Synthesis and single crystal structures of n-substituted benzamides and their chemoselective selenation/reduction derivatives

Article abstract of DOI:10.3390/molecules26082367

A series of N-aryl-N-(2-oxo-2-arylethyl) benzamides and cinnamides has been prepared. The reaction of the benzamides with Woollins’ reagent, a highly efficient chemoselective selena-tion/reduction reagent, gave the corresponding N-aryl-N-(arylenethyl) benzoselenoamides in good yields. Five representative single crystal X-ray structures are discussed.

Full text of DOI:10.3390/molecules26082367

molecules
Article
Synthesis and Single Crystal Structures of N-Substituted
Benzamides and Their Chemoselective
Selenation/Reduction Derivatives
Guoxiong Hua 1, Cameron L. Carpenter-Warren 1, David B. Cordes 1 , Alexandra M. Z. Slawin 1,†
and J. Derek Woollins 1,2,
*
1
EaStCHEM School of Chemistry, University of St Andrews, St Andrews Fife KY16 9ST, UK;
gh15@st-andrews.ac.uk (G.H.); clcw@st-andrews.ac.uk (C.L.C.-W.); dbc21@st-andrews.ac.uk (D.B.C.);
amzs@st-andrews.ac.uk (A.M.Z.S.)
Department of Chemistry, Khalifa University, Abu Dhabi 127788, United Arab Emirates
Correspondence: jdw3@st-andrews.ac.uk; Tel./Fax: +44-1334-463861
2
*
†
Dedication: The co-authors dedicate this paper to Prof. Slawin on the occasion of her 60th birthday.
Abstract: A series of N-aryl-N-(2-oxo-2-arylethyl) benzamides and cinnamides has been prepared.
The reaction of the benzamides with Woollins’ reagent, a highly efficient chemoselective selena-
tion/reduction reagent, gave the corresponding N-aryl-N-(arylenethyl) benzoselenoamides in good
yields. Five representative single crystal X-ray structures are discussed.
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Keywords: N-Substituted Benzamides; Woollins’ reagent; selenation reagent; reduction reagent;
single crystal X-ray structures
Citation: Hua, G.; Carpenter-Warren,
C.L.; Cordes, D.B.; Slawin, A.M.Z.;
Woollins, J.D. Synthesis and Single
Crystal Structures of N-Substituted
Benzamides and Their
1. Introduction
Chemoselective
Selenation/Reduction Derivatives.
Molecules 2021, 26, 2367.
2,4-Bis (phenyl)-1,3-diselenadiphosphetane-2,4-diselenide (Woollins’ reagent, WR) has
played a role in synthetic chemistry in the past two decades [1–13]. It has been successfully
https://doi.org/10.3390/
applied as an efficient building unit to synthesize a series of eight-, nine-, and ten-membered
selenophosphorus heterocycles with P-Se-Se-P linkage [14], as well as unique octaselenocy-
clododecane with four carbon atoms and eight selenium atoms in this twelve-membered
cycle [15]. Another attractive application has been that it acts as a highly chemoselec-
tive reagent, e.g., the reduction of a wide range of 1,4-enediones and 1,4-ynediones in
methanol led to saturated 1,4-diketones [16] and the selective reduction of the double
molecules26082367
Academic Editors: Roberto Centore
and Igor Djerdj
Received: 19 March 2021
Accepted: 15 April 2021
Published: 19 April 2021
bond of 2-α,β-unsaturated thiazo- and selenazolidinones gave the corresponding saturated
heterocycles [17]. Woollins’ reagent has also been used as a reducting agent to transfer
porpholactone into dihydroporpholactone or into adjacent-tetrahydroporpholactone [18].
Organoselenium compounds have received growing attention during the last decades
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in
published maps and institutional affil-
iations.
due to their importance as useful precursors in synthetic chemistry [19,20], as new syn-
thetic materials [20], and their biological and medicinal significance [21]. To continue
our interest in the chemistry of Woollins’ reagent towards various organic substrates, we
report an investigation on the use of WR as a selenation/reduction reagent for transferring
N-aryl-N-(2-oxo-2-arylethyl) benzamides into the corresponding N-aryl-N-(arylenethyl)
benzoselenoamides.
Copyright:
© 2021 by the authors.
2. Results and Discussion
2.1. Synthesis and Characterization
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
The synthesis of anilinoacetophenones
and N-aryl-N-cinnamidoacetophenones
method [22]. The reaction of anilines and an equivalent of the appropriate bromoacetophe-
nones in dry acetonitrile at room temperature gave anilinoacetophenones in 81–87%
yields, respectively. Anilinoacetophenones and are new compounds, while 3 is a known
1
–
3
, N-aryl-N-arylamidoacetophenones
4–6
7–9 was carried out using a modified literature
1–
3
1
2
Molecules 2021, 26, 2367. https://doi.org/10.3390/molecules26082367
https://www.mdpi.com/journal/molecules

Molecules 2021, 26, 2367
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compound, prepared previously by a similar method [23
,24]; however, its single-crystal
X-ray structure has not been reported previously. Acylation of anilinoacetophenones
with the appropriate acid chlorides in 1,2-dichloroethane at reflux led to the N-aryl-N-
arylamidoacetophenones and N-aryl-N-cinnamidoacetophenones in 76–91% yields,
as shown in Scheme 1. All the new compounds were characterized by standard analytical
and spectroscopic techniques.
show the anticipated [M]+ or [M + H]+ peak in their
1–3
4
–6
7–9
1–9
mass spectra, satisfactory accurate mass measurements, and appropriate isotopic distribu-
tions; the 1H NMR spectra display all the characteristic peaks of the phenyl backbones in
compounds and the characteristic peaks of the NH group in compound
spectra of compounds 1–9 display the characteristic signals of the C=O groups.
1–3
. The 13C NMR
Scheme 1. Synthesis of anilinoacetophenones
ophenones 7–9.
1–3, N-aryl-N-arylamidoacetophenones 4–6 and N-aryl-N-cinnamidoacet-
Selenation of N-aryl-N-arylamidoacetophenones
4–6 by WR gave rise to N-aryl-N-
arylethylbenzoselenoamides 10 12 in 50%, 46% and 40% yields, respectively, rather than the
–
expected 1,3-selenazole products (Scheme 2). One C=O group has been converted to C=Se
and the other reduced to CH2 to give the final product N-Aryl-N-arylethylbenzoselenoamides
10
tones [16],
search and our findings, a possible mechanism for the selective reduction of N-substituted-
N-phenylamidoacetophenones is broadly similar to that of NaSeH and LiSeH as
selective reducing agents of -unsaturated carbonyl compounds [13] and of PhSe-SePh
–
12. It is well known that WR is an efficient chemoselective reduction agent for dike-
α
,β
-unsaturated thioazo and selenoazolidinones [ ]. Based on the literature re-
6
4–6
α,β
as a reducing agent for electron deficient olefins [25], and it is probable that the reduction
proceed through a Micheal reaction [26–28].
Reacting N-aryl-N-cinnamidoacetophenones
conditions did not lead to a reaction, with the starting materials being recovered (Scheme 3)
We speculate that the extra C=C bond in N-substituted-N-phenylamidoacetophenones 7–9
7–9 with WR under similar reaction
.
which gives a conjugated structure, may be more stable and robust than N-substituted-N-
phenylamidoacetophenones 4–6 towards WR.

Molecules 2021, 26, 2367
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Scheme 2. Selenation of N-aryl-N-phenylamidoacetophenones 4–6.
Scheme 3. Attempted selenation of N-aryl-N-cinnamidoacetophenones 7–9.
The new selenium derivatives 10–12 are quite stable both as solids and in solution, in
air and moist atmospheres, and are soluble in common organic solvents. They show the
anticipated molecular ion peaks [M + H]+ in their CI spectra and [M]+ in their EI spectra,
and satisfactory accurate mass measurements (EI). All the characteristic peaks of the phenyl
backbones were found, and the characteristic peaks of the NH group disappeared in their
1H NMR spectra. Their 13C NMR spectra all show the normal signals for the C=Se groups
(
δC, 204.8–206.8 ppm). Their 77Se NMR spectra exhibit singlet signals at δSe = 598.4, 601.5
and 601.4 ppm for 10–12, respectively.
2.2. Single Crystal Structure Analysis
Single crystals of 3, 7, 10–12 suitable for X-ray crystallographic analysis were grown by
slow evaporation of dichloromethane solutions of the compound in air at room temperature.
Selected crystallographic data are given in Table 1 and the resulting molecular structures
are illustrated in Figures 1 and 2.
The molecular structure of anilinoacetophenone 3 (Figure 1) shows a planar arrange-
ment, with a mean deviation of non-hydrogen atoms from the plane of 0.047 Å. Adjacent
molecules of
bonds at a H···O distance of 2.59(4) Å, and N···O separation of 3.360(5) Å. The structure of
the N-aryl-N-cinnamidoacetophenone shows the compound in a twisted-T conformation
3
interact to form hydrogen-bonded dimers via a pair of NH···O hydrogen
7
(Figure 1). As expected, the acetophenone group retains its planarity (mean deviation of
non-hydrogen atoms from the plane of 0.004 Å). Meanwhile, the other two phenyl ring
planes are twisted out of the acetophenone plane, with angles between planes of 71.36 and
50.74◦ for C(10)-C(15) and C(21)-C(26), respectively.

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Table 1. Details of the X-ray data collections and refinements for compounds 3, 7, 10–12.
Compound
3
7
10
11
12
Formula
C14H11BrClNO
324.60
C25H22ClNO2
403.91
C24H24BrNOSe
501.32
C24H24ClNOSe
456.87
C22H19BrClNOSe
507.72
M
Temperature/K
Crystal system
93
triclinic
93
173
triclinic
173
triclinic
173
triclinic
monoclinic
Space group
P21/c
P1
P1
P1
P1
5.718 (3)
7.296 (4)
15.461 (8)
95.472 (13)
90.3200 (10)
906.126 (12)
638.3 (6)
2
6.00023 (18)
22.8404 (6)
14.7270 (4)
9.2004 (17)
10.541 (3)
11.146 (3)
101.842 (4)
94.351 (6)
90.478 (6)
1054.6 (5)
2
9.1375 (12)
10.6864 (14)
11.1485 (15)
103.062 (4)
95.439 (3)
91.412 (4)
1054.5 (2)
2
9.98830 (10)
10.0160 (2)
12.3778 (18)
99.855 (14)
110.822 (8)
108.988 (12)
1035.2 (2)
2
a/Å
b/Å
c/Å
α
β
93.111 (3)
γ
U/A3
Z
2015.33 (10)
4
−1
3.424
0.211
3.695
1.922
3.890
µ/mm
Reflections
collected
Independent
reflections
Rint
R1 [I > 2σ (I)]
wR2
8491
34,715
14,106
21,665
21,452
2296
4515
3785
3832
3776
0.0769
0.0529
0.1479
0.0669
0.0341
0.0883
0.0448
0.0240
0.0768
0.0283
0.0304
0.0973
0.0314
0.0207
0.0569
Figure 1.
Single crystal X-ray structures of anilinoacetophenone 3 and N-aryl-N-
cinnamidoacetophenone 7.

Molecules 2021, 26, 2367
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Figure 2. Single crystal X-ray structures of selenoamides 10, 11 and 12.
The X-ray structures of 10 11 and 12 are depicted in Figure 2, each displaying similar
,
twisted-T conformations. The three aryl rings [C(5)-C(10) (ring 1), C(11)-C(16) (ring 2) and
C(18)-C(23) (ring 3) in all three compounds] are all twi◦sted with respect to each oth◦er, the
angles between ring planes being 28.92, 69.02 and 62.00 in 10, 18.92, 62.23 and 64.51 in 11
and 55.76, 61.91 and 68.23◦ in 12 for rings 1 and 2, 1 and 3, and 2 and 3, respectively. This
pattern of ring twists puts all the rings out of the plane of the selenoamide, except for ring
1 in compound 12, which is near parallel to the selenoamide, inclined at 9.24◦. The C=Se
double bond lengths [1.832(3) Å in 10, 1.833(2) Å in 11 and 1.8264(19) Å in 12] are very
similar, falling at the middle of the range of C=Se bonds in known selenoamides [1.81(5) to
1.856(4) Å]. [29] The conformations of 10–12 are all very similar, that between 10 and 11,
being almost identical. The difference between this conformation and that adopted by 12 is
in the orientation of ring 1, which differs by ~67◦ between the two conformations.

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3. Materials and Methods
3.1. General
Unless otherwise stated, all reactions were carried out under an oxygen-free nitro-
gen atmosphere using pre-dried solvents and standard Schlenk techniques, subsequent
1
chromatographic and work up procedures were performed in air. H (400.1 MHz), 13
C
(100.6 MHz) and 77Se-{1H} (51.5 MHz, referenced to external Me2Se) NMR spectra were
◦
recorded at 25 C (NMR Jeol GSX270). IR spectra were recorded as KBr pellets in the range
of 4000–250 cm−1 on a Perkin-Elmer 2000 FTIR/Raman spectrometer Mass spectrometry
was performed by the EPSRC National Mass Spectrometry Service Centre, Swansea.
Crystallography
X-ray diffraction data for compounds
or 173 K using a Rigaku FR-X Ultrahigh Brilliance Microfocus RA generator/confocal
optics with XtaLAB P200 diffractometer [Mo K radiation ( = 0.71075 Å)]. Intensity
data were collected using steps accumulating area detector images spanning at least a
3, 7 and 10–12 were collected at either 93 K
α
λ
ω
hemisphere of reciprocal space. Data for all compounds were collected using CrystalClear
2.1 [30] and processed (including correction for Lorentz, polarization and absorption)
using either CrystalClear [30] or CrysAlisPro 1.171.38.43. [31] Structures were solved by
dual-space (SHELXT-2014/4 [32]) or Patterson (PATTY [33]) methods and refined by full-
matrix least-squares against F2 (SHELXL-2018/3 [34]). Non-hydrogen atoms were refined
anisotropically, and hydrogen atoms were refined using a riding model, except for the
amine hydrogen in
3 which was located from the difference Fourier map and refined
isotropically subject to a distance restraint. All calculations were performed using the
CrystalStructure 4.3 interface [35]. Selected crystallographic data are presented in Table 1.
Deposition numbers 2071413–2071417 contains the supplementary crystallographic data for
this paper. These data are provided free of charge by the joint Cambridge Crystallographic
Data Centre and Fachinformationszentrum Karlsruhe Access Structures service www.ccdc.
cam.ac.uk/structures.
3.2. Synthesis
3.2.1. General Procedure for Synthesis of Compounds 1–3
The appropriate aniline (20 mmol) and the phenacyl bromide (10 mmol) were com-
bined in MeCN (40 mL) and allowed to stir at room temperature for 24 h. The amine salt
was filtered off and the filtrate was concentrated under vacuum. The residue was dissolved
in EtOAc (40 mL) and washed sequentially with H2O (50 mL), 5% citric acid (50 mL) and
brine (25 mL). The organic layer was dried over Na2SO4, filtered through a pad of silica gel
and the solvent was evaporated to give the product aminoacetophenones 1–3 in good yield.
1-(4-Bromophenyl)-2-((4-ethylphenyl)amino)ethan-1-one (1). Brown solid (83% yield).
◦
M.p. 151–153 C. Selected IR (KBr, cm−1), 1679(vs), 1617(s), 1583(s), 1522(vs), 1585(m),
1388(m), 1351(m), 1311(m), 1216(m), 1178(m), 1140(m), 1068(s), 992(vs), 812(vs), 576(m),
1
501(m). H NMR (CDCl3,
δ), 7.80 (d, J(H,H) = 8.6 Hz, 2H), 7.69 (d, J(H,H) = 8.4 Hz, 2H),
7.32 (s, 1H), 7.09 (d, J(H,H) = 8.6 Hz, 2H), 6.68 (d, J(H,H) = 8.6 Hz, 2H), 4.60 (s, 2H), 2.58 (d,
J(H,H) = 7.6 Hz, 2H), 1.22 (d, J(H,H) = 7.6 Hz, 3H) ppm. 13C NMR (CDCl3,
δ
), 194.4, 145.0,
133.9, 133.7, 132.2, 129.3, 129.0, 128.7, 113.2, 50.7, 28.0, 16.0 ppm. Accurate mass measure-
ment [ESI+, m/z]: found 318.0482 [M + H]+, calculated mass for C16H16BrNOH: 318.0486.
1-(4-Chlorophenyl◦)-2-((4-ethylphenyl)amino)ethan-1-one (
2). Dark yellow solid (81%
yield). M.p. 148–149 C. Selected IR (KBr, cm−1), 1678(vs), 1618(m), 1598(s), 1522(s),
1489(m), 1440(m), 1395(m), 1352(s), 1312(m), 1218(s), 1090(s), 993(s), 815(vs), 577(m),
529(m). 1H NMR (CDCl3,
δ), 7.99 (d, J(H,H) = 8.6 Hz, 2H), 7.52 (d, J(H,H) = 8.6 Hz,
2H), 7.32 (s, 1H), 7.09 (d, J(H,H) = 8.4 Hz, 2H), 6.68 (d, J(H,H) = 8.4 Hz, 2H), 4.41 (s,
2H), 2.60 (q, J(H,H) = 7.6 Hz, 2H), 1.23 (t, J(H,H) = 7.6 Hz, 3H) ppm. 13C NMR (CDCl3,
δ
), 194.2, 145.0, 140.3, 133.9, 133.3, 129.3, 129.2, 129.1, 128.7, 113.2, 50.8, 28.0, 16.0 ppm.
Accurate mass measurement [ESI+, m/z]: found 274.0992 [M + H]+, calculated mass for
C16H16ClNOH: 274.0994.

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2-((4-Bromophenyl)amino)-1-(4-chlorophenyl)ethan-1-one (
3). Greenish yellow solid
(87% yield). M.p. 165–166 ◦C. Selected IR (KBr, cm−1), 1678(vs), 1595(s), 1510(s), 1491(s),
1400(m), 1357(s), 1256(m), 1218(m), 1094(s), 991(s), 814(s), 797(m), 574(m), 499(m). 1H
NMR (CDCl3,
δ), 7.98 (d, J(H,H) = 8.6 Hz, 2H), 7.52 (d, J(H,H) = 8.6 Hz, 2H), 7.32 (d,
J(H,H) = 8.4 Hz, 2H), 7.28 (s, 1H), 6.60 (d, J(H,H) = 8.4 Hz, 2H), 4.56 (s, 2H) ppm. 13C
NMR (CDCl3, δ), 194.2, 145.0, 140.3, 133.9, 133.3, 129.3, 129.2, 129.2, 128.7, 113.2, 50.8, 28.0,
16.0 ppm. Accurate mass measurement [ESI+, m/z]: found 323.9789 [M + H]+, calculated
mass for C14H11BrClNOH: 323.9791.
3.2.2. General Procedure for Synthesis of Compounds 4–9
The appropriate aminoacetophenone (5.0 mmol) was dissolved in dichloroethane
(25 mL) and refluxed for 2 h with the appropriate acid chloride (5.0 equiv). Volatiles were
evaporated in vacuo, and the residue was recrystallized from ethyl acetate to give the
expected products 4–9.
N-(2-(4-Bromophenyl)-2-oxoet◦hyl)-N-(4-ethylphenyl)-4-methoxybenzamide (
4). Yel-
low solid (91% yield). M.p. 127–129 C. Selected IR (KBr, cm−1), 1678(vs), 1617(m), 1590(m),
1521(s), 1352(m), 1306(m), 1262(m), 1219(m), 1091(m), 994(s), 844(m), 815(s), 772(m), 696(m),
613(m), 546(m), 503(m). 1H NMR (CDCl3,
δ), 8.09 (d, J(H,H) = 8.9 Hz, 2H), 7.90 (d,
J(H,H) = 8.7 Hz, 2H), 7.68 (d, J(H,H) = 8.6 Hz, 2H), 7.09 (d, J(H,H) = 8.6 Hz, 2H), 6.97
(d, J(H,H) = 8.9 Hz, 2H), 6.68 (d, J(H,H) = 8.5 Hz, 2H), 4.59 (s, 2H), 3.91 (s, 3H), 2.59 (q,
J(H,H) = 7.6 Hz, 2H), 1.22 (t, J(H,H) = 7.6 Hz, 3H) ppm. 13C NMR (CDCl3,
δ), 194.5, 171.3,
164.2, 145.0, 133.9, 133.7, 132.4, 133.2, 132.0, 129.3, 129.0, 128.7, 121.7, 113.8, 113.3, 55.5,
50.8, 28.0, 16.0 ppm. Accurate mass measurement [CI+, m/z]: found 452.0859 [M + H]+,
calculated mass for C24H22BrNO3H: 452.0861.
N-(2-(4-Chlorophenyl)-2-oxoethyl)-N-(4-ethylphenyl)-4-methoxybenzamide (5). Bright
◦
yellow solid (81% yield). M.p. 126–128 C. Selected IR (KBr, cm−1), 1678(vs), 1617(s),
1590(s), 1512(vs), 1396(m), 1352(m), 1307(m), 1262(m), 1218(m), 1179(m), 1090(s), 994(s),
1
815(s), 772(m), 613(m), 578(m), 546(m), 503(m). H NMR (CDCl3,
δ), 8.10 (d, J(H,H) = 8.9 Hz,
2H), 7.99 (d, J(H,H) = 8.6 Hz, 2H), 7.51 (d, J(H,H) = 8.6 Hz, 2H), 7.09 (d, J(H,H) = 8.4 Hz,
2H), 6.97 (d, J(H,H) = 8.9 Hz, 2H), 6.68 (d, J(H,H) = 8.4 Hz, 2H), 4.61 (s, 2H), 3.91 (s, 3H),
2.59 (q, J(H,H) = 7.6 Hz, 2H), 1.23 (t, J(H,H) = 7.6 Hz, 3H) ppm. 13C NMR (CDCl3,
δ), 194.2,
171.5, 164.0, 145.0, 140.3, 133.9, 133.3, 132.4, 129.3, 129.2, 129.0, 128.8, 121.7, 113.7, 113.2, 55.5,
50.8, 28.0, 16.0 ppm. Accurate mass measurement [CI+, m/z]: found 408.1366 [M + H]+,
calculated mass for C24H22ClNO3H: 408.1367.
N-(4-Bromophenyl)-N-(2-(4-chlorophenyl)-2-oxoethyl)-4-methoxybenzamide (6). Gray
◦
solid (83% yield). M.p. 150–152 C. Selected IR (KBr, cm−1), 1680(s), 1601(s), 1574(m),
1513(m), 1487(m), 1427(s), 1301(s), 1260(s), 1166(s), 1025(m), 926(m), 844(s), 816(m), 772(s),
1
696(m), 613(s), 547(s), 503(m), 484(m). H NMR (CDCl3,
δ), 8.09 (d, J(H,H) = 8.9 Hz, 2H),
7.98 (d, J(H,H) = 8.6 Hz, 2H), 7.52 (d, J(H,H) = 8.6 Hz, 2H), 7.32 (d, J(H,H) = 8.9 Hz, 2H),
6.97 (d, J(H,H) = 8.8 Hz, 2H), 6.61 (d, J(H,H) = 8.8 Hz, 2H), 4.57 (s, 2H), 3.91 (s, 3H) ppm.
13C NMR (CDCl3,
δ), 193.5, 171.3, 164.0, 145.8, 140.6, 133.0, 132.4, 132.1, 129.3, 129.2, 121.6,
114.7, 113.8, 110.8, 109.7, 55.5, 50.2 ppm. Accurate mass measurement [CI+, m/z]: found
458.0157 [M + H]+, calculated mass for C22H17BrClNO3H: 458.0159.
N-(2-(4-Bromophenyl)-2-oxoethyl)-N-(4-ethylphenyl)cinnamamide (7). Yellow solid (79%
yield). M.p. 126–127 ◦C. Selected IR (KBr, cm−1), 1697(s), 1656(vs), 1620(s), 1584(s), 1510(s),
1401(m), 1376(s), 1327(m), 1209(s), 1069(s), 1005(s), 982(s), 840(m), 812(s), 703(s), 698(s), 569(m),
1
549(s). H NMR (CDCl3,
δ), 7.87 (d, J(H,H) = 7.6 Hz, 2H), 7.73 (d, J(H,H) = 15.6 Hz, 1H),
7.63 (d, J(H,H) = 7.8 Hz, 2H), 7.38–7.26 (m, 8H), 6.49 (d, J(H,H) = 15.6 Hz, 1H), 5.18 (s,
2H), 2.72 (q, J(H,H) = 7.6 Hz, 2H), 1.29 (t, J(H,H) = 7.6 Hz, 3H) ppm. 13C NMR (CDCl3, δ),
192.9, 166.4, 144.3, 142.7, 140.0, 135.1, 134.1, 132.1, 129.9, 129.6, 129.5, 129.1, 128.7, 128.1,
128.0, 118.0, 56.5, 28.5, 15.4 ppm. Accurate mass measurement [CI+, m/z]: found 448.0916
[M + H]+, calculated mass for C25H22BrNO2H: 448.0912.
N-(2-(4-Chlorophenyl)-2-oxoethyl)-N-(4-ethylphenyl)cinnamamide (
8
). Dark yellow
◦
solid (80% yield). M.p. 155–157 C. Selected IR (KBr, cm−1), 1697(s), 1653(s), 1617(s), 1587(s),

Molecules 2021, 26, 2367
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1510(s), 1402(m), 1380(s), 1329(m), 1214(s), 1089(s), 1000(m), 981(s), 819(s), 766(m), 703(m),
1
548(m), 525(m). H NMR (CDCl3,
δ), 7.92 (d, J(H,H) = 7.6 Hz, 2H), 7.70 (d, J(H,H) = 15.1 Hz,
1H), 7.43 (d, J(H,H) = 7.8 Hz, 2H), 7.28–7.21 (m, 8H), 6.45 (d, J(H,H) = 16.1 Hz, 1H), 5.16
(s, 2H), 2.68 (q, J(H,H) = 7.6 Hz, 2H), 1.25 (t, J(H,H) = 7.6 Hz, 3H) ppm. 13C NMR (CDCl3,
δ
), 192.8, 166.5, 144.4, 142.8, 140.1, 140.0, 135.2, 133.7, 129.7, 129.5, 129.1, 129.0, 128.8, 128.1,
128.0, 118.0, 56.6, 28.6, 15.5 ppm. Accurate mass measurement [CI+, m/z]: found 404.1408
[M + H]+, calculated mass for C25H22ClNO2H: 404.1412.
N-(4-Bromophenyl)-N-(2-(4-c◦hlorophenyl)-2-oxoethyl)cinnamamide (
9). Off-white
solid (76% yield). M.p. 174–176 C. Selected IR (KBr, cm−1), 1696(s), 1657(s), 1617(s),
1587(m), 1486(vs), 1408(m), 1373(s), 1207(s), 1092(m), 1070(m), 1013(s), 816(s), 763(m),
1
696(m), 484(s). H NMR (CDCl3,
δ
), 7.95 (d, J(H,H) = 8.6 Hz, 2H), 7.74 (d, J(H,H) = 15.5 Hz,
1H), 7.58 (d, J(H,H) = 8.6 Hz, 2H), 7.48 (d, J(H,H) = 8.6 Hz, 2H), 7.39–7.32 (m, 6H), 6.46 (d,
J(H,H) = 15.5 Hz, 2H), 5.18 (s, 2H) ppm. 13C NMR (CDCl3,
δ), 192.4, 166.1, 143.5, 141.5,
140.2, 134.8, 133.4, 132.9, 130.0, 129.9, 129.5, 129.2, 128.8, 128.1, 122.0, 117.3, 56.3 ppm.
Accurate mass measurement [CI+, m/z]: found 456.0184 [M + H]+, calculated mass for
C23H17BrClNO2H: 456.0189.
3.2.3. General Procedure for Synthesis of Compounds 10–12
A mixture of the appropriate benzamide or cinnamide with an equivalent of WR in
dry toluene was refluxed for 6 h. Following cooling to room temperature and filtration to
remove unreacted solid, the filtrate was evaporated in vacuo, the residue was dissolved
in 2 mL of dichloromethane and purified by silica gel column chromatography (1:1 hex-
ane/dichloromethane as eluant) to give the products 10
any reaction with WR, returning the starting materials.
–12. Cinnamides 7–9 did not show
N-(4-Bromophenethyl)-N-(4-ethylphenyl)-4-methoxybenzoselenoamide (10). Greyish
yellow paste (0.25g, 50%). Selected IR (KBr, cm−1), 1601(s), 1508(s), 1488(m), 1448(s), 1399(s),
1
1300(m), 1250(vs), 1170(s), 1073(m), 1029(m), 830(m), 806(m). H NMR (CD2Cl2,
δ), 8.03 (d,
J(H,H) = 8.0 Hz, 1H), 7.45 (d, J(H,H) = 8.4 Hz, 2H), 7.26–7.23 (m, 4H), 7.10–7.02 (m, 3H), 6.94
(d, J(H,H) = 8.0 Hz, 2H), 6.10 (d, J(H,H) = 8.4 Hz, 2H), 4.72 (t, J(H,H) = 8.1 Hz, 2H), 3.74(s,
3H), 3.24 (t, J(H,H) = 8.1 Hz, 2H), 2.60 (q, J(H,H) = 7.6 Hz, 2H), 1.21 (t, J(H,H) = 7.6 Hz,
3H) ppm. 13C NMR (CD2Cl2,
δ), 206.6, 159.5, 143.7, 140.0, 137.6, 131.5, 130.7, 129.0, 128.6,
126.2, 120.2, 114.4, 112.4, 62.4, 55.2, 31.4, 28.3, 15.0 ppm. 77Se NMR (CDCl3,
δ), 598.4 ppm.
Accurate mass measurement [CI+, m/z]: found 502.0283 [M + H]+, calculated mass for
C24H24BrNOSeH: 502.0285.
N-(4-Chlorophenethyl)-N-(4-ethylphenyl)-4-methoxybenzoselenoamide (11). Reddish
yellow paste (0.21 g, 46%). Selected IR (KBr, cm−1), 1602(s), 1508(s), 1488(m), 1448(s),
1
1398(s), 1300(m), 1251(vs), 1170(s), 1030(m), 832(m), 809(m). H NMR (CDCl3,
δ), 7.25–7.23
(m, 4H), 7.19 (d, J(H,H) = 8.6 Hz, 2H), 7.02 (d, J(H,H) = 8.0 Hz, 2H), 6.85 (d, J(H,H) = 8.0 Hz,
2H), 6.55 (d, J(H,H) = 8.0 Hz, 2H), 6.55 (d, J(H,H) = 8.0 Hz, 2H), 4.67 (d, J(H,H) = 8.0 Hz,
2H), 3.69 (s, 3H), 3.21 (d, J(H,H) = 8.0 Hz, 2H), 2.54 (q, J(H,H) = 8.1 Hz, 2H), 1.18 (t,
J(H,H) = 8.0 Hz, 3H) ppm. 13C NMR (CDCl3,
δ), 206.8, 159.7, 143.7, 139.8, 136.8, 132.5,
130.4, 129.2, 128.8, 128.7, 126.2, 112.7, 62.8, 55.3, 31.5, 28.4, 15.2 ppm. 77Se NMR (CDCl3,
δ),
601.5 ppm. Accurate mass measurement [CI+, m/z]: found 458.0789 [M + H]+, calculated
mass for C24H24ClNOSeH: 458.0790.
N-(4-Bromophenyl)-N-(4-chlorophenethyl)-4-methoxybenzoselenoamide (12). Pale
orange paste (0.20 g, 40%). Selected IR (KBr, cm−1), 1601(s), 1489(m), 1485(s), 1446(m),
1
1392(m), 1302(m), 1251(vs), 1170(vs), 1068(m), 1011(m), 832(m), 801(m). H NMR (CDCl3,
δ
), 7.33 (d, J(H,H) = 8.2 Hz, 2H), 7.27–7.16 (m, 6H), 6.82 (d, J(H,H) = 8.2 Hz, 2H), 6.58 (d,
J(H,H) = 8.3 Hz, 2H), 4.63 (q, J(H,H) = 8.4 Hz, 2H), 3.72 (s, 3H), 3.16 (d, J(H,H) = 8.4 Hz,
3H) ppm. 13C NMR (CDCl3,
), 204.8, 160.0, 145.0, 139.6, 136.5, 132.7, 130.3, 129.6, 129.2,
δ
128.8, 128.0, 121.1, 113.0, 62.3, 55.4, 29.8 ppm. 77Se NMR (CDCl3,
δ), 601.4 ppm. Ac-
curate mass measurement [CI+, m/z]: found 507.9580 [M + H]+, calculated mass for
C22H19BrClNOSeH: 507.9582.

Molecules 2021, 26, 2367
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4. Conclusions
In summary, we have disclosed Woollins’ reagent used as a highly efficient chemoselec-
tive selenation/reduction reagent for benzamide leading to N-aryl-N-(arylenethyl)benzosel-
enoamides. The reported results enhance the application of Woollins0 reagent further,
providing an efficient route to the preparation of the unusual substituted selenoamides.
Author Contributions: G.H. and J.D.W. conceived and designed the project; G.H. performed the
experiments; D.B.C., C.L.C.-W. and A.M.Z.S. did the crystallography; All authors have read and
agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Acknowledgments: We are grateful to the University of St Andrews for financial support and the
EPSRC National Mass Spectrometry Service Centre (Swansea) for mass spectral measurements.
Conflicts of Interest: The authors declare no conflict of interest.
Sample Availability: Samples of all compounds are not available from the authors.
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