ET) processes play a fundamental role in many

biological and organic processes. For this reason, an increasing number of studies have been focused

on the reactivity and the properties of the radical ions, the primary species obtained from these

processes (1,2). Among the classes of organic compounds whose reactivity in ET process have been

the subject of intense investigation, sulfides have attracted a special interest (3-8) since their

monoelectronic oxidation is involved in many biological processes (9), in organic synthesis (10) and

in the initiation of radical polymerization (11). To better elucidate the reaction mechanisms involved

in sulfides oxidation initiated by an ET process, the use of photosensitizers as initiators has been

widely employed particularly in type I (12) sulfide photooxygenation (6,13,14). Despite the large

number of studies on the monoelectronic oxidation of organic sulfides, the same process on their

oxidized form, organic sulfoxides, is much less investigated albeit, in the past decades, the

comprehension of their reactivity and properties has attracted the interest of several research groups

since sulfoxides are involved in many synthetic and biological processes (15-19). The main reason for

the scarce information on the reactivity and properties of sulfoxide cation radicals is due to the fact

that sulfoxides generally exhibit redox potentials 0.5 V higher than those of the corresponding sulfides

(20,21) making them less prone to undergo monoelectronic oxidation. As an example, the redox

potentials of methyl phenyl sulfoxide and thioanisole are 2.01 (21) and 1.47 V (22) (vs SCE)

respectively.

+

•

Previous studies on the reactivity of alkyl aryl sulfoxide cation radicals (ArSOR ) have shown

that the fate of these oxidized species largely depends on the nature of the alkyl substituent R. When R

is a methyl or a primary alkyl group (except the benzyl group), once formed by photosensitized

oxidation, the sulfoxide cation radical undergoes unproductive back electron transfer (BET) (21).

When R is a benzylic, secondary, or tertiary alkyl group, the cation radical undergoes C -S bond

α

+

•

cleavage affording the R carbocation and the phenyl sulfinyl radical ArSO (Scheme 1) (23-25).

<

Scheme 1>

The C -S bond cleavage is a peculiar process characterizing both sulfide and sulfoxide cation

α

radicals (23-34) since fragmentation of cation radicals of other classes of organic compounds often

involves the bonds in β position with respect to the charged center. In a previous study on the

reactivity of aryl sulfide cation radicals bearing a hydroxy group in β position, we showed that the OH

group determines the C -C instead of the C -S bond cleavage (35). The favorable effect of the

α

β

α

hydroxy group on the C -C bond cleavage was proposed to be due to a transition state stabilization by

α

β

a hydrogen bonding between the OH and the solvent (MeCN). In view of the above mentioned higher

redox potential of sulfoxides with respect to sulfides and of the higher stability of the phenyl sulfinyl

•

radical PhSO as compared to the phenylthiyl radical PhS (36), the C -S bond cleavage is very much

α

faster for sulfoxide cation radicals rather than for sulfide ones (24,35), thus competition between C -S

α

and C -C bond cleavage for β-hydroxysulfoxides cation radicals can be foreseen. On these bases we

α

β

now report a kinetic and product study of the fragmentation process of a series of β-hydroxysulfoxide

Chart 1) cation radicals. To better understand the role played by the β-hydroxy group, the

investigation was also extended to two β-methoxysulfoxides (5 and 6).

(

<

Chart 1>

The cation radicals were generated by photosensitized monoelectronic oxidation of the parent

β-hydroxysulfoxides as already reported in previous studies on the reactivity of alkyl aryl sulfoxide

cation radicals (21,23-25). The photosensitizer chosen for this purpose was the 3-cyano-N-

+

-

methylquinolinium perchlorate (3-CN-NMQ ClO , Scheme 2) for the following reasons: i) it is a

4

powerful oxidant in its excited singlet state having a reduction potential of 2.72 V vs SCE in MeCN

1

+

(

37); ii) the [3-CN-NMQ ]* lifetime is sufficiently long (τ = 45 ns ) (37) to efficiently interact with

+

the substrates investigated; iii) the UV absorption maximum of 3-CN-NMQ at ca 330 nm allows a

selective photosensitizer excitation thus avoiding a direct photolysis of the sulfoxides 1-6 which

absorb below 320 nm. Finally, since the photosensitizer is positively charged, upon the ET process a

cation radical/radical couple is formed with a consequent easier separation of the two species (lack of

electrostatic barrier) thus depressing the unproductive BET process.

<

Scheme 2>

MATERIALS AND METHODS

Chemicals and instrumentation

¹H and ¹³C NMR spectra were recorded on a Bruker Avance spectrometer at 300 and 75 MHz

respectively in CD CN or CDCl (Sigma-Aldrich) and using tetramethylsilane as the internal standard.

3

GC-MS analyses were performed on a HP 5890 series II GC equipped with a HP-5 capillary column

30 m × 0.25 mm × 0.25 μm) and coupled with a HP 5972 MSD mass spectrometer. HPLC analyses

(

were performed on an Agilent 1100 chromatograph coupled with an UV-Vis detector (set at 263 nm

wavelength) and equipped with an Alltima C18 column (5μ, 250 mm × 4.6 mm), equilibrated with

MeOH/H O (75/25), with an ascending gradient of MeOH (75− 100%) at a flow rate of 0.7 mL/min.

2

GC analyses were performed on an Agilent series II instrument equipped with a HP-1 column (30 m ×

0

.32 mm × 0.25 μm). Spectrophotometric analyses were carried out on a Varian Cary 300 Bio double

ray spectrophotometer. FT-IR spectra were recorded on a Shimadzu FTIR-8400S infrared

spectrophotometer. Steady state photoreactions were carried out on a Helios Italquartz photoreactor

equipped with four external fluorescence lamps (14 W each) with emission centered at 360 nm and

carried out in jacketed Pyrex tubes thermostated using a water circulation Haake F3 thermostat.

All the solvents used were commercially available at the highest purity. Acetonitrile (spectrometric

grade) was distilled over CaH prior use. THF was refluxed over sodium and then distilled under inert

2

(Ar) atmosphere.

3

-Cyano-N-methylquinolinium perchlorate (38) and 1-phenyl-2-phenylsulfinyl-2-methylpropan-1-ol

(3) were synthesized according to a previously reported procedure (39). 1,2-Diphenyl-2-

phenylsulfinylethanol (4) was synthesized by oxidation of the corresponding sulfide (1,2-diphenyl-2-

phenylsulfanylethanol) (35), with NaIO as described elsewhere (40).

4

Synthesis of 1-phenyl-2-phenylsulfinylethanol (1). A solution of thiophenol (4.4 g, 40 mmol) in

acetone (20 mL) was slowly added in a 500 mL three-necked round bottomed flask containing an Ar

saturated stirred mixture of α-bromoacetophenone (8.0 g, 40 mmol) and anhydrous K CO (6.1 g, 44

2

3

mmol) in acetone (250 mL) at room temperature. The mixture was stirred for 6 h, quenched by

addition of HCl (2 M) until complete carbonate dissolution and extracted with three portions of

diethyl ether (100 mL each). The collected ethereal phases were washed with saturated NaHCO₃,

dried over anhydrous Na SO and concentrated at reduced pressure. Recrystallization from hexane

2

4

afforded pure (> 99 %, GC) 1-phenyl-2-phenylsulfanylethanone (5.1 g, 22.4 mmol, 56 % yield) as a

1

white solid. H NMR (CDCl ) δ (ppm): 7.95-7.93 (m, 2H), 7.48-7.24 (m, 8H), 4.27 (s, 2H), in

3

agreement with that reported in ref. 41. 1-Phenyl-2-phenylsulfanylethanone was then converted to 1-

phenyl-2-phenylsulfanylethanol by reduction with NaBH as reported in ref. 42. 1-Phenyl-2-

4

phenylsulfanylethanol was then converted to the title compound as follows. NaIO (1.3 g, 6.3 mmol)

4

was added to a solution of 1-phenyl-2-phenylsulfanylethanol (1.3 g, 5.7 mmol) in 5:1 EtOH/H O (60

2

mL) and stirred for 24 h at room temperature. The mixture was concentrated under reduced pressure

and extracted with three portions of ethyl acetate (20 mL each). The collected organic phases were

dried over anhydrous Na SO and concentrated under reduced pressure. Column chromatography

2

4

purification (silica gel, hexane/ethyl acetate 1:1) afforded pure (> 99 %, HPLC) 1-phenyl-2-

phenylsulfinylethanol (1.3 g, 93 %) as a white solid. H and ¹³C NMR analysis agreed with those

1

reported in ref. 43. Major diastereomer (ca 60 %): H NMR (CDCl ) δ (ppm): 7.68-7.27 (m, 10H),

3

1

3

5

.27 (d, 1H, J = 10 Hz), 4.16 (s, 1H), 3.33-3.19 (m, 1H). 2.86 (d, 1H, J = 13 Hz). C NMR (CDCl ) δ

3

(ppm): 132.2, 131.9, 130.1, 129.3, 128.8, 128.6, 126.4, 126.2, 124.7, 124.6, 71.7, 69.3.

1

Minor diastereomer (ca 40 %): H NMR (CDCl ) δ (ppm): 7.68-7.27 (m, 10H), 5.42 (d, 1H, J = 10

3

Hz), 4.28 (s, 1H), 3.33-3.19 (m, 1H). 2.98 (dd, 1H, J = 13 Hz, J = 2.5 Hz).

Synthesis of 1-phenyl-2-phenylsulfinylpropan-1-ol (2). The title compound was obtained by

oxidation of the corresponding sulfide 1-phenyl-2-phenylsulfanylpropan-1-ol prepared by reaction of

cis-β-methylstyrene oxide with thiophenol according to ref. 44. The sulfoxidation procedures are the

same as reported above for 1 using 1-phenyl-2-phenylsulfanylpropan-1-ol (1.0 g, 4.1 mmol) and

NaIO (1.0 g, 4.7 mmol) as starting material. After the workup procedure pure (> 99 %, HPLC) 1-

4

1

phenyl-2-phenylsulfinylpropan-1-ol (826 mg, 3.2 mmol, 78 %) was obtained as a white solid. H and

¹³C NMR analysis are in agreement with those reported in ref. 45.

1

H NMR (CD CN) δ (ppm): 7.45-7.05 (m, 10H), 4.70 (dq, 1H, J = 6.45 Hz, J = 2.94 Hz), 3.63 (d, 1H,

3

J = 2.94 Hz), 1.03 (d, 3H, J = 6.45 Hz).

1

3

C NMR (CD CN) δ (ppm): 131.9, 131.8, 131.6, 131.5, 129.5, 129.1, 128.7, 128.4, 126, 125.4, 78.7,

3

6

5.0, 21.6.

Synthesis of [(1-mehoxy-1-phenylpropyl)sulfinyl]benzene (5). To a stirred suspension of NaH (281

mg, 12 mmol) in anhydrous THF (10 mL) 1-phenyl-2-phenylsulfanylpropan-1-ol (1.2 g, 4.9 mmol)

was slowly added under an Ar atmosphere. After 30 min stirring at room temperature CH I (1.7 g, 12

3

mmol) was slowly added and the mixture was then allowed to react overnight. After water addition

(50 mL), the mixture was concentrated at reduced pressure, solubilized in diethyl ether (100 mL),

washed twice with water (50 mL), dried over anhydrous Na SO and concentrated at reduced pressure.

2

4

Column chromatography (silica gel, hexane/ethyl acetate 10:1) afforded pure (> 99 % GC) [(1-

mehoxy-1-phenylpropyl)sulfanyl]benzene (1.2 g, 4.7 mmol, 95 %). The β-methoxysulfide (1.2 g, 4.7

mmol) was then oxidized with NaIO (1.1 g, 5.3 mmol) in ethanol following the same procedure

4

reported above for 2. Pure (> 99%, HPLC) [(1-mehoxy-1-phenylpropyl)sulfinyl]benzene (1.1 g, 3.9

mmol, 83 %) was obtained.

1

Major diastereomer (ca 60%): H NMR (CDCl ) δ (ppm): 7.46-7.04 (m, 10H), 4.42 (m, 1H), 3.58 (s,

3

1

3

H), 3.54 (d, 1H, J = 3.2 Hz), 1.08 (d, 3H, J = 6.6 Hz). C NMR (CDCl ) δ (ppm): 131.1, 130.9,

3

1

30.3, 128.5, 128.1, 125.6, 80.1, 73.7, 58.0, 16.8.

1

Minor diastereomer (ca 40%): H NMR (CDCl ) δ (ppm): 7.46-7.04 (m, 10H), 4.42 (m, 1H), 3.58 (s,

3

H), 3.54 (d, 1H, J = 3.2 Hz), 1.07 (d, 3H, J = 6.6 Hz).

-1

FT-IR: υ (cm ) 1038 (S=O), 1097 (C-O-C), 1130 (C-O-C).

Synthesis of [(1-methoxy-2-methyl-1-phenylpropyl)sulfinyl]benzene (6). To a stirred suspension of

NaH (70 mg, 3 mmol) in anhydrous THF (10 mL) 2-methyl-1-phenyl-2-phenylsulfinylpropan-1-ol (3)

(300 mg, 1.2 mmol) was slowly added under an Ar atmosphere. After 30 min stirring at room

temperature CH I (426 mg, 3 mmol) was slowly added and the mixture was stirred for 3 h. After water

3

addition (20 mL), the mixture was concentrated at reduced pressure, solubilized in chloroform (100

mL), washed twice with water (50 mL), dried over anhydrous Na SO and concentrated at reduced

2

4

pressure. Recrystallization from hexane afforded pure (> 99 %, HPLC) as a white solid (316 mg, 1.1

mol 92 %).

1

H NMR (CDCl ) δ (ppm): 7.64-7.26 (m, 10H), 4.65 (s, 1H), 3.36 (s, 3H), 0.98 (s, 3H), 0.68 (s, 3H).

3

1

3

C NMR (CDCl ) δ (ppm): 137.4, 131.8, 129.3, 129.1, 128.8, 128.7, 127.5, 83.9, 65.1, 58.1, 16.4,

3

1

5.5.

-1

FT-IR: υ (cm ) 1038 (S=O), 1074 (C-O-C), 1095 (C-O-C).

Cyclic Voltammetry

Anodic peak potential values ( ) for 1-6 were obtained by cyclic voltammetry experiments,

conducted with a potentiostat controlled by a programmable function generator (cyclic voltammetry at

00 mV s ⁻¹, 1.5 mm diameter glassy carbon disc anode, 1 cm platinum counter electrode and

2

5

Ag/AgCl (KCl 3M) as reference) in Ar-saturated anhydrous MeCN−Bu NBF (0.1 M) at 25 °C.

4

Sulfoxide concentration was 2 mM.

Fluorescence Quenching

Measurements were carried out at 25 °C on a Shimadzu RF5001PC spectrofluorophotometer. For

1

+

-5

quenching of [3-CN-NMQ ]* by 1-5, a solution of 3-CN-NMQ (1.7 × 10 M) and 1-5 at variable

-2

concentration (from 0 to 1 × 10 M) in argon-saturated acetonitrile was irradiated at 330 nm (3-CN-

+

NMQ absorption maximum) collecting the relative emission intensities at 425 nm (3-CN-NMQ

emission maximum).

Laser Flash Photolysis

Nanosecond laser flash photolysis experiments were carried out with a laser kinetic spectrometer

using the third harmonic (355 nm) of a Q-switched Nd:YAG laser delivering 7 ns pulses. The laser

energy was < 3 mJ per pulse. In all the experiments a 3 mL quartz cell containing a solution of 1-6

-2

+

-

-4

(

1.0 × 10 M), 3-CN-NMQ ClO (0.5 × 10 M), and the cosensitizer toluene (1 M) in N -saturated

4

2

MeCN was flashed at 22 ± 2 °C. The transient spectra were obtained by a point-to-point technique,

monitoring the ΔA values after the laser flash at 5-10 nm intervals, averaging at least 10 decays at

each wavelength. The estimated error for the decay rate constants was ± 10 %.

Photooxidation general procedure

Photooxidation reactions were carried out irradiating (10 or 30 min) an Ar-saturated MeCN (5 mL)

+

-

stirred solution of the sulfoxide (50 μmol) and 3-CN-NMQ ClO (10 μmol) placed in a rubber cap-

4

sealed jacketed pyrex tube thermostated at 25 °C by water circulation. Bibenzyl (10 μmol) was added

as the internal standard. The reaction mixture was analyzed by HPLC, GC, GC-MS and (after solvent

1

evaporation under reduced pressure) H NMR. Blank experiments were carried out under the same

reaction condition reported above but in the absence of photosensitizer.

Product analysis

1

Qualitative analyses were performed by GC-MS and H NMR whereas quantitative product

1

determination was carried out by H NMR, GC and HPLC by comparison with authentic specimens.

Quantitative determination of diphenyl disulfide and phenyl phenylthiosulfonate was exclusively

carried out by HPLC. Benzaldehyde, diphenyl disulfide, benzyl methyl ketone and

diphenylacetaldehyde were commercially available. Phenyl phenylthiosulfonate was prepared as

previously reported (46). 2-Methoxy-1-phenylpropan-1-ol (47,48) and 2-methyl-2-phenylpropanal

1

(

49) were identified by comparison with spectral properties ( H NMR and GC-MS) reported in the

literature.

RESULTS AND DISCUSSION

The sulfoxides investigated in this work contain two (1 and 3) or three (2, 4, 5 and 6) chiral centers.

The following results are thus referred to the stereoisomers mixture for compounds 1-6.

Electrochemical properties

Sulfoxides 1-6 were electrochemically characterized by cyclic voltammetry experiments. The

experiments were carried out on a solution of 1-6 (2 mM) in dry MeCN under inert atmosphere at 25

°

C, using Bu NBF (0.1 M) as support electrolyte, an Ag/AgCl (KCl 3M) reference electrode with a

4 4

-1

0

.5 V s scan rate. For all the sulfoxides investigated an irreversible oxidation process was observed

-1

even at higher scan rates (up to 5 V s ) as described in Fig. 1 for 3 (see Figures S1-S5 for the

voltammograms of 2-6). Because of the irreversibility observed, only the anodic peak potential values

(

) were determined, and their values (vs SCE) are reported in Table 1.

Figure 1<

Table 1<

>

The measured

similar to that measured for methyl phenyl sulfoxide under the same experimental conditions (

.01 V vs SCE) (21). The differences of values for the sulfoxides 1-6 are very likely due to the

values span from 1.77 to 2.04 V for 4 and 1 respectively with the latter very

=

2

ability of the α-alkyl group to stabilize the cation radical in which both the charge and the spin density

are mainly located on the sulfinyl group (21). Accordingly, in 1 the primary alkyl group should have a

stabilizing effect closer to that observed for the methyl group in methyl phenyl sulfoxide whereas for

2

-6 the higher degree of substitution should better stabilize the cation radical thus decreasing the

oxidation potential. Comparing the values of 2-3 with those of the corresponding methyl ethers (5

and 6 respectively), it appears that in both cases the substitution of the hydroxy with a methoxy group

is reflected in a slight decrease of the oxidation potential ( = 0.05 V). This is probably due to the

presence in 2-3 of an intramolecular hydrogen bonding between the hydroxy group and the sulfinyl

oxygen atom which determines a decrease of the electron density on the sulfinyl group thus increasing

1

the oxidation potential. In all cases, the

values reported in Table 1 are largely below the [3-CN-

+

NMQ ]* reduction potential (2.72 V vs SCE in MeCN) (37) thus allowing an exergonic ET process

with all the examined sulfoxides. Accordingly, by applying the Weller equation (50), it results that for

-1

all the sulfoxides ΔG_E_T< -16 kcal mol .

Fluorescence quenching experiments

1

Having established the thermodynamic feasibility of the ET process from sulfoxides 1-6 to [3-CN-

+

NMQ ]*, fluorescence quenching experiments were performed in order to determine the rate

1

+

constants of the interaction of [3-CN-NMQ ]* with the substrates investigated. The measurements

+

-5

were carried out irradiating a deaerated MeCN solution of 3-CN-NMQ (1.7 × 10 M) at its

absorbtion maximum wavelength (λ_m_a_x= 329 nm) and following the decrease of the emission at its

-4

maximum intensity (λ_m_a_x= 425 nm) on increasing the sulfoxide concentration (from 2 × 10 to 0.01

M). According to the Stern-Volmer equation, by plotting the (I /I)-1 vs the sulfoxide concentration,

0

very good linear plots were obtained (Figures S6-S10) from whose slopes the fluorescence quenching

kinetic constants (k ) were obtained (Table 1). For all the sulfoxides examined the rate constants for

q

1

+

10

-1 -1

the [3-CN-NMQ ]* quenching are close to the diffusion limit in MeCN (1.9 × 10 M s ) (51) in

agreement with a photoinduced ET process.

Steady state photolysis: product study

Steady state photolysis experiments were carried out irradiating an Ar saturated MeCN solution (5

-2

+

-

-3

mL) of the sulfoxide (1 × 10 M) and 3-CN-NMQ ClO (2× 10 M) at 25 °C in a photoreactor

4

equipped with four fluorescence lamps with a maximum emission at 360 nm. At this wavelength only

the photosensitizer is excited as confirmed by the total absence of oxidation products observed in

blank experiments where substrate solutions were irradiated in the absence of the photosensitizer. All

1

the reaction products were identified and characterized by H NMR and GC-MS analysis (comparison

1

with authentic specimens and literature data). Product quantitative analysis was performed by H

NMR and GC (products derived from alkyl fragments) and HPLC (sulfur containing products). In all

cases the overall material recovery was satisfactory (> 90%).

>Table 2<

After irradiation of the β-hydroxysulfoxide 1, product analysis did not show the presence of

any reaction product even after prolonging the irradiation time to two hours whereas irradiation of 2

led, after only 10 min, to significant amounts of fragmentation reaction products i.e., benzaldehyde,

benzyl methyl ketone, diphenyl disulfide and phenyl phenylthiosulfonate (entries 1 and 2 in Table 2).

On increasing the irradiation time to 30 min the same reaction products were observed with higher

yields but they were accompanied by other unknown products probably derived from overoxidation.

In Table 2 products and yields for the photosensitized oxidation of the corresponding methyl ether 5

under the same reaction condition are also reported (entries 3 and 4). The products observed are the

same as for 2 with the additional formation of 1-phenyl-2-methoxy-1-propanol and, after the same

irradiation time (10 min), the overall no sulfur-containing product yields for 5 (3.4 %) is slightly

higher than that for 2 (2.6 %).

When the β-hydroxysulfoxide 3 was irradiated under the same reaction condition of 2, beside

the same sulfur containing fragmentation products observed for 2, 2-phenyl-2-methylpropanal was the

exclusive product deriving from the alkyl moiety (entries 5 and 6 in Table 2). As already observed for

2

, also for 3 a prolongation of the irradiation time to 30 min resulted in the formation of the same

reaction products in higher yields but accompanied by unidentified products. A comparison with the

results obtained with 2 shows a significantly increased product yield for the photosensitized oxidation

of 3 with the overall yield, for the fragmentation products deriving from the alkyl moiety, passing

from 2.6 % to 11 % after 10 min irradiation for 2 and 3 respectively. The photooxidation of the

corresponding methyl ether 6 afforded the same fragmentation products observed for 3 but with

slightly higher yields (entries 7 and 8 in Table 2).

A 10 min irradiation of the β-hydroxysulfoxide 4 under the same reaction condition as for 2

and 3, leads to the formation of the fragmentation products (entry 9 in Table 2): benzaldehyde and

diphenylacetaldehyde from the alkyl moiety, diphenyl disulfide and phenyl phenylthiosulfonate from

the sulfur containing one. Comparison between entry 9 with entries 1 and 5 in Table 2, shows that the

photooxidation of 4 is more efficient than those of 2 and 3 with an overall yield for products deriving

from the alkyl moiety of 20 %.

Laser flash photolysis study

To have a deeper insight in both the nature and the reactivity of the reaction intermediates involved in

these processes, a laser flash photolysis (LFP) investigation was carried out. LFP experiments were

carried out in N -saturated MeCN at 22 °C in the presence of 1 M toluene as cosensitizer to minimize

2

the BET process and thus increasing the cation radical yield (52). For all the substrates investigated,

the time resolved absorption spectra show the formation of two transient species absorbing at ca 390

and 520 nm respectively (Fig. 2, for 3 and Figures S11- S15 for 1, 2, 4, 5 and 6). On the basis of the

absorption spectra of aromatic sulfoxide cation radicals reported in the literature (24,21), the

+

•

+•

absorption band at 520 nm can be assigned to 1 -6 whereas the absorption band at 390 nm can be

•

assigned to the 3-CN-NMQ radical (24).

>

Figure 2<

The observed intermediates confirm the occurrence of an ET process, from the sulfoxides to

+

the singlet excited state of 3-CN-NMQ , as the main reaction process (Scheme 2). Interestingly, the

absorbance decay at 520 nm does not follow the same kinetic order for all of the substrates. A clean 1^s^t

+

•

+•

order kinetic profile is only observed for 3 ,4 and 6 (Fig. 2 for 3 and Figures S13 and S15 for 4

nd

+•

st nd

+•

and 6) whereas the other cation radicals show a 2 order (1 ) or a mixed 1 -2 order (2 and 5 )

+

•

+•

kinetic profile (Figures S11, S12 and S14). This observation suggests that only 3 ,4 and 6 mainly

undergo unimolecular fragmentation process whereas for the other cation radicals their decay is

+

•

+•

partially (2 and 5 ) or totally (1 ) associated to a BET process. Such a different behavior is in full

agreement with the steady state photolysis experiments results (Table 2) where product yields for 3, 4

and 6 (entries 5, 7 and 9), for which the unproductive BET poorly competes with the fragmentation

process, are significantly higher than those for 2 and 5 (entries 1 and 3). Accordingly, 1, whose cation

radical exclusively undergoes BET, was unreactive even at prolonged irradiation times. The values of

st

+• +•

+•

the 1 order rate constants, k , obtained for 3 ,4 and 6 are reported in Table 3.

frag

>

Table 3<

+

•

+•

Comparison between the k_f_r_a_gvalues for 3 and 6 shows that the presence of the β-methoxy

group slightly speeds up the cation radical fragmentation process with respect to the β-hydroxy group.

+

•

The reason for the lower fragmentation rate observed for 3 could be tentatively attributed to a slight

stabilizing effect related to the presence of an intramolecular hydrogen bond between the β-hydroxy

group and the oxygen centered radical as recently reported for the stabilizing effect of alkoxyl radicals

+

•

by hydrogen bonding (53). Interestingly, the higher fragmentation rate constant observed for 6 seems

to be reflected in the slightly higher product yields observed in the photooxidation of 6 with respect to

those for 3 (Compare entries 5 and 7 in Table 2). Indeed, a higher fragmentation rate makes this

process more competitive toward the unproductive BET. In the same way, the significantly faster

+

•

+•

fragmentation process of 4 , with respect to those of 3 and 6 , accounts for the higher product

yields observed in the photooxidation of 4 (compare entry 5 and 9 in Table 2).

DISCUSSION

+

The results obtained in the 3-CN-NMQ photosensitized oxidation of sulfoxides 2-6 show the

formation of significant amount of fragmentation products. No products were observed in the

oxidation of 1, a result that can be attributed to the low fragmentation rate for the cation radical 1⁺^•

+

•

that favors the competitive and unproductive BET process as shown by the LFP experiments. For 1 ,

+

•

+•

the C -S bond cleavage rate is expected to be slower than those for the cation radicals 2 -6 because

α

of the primary alkyl group bonded to the sulfur atom. Moreover, the presence of the β-OH group

seems not to be able to induce an efficient C -C bond fragmentation as observed for the β-hydroxy

α

β

sulfides (35).

In a previous study it was observed that the presence of bases, i.e. substituted pyridines, in the

reaction medium is reflected in a dramatic acceleration of the C -C bond cleavage in β-

α

β

hydroxysulfide cation radicals (35). Such acceleration was rationalized invoking a transition state

where the C -C bond cleavage and the intramolecular ET from this bond to the sulfur atom are

α

β

coupled with the O-H bond cleavage induced by the base. On these bases we carried out some 3-CN-

+

NMQ photosensitized oxidation reactions on 1 in the presence of pyridine (from 0.001 to 0.1 M) or

4

-CN-pyridine (from 0.02 to 0.1 M) in order to induce the C -C bond cleavage but, also under these

α β

reaction conditions, no reaction products were observed. The lack of oxidation products observed also

in the presence of pyridines may be likely due to the possibility that these species could favorably

compete with 1 in the ET process to the excited sensitizer. In contrast, when more oxidizable sulfides

are used as substrates, this possibility can be excluded.

In the oxidation of the β-hydroxysulfoxide 2, two fragmentation products deriving from the

alkyl moiety (benzaldehyde and phenylacetone) are observed accompanied by two sulfur containing

ones i.e. diphenyl disulfide and phenyl phenylthiosulfonate. The formation of these products suggests

+

•

that both C -C and C -S bond cleavage take place on 2 as described in Scheme 3. According to the

α

β

α

proposed mechanism, phenylacetone derives from the C -S bond cleavage (path a) whereas

α

benzaldehyde derives from the C -C scission (path b). The mechanism for the formation of

α

β

+

phenylacetone from the carbocation C H CH(OH)CH CH involves the conversion of the latter into a

6

5

3

protonated epoxide (path c) followed by a 1,2- hydride shift (path d) as already reported (54). Since

benzaldehyde and phenylacetone come from competitive C -C and C -S bond cleavage respectively,

α

β

α

from their molar ratio (see entry 1 in Table 2) it is possible to estimate the relative rates for these two

processes with the C -S bond cleavage being ca 4 fold faster than C -C one.

α

β

<

Scheme 3.>

+

•

The sulfur containing products observed in the photooxidation of 2 are those expected to

derive from the phenyl sulfinyl radical formed upon C -S bond scission. Accordingly, the same

α

products were already observed in previous studies concerning the photosensitized oxidation of alkyl

aryl sulfoxides (24) and their formation was proposed to involve the first reduction of the phenyl

sulfinyl radical to phenyl sulfenate by the reduced form of 3-cyano-N-methylquinolinium, 3-CN-

•

NMQ (Scheme 4, path a). This process is thermodynamically favored since the reduction potential of

•

+

PhSO (1.08 V vs SCE in MeCN) (24) is much higher than that of 3-CN-NMQ (-0.60 V vs SCE in

MeCN) (55) and accounts for the high photosensitizer recovery observed in the reaction mixtures after

irradiation (> 77 %). Once formed, the sulfenate anion or its protonated form, sulfenic acid, are

converted to the observed products PhSSPh and PhSO SPh as described in Scheme 4 (36).

2

<

Scheme 4>

+

•

As described in Scheme 3 (path b), the C -C bond cleavage on 2 leads to the formation,

α

β

besides benzaldehyde, of an α-sulfinylmethyl radical. Since there was no evidence for the formation of

its dimerization product, a possible fate for this species could involve its oxidation to the

corresponding carbocation followed by reaction with trace of water to form sulfenic acid (and then

PhSSPh and PhSO SPh) and acetaldehyde (Scheme 3, path e). The photoinduced oxidation of the β-

2

methoxy sulfoxide 5 provides the same reaction products observed for the corresponding β-hydroxy

sulfoxide 2 accompanied by a significant amount of 2-methoxy-1-phenyl-1-propanol. According to

the mechanism proposed for 2 (Scheme 3), product formation from 5 can be rationalized as described

in Scheme 5 where the carbocation deriving from the C -S bond cleavage (path a) can be converted

α

into an oxiranium intermediate (path c) that can undergo both nucleophilic water addition (path d) to

give 2-methoxy-1-phenyl-1-propanol or 1,2- hydride shift (path e) to provide a carbocation precursor

of benzyl methyl ketone. The alkyl fragment deriving from the C -C bond cleavage (path b), after

α

β

water addition, provides the hemiacetal precursor of benzaldehyde. On the basis of the relative amount

of 2-methoxy-1-phenyl-1-propanol, benzyl methyl ketone and benzaldehyde (Table 2), a significant

+

•

predominance of C -S over C -C bond cleavage seems to take place within 5 .

α

β

<

Scheme 5>

The photooxidation of 3 and 6, afforded 2-methyl-2-phenylpropanal as the exclusive product

deriving from the alkyl moiety whereas the sulfur containing products were the same as observed for

2

: diphenyl disulfide and phenyl phenythiosulfonate (Table 2, entries 5-8). This result suggests the

+

•

+•

occurrence of C -S bond cleavage as the exclusive fragmentation process for 3 and 6 (Scheme 6).

α

+

•

+•

The formation of 2-methyl-2-phenylpropanal from 3 and 6 can be rationalized taking into account a

+

+•

1

,2-phenyl shift within the carbocation PhCH(OR)C(CH ) (Scheme 6, path a for 3 and b for 6 ) as

3

2

already reported (54).

<

Scheme 6>

The formation of diphenylacetaldehyde, and benzaldehyde from the alkyl moiety, and diphenyl

disulfide and phenyl phenylthiosulfonate as sulfur containing products (Table 2, entry 9) in the

+

•

photooxidation of 4 suggests that 4 can undergo both C -S and C -C bond cleavage as described in

α

β

Scheme 7 where diphenylacetaldehyde derives from the C -S scission (path a) followed by a 1,2-

α

phenyl shift within the carbocation thus formed (path c) as previously proposed for 3⁺^•(54). In

contrast, benzaldehyde is formed upon C -C bond cleavage (path b) in a similar way as described for

α

β

+

•

the same process with 2. Moreover, it should be considered that for 4 the C -C bond cleavage leads

α

β

not only to benzaldehyde but also to the formation of an α-sulfinyl radical that, upon further oxidation

path d), should convert to a sulfenic acid and a second benzaldehyde molecule following the pathway

(

+

•

proposed above for 2 .

Under the assumption that two molecules of benzaldehyde are formed upon C -C

α

β

fragmentation, the corrected benzaldehyde and diphenylacetaldehyde yields ratio (Table 2, entry 9)

indicates an almost equal percentage of C -C and C -S bond cleavage thus suggesting that the

α

β

α

presence of the α-phenyl group can stabilize to the same extent both the secondary benzylic

carbocation, from C -S scission, and the secondary benzylic α-sulfinyl radical deriving from the C -C

α

β

scission.

<

Scheme 7>

The collected results show that the presence of a β-hydroxy or -methoxy substituent in the

sulfoxide cation radicals investigated renders the C -C bond cleavage competitive with the C -S

α

β

α

scission. The extent of this competition appears to be highly dependent on the relative stabilities of the

fragments formed from these two processes. Since all the β-hydroxysulfoxide cation radicals afford

•

+

two common fragments from the C -S and C -C bond cleavage i.e. PhSO and [PhCHOH]

α

β

respectively, the competition between these two processes is only governed by the relative stability of

+

•

the other two fragments formed: PhCH(OH)C RR’ from C -S fragmentation and PhS(O)C RR’ from

α

+

•

C -C bond cleavage. Thus, the exclusive C -S bond cleavage observed for 3 should be likely due to

α

β

α

the stability of the tertiary carbocation formed that would result higher than that of the alkyl radical

deriving from the C -C scission. Moreover, the observation that the C -C bond cleavage competes

α

β

α

β

+

•

+•

more favorably in 4 (C -S/C -C ≈ 1) rather than in 2 (C -S/C -C ≈ 4) suggests that the α-phenyl

α

β

α

β

•

substituent would stabilize the radical fragment formed upon C -C cleavage (PhS(O)C HPh), with

α

β

+

respect to the carbocation deriving from the C -S scission (PhCH(OH)CH Ph), more efficiently than

α

the α-methyl group. Accordingly, the lower stabilities of both the primary carbocation and radical that

+

•

would have been formed from the C -S and C -C bond cleavage in 1 determine a fragmentation rate

α

β

too low to compete with the unproductive BET.

Concerning the role of the hydroxyl substituent on the cation radical fragmentation, both

product analysis and LPF experiments on 2-5 and 3-6 show a negligible effect of the substitution of

the -OH with the -OMe group. These observations suggest that the previously proposed favorable

effect on the C -C bond cleavage, within β-hydroxysulfide cation radicals, exerted by a hydrogen

α

β

bonding between the -OH and the solvent in the transition state (35) is no longer valid for β-

hydroxysulfoxides. Thus, the favorable effect of the β-oxygenated substituents on the C -C bond

α

β

scission seems to be exclusively due to the stabilization of the formed carbocation, exerted by the

vicinal oxygen atom.

To better investigate the role of a β-oxygenated group (-OH or -OMe) on the C -S bond

α

cleavage within a sulfoxide cation radical, it could be worthy of interest to compare the k_f_r_a_gvalues for

3⁺^•

and 6 with that of the t-butyl phenyl sulfoxide cation radical previously measured under the same

+•

+

•

+•

experimental condition (24). As for 3 and 6 , the cation radical of t-butyl phenyl sulfoxide has a

tertiary alkyl group bonded to the sulfur atom and was shown to exclusively undergo C -S bond

α

6

-1

cleavage with a rate constant of 1.6 × 10 s , one order of magnitude higher than those measured for

3⁺^•

and 6 (Table 3). Interestingly, the presence of the β-oxygenated substituent seems to stabilize the

+•

cation radical thus discarding a significant contribution of an intramolecular nucleophilic assistance,

exerted by the β-OH or -OMe substituent, on the C -S bond cleavage. Such a stabilization could be

α

associated to the formation of a two center-three electrons intramolecular bond between the β-oxygen

atom and the cation radical localized on the sulfinyl group, as previously proposed for the

intermolecular stabilization of DMSO cation radical by water molecules (56).

CONCLUSION

All the β-hydroxysulfoxides investigated in this work have been shown to rapidly react with the

+

singlet excited state of 3-CN-NMQ via an ET process affording the corresponding cation radicals as

unequivocally revealed by LFP experiments. Once formed, the cation radicals can undergo either BET

or fragmentation processes whose competition depends on the relative stability of the fragments

formed in the latter process. Beside the expected C -S bond cleavage, product analysis in steady-state

α

photolysis experiments showed, in some cases, the occurrence of the unprecedented C -C bond

α

β

scission as well. In this case too, the competition between these two fragmentation processes in β-

hydroxysulfoxides cation radicals seems to depend mainly on the relative stability of the fragments

formed. Finally, the similar behavior observed for the β-methoxysulfoxides 5 and 6 and the

corresponding β-hydroxysulfoxides (2 and 3) in both LFP and steady-state experiments clearly

indicates that the role of the β-hydroxy substituent in promoting the C -C bond cleavage is limited to

α

β

the stabilization of the α-carbocation formed. This evidence discards the hypothesis of a solvent

assistance, via hydrogen bonding, previously proposed for the same process in β-hydroxysulfides

cation radicals.

ACKNOWLEDGEMENTS: This work was financially supported by the University of Rome

La Sapienza and MIUR (Ministry of Education, University and Research).

SUPPORTING INFORMATION

Additional supporting information may be found online in the Supporting Information section at the

end of the article:

Figure S1. Cyclic voltammogram of 2 in MeCN.

Figure S2. Cyclic voltammogram of 3 in MeCN.

Figure S3. Cyclic voltammogram of 4 in MeCN.

Figure S4. Cyclic voltammogram of 5 in MeCN.

Figure S5. Cyclic voltammogram of 6 in MeCN.

1

+

Figure S6. Stern-Volmer plot for the fluorescence quenching of [3-CN-NMQ ]* by 1 at different