A new procedure for the synthesis of α-acyloxy aldehydes from ketones via α,β-epoxy sulfides

Article abstract of DOI:10.1080/17415993.2015.1057823

α-Acyloxy aldehydes, as O-protected α-hydroxy aldehydes, have been prepared in good yields via a new procedure involving the sequence: (1) reaction of ketones with sulfur ylides to give α,β-epoxy sulfides, (2) ring opening with carboxylic acids, (3) oxida

Full text of DOI:10.1080/17415993.2015.1057823

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
A new procedure for the synthesis of α-acyloxy
aldehydes from ketones via α,β-epoxy sulfides
Kamal Elberembally
To cite this article: Kamal Elberembally (2015) A new procedure for the synthesis of α-acyloxy
aldehydes from ketones via α,β-epoxy sulfides, Journal of Sulfur Chemistry, 36:5, 482-493, DOI:
10.1080/17415993.2015.1057823
To link to this article: http://dx.doi.org/10.1080/17415993.2015.1057823
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Date: 14 October 2015, At: 08:46

Journal of Sulfur Chemistry, 2015
Vol. 36, No. 5, 482–493, http://dx.doi.org/10.1080/17415993.2015.1057823
A new procedure for the synthesis of α-acyloxy aldehydes
from ketones via α,β-epoxy sulfides
Kamal Elberembally∗
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt
(Received 9 September 2014; accepted 31 May 2015)
α-Acyloxy aldehydes, as O-protected α-hydroxy aldehydes, have been prepared in good yields via a new
procedure involving the sequence: (1) reaction of ketones with sulfur ylides to give α,β-epoxy sulfides, (2)
ring opening with carboxylic acids, (3) oxidation of the α-acyloxy-β-hydroxy sulfide products by mCPBA
to the corresponding sulfones; and (4) acyl migration followed by elimination of the sulfinate group. The
last transformation was readily accomplished, in very good yields, by equivalent amounts of triethylamine
in dichloromethane at room temperature (method A); or by acyl migration assisted by complexation of the
liberated alkanthiol accomplished in the α-acyloxy-β-hydroxy sulfides by Ag2O in acetonitrile to give the
same α-acyloxy aldehydes (method B). The presented procedure, compared to alternative procedures, has
advantages including easily available key intermediates (α,β-epoxy sulfides), mildness of the reactions
conditions, more general procedure (applied to different types of α-hydroxy aldehydes).
Keywords: α-Acyloxy aldehydes; α,β-epoxy sulfides; ring opening; α-acyloxy-β-hydroxy sulfides; acyl
migration
*Email: kberembal@gmail.com
© 2015 Taylor & Francis

Journal of Sulfur Chemistry 483
1. Introduction
The α-hydroxy carbonyl functionality represents a significant building block in organic synthesis
and is present in a substantial number of both naturally occurring and synthetic biologically sig-
nificant molecules.[1–6] α-Hydroxy aldehydes have been synthesized starting from aldehydes or
ketones via many routes. An excellent summary of these routes has been already given.[7] How-
ever, many of the above-mentioned approaches suffer from restrictions and disadvantages [6–9]
that include limited scope, poor overall yields, numerous intermediates, competing rearrange-
ment reactions and the absence of stereoselectivity in generating the α-hydroxy aldehydes. The
tendency of certain α-hydroxy aldehydes to dimerize to 1,4-dioxanes and/or 1,3-dioxolanes [6,7]
presents another potential difficulty in their isolation and characterization.[7] In addition, such
dimers, occasionally, have decreased reactivity.[6] To avoid problems, for example, competing
rearrangement reactions [10] as well as the tendency to dimerize [6,7] O-protected α-hydroxy
aldehydes have been generated.[6,11] α-Acyloxy aldehydes (as O-protected α-hydroxy aldehy-
des) have been prepared via many approaches.[1,2,4,12,13] Particularly noteworthy among these
contributions is the general and practical method for α-acyloxylation of carbonyl compounds
using N-methyl-O-benzoylhydroxylamine hydrochloride reported by Tomkinson.[1]
A few α,β-epoxy sulfides have been occasionally isolated and prepared via different
reactions.[14–16] However, this functional group has been synthesized, in good yield, via reac-
tions of ketones with alkylthio-substituted sulfonium ylides using simple controlled techniques
Scheme 1. (a) Preparation of α,β-epoxy sulfides via reactions of ketones with sulfur ylides. (b) Proposed mechanism
for acyl migration with the formation of the α-acyloxy aldehyde 5.

484 K. Elberembally
(1(a)).[17] In related work, Makosza et al. [18] prepared additional derivatives of α,β-epoxy
sulfides using aromatic aldehydes.
During the oxidation of this group with mCPBA, we observed that only one member, namely,
2-(methylsulfanyl)-1-oxaspiro[2.5]octane (2a), undergoes fragmentation readily to yield the
α-acyloxy aldehyde, 1-formylcyclohexyl 3-chlorobenzoate (5, 1(b)) in good yield.[19] Ring
Scheme 2. Preparation of α-acyloxy aldehydes via α,β-epoxy sulfides.

Journal of Sulfur Chemistry 485
opening, oxidation of the formed sulfide, followed by acyl migration in the β-hydroxy sulfone, 4,
and then elimination of the sulfinate group, has been proposed as a pathway for this transforma-
tion (1(b)).[19] Thus, our aim was to explore the application of these reactions for the synthesis
of α-acyloxy aldehydes, as O-protected α-hydroxy aldehydes, from ketones as shown in 2. We
report here the results of our study.
2. Results and discussion
Reactions of α,β-epoxy sulfides 2–3 with benzoic acid, p-nitrobenzoic acid, or phenylacetic
acid in dichloromethane at room temperature were investigated. Examination of the crude prod-
1
ucts by TLC (silica gel) indicated practically one compound in the product. Also, HNMR of
the crude product of each reaction indicated the absence of an aldehydic proton that might
result from the attack by the oxygen nucleophile at the β carbon of the α,β-epoxy sulfide
generating the hemimercaptal. Hemimercaptals are known to exist in equilibrium with alde-
hydes and thiols,[20] or undergo disproportionation reactions to aldehydes and mercaptals.[10]
In addition, the characteristic signal of the methine proton of an α-acyloxy-β-hydroxy sulfide
was found (δ = 6.01–6.83) and was consistent with a single compound in each crude prod-
uct. The results are summarized in Table 1. The observed regioselectivity as well as the facile
ring cleavage (under such mild conditions) might be attributed to the presence of the electron-
releasing alkylthio group,[21] in addition the α-carbon of the α,β-epoxy sulfides is sterically
more accessible. The oxidation of the sulfides 6 to the sulfones 7 was carried out by a solution
of m-chloroperbenzoic acid in dichloromethane at –10°C to −15°C (Table 2). Trials for the oxi-
dation of 6a and 6c with a literature procedure [22] using potassium permanganate gave a low
yield of the corresponding sulfones.
Acyl migration followed by elimination of the sulfonyl group, as sulfinate, was readily accom-
plished by an equivalent amount of triethylamine in dichloromethane at room temperature. TLC
Table 1. α-Acyloxy-β-hydroxy sulfides (6) from α,β-epoxy sulfides
(2/3) with carboxylic acids.
Entry Epoxy sulfide 2(3) Acida
Time Sulfide 6 Yieldb (%)
1
2
3
4
5
6
2a
3a
3a
3b
3b
3b
A
B
A
A
B
C
6 h
12 h
12 h
20 h
20 h
18 h
6a
6b
6c
6d
6e
6f
73
55
70
66
60
70
aA: p-Nitrobenzoic acid, B: benzoic acid, C: phenylacetic acid.
bIsolated yield.
Table 2. α-Acyloxy-β-hydroxy sulfones (7) from α-acyloxy-β-
hydroxy sulfides (6) with mCPBA.
Entry
Sulfide 6
Time
Sulfone 7
Yielda (%)
1
2
3
4
5
6a
6c
6d
6e
6f
24 h
40 h
44 h
46 h
44 h
7a
7c
7d
7e
7f
77
76
82
75
62
aIsolated yield.

486 K. Elberembally
Table 3. α-Acyloxy aldehydes (8) from sulfones (7) and/or sulfides (6).
Entry
Sulfone 7 or Sulfide 6
Method (Time)
α-Acyloxy aldehydes 8
Yielda %
1
2
3
4
5
6
7
8
9
7a
7c
7d
7e
7f
6b
6c
6e
6f
A (30 min)
A (30 min)
A (30 min)
A (90 min)
A (60 min)
B (42 h)
B (40 h)
B (62 h)
B (6 h)
8a
8a
8c
8d
8e
8b
8a
8d
8e
54
40
68
50
78
46
48
34
76
aIsolated yield.
indicated that the reaction goes to completion in 30–90 min (Table 3, method A). The desired
α-acyloxy aldehydes 8 were obtained cleanly in good yield (see the experimental part and
Table 3). The crude products, in several examples, were practically pure. The study included
p-nitrobenzoic acid to increase the electrophilicity of the carbonyl of the acyloxy group and so
enhances the expected acyl migration.[23,24]
The acyl migration with the β-hydroxy sulfides 6a, 6f was also attempted. However, under the
above-mentioned conditions, even after prolonged reaction times of 24 h, both compounds were
resistant to acyl migration. Also, phase transfer conditions involving dichloromethane–water
mixture utilizing tetrabutylammonium iodide or benzyltriethylammonium chloride catalyst and
NaOH base [25] could not bring about the desired acyl migration. This behavior is different
from that already reported for the related 1-alkoxy-1,2-diol 1-(3,5-dinitrobenzoate) and 1-alkoxy-
1,2-diol 1-acetate derivatives which both undergo acyl migration readily.[26] However, using
silver oxide (Ag2O) in acetonitrile, at room temperature, (experimental part, and Table 3, method
B) afforded the desired products 8. As TLC indicated, longer reaction time using method B
(Table 3) was required. Ag2O is proposed to act as a base [27] (catalyzes the nucleophilic attack
at the acyloxy group). In addition, Ag+ ion complexes with the liberated alkanethiol and hinders
the reversible reaction.[28] The α-acyloxy aldehydes (8a–e) are stable enough to be kept in
a desiccator, at room temperature, for about three months. However, work-up at temperatures
above 40°C resulted in loss of CO.
These results indicate that the method A, compared to the method B, affords the advantage
of a cleaner acyl migration reaction (easier separation and purification of the end prod-
ucts; α-acyloxy aldehydes). Both methods A and B, compared to the reported alternative
methods for the one-carbon homologation of ketones to α-hydroxy aldehydes, possess advan-
tages including: the easily available key intermediates (the α,β-epoxy sulfides), mildness of
the reactions conditions compared to the strongly basic reagents used in many procedures
involving carbinols which possess masked aldehyde groups,[7] or the highly acidic medium
used with the Pummerer rearrangement of β-hydroxy sulfoxides,[5,10] and more general
procedures.[5–8,10]
Thus, the submitted methods (A, B) will be a valuable addition to the existing literature
procedures for the synthesis of O-protected α-hydroxy aldehydes: α–acyloxy aldehydes.
3. Experimental
All melting points were measured on a Gallenkamp melting point apparatus and are uncorrected.
Infrared (IR) spectra were measured directly on a NaCl plate or in KBr disks with a Shimadzu FT
IR 8101 PC IR spectrometer. 1H and 13C NMR spectra were measured in deuterated chloroform

Journal of Sulfur Chemistry 487
(CDCl3) or dimethylsulfoxide (DMSO-d6) with a Varian Mercury VX-300 NMR spectrome-
ter. Chemical shifts are quoted in δ and were related to that of the solvents. Electron impact
mass spectra (MS) were recorded on a Shimadzu GCMS-QP-1000EX mass spectrometer at 70
e.V. X ray powder diffraction spectra were determined on GNR, APD pro 2000 diffractometer.
Elemental analyses were carried out at the micro-analytical center of Cairo University. Col-
umn chromatography was performed with silica gel (Prolabo) 60–120 mesh. All the reactions
were performed under dry nitrogen atmosphere. Dichloromethane was distilled under N2 over
CaH2. α,β-Epoxy sulfides 2a, 3a, 3b, used in this study, were prepared by the procedures already
reported by us.[17] However, the epoxide 2a was obtained in better yield (61%) via the modi-
fication involving the use of aqueous NaOH 18 M and benzyltriethylammonium chloride as the
phase transfer catalyst [29] as follows:
3.1. 2-(methylsulfanyl)-1-oxaspiro[2.5]octane (2a)
A mixture of dimethyl(methylthiomethyl)sulfonium chloride (33.3 g, 210 mmol), cyclohex-
anone (19.5 g, 199 mmol), CH2Cl2 (100 ml) and benzyltriethylammonium chloride (1.0 g) was
treated with aqueous NaOH 18 M (125 ml), stirred rapidly at room temperature for 10 h. The
reaction mixture was then poured into ice–water mixture (200 ml). The organic phase was sepa-
rated, washed with water and dried (anhydrous K2CO3). CH2Cl2 was evaporated, and the residue
was fractionally distilled under reduced pressure using 15 cm long Vigreux column and the frac-
tion boiling at 114–118°C/15 mmHg was collected (yield: 19.2 g, 61%). Spectroscopic data are
identical to that already cited in.[17]
3.2. General procedure for the preparation of α-acyloxy-β-hydroxy sulfides (6) from
α,β-epoxy sulfides (2,3)
A solution of the epoxide 2 (3) (10 mmol) in dry CH2Cl2 (20 ml) was added slowly, with stir-
ring, to the carboxylic acid (10 mmol) in dry CH2Cl2 (60 ml). The reaction mixture was stirred at
room temperature, under N2 (monitored by TLC), until the reaction was complete. The CH2Cl2
solution was then quickly washed with 10% cold aqueous NaHCO3 solution (2 × 20 ml), dried
with MgSO4 and CH2Cl2 removed under reduced pressure. The residue was purified by recrys-
tallization from CH2Cl2/n-pentane, ether/n-pentane or by column chromatography on silica gel
to afford the desired products (6).
3.2.1. (Rac)-(1-hydroxycyclohexyl)(methylsulfanyl)methyl 4-nitrobenzoate (6a)
=
Colorless needles; mp 91–93°C (CH2Cl2/n-pentane). IR (KBr) 3550, 3529 (OH), 1720 (C O),
1519, 1317 (NO2), 1271, 1101 (C–O) cm−1.1H NMR (300 MHz, CDCl3): δ = 1.56–1.76 (m,
10 H, (CH2)5), 2.20 (br, 1 H, OH), 2.32 (s, 3 H, SCH3), 6.01 (s, 1 H, CH), 8.23–8.32
(m, AA/BB/system, 4 H, ArH).13C NMR (75 MHz, CDCl3): δ = 15.7 (SCH3), 21.2, 21.4
(diastereotopic CH2), 25.4 (CH2), 33.2, 33.7 (diastereotopic CH2), 73.5 (C), 90.7 (OCHS), 123.6,
=
130.9 (CHAR), 134.9, 150.7 (C), 164.2 (C O). Anal. Calcd for C15H19NO5S: C, 55.43%; H,
5.87%; S, 9.83%; N, 4.29%. Found: C, 55.70%; H, 6.00%; S, 10.20%; N, 4.20%.
3.2.2. (Rac)-(1-hydroxycyclohexyl)(3-(methylsulfanyl)propylthio)methyl benzoate (6b)
=
Colorless thick oil; Rf = 0.57 (CHCl3:EtOAc = 14:1). IR (neat): 3504 (OH), 1716 (C O),
1259, 1095 (C–O) cm−1.1H NMR (300 MHz, CDCl3): δ = 1.48–1.74 (m, 10 H, (CH2)5), 1.84–
1.90 (m, 2 H, CH2CH2CH2), 1.98 (s, 3 H, SCH3), 2.50 (t, J = 7.2 Hz, 2 H, CH2SCH3), 2.79–2.88

488 K. Elberembally
(m, 2 H, SCH2CH2), 3.30–3.50 (br, 1 H, OH), 6.06 (s,1 H, CH), 7.37–7.52 (m, 3 H, ArH), 8.03–
8.06 (m, 2 H, ArH). 13C NMR (75 MHz, CDCl3): δ = 15.0 (SCH3), 21.0, 21.2 (diastereotopic
CH2), 25.3, 29.0, 30.7, 32.5 (CH2), 33.00, 33.4 (diastereotopic CH2), 73.3 (C), 87.7 (OCHS),
=
128.2, I29.5 (CHAR), 129.7 (C), 132.9 (CHAR), 165.6 (C O). Anal. Calcd for C18H26O3S2: C,
60.98%; H, 7.39%; S, 18.08%. Found: C, 60.80%; H, 7.20%; S, 17.60%.
3.2.3. (Rac)-(1-hydroxycyclohexyl)(3-(methylsulfanyl)propylthio)methyl 4-nitrobenzoate (6c)
=
Creamy needles, mp 69–71°C (CH2Cl2/n-pentane). IR (KBr) 3539 (OH), 1716 (C O), 1520,
1348 (NO2), 1268, 1097 (C O) cm−1. 1H NMR (300 MHz, CDCl3): δ = 1.60–1.68 (m, 10 H,
−
(CH2)5), 1.91–1.97 (m, 2 H, CH2CH2CH2), 2.071 (s, 3 H, SCH3), 2.077 (s, 1 H, OH), 2.58
(t, J = 7.2 Hz, 2 H, CH2SCH3), 2.88–2.93 (m, 2 H, SCH2CH2), 6.07 (s, 1 H, CH), 8.23–8.34
(m, AA/BB/system, 4 H, ArH). 13C NMR (75 MHz, CDCl3): δ = 15.2 (SCH3), 21.2, 21.3
(diastereotopic CH2), 25.4, 29.0, 31.1, 32.6 (CH2), 33.2, 33.5 (diastereotopic CH2), 73.4 (C), 89.1
=
(OCHS), 123.5, 130.8 (CHAR), 134.9, 150.6 (C), 164.1 (C O). Anal. Calcd for C18H25NO5S2:
C, 54.11%; H, 6.30%; N, 3.50%; S, 16.04%. Found: C, 54.30%; H, 6.10%; N, 3.80%; S, 16.40%.
3.2.4. (Rac)-2-hydroxy-1-(3-(methylsulfanyl)propylthio)-2,2-diphenylethyl
4-nitrobenzoate (6d)
=
Colorless solid, mp 60–62°C (ether/n-pentane). IR (KBr) 3527 (OH), 1708 (C O), 1523,
1
1346 (NO2), 1269, 1099 (C O) cm−1. H NMR (300 MHz, CDCl3): δ = 1.83–1.90 (m, 2 H,
−
CH2CH2CH2)), 2.00 (s, 3 H, SCH3), 2.46 (t, J = 6.9 Hz, 2 H, CH2SCH3), 2.90–2.96 (m, 2
H, SCH2CH2), 3.65 (br, 1 H, OH), 6.83 (s, 1 H, CH), 7.18–7.69 (m, 10 H, ArH), 7.97–8.16
(AA/BB/system, 4 H, ArH). 13CNMR (75 MHz, CDCl3): δ = 15.3 (SCH3), 28.9, 32.3, 32.6
(CH2), 80.7 (C), 88.7 (OCHS), 123.5 (CHAR), 126.7, 126.8 (diastereotopic CHAR), 127.7, 127.8
(diastereotopic CHAR), 128.0, 128.2 (diastereotopic CHAR), 130.7 (CHAR), 134.5 (C), 142.8,
=
143.0 (diastereotopic C), 150.6 (C), 163.8 (C O). Anal. Calcd for C25H25NO5S2: C, 62.09%;
H, 5.21%; N, 2.89%; S, 13.25%. Found: C, 62.20%; H, 4.90%; N, 2.77%; S, 13.20%.
3.2.5. (Rac)-2-hydroxy-1-(3-(methylsulfanyl)propylthio)-2,2-diphenylethyl benzoate (6e)
=
Colorless solid; mp 104–106°C (CH2Cl2/n-pentane). IR (KBr) 3523 (OH), 1697 ((C O), 1265,
1097 (C O) cm−1. 1H NMR (300 MHz, CDCl3): δ = 1.87–1.94 (m, 2 H, CH2CH2CH2), 2.05
−
(s, 3 H, SCH3), 2.49 (t, J = 7.2 Hz, 2 H, CH2SCH3), 2.91–2.98 (m, 2 H, SCH2CH2), 3.55
(br, 1H, OH), 6.79–6.81 (m, 1 H, CH), 7.21–7.54 (m, 11 H, ArH), 7.73–7.76 (m, 2 H, ArH),
7.91(d,3J = 7.5 Hz, 2 H, ArH). 13C NMR (75 MHz, CDCl3): δ = 15.3 (SCH3), 29.0, 32.3, 32.7
(CH2), 80.6 (C), 87.7 (OCHS), 126.8, 127.0 (diastereotopic CHAr), 127.5, 127.7 (diastereotopic
CHAr), 127.9 (CHAr), I28.1, 128.4 (diastereotopic CHAr), 129.3 (C), 129.6, 133.3 (CHAr), 143.0,
=
143.5 (diastereotopic C), 166.0 (C O). Anal. Calcd for C25H26O3S2: C, 68.46%; H, 5.97%; S,
14.61%. Found: C, 68.90%; H, 5.60%; S, 14.90%.
3.2.6. (Rac)-2-hydroxy-1-(3-(methylsulfanyl)propylthio)-2,2-diphenylethyl
2-phenylacetate (6f)
=
Colorless solid; mp 87–89°C (CH2Cl2/n-pentane). IR (KBr): 3475 (OH), 1716 (C O), 1155,
1
1068 (C O) cm−1. H NMR (300 MHz, CDCl3): δ = 1.79–1.87 (m, 2 H, CH2CH2CH2), 2.06
−
(s, 3 H, SCH3), 2.45 (t, J = 7.2 Hz, 2 H, CH2SCH3), 2.74–2.87 (m, 2 H, SCH2CH2), 3.29 (s, 1
H, OH), 3.50, 3.52 (distorted dd, J = 15.6 Hz, 2 H, diastereotopic CH2Ph), 6.61 (s, 1 H, CH),

Journal of Sulfur Chemistry 489
7.03–7.06 (m, 2 H, ArH), 7.24–7.41 (m, 11 H, ArH), 7.54–7.58 (m, 2 H, ArH). 13C NMR (75
MHz, CDCl3): δ = 15.2 (SCH3), 28.8 (SCH2), 31.7 (CH2CH2CH2), 32.5 (CH2S), 41.0 (CH2Ph),
80.2 (C), 87.1 (CHOS), 126.4, 126.6 (diastereotopic CHAR), 127.0, 127.3 (diastereotopic CHAR)
,
127.5, 127.8 (diastereotopic CHAR), 127.9, 128.4, 129.1 (CHAR)), 132.9 (C), 142.5, 142.9
=
(diastereotopic C), 170.2 (C O). Anal. Calcd for C26H28O3S2: C, 68.99%; H, 6.23%; S, 14.16%.
Found: C, 69.00%; H, 6.10%; S, 14.00%.
3.3. General procedure for the preparation of α-acyloxy-β-hydroxy sulfones (7) via the
oxidation of the corresponding sulfides with mCPBA
To a solution of the sulfide 6 (3 mmol) in CH2Cl2 (80 ml) at –15°C, was drop-wise added,
during 30 min, under anhydrous conditions and with stirring a solution of mCPBA in CH2Cl2
(equivalent to 6.5 mmol of mCPBA in the case of 6a and to 13 mmol with the other
sulfides).Then, the mixture was stirred at room temperature (monitored by TLC) until the reac-
tion was complete. The reaction mixture was cooled in an ice-bath and the precipitate removed
by filtration. The filtrate and washings with CH2Cl2 were combined and the solvents were evap-
orated at reduced pressure, first using a rotary evaporator, then using a vacuum oil pump (to
remove completely dioxane used in the preparation of mCPBA in CH2Cl2 solution). The tem-
perature of the bath should be kept all time below 40°C. The residue was treated with CH2Cl2
(50 ml) and extracted with 10% aqueous sodium bicarbonate (2 × 10 ml). The organic layer was
dried (MgSO4) and the solvent was then evaporated under reduced pressure. The resulting solid
was recrystallized from the indicated solvents to afford the desired products.
3.3.1. (Rac)-(1-hydroxycyclohexyl)(methylsulfonyl)methyl 4-nitrobenzoate (7a)
Creamy minute needles; mp 158–160°C (CH2Cl2/n-pentane). IR (KBr): 3303 (OH), 1735
(C O), 1521, 1346 (NO2), 1321 (SO2), 1257 (C O), 1139 (SO2), 1097 (C O) cm−1.1H
NMR (300 MHz, CDCl3): δ = 1.58–1.98 (m, 10 H, (CH2)5), 2.86 (s, 1 H, OH), 3.05 (s, 3 H,
SO2CH3), 5.83 (s, 1 H, CH), 8.28–8.37 (m, AA/BB/system, 4H, ArH). 13C NMR (75 MHz,
CDCl3): δ = 20.8, 20.8 (diastereotopic CH2), 24.9 (CH2), 33.2, 34.5 (diastereotopic CH2), 42.3
=
−
−
=
(SO2CH3), 73.6 (C), 89.4 (OCHSO2), 123.8, 131.3 (CHAr), 133.1, 151.00 (C), 163.0 (C O). MS
(EI, 70 eV): m/z (%) = 278 (10.0), 150 (100%), 120 (11.0), 99 (28.0), 81 (10.0). Anal. Calcd for
C15H19NO7S: C, 50.48%; H, 5.35%; N, 3.92%; S, 8.97%. Found: C, 50.70%; H, 5.10%; N,
3.50%; S, 9.20%.
3.3.2. (Rac)-(1-hydroxycyclohexyl)(3-(methylsulfonyl)propylsulfonyl)methyl
4-nitrobenzoate (7c)
=
Colorless solid; mp 152–154°C (methanol). IR (KBr): 3450 (OH), 1738 (C O), 1525 (NO2),
1295 (SO2), 1265 (C O), 1137 (SO2), 1092 (C O) cm−1.1H NMR (300 MHz, CDCl3):
δ = 1.62–1.72 (m, 6 H, (CH2)3, 1.92–1.95 (m, 4 H, (CH2)2), 2.45–2.53 (m, 2 H, CH2CH2CH2),
2.62 (br, 1 H, OH), 2.94 (s, 3 H, SO2CH3), 3.25 (t, J = 7.2 Hz, 2 H, CH2SO2CH3), 3.42–3.57
(m, 2 H, SO2CH2), 5.85 (s, 1 H, CH), 8.28–8.36 (m, AA/BB/system 4 H, ArH). 13C NMR
(75 MHz, CDCl3): δ = 15.2 (CH2), 20.90, 20.94 (diastereotopic CH2), 25.0 (CH2), 33.3, 34.5
(diastereotopic CH2), 40.9 (SO2CH3), 52.36, 52.38 (CH2), 73.6 (C), 89.4 (OCSO2), 123.9, 131.4
−
−
=
(CHAR), 133.0, 151.2 (C), 163.1 (C O). Anal. Calcd for C18H25NO9S2: C, 46.64%; H, 5.43%;
N, 3.02%; S, 13.83%. Found: C, 46.70%; H, 5.50%; N, 3.20%; S, 13.60%.

490 K. Elberembally
3.3.3. (Rac)-2-hydroxy-1-(3-(methylsulfonyl)propylsulfonyl)-2,2-diphenylethyl
4-nitrobenzoate (7d)
Colorless very light (flour-like) powder ; mp 112–114°C (CH2Cl2/n-pentane). IR (KBr) 3523
(OH), 1728 (C O), 1531 (NO2), 1311 (SO2), 1247 (C O), 1141 (SO2), 1091 (C O) cm−1.1H
NMR (300 MHz, CDCl3): δ = 1.80 (br, 1 H, OH), 2.42 (quintet, J = 7.2 Hz, 2 H, CH2CH2CH2),
2.92 (s, 3 H, SO2CH3), 3.12–3.18 (m, 4 H, SO2CH2CH2CH2SO2), 6.68 (s, 1 H, CH), 7.26–7.63
(m, 10 H, ArH), 8.12–8.29 (m, AA/BB/system, 4 H, ArH).13C NMR (75 MHz, CDCl3): δ = 15.2
(CH2), 41.00 (SO2CH3), 52.2, 53.3 (CH2), 79.6 (C), 88.8 (OCHSO2), 123.7 (CHAR), 125.8, 126.3
=
−
−
(diastereotopic CHAR), 128.2, 128.4 (diastereotopic CHAR), 128.5, 128.6 (diastereotopic CHAR ,
)
=
131.3 (CHAR), 132.7 (C), 141.6, 141.8 (diastereotopic C), 163.1 (C O). MS (EI, 70 eV): m/z
(%) = 183 (18.0), 165 (90), 150 (100.0), 104 (62.0). Anal. Calcd for C25H25NO9S2: C, 54.83%;
H, 4.60%; N, 2.55%; S, 11.70%.). Found: C, 54.80%; H, 5.00%; N, 2.57%; S, 11.73%.
3.3.4. (Rac)-2-hydroxy-1-(3-(methylsulfonyl)propylsulfonyl)-2,2-diphenylethyl benzoate (7e)
=
Colorless platelets; mp 192–194°C (CH2Cl2). IR (KBr) 3500 (OH), 1726 (C O), 1330, 1307
(SO2), 1255 (C O), 1139, 1130 (SO2), 1089 (C O) cm−1. H NMR (300 MHz, DMSO):
δ = 1.91–2.20 (m, 2 H, H2CH2CH2), 2.96 (s, 3 H, SO2CH3), 3.23 (t, J = 7.5 Hz, 2 H,
CH2SO2CH3), 3.36–3.42 (br, 1 H, OH), 3.47–3.55 (m, 2 H, SO2CH2CH2), 6.95 (s, 1 H,
CH), 7.11–7.71 (m, 13 H, ArH), 8.05–8.07 (m, 2 H, ArH).13C NMR (75 MHz, CDCl3):
δ = 15.2 (H2CH2CH2), 40.3 (SO2CH3), 51.8, 52.1 (CH2), 78.2 (C), 89.6 (OCHSO2), 125.4,
125.9 (diastereotopic CHAR), 126.8, 127.02 (diastereotopic CHAR), 127.08, 127.5 (diastereotopic
CHAR), 127.7, 127.9, 128.6, 128.7, 130.0 (CHAR), 134.3 (C), 142.5, 144.2 (diastereotopic C),
1
−
−
=
163.8 (C O). MS (EI, 70 eV): m/z (%) = 183 (16.2), 166 (11.0), 105 (100), 79 (4.4). Anal.
Calcd for C25H26O7S2: C, 59.74% H, 5.21%; S, 12.75%.). Found: C, 59.93%; H, 5.25%; S,
12.80%.
3.3.5. (Rac)-2-hydroxy-1-(3-(methylsulfonyl)propylsulfonyl)-2,2-diphenylethyl
2-phenylacetate (7f)
=
Colorless needles, mp 142–144°C (CH2Cl2/n-pentane). IR (KBr) 3485 (OH), 1755 (C O),
1321, 1301 (SO2), 1145 (C O), 1112 (SO2), 1064 (C O) cm−1.1H NMR (300 MHz, CDCl3):
δ = 2.25 (quintet, J = 7.2 Hz, 2 H, CH2CH2CH2), 2.84 (S, 3 H, SO2CH3), 2.86–2.94 (m,
2 H, SO2CH2CH2), 3.04 (t, J = 7.2 Hz, 2 H, CH2SO2CH3), 3.64 (s, 2 H, CH2Ph), 6.45
(s, 1 H, CH), 7.05–7.08 (m, 2 H, ArH), 7.29–7.49 (m, 13 H, ArH). 13C NMR (75 MHz,
CDCl3): δ = 15.1 (CH2CH2CH2), 40.4 (CH2Ph), 40.7 (SO2CH3), 52.3, 52.4 (CH2), 79.2 (C),
88.6 (OCHSO2), 126.1, 126.4 (diastereotopic CHAR), 127.4, 128.0 (diastereotopic CHAR),
128.21, 128.31 (diastereotopic CHAR), 128.37, 128.6, 129.3 (CHAr), 132.1 (C), 141.4, 141.5
−
−
=
(diastereotopic C), 169.2 (C O). MS (EI, 70 eV): m/z (%) = 183 (94.6), 166 (18.8), 105 (50.0),
91 (100). Anal. Calcd for C26H28O7S2: C, 60.44%; H, 5.46%; S, 12.41%. Found: C, 60.80%; H,
5.50%; S, 12.49%.
3.4. General procedures for the preparation of α-acyloxy aldehydes (8)
3.4.1. Method A: using α-acyloxy-β-hydroxy sulfones (7)
To a solution of the sulfone 7 (0.96 mmol) in dry CH2Cl2 (25 ml) was added rapidly dry NEt3
(0.135 ml, 0.96 mmol). The mixture was stirred under anhydrous conditions, at room temperature

Journal of Sulfur Chemistry 491
(monitored by TLC), until the reaction was complete. Then, the mixture was washed with 10%
cold aqueous sodium bicarbonate solution (10 ml, twice), and dried (MgSO4). CH2Cl2 was evap-
orated under reduced pressure (the temperature of the bath was kept below 40°C). The very thick
oily residue (crude product) crystallized on keeping in a refrigerator overnight (but in case of 8b)
and was purified by recrystallization from the indicated solvent or by column chromatography
on silica gel to give the desired products.
3.4.1.1. 1-Formylcyclohexyl 4-Nitrobenzoate (8a). Colorless clusters of fine needles; mp
− =
108–110°C (CH2Cl2/n-pentane), reported [2] mp 92–94°C. IR (KBr) 2829 (H C O), 1737
(H C O) 1708 (C( O) O), 1529, 1346 (NO2), 1305, 1118 (C O) cm−1. 1H NMR (300 MHz,
− =
=
−
−
CDCl3): δ = 1.34–1.45 (m, 1 H, CH2), 1.55–1.85 (m, 7 H, CH2), 2.14–2.19 (m, 2 H, CH2), 8.24–
8.34 (m, AA/BB/system, 4 H, ArH), 9.62 (s, 1 H, CHO). 1H NMR data are in accordance with the
+
−
literature.[2] MS (EI, 70 eV): m/z (%) = 249 (2.5, M . CO), 205 (0.4), 2.4 (1.6), 150 (100), 111
(2), 100 (0.7). Anal. Calcd For C14H15NO5: C, 60.64%; H, 5.45%; N, 5.05%. Found: C, 60.30%;
H, 5.50%; N, 5.10%.
3.4.1.2. 2-oxo-1,1-diphenylethyl 4-Nitrobenzoate (8c). Creamy solid; mp 155–158°C (CH2Cl2/
− =
− =
=
−
n-pentane). IR (KBr) 2842 (H C O), 1733 (H C O), 1716 (C( O) O), 1521, 1348 (NO2),
1292, 1278, 1101 (C O) cm−1. 1H NMR (300 MHz, CDCl3): δ = 7.36–7.58 (m, 10 H, ArH);
−
8.33 (s, 4 H, ArH), 9.91 (s, 1 H, CHO).13C NMR (75 MHz, CDCl3): δ = 89.2 (C), 123.7, 127.8,
=
=
128.6, 128.9, 131.0 (CHAR), 134.7, 136.7, 150.8 (C), 163.2 (OC O), 191.6 (HC O).
Anal. Calcd for C21H15NO5: C, 69.80%; H, 4.18%; N, 3.87%. Found: C, 69.51%; H, 4.36%;
N, 3.85%.
3.4.1.3. 2-oxo-1,1-diphenylethyl benzoate (8d). Colorless fine granules; mp 98–100°C,
− =
− =
Rf = 0.7 (CH2Cl2:n-hexane = 2.7:1.0). IR (KBr) 2850 (H C O), 1733 (H C O), 1712
1
(C( O) O), 1272, 1093 (C O) cm−1. H NMR (300 MHz, CDCl3): δ = 7.29–7.63 (m, 13
=
−
−
H, ArH), 8.14–8.17 (m, 2 H, ArH), 9.81 (s, 1 H, COH).13C NMR (75 MHz, CDCl3): δ = 88.0
(C), 127.9, 128.5 (CHAr), 128.63, 128.66 (diastereotopic CHAr), 129.2 (C), 129.9, 133.8 (CHAr),
+
=
=
−
137.3 (C), 165.2 (OC O), 192.5 (HC O). MS (EI, 70 eV): m/z (%) = 288 (2.9, M . CO), 195
(0.7), 105 (100), 77 (32.3). Anal. Calcd for C21H16O3: C, 79.73%, H, 5.09%. Found: C, 79.79%;
H, 5.01%.
3.4.1.4. 2-Oxo-1,1-diphenylethyl 2-phenylacetate (8e). Colorless sand-like crystals, mp 72–
− =
− =
74°C (dichloromethane/n-pentane). IR (KBr) 2839, 2729 (H C O), 1741 (H C O), 1732
(C ( O) O), 1143, 1022 (C O) cm−1.1H NMR (300 MHz, CDCl3): δ 3.78 (s, 2 H,+CH2Ph),
=
−
−
−
7.27–7.37 (m, 15 H, ArH), 9.64 (s, 1 H, CHO). MS (EI, 70 eV): m/z (%) = 302 (2.4, M . CO),
195 (4.5), 183 (100), 91(92.3). Anal. Calcd for C22H18O3: C, 79.98%; H, 5.49%. Found: C, 79.
68%; H, 5.53%.
3.4.2. Method B: using α-acyloxy-β-hydroxy sulfides (6)
A mixture of the sulfide 6 (1.12 mmol) and Ag2O (283 mg, 1.22 mmol), in dry freshly distilled
acetonitrile (10 ml), was vigorously stirred (by magnetic stirrer) at room temperature under
nitrogen (monitored by TLC) until the reaction was complete. Then, the solid material was
removed with filtration, and triturated with dry acetonitrile (10 ml). The filtrate and washings
were combined and the solvent evaporated under reduced pressure (the temperature of the bath
was kept below 40°C). The obtained very thick oily residue was submitted to silica gel column
chromatography to afford the desired 8.

492 K. Elberembally
3.4.2.1. 1-Formylcyclohexyl benzoate (8b). Colorless oil, Rf = 0.78 (CHCl3: ethyl acetate =
1
− =
13:1). H NMR data are in accordance with the literature.[1] IR (neat) 2813 (H C O), 1730
(H C O), 1712 (C ( O) O), 1296, 1245, 1109 (C O) cm−1. 1H NMR (300 MHz, DMSO):
δ = 1.24–1.30 (m, 1 H, CH2), 1.48–1.69 (m, 7 H, CH2), 1.96–2.05 (m, 2 H, CH2), 7.46–7.58 (m,
2 H, ArH), 7.68 (t, J = 7.4 Hz, 1 H, Ar-H), 7.95–8.04 (m, 2 H, Ar-H), 9.57 (s, 1, CHO). Anal.
Calcd for C14H16O3: C, 72.39%; H, 6.94%. Found: C, 72.63%; H, 6.85%.
− =
=
−
−
Compounds 8a, 8d, and 8e were prepared by the two methods A and B; samples (of the same
compound) obtained via both methods have identical physical properties and spectroscopic data.
X-Ray powder diffraction spectrum of (rac)-2-hydroxy-1-(3-(methylsulfanyl)propylthio)-2,2-
diphenylethyl 2-phenylacetate (6f). The spectrum (see supplementary material) exhibits
sharp peaks consistent with a crystalline structure (as indicated by peaks at 2θ 7.75° (d-
spacing = 11.399 Å), 9.58° (d-spacing = 9.225 Å), 19.51° (d-spacing = 4.5453 Å), 21.21° (d-
spacing = 4.1851 Å), 22.05 (d-spacing = 4.0276 Å), 24.90° (d-spacing = 3.5729 Å), 39.64°
(d-spacing = 2.2716 Å).
X-Ray powder diffraction spectrum of (rac)-2-hydroxy-1-(3-(methylsulfonyl)propylsulfonyl)-
2,2-diphenylethyl 2-phenylacetate (7f). The spectrum (see supplementary material) exhibits
sharp peaks consistent with a crystalline structure (as indicated by peaks at 2θ 7.33°
(d-spacing = 12.0515 Å), 10.48° (d-spacing = 8.4358 Å), 14.69° (d-spacing = 6.0265 Å),
16.32° (d-spacing = 5.4268 Å), 19.05° (d-spacing = 4.6548 Å), 21.05° (d-spacing = 4.2171
Å), 22.11° (d-spacing = 4.0170 Å).
Disclosure statement
No potential conflict of interest was reported by the author.
Funding
We gratefully acknowledge the support of this study by the Department of Pharmaceutical Chemistry, Faculty of
Pharmacy, University of Tanta, Tanta, Egypt.
Supplemental data
Supplemental data for this article can be accessed at 10.1080/17415993.2015.1057823
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