Copper(II)-Catalyzed Reactions of α-Keto Thioesters with Azides via C-C and C-S Bond Cleavages: Synthesis of N-Acylureas and Amides

Article abstract of DOI:10.1021/acs.joc.7b03054

Cu(II)-catalyzed reaction of α-keto thioesters with trimethylsilyl azide (TMSN₃) proceeds with the transformation of the thioester group into urea through C-C and C-S bond cleavages, constituting a practical and straightforward synthesis of N-acylureas. When diphenyl phosphoryl azide (DPPA) is used instead as the azide source in an aqueous environment, primary amides are formed via substitution of the thioester group. The reactions are proposed to proceed through Curtius rearrangement of the initially formed α-keto acyl azide to generate an acyl isocyanate intermediate, which reacts further with an additional amount of azide or water and rearranges to afford the corresponding products. To demonstrate the potentiality of the method, one-step syntheses of pivaloylurea and isovaleroylurea, displaying anticonvulsant activities, have been carried out.

Full text of DOI:10.1021/acs.joc.7b03054

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Article
Copper(II)-Catalyzed Reactions of #-Keto Thioesters with Azides via
C-C and C-S Bond Cleavages: Synthesis of N-Acylureas and Amides
Rajib Maity, Sandip Naskar, and Indrajit Das
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b03054 • Publication Date (Web): 02 Feb 2018
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Copper(II)ꢀCatalyzed Reactions of αꢀKeto Thioesters with Azides via CꢀC
and CꢀS Bond Cleavages: Synthesis of NꢀAcylureas and Amides
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Rajib Maity, Sandip Naskar, and Indrajit Das*
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Organic and Medicinal Chemistry Division, CSIRꢀIndian Institute of Chemical Biology, 4,
Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, India. Eꢀmail: indrajit@iicb.res.in
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ABSTRACT
Cu(II)ꢀcatalyzed reaction of αꢀketo thioesters with trimethylsilyl azide (TMSN3) proceeds
with the transformation of the thioester group into urea through CꢀC and CꢀS bond cleavages,
constituting a practical and straightforward synthesis of Nꢀacylureas. When diphenyl
phosphoryl azide (DPPA) is used instead as the azide source in an aqueous environment,
primary amides are formed via substitution of the thioester group. The reactions are proposed
to proceed through Curtius rearrangement of the initially formed αꢀketo acyl azide to generate
an acyl isocyanate intermediate, which reacts further with an additional amount of azide or
water and rearranges to afford the corresponding products. To demonstrate the potentiality of
the method, oneꢀstep syntheses of pivaloylurea and isovaleroylurea, displaying
anticonvulsant activities, have been carried out.
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INTRODUCTION
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The Nꢀacylurea moiety is a functional group commonly found in a broad spectrum of
medicinal and therapeutic agents.1ꢀ2 For example, some are known to possess promising
anticonvulsant, antiꢀinflammatory, analgesic, antiꢀfungal, antiꢀtumor, and antiproliferative
activities,1 or are used in agriculture as insecticides.2 NꢀAcylureas are also important building
blocks in organic syntheses.3
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Various synthetic strategies have been developed for accessing Nꢀacylureas.4ꢀ9 Traditionally,
these are synthesized by coupling activated carboxylic acids such as acid chlorides,
anhydrides, esters, and carbodiimides with ureas4 or by the condensation of amines with acyl
isocyanates/Sꢀallyl Nꢀacylmonothiocarbamates.5 Other methods starting from ureas include
arylboronic acidꢀcatalyzed direct condensation with carboxylic acids6a and acylation with alkꢀ
1ꢀenꢀ2ꢀyl esters.6b Recently, the syntheses of Nꢀacylureas have also been accomplished via
microwaveꢀassisted Pdꢀcatalyzed carbonylation of aryl or heteroaryl halides with urea
nucleophiles using CO gas/Mo(CO)6,7 Rh(III)ꢀcatalyzed CꢀH functionalization of indolines
with aryl and alkyl isocyanates,8 or NHCꢀcatalyzed oxidative coupling of aldehydes with N,
Nʹꢀdisubstituted carbodiimides under aerobic conditions.9a Solidꢀphase synthesis of Nꢀ
acylureas or cinnamoyl ureas from resinꢀbound ureas and acyl chlorides has also been
reported.9b Despite these different approaches, most of the published methods require either
ureas or suitably activated carboxylic acids in the form of labile compounds such as the acyl
chlorides, which can, in some cases, be difficult to handle or synthesize. Consequently,
development of efficient routes to synthesize Nꢀacylureas from readily accessible starting
materials continues to captivate organic chemists.
Continuing our efforts for the exploration of αꢀketo thioesters as building blocks for
accessing diverse heterocycles,10 we investigated their reactivity with different azides.11 This
revealed that with TMSN3 in the presence of Cu(OAc)2 as a catalyst they delivered Nꢀ
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acylureas, Nꢀcinnamoyl ureas, and Nꢀaroylureas; the results provided a practical and
straightforward synthesis of the products. The substrates possibly underwent Curtius
rearrangement,12 the in situ generated acyl isocyanate intermediate reacting further to deliver
the products (Scheme 1). The reaction seems to proceed with the transformation of the
thioester group into a urea moiety via cleavage of the CꢀC and CꢀS bonds with retention of
the thioester carbonyl group. Furthermore, use of DPPA instead of TMSN3 as the azide
source and carrying out the reaction in an aqueous milieu provided an alternative procedure
to generate primary amides from αꢀketo thioesters via removal of the thioester group (Scheme
1).
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Scheme 1. Proposed synthesis of Nꢀacylureas 3 and primary amides 4 from αꢀketo thioesters and azides
RESULTS AND DISCUSSION
To optimize the reaction conditions for cinnamoyl urea, we initiated model studies with γꢀ
phenyl substituted β,γꢀunsaturated αꢀketo methylthioesters 1a, different azide sources 2, dry
o
DMF, and 3 Å MS under 30 mol% copper catalysis at 80 C (Table 1). We were pleased to
observe that CuCl could catalyze this transformation in the presence of TMSN3 to afford 3a
in 66% yield (entry 1). Though other Cu(I) and Cu(II) salts such as CuBr, Cu2O, CuCl2,
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CuBr2, Cu(acac)2, and Cu(OTf)2 proved inferior (entries 2ꢀ7), utilization of Cu(OAc)2 as a
catalyst could significantly improve the yield to 89%, and the reaction proceeded to
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Table 1. Optimization studies for accessing cinnamoyl urea 3aa,b
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completion within 1 h (entry 8). Subsequent attempts with commercially available azide
sources such as tetrabutylammonium azide (TBAA), NaN3, and pꢀtoluenesulfonyl azide
(TsN3) proved discouraging (entries 9ꢀ11). The use of diphenylphosphoryl azide (DPPA) as
an azide source failed to deliver 3a (entry 12), furnishing 4a instead in 78% yield (Table 5,
vide infra). The reaction did not work well either with 3.0 equiv. TMSN3 (entry 13) or 10
mol% Cu(OAc)2 (entry 14), generating only moderate yields. Different solvents such as
DMSO and MeCN were also screened (entries 15ꢀ16), but without success. The yield of the
o
o
product 3a also went down when the reaction was conducted at 60 C or 100 C (entries 17ꢀ
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18). Only moderate yields were achieved in the absence of any catalyst or solvent, as side
reactions were observed (entries 19ꢀ20).
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With the optimal reaction conditions (entry 8, Table 1), the substrate scope and generality for
this transformation was investigated using various γꢀsubstituted β,γꢀunsaturated αꢀketo
methylthioesters 1 and TMSN3 2a, the results of which are given in Table 2. The reaction
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Table 2. Substrate scope of the Cu(OAc)2/TMSN3ꢀmediated synthesis of Nꢀacylureas from γꢀsubstituted β,γꢀ
unsaturated αꢀketo methylthioestersa
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tolerates a wide range of γꢀsubstituted αꢀketo methylthioesters. Substrates containing an
aromatic ring at the γꢀposition of thioesters with electronꢀrich (1bꢀj) or electronꢀpoor 1kꢀn)
substituents delivered the corresponding substituted cinnamoyl ureas in moderate to good
yields (3bꢀn).9b,13 The pꢀbromo substituted phenyl derivative (1o) gave the expected product
(3o) in low yield, perhaps due to the competitive coupling reaction,14 though no aromatic
azide was isolated. The reaction with a strong electronꢀwithdrawing substituent (ꢀCN) on the
aromatic ring also turned out to be rather sluggish (3p), ostensibly owing to the poor
migratory aptitude during Curtius rearrangement. However, it proceeded uneventfully in the
presence of a heteroaromatic substituent, delivering the product in moderate yield (3q). Even
thioesters 1r and 1s containing γꢀnaphthyl substituents yielded the corresponding products
(3rꢀs). Moreover, αꢀketo thioesters with an alkyl group at the γꢀposition (1tꢀv) also furnished
the desired products 3tꢀv in moderate yields. The structures of 3a and 3l were established by
single crystal Xꢀray diffraction analysis (Table 2).15
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Subsequently, we extended the scope of the reaction with aryl rather than styryl substituted αꢀ
keto thioesters (Table 3). Under the standard reaction conditions shown in Table 2, substrates
containing electronꢀneutral (1aa), electronꢀdonating (1abꢀ1ad), and electronꢀwithdrawing
(1ae) substituents in the aromatic ring or with a fused aromatic ring (1af) or a biphenyl
Table 3. Substrate scope of the Cu(OAc)2/TMSN3ꢀmediated synthesis of Nꢀaroylureas from αꢀketo thioestersa
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substituent (1ag) at the αꢀposition of the αꢀketo thioesters delivered the corresponding Nꢀ
aroylureas in moderate yields (3aaꢀag).9b,16
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The synthetic versatility of this developed methodology was established by singleꢀstep
syntheses of pivaloylurea (PVU) 3ah, isovaleroylurea (IVU) 3ai, 2ꢀmethylbutanoylurea 3aj,
and nꢀbutyrylurea 3ak from the corresponding αꢀketo thioesters 1ahꢀ1ak (Scheme 2).1b,17
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Scheme 2. Syntheses of pivaloylurea, isovaleroylurea, 2ꢀmethylbutanoylurea, and nꢀbutyrylureaa
Based on the experimental results, we propose a plausible mechanistic pathway as detailed in
Scheme 3. We presume that Cu(II) may form a complex I by coordinating with the sulphur
atom of the thioesters, increasing their electrophilicity. Nucleophilic substitution by azide
followed by elimination of thiolate anion could then lead via intermediate II to intermediate
III. This in turn undergoes Curtius rearrangement via elimination of nitrogen to generate an
acyl isocyanate intermediate IV, which reacts with TMSN3 by pathway a or b. Pathway a
envisages cycloadduct formation with intermediate IV to produce silylated tetrazole V, which
expels molecular nitrogen to generate intermediate VI.18 VI could exist in equilibrium with
an acyl nitrene species VII, which undergoes reduction with thiolate anion catalyzed by
copper, as described in the literature, to yield product 3.19 Alternatively (pathway b), IV
could react with TMSN3 to produce the carbamoyl azide VIII (a 1,4ꢀadduct), which
undergoes similar reduction with [Cu]ꢀthiolate via elimination of nitrogen to form 3.19
Attempts to isolate any of the proposed intermediates in Scheme 3 were unsuccessful. It is
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Scheme 3. Proposed mechanism for the formation of Nꢀacylureas from γꢀsubstituted β,γꢀunsaturated αꢀketo
methylthioesters or αꢀketo thioesters
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TMSN3
R1
O
O
O
TMSN3
S
O
O
[Cu][SR1]
O
-
R
R
R
N3
N
N
N
Cu(OAc)2, DMF,
3 Å MS, 80 o
R
[
S
I
O
S
C
R1
R1
[Cu]
Me3Si
O
II
1
-keto acyl azide]
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III
[Cu][-SR1]
- N2
Intermediate
VI or VII
"reduction"
R1SSR1
O
Me3SiO
R
[Curtius
rearrangement]
O
O
O
TMSN3
N
N
N
N
path b
R
N
C O
R
N
NH2
H
N2
[Carbamoyl azide]
[acyl isocyanate]
N-acylurea
IV
VIII
3
TMSN3
path a
H3O
"reduction"
SiMe3
N
SiMe3
O
[Cu][-SR1
]
O
SiMe3
N
O
O
O
N
R
N
C
R
N
C
N
R
N
N
V
O
VII
R1SSR1
N2
VI
silylated tetrazole
acyl nitrene
noteworthy that a large excess of TMSN3 (5 equiv.) is critical to obtain Nꢀacylureas in
moderate to high yields.
In order to support our proposed mechanistic model, we next decided to use ESIꢀHRMS
(LTQ Orbitrap) studies as a means of probing the proposed intermediates from the reaction
mixtures. αꢀKeto thioester 1aa was chosen to study the reaction under the standard
conditions. An aliquot was taken from the reaction mixture after 5 min, diluted with
acetonitrile and analysed by ESIꢀHRMS (Figure 1). The spectrum showed [M + Na] peaks
corresponding to the desilylated product of the intermediates silylated tetrazole or carbamoyl
azide V or VIII (m/z 213.0396) and for acyl nitrene VI or VII (m/z 185.0332). This
experiment supports the formation of the intermediates V or VIII and VI or VII, as described
in our proposed mechanism. However, acyl isocyanate intermediate IV was hardly
detectable, perhaps due to its high reactivity towards azide in solution. Interestingly, the
spectrum showed peaks at m/z 215.0804 and 202.0487, attributed to the [M + Na] peak of
PhCONHCONMe2 [derived by the addition of NMe2 (from DMF)] and [M – CO + Na] peak
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of PhCONHCOOAc [derived by the addition of OAc from Cu(OAc)2] to intermediate IV
(Figure 1), which indirectly supports the formation of a shortꢀlived acyl isocyanate
intermediate derived via Curtius rearrangement. It must be mentioned here that a
thiocarbamate should be formed if the thiolate anion, released in the first step, acts as a
nucleophile to intermediate IV. But we neither encountered such product nor detected the
corresponding mass spectral peak during ESIꢀHRMS studies. However, we isolated diphenyl
disulfide (Ph2S2) in 10ꢀ12% yield during all the reactions discussed above.
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Figure 1. ESIꢀHRMS (LTQ Orbitrap) spectrum of the crude reaction mixture after 5 min. Aliquot taken
was diluted with MeCN.
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In order to gain further evidence for the intermediacy of the acyl isocyanate IV, we
performed control experiments (Scheme 4). DMSO was preferred as a solvent over DMF to
slow down the reaction. When 1aa was treated with 3 equiv. TMSN3 and Cu(OAc)2 in
DMSO at room temperature, and the reaction was quenched either with MeOH or piperidine
after 5 min, the carbamate 5a or urea 5b derivative was obtained, as expected, along with the
desired Nꢀacylurea 3aa. These two parallel experiments support the formation of the
intermediate IV. Moreover, the formation of primary amides 4 (Table 6, vide infra) from αꢀ
keto thioesters 1 in the presence of water provides direct evidence for the generation of acyl
isocyanate IV intermediate via Curtius rearrangement.
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Scheme 4. Control Experiments
Furthermore, to clarify the mechanism of the reduction of azide to amine via nitrene
intermediate, carbamoyl azide VIII was prepared independently from the literature
precedent,19a and subjected to reductions in the presence of different reducing agents.
However, no expected product was ever observed even after heating the reaction mixtures for
prolonged periods; the starting materials either underwent degradation or were recovered.
Parallely, commercially available benzoyl isocyanate IV was treated with TMSN3 and
different reducing agents, but only carbamoyl azide VIII was isolated. However, the pathway
by which the reduction of nitrenes to amines take place is uncertain at this point, and further
investigations are going on to find it out.19bꢀc,20
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The utility and practical usefulness of the protocol were further investigated by carrying out
the reactions on scaleꢀup batches to isolate 3a, 3b, and 3s without any significant decrease in
the yields (Table 4).
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Table 4. Scaleꢀup batches for Nꢀacylureasa,b
Interestingly, during the optimization studies for accessing cinnamoyl urea, we observed
that DPPA in the presence of 30 mol% Cu(OAc)2 provided the cinnamamide in 78% yield
(vide supra, Table 1, entry 12). However, the reason behind this unusual behaviour of DPPA
is not very clear at present. Perhaps the acyl isocyanate intermediate formed via Curtius
rearrangement undergoes hydrolysis during workꢀup process to produce the cinnamamide.
Formation of the primary amide as the exclusive product led us to consider whether this
method could provide a general access to this valuable scaffold as a complement to the
existing procedures.21,22 After optimization with different conditions, use of 2.0 equiv. DPPA
and 30 mol% Cu(OTf)2 in DMF/H2O (9.5:0.5) proved to be optimal (entry 4, Table 5). Next,
the scope of αꢀketo thioesters 1 was explored, as shown in Table 6. Various γꢀsubstituted β,γꢀ
unsaturated αꢀketo methylthioesters or αꢀsubstituted αꢀketo thioesters were successfully
converted to their corresponding primary amides in moderate to good yields (4aꢀs).22 It is
noteworthy that the αꢀketo thioesters having an alkyl group at the αꢀposition were also found
to be compatible under the reaction conditions (4tꢀu).22h
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Table 5. Optimization studies for accessing cinnamamide 4aa
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Table 6. Substrate scope of the Cu(OTf)2/DPPAꢀmediated synthesis of primary amidesa
Cu(OTf)2 (30 mol%),
O
2 mL DMF-H2O (v/v 9.5:0.5),
100 oC, 2.5-4 h
O
P
O
SR1
PhO
OPh
R
R
NH2
N3
O
- N2
- CO2
4
1 (1.0 equiv.)
2b (2 equiv.)
Yield up to 92%
20 entries
R = (Het)Ar, Alk; R1 = Alk, Ar
O
O
O
O
NH2
NH2
NH2
NH2
Me
Me
MeO
OMe
4a, 3 h, 90%
4b, 3.5 h, 87%
4c, 4 h, 57%
4d, 3.5 h, 80%
O
O
O
NH2
NH2
NH2
Cl
Br
Cl
(X-ray of 4e)b
4f, 3 h, 74%
4g, 3 h, 63%
4e, 3 h, 77%
O
Cl
O
O
O
Br
NH2
NH2
NH2
NH2
Br
Cl
O2N
Br
4j, 2.5 h, 92%
4i, 3.5 h, 81%
4k, 3 h, 57%
4h, 4 h, 53%
O
O
O
O
NH2
NH2
NH2
NH2
S
NC
4l, 2.5 h, 78%
4o, 4 h, 57%
4n, 3 h, 65%
4m, 3.5 h, 83%
O
O
O
O
NH2
NH2
NH2
NH2
Cl
MeO
4p, 3 h, 72%
4q, 3 h, 43%
4r, 3 h, 60%
4s, 3 h, 72%
O
O
NH2
NH2
4u, 3 h, 54%c
4t, 2.5 h, 66%
aReaction conditions: -Substituted , -unsaturated -keto methylthioesters or
-keto thioesters (0.05 g, equiv.), Cu(OTf)2 (30 mol%), and DPPA 2b
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(2 equiv./mmol) in 2 mL DMF/H2O (v/v 9.5:0.5 mL) at 100 oC. bThe thermal ellipsoids
are shown in 50% probability level. cAlong with 4u, some inseparable mixtures were
present.
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In analogy with the mechanism outlined in Scheme 3, the formation of primary amides 4
could be explained (Scheme 5) by invoking in situ generation of an acyl isocyanate
intermediate IV, which on subsequent reaction with water and elimination of carbon dioxide
could lead to 4 via the unstable intermediate acyl carbamic acid IX.
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Scheme 5. Proposed mechanism for the formation of primary amides 4 from γꢀsubstituted β,γꢀunsaturated αꢀ
keto methylthioesters or αꢀketo thioesters 1
CONCLUSIONS
In summary, we have developed a new and efficient route to Nꢀacylureas from αꢀketo
thioesters, TMSN3, and catalytic Cu(II). CꢀC and CꢀS bond cleavages with retention of the
keto group in αꢀketo thioester are thereby achieved. Examples of the cleavage of these bonds
in a single transformation are still rare. The introduction of DPPA instead of TMSN3 as the
azide source in presence of water provides an alternative synthesis of primary amides via
removal of thioester group from αꢀketo thioesters. Both the reactions are proposed to proceed
through Curtius rearrangement leading to the formation of an acyl isocyanate intermediate,
which then reacts with an additional amount of azide or water and rearranges to afford the
corresponding products. The formation of the reactive intermediates in the proposed
mechanism has been supported by ESIꢀHRMS studies and control experiments. To exhibit
the potentiality of the developed method for Nꢀacylureas, singleꢀstep syntheses of
pivaloylurea and isovaleroylurea are reported.
EXPERIMENTAL SECTION
General Information. Melting points were determined in openꢀend capillary tubes and are
uncorrected. TLC was performed on silica gel plates (Merck silica gel 60, f254), and the spots
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were visualized with UV light (254 and 365 nm) or by charring the plate dipped in 5%
H2SO4ꢀMeOH or vanillin charring solution. 1H and 13C NMR spectra were recorded in CDCl3
or DMSOꢀd6 solvent using TMS as the internal standard. HRMS (m/z) were measured using
EI (magnetic sector, positive ion), ESI (QꢀTOF or LTQ Orbitrap, positive ion) techniques.
Infrared (IR) spectra were recorded on Fourier transform infrared spectroscopy, only intense
peaks were reported.
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General procedure for the synthesis of 3. Cu(OAc)2 (30 mol %) and 3 Å MS (0.05 g) were
taken in a 25 mL flameꢀdried, twoꢀneck, roundꢀbottomed flask, equipped with a magnetic
stirring bar and a condenser, under an argon atmosphere and dried by heating in vacuum. β,γꢀ
Unsaturated αꢀketo methylthioester or αꢀketo thioester 1 (0.05 g, 1.0 equiv) was added into
the mixture. Dry DMF (2.0 mL) and TMSN3 2a (5.0 equiv./mmol) were introduced
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successively, and the resulting reaction mixture was stirred at 80 C, employing time as
mentioned. After completion of the reaction (TLC), saturated NH4Cl solution was added, and
the mixture was extracted with dichloromethane (10 mL). The combined organic layers were
dried over anhydrous Na2SO4 and filtered, and the filtrate was concentrated under reduced
pressure to get a residue. The crude residue was purified by silica gel column
chromatography [230–400; eluent: ethyl acetate/nꢀhexane] to obtain 3.
General procedure for the synthesis of 4. A mixture of β,γꢀUnsaturated αꢀketo
methylthioesters or αꢀketo thioester 1 (0.05 g, 1.0 equiv.), Cu(OTf)2 (30 mol%), 2 mL DMFꢀ
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H2O (v/v 9.5:0.5), and diphenyl phosphoryl azide 2b (2 equiv./mmol) was heated at 100 C,
employing time as mentioned. After completion of the reaction (TLC), saturated NH4Cl
solution was added, and the mixture was extracted with dichloromethane (10 mL). The
combined organic layers were dried over anhydrous Na2SO4 and filtered, and the filtrate was
concentrated under reduced pressure to get a residue. The crude residue was purified by silica
gel column chromatography [230–400; eluent: ethyl acetate/nꢀhexane] to obtain 4.
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NꢀCarbamoylcinnamamide 3a:9b Prepared according to the general procedure discussed
above: Rf = 0.3; eluent, EtOAc/nꢀhexane (45%); white solid (0.041 g, 89% yield); mp 204ꢀ
206 oC (lit.9b 202ꢀ204 oC); solvent of crystallization: dichloromethane/methanol. Spectral data
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are consistent with previously reported values. H NMR (300 MHz, d6ꢀDMSO): δ = 10.33
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(br. s., 1 H), 7.92 (br. s., 1 H), 7.66 (d, J = 15.9 Hz, 1 H), 7.59 ꢀ 7.62 (m, 2 H), 7.44 ꢀ 7.46 (m,
3 H), 7.33 (br. s., 1 H), 6.81 ppm (d, J = 15.9 Hz, 1 H); 13C{1H} NMR (75 MHz, d6ꢀDMSO):
δ = 166.3, 154.2, 143.0, 134.2, 130.5, 129.1 (2 CH), 128.1 (2 CH), 120.4 ppm.
(E)ꢀNꢀCarbamoylꢀ3ꢀ(2,4,5ꢀtrimethylphenyl)acrylamide 3b: Prepared according to the
general procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (45%); white solid
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(0.039 g, 83% yield); mp 214ꢀ216 C. H NMR (600 MHz, d6ꢀDMSO): δ = 10.26 (br. s., 1
H), 7.92 (br. s., 1 H), 7.79 (d, J = 15.6 Hz, 1 H), 7.29 (s, 2 H), 7.03 (br. s., 1 H), 6.66 (d, J =
15.6 Hz, 1 H), 2.30 (s, 3 H), 2.19 ppm (s, 6 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ =
167.0, 154.7, 140.8, 139.4, 135.4, 134.6, 132.6, 130.7, 127.7, 120.5, 19.7, 19.4, 19.2 ppm; IR
(KBr): ṽmax = 3379, 3318, 3223, 1667, 1618, 1417, 1189, 1097 cmꢀ1; HRMS (EI): m/z calcd
for C13H16N2O2 [M]+: 232.1212; found: 232.1203.
(E)ꢀNꢀCarbamoylꢀ3ꢀ(3,5ꢀdimethylphenyl)acrylamide 3c: Prepared according to the
general procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (45%); white solid
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(0.033 g, 71% yield); mp 213ꢀ215 C. H NMR (300 MHz, d6ꢀDMSO): δ = 10.27 (br. s., 1
H), 7.92 (br. s., 1 H), 7.58 (d, J = 15.9 Hz, 1 H), 7.32 (br. s., 1 H), 7.20 (s, 2 H), 7.08 (br. s., 1
H), 6.78 (d, J = 15.6 Hz, 1 H), 2.29 ppm (s, 6 H); 13C{1H} NMR (75 MHz, d6ꢀDMSO): δ =
166.3, 154.2, 143.2, 138.1 (2 CH), 134.1, 132.0, 125.9 (2 CH), 120.1, 20.8 (2 x CH3) ppm; IR
(KBr): ṽmax = 3421, 3316, 1679, 1625, 1405, 1192, 1098 cmꢀ1; HRMS (EI): m/z calcd for
C12H14N2O2 [M]+: 218.1055; found: 218.1056.
(E)ꢀNꢀCarbamoylꢀ3ꢀ(pꢀtolyl)acrylamide 3d:13b Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (45%); white solid (0.028 g, 60% yield);
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mp 219ꢀ221 C. Spectral data are consistent with previously reported values. H NMR (600
MHz, d6ꢀDMSO): δ = 10.28 (br. s., 1 H), 7.91 (br. s., 1 H), 7.61 (d, J = 15.6 Hz, 1 H), 7.47
(d, J = 7.2 Hz, 2 H), 7.30 (br. s., 1 H), 7.24 (d, J = 7.2 Hz, 2 H), 6.73 (d, J = 15.6 Hz, 1 H),
2.31 ppm (s, 3 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 166.9, 154.7, 143.4, 140.9,
131.9, 130.1 (2 CH), 128.5 (2 CH), 119.7, 21.5 ppm.
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(E)ꢀNꢀCarbamoylꢀ3ꢀ(oꢀtolyl)acrylamide 3e: Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (45%); white solid (0.027 g, 58% yield);
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mp 209ꢀ211 C. H NMR (300 MHz, d6ꢀDMSO): δ = 10.37 (br. s., 1 H), 7.93 (br. s., 1 H),
7.87 (d, J = 15.9 Hz, 1 H), 7.53 (d, J = 6.9 Hz, 1 H), 7.27 ꢀ 7.35 (m, 4 H), 6.71 (d, J = 15.9
Hz, 1 H), 2.39 ppm (s, 3 H); 13C{1H} NMR (75 MHz, d6ꢀDMSO): δ = 166.7, 154.6, 140.8,
137.9, 133.4, 131.3, 130.6, 126.9, 126.7, 122.0, 19.8 ppm; IR (KBr): ṽmax = 3375, 3322, 1697,
1603, 1388, 1183, 1100 cmꢀ1; HRMS (ESI): m/z calcd for C11H12N2O2Na [M + Na]+:
227.0797; found: 227.0799.
(E)ꢀNꢀCarbamoylꢀ3ꢀ(2,3,4ꢀtrimethoxyphenyl)acrylamide 3f: Prepared according to the
general procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (50%); white solid
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(0.033 g, 70% yield); mp 190ꢀ192 C. H NMR (300 MHz, d6ꢀDMSO): δ = 10.30 (br. s., 1
H), 7.96 (br. s., 1 H), 7.72 (d, J = 15.9 Hz, 1 H), 7.30 (d, J = 8.7 Hz, 2 H), 6.92 (d, J = 8.7 Hz,
1 H), 6.77 (d, J = 15.9 Hz, 1 H), 3.84 (s, 3 H), 3.83 (s, 3 H), 3.76 ppm (s, 3 H); 13C{1H}
NMR (75 MHz, d6ꢀDMSO): δ = 166.8, 155.5, 154.4, 152.8, 141.9, 137.9, 123.5, 120.5,
119.1, 108.6, 61.3, 60.5, 56.1 ppm; IR (KBr): ṽmax = 3428, 3135, 1690, 1572, 1492, 1286,
1176, 1100, 783 cmꢀ1; HRMS (EI): m/z calcd for C13H16N2O5 [M]+: 280.1059; found:
280.1049.
(E)ꢀNꢀCarbamoylꢀ3ꢀ(3,4ꢀdimethoxyphenyl)acrylamide 3g: Prepared according to the
general procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (50%); white solid
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(0.029 g, 62% yield); mp 210ꢀ212 C. H NMR (300 MHz, d6ꢀDMSO): δ = 10.17 (br. s., 1
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H), 7.94 (br. s., 1 H), 7.60 (d, J = 15.6 Hz, 1 H), 7.29 (br. s., 1 H), 7.17 ꢀ 7.19 (m, 2 H), 7.02
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(d, J = 9.0 Hz, 1 H), 6.69 (d, J = 15.6 Hz, 1 H), 3.80 ppm (s, 6 H); C{1H} NMR (75 MHz,
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d6ꢀDMSO): δ = 166.6, 154.3, 151.0, 148.9, 143.1, 126.9, 122.2, 118.0, 111.8, 110.5, 55.6,
55.5 ppm; IR (KBr): ṽmax = 3372, 3312, 1668, 1599, 1516, 1262, 1182, 1147 cmꢀ1; HRMS
(EI): m/z calcd for C12H14N2O4 [M]+: 250.0954; found: 250.0946.
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(E)ꢀNꢀCarbamoylꢀ3ꢀ(3ꢀmethoxyphenyl)acrylamide 3h: Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (50%); white solid (0.031 g,
66% yield); mp 157ꢀ159 oC. 1H NMR (300 MHz, d6ꢀDMSO): δ = 10.29 (br. s., 1 H), 7.91 (br.
s., 1 H), 7.63 (d, J = 15.9 Hz, 1 H), 7.37 ꢀ 7.40 (m, 1 H), 7.34 (br. s., 1 H), 7.15 ꢀ 7.19 (m, 2
H), 7.01 (dd, J = 2.1, 8.1 Hz, 1 H), 6.81 (d, J = 15.6 Hz, 1 H), 3.79 ppm (s, 3 H); 13C{1H}
NMR (75 MHz, d6ꢀDMSO): δ = 166.6, 160.0, 154.6, 143.2, 136.0, 130.6, 121.2, 120.6,
116.5, 113.7, 55.6 ppm; IR (KBr): ṽmax = 3364, 3221, 1680, 1578, 1382, 1255, 1175 cmꢀ1;
HRMS (EI): m/z calcd for C11H12N2O3 [M]+: 220.0848; found: 220.0842.
(E)ꢀNꢀCarbamoylꢀ3ꢀ(4ꢀhydroxyphenyl)acrylamide 3i:13c Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (50%); white solid (0.025 g,
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54% yield); mp 232ꢀ234 C. Spectral data are consistent with previously reported values. H
NMR (300 MHz, d6ꢀDMSO): δ = 10.20 (br. s., 1 H), 10.06 (br. s., 1 H), 7.95 (br. s., 1 H),
7.56 (d, J = 15.6 Hz, 1 H), 7.44 (d, J = 8.7 Hz, 2 H), 7.26 (br. s., 1 H), 6.82 (d, J = 8.4 Hz, 2
H), 6.58 ppm (d, J = 15.9 Hz, 1 H); 13C{1H} NMR (75 MHz, d6ꢀDMSO): δ = 166.7, 159.9,
154.4, 143.3, 130.1 (2 CH), 125.2, 116.5, 116.0 (2 CH) ppm.
(E)ꢀ3ꢀ(4ꢀ(tertꢀButyl)phenyl)ꢀNꢀcarbamoylacrylamide 3j: Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (45%); white solid (0.037 g,
79% yield); mp 197ꢀ199 oC. 1H NMR (300 MHz, d6ꢀDMSO): δ = 10.30 (br. s., 1 H), 7.93 (br.
s., 1 H), 7.63 (d, J = 15.6 Hz, 1 H), 7.53 (d, J = 8.7 Hz, 2 H), 7.47 (d, J = 8.7 Hz, 2 H), 7.31
(br. s., 1 H), 6.77 (d, J = 15.9 Hz, 1 H), 1.29 ppm (s, 9 H); 13C{1H} NMR (75 MHz, d6ꢀ
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DMSO): δ = 166.4, 154.2, 153.4, 142.8, 131.4, 127.9 (2 CH), 125.9 (2 CH), 119.5, 34.6, 30.9
ppm (3 CH3); IR (KBr): ṽmax = 3386, 2961, 1683, 1579, 1381, 1179 cmꢀ1; HRMS (EI): m/z
calcd for C14H18N2O2 [M]+: 246.1368; found: 246.1364.
(E)ꢀNꢀCarbamoylꢀ3ꢀ(4ꢀchlorophenyl)acrylamide 3k:13b Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (45%); white solid (0.027 g,
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58% yield); mp 234ꢀ236 C. Spectral data are consistent with previously reported values. H
NMR (600 MHz, d6ꢀDMSO): δ = 10.33 (br. s., 1 H), 7.88 (br. s., 1 H), 7.63 (d, J = 15.6 Hz, 1
H), 7.60 (d, J = 8.4 Hz, 2 H), 7.50 (d, J = 8.4 Hz, 2 H), 7.33 (br. s., 1 H), 6.78 ppm (d, J =
15.6 Hz, 1 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 166.5, 154.6, 142.0, 135.3, 133.5,
130.2 (2 CH), 129.6 (2 CH), 121.6 ppm.
(E)ꢀNꢀCarbamoylꢀ3ꢀ(3ꢀchlorophenyl)acrylamide 3l: Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (45%); white solid (0.037 g,
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79% yield); mp 186ꢀ188 C; solvent of crystallization: dichloromethane/acetone. 1H NMR
(600 MHz, d6ꢀDMSO): δ = 10.32 (br. s., 1 H), 7.87 (br. s., 1 H), 7.65 (s, 1 H), 7.63 (d, J =
16.2 Hz, 1 H), 7.55 (d, J = 7.2 Hz, 1 H), 7.45 ꢀ 7.48 (m, 2 H), 7.35 (br. s., 1 H), 6.83 ppm (d,
J = 15.6 Hz, 1 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 166.4, 154.5, 141.7, 136.9,
134.2, 131.4, 130.5, 128.2, 126.8, 122.6 ppm; IR (KBr): ṽmax = 3389, 3338, 3209, 1668, 1626,
1418, 1188, 1093 cmꢀ1; HRMS (EI): m/z calcd for C10H9ClN2O2 [M]+: 224.0353; found:
224.0349.
(E)ꢀNꢀCarbamoylꢀ3ꢀ(2,5ꢀdichlorophenyl)acrylamide 3m:13c Prepared according to the
general procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (45%); white solid
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(0.032 g, 68% yield); mp 209ꢀ211 C. Spectral data are consistent with previously reported
values. 1H NMR (600 MHz, d6ꢀDMSO): δ = 10.37 (br. s., 1 H), 7.83 (br. s., 1 H), 7.79 (d, J =
15.6 Hz, 1 H), 7.70 (d, J = 2.4 Hz, 1 H), 7.59 (d, J = 9.0 Hz, 1 H), 7.52 (dd, J = 2.4, 9.0 Hz, 1
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H), 7.40 (br. s., 1 H), 6.88 ppm (d, J = 15.6 Hz, 1 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO):
δ = 165.9, 154.3, 136.9, 134.3, 132.9, 132.7, 132.3, 131.8, 127.8, 125.7 ppm.
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(E)ꢀNꢀCarbamoylꢀ3ꢀ(2,4ꢀdichlorophenyl)acrylamide 3n: Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (45%); white solid (0.024 g,
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51% yield); mp 200ꢀ202 C. H NMR (600 MHz, d6ꢀDMSO): δ = 10.44 (br. s., 1 H), 7.82 ꢀ
7.85 (m, 2 H), 7.74 (d, J = 1.8 Hz, 1 H), 7.68 (d, J = 8.4 Hz, 1 H), 7.54 (dd, J = 1.8, 9.0 Hz, 1
H), 7.38 (br. s., 1 H), 6.85 ppm (d, J = 15.6 Hz, 1 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO):
δ = 166.0, 154.4, 137.1, 135.9, 135.0, 131.5, 130.1, 129.5, 128.7, 124.6 ppm; IR (KBr): ṽmax
=
3392, 3329, 1667, 1622, 1477, 1187, 1098 cmꢀ1; HRMS (ESI): m/z calcd for
C10H8Cl2N2O2Na [M + Na]+: 280.9861; found: 280.9854.
(E)ꢀ3ꢀ(4ꢀBromophenyl)ꢀNꢀcarbamoylacrylamide 3o: Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (45%); white solid (0.019 g,
40% yield); mp 250ꢀ252 oC. 1H NMR (600 MHz, d6ꢀDMSO): δ = 10.34 (br. s., 1 H), 7.88 (br.
s., 1 H), 7.61 ꢀ 7.66 (m, 3 H), 7.53 (d, J = 8.4 Hz, 2 H), 7.34 (br. s., 1 H), 6.80 ppm (d, J =
16.2 Hz, 1 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 166.5, 154.6, 142.1, 133.9, 132.6 (2
CH), 130.4 (2 CH), 124.2, 121.7 ppm; IR (KBr): ṽmax = 3376, 1739, 1692, 1585, 1397, 1326,
1185 cmꢀ1; HRMS (ESI): m/z calcd for C10H9BrN2O2Na [M + Na]+: 292.9725; found:
292.9725.
(E)ꢀNꢀCarbamoylꢀ3ꢀ(3ꢀcyanophenyl)acrylamide 3p: Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (50%); white solid (0.019 g,
41% yield); mp 236ꢀ238 oC. 1H NMR (600 MHz, d6ꢀDMSO): δ = 10.37 (br. s., 1 H), 8.05 (br.
s., 1 H), 7.91 (d, J = 7.8 Hz, 1 H), 7.88 (d, J = 7.8 Hz, 2 H), 7.68 (d, J = 15.6 Hz, 1 H), 7.65
(d, J = 7.2 Hz, 1 H), 7.36 (br. s., 1 H), 6.87 ppm (d, J = 15.6 Hz, 1 H); 13C{1H} NMR (150
MHz, d6ꢀDMSO): δ = 166.3, 154.5, 141.0, 135.9, 134.0, 132.4 (2 CH), 130.8, 123.3, 118.8,
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112.7 ppm; IR (KBr): ṽmax = 3367, 3330, 3215, 2231, 1665, 1618, 1403, 1184, 1101 cmꢀ1;
HRMS (EI): m/z calcd for C11H9N3O2 [M]+: 215.0695; found: 215.0689.
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(E)ꢀNꢀCarbamoylꢀ3ꢀ(thiophenꢀ2ꢀyl)acrylamide 3q: Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (45%); white solid (0.0282 g,
61% yield); mp 203ꢀ205 oC. 1H NMR (600 MHz, d6ꢀDMSO): δ = 10.26 (br. s., 1 H), 7.89 (br.
s., 1 H), 7.81 (d, J = 15.0 Hz, 1 H), 7.69 (d, J = 4.8 Hz, 1 H), 7.47 (d, J = 3.6 Hz, 1 H), 7.30
(br. s., 1 H), 7.13 (t, J = 4.8 Hz, 1 H), 6.54 ppm (d, J = 15.0 Hz, 1 H); 13C{1H} NMR (150
MHz, d6ꢀDMSO): δ = 166.5, 154.6, 139.6, 136.4, 133.0, 130.1, 129.1, 119.1 ppm; IR (KBr):
ṽmax = 3378, 3332, 1690, 1613, 1388, 1169, 1105 cmꢀ1; HRMS (EI): m/z calcd for C8H8N2O2S
[M]+: 196.0306; found: 196.0300.
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(E)ꢀNꢀCarbamoylꢀ3ꢀ(naphthalenꢀ2ꢀyl)acrylamide 3r: Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (40%); white solid (0.032 g,
68% yield); mp 179ꢀ181 oC. 1H NMR (600 MHz, d6ꢀDMSO): δ = 10.36 (br. s., 1 H), 8.13 (br.
s., 1 H), 7.92 ꢀ 7.98 (m, 4 H), 7.81 (d, J = 15.6 Hz, 1 H), 7.69 (d, J = 9.0 Hz, 1 H), 7.56 ꢀ 7.57
(m, 2 H), 7.34 (br. s., 1 H), 6.92 ppm (d, J = 15.6 Hz, 1 H); 13C{1H} NMR (150 MHz, d6ꢀ
DMSO): δ = 166.7, 154.7, 143.4, 134.2, 133.4, 132.2, 130.5, 129.2, 129.0, 128.2, 127.9,
127.4, 123.7, 121.2 ppm; IR (KBr): ṽmax = 3386, 3321, 3204, 1684, 1628, 1479, 1180 cmꢀ1;
HRMS (EI): m/z calcd for C14H12N2O2 [M]+: 240.0899; found: 240.0895.
(E)ꢀNꢀCarbamoylꢀ3ꢀ(naphthalenꢀ1ꢀyl)acrylamide 3s: Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (40%); white solid (0.033 g,
70% yield); mp 210ꢀ212 oC. 1H NMR (300 MHz, d6ꢀDMSO): δ = 10.45 (br. s., 1 H), 8.42 (d,
J = 15.3 Hz, 1 H), 8.22 (d, J = 7.8 Hz, 1 H), 7.97 ꢀ 8.04 (m, 3 H), 7.79 (d, J = 7.2 Hz, 1 H),
7.55 ꢀ 7.65 (m, 3 H), 7.36 (br. s., 1 H), 6.86 ppm (d, J = 15.3 Hz, 1 H); 13C{1H} NMR (75
MHz, d6ꢀDMSO): δ = 166.2, 154.2, 139.4, 133.4, 131.2, 130.8, 130.6, 128.8, 127.2, 126.4,
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125.8, 125.1, 123.3, 123.2 ppm; IR (KBr): ṽmax = 3373, 1742, 1687, 1585, 1389, 1181, 782
cmꢀ1; HRMS (EI): m/z calcd for C14H12N2O2 [M]+: 240.0899; found: 240.0895.
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(E)ꢀNꢀCarbamoylꢀ3ꢀcyclohexylacrylamide 3t: Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (30%); white solid (0.0216 g, 47% yield);
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mp 189ꢀ191 C. H NMR (300 MHz, d6ꢀDMSO): δ = 10.17 (br. s., 1 H), 7.88 (br. s., 1 H),
7.25 (br. s., 1 H), 6.84 (dd, J = 6.6, 15.3 Hz, 1 H), 6.04 (d, J = 15.3 Hz, 1 H), 2.09 ꢀ 2.18 (m,
1 H), 1.61 ꢀ 1.72 (m, 5 H), 1.03 ꢀ 1.34 ppm (m, 5 H); 13C{1H} NMR (75 MHz, d6ꢀDMSO): δ
= 166.4, 154.3, 152.8, 120.8, 39.6, 31.2 (2 CH2), 25.5 (CH2), 25.2 ppm (2 CH2); IR (KBr):
ṽmax = 3381, 3338, 2925, 2112, 1674, 1616, 1406, 1101 cmꢀ1; HRMS (ESI): m/z calcd for
C10H16N2O2Na [M + Na]+: 219.1110; found: 219.1130.
(E)ꢀNꢀCarbamoylꢀ4ꢀmethylꢀ5ꢀphenylpentꢀ2ꢀenamide 3u: Prepared according to the
general procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (40%); white solid
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(0.020 g, 43% yield); mp 140ꢀ142 C. H NMR (600 MHz, d6ꢀDMSO): δ = 10.15 (br. s., 1
H), 7.81 (br. s., 1 H), 7.16 ꢀ 7.32 (m, 6 H), 6.71 ꢀ 6.76 (m, 1 H), 6.02 (d, J = 15.0 Hz, 1 H),
2.85 ꢀ 2.89 (m, 1 H), 2.42 ꢀ 2.53 (m, 2 H), 1.18 ppm (d, J = 6.6 Hz, 3 H); 13C{1H} NMR (150
MHz, d6ꢀDMSO): δ = 166.3, 154.7, 146.9, 146.4, 128.9 (2 CH), 127.3 (2 CH), 126.6, 124.6,
40.4 (CH2), 38.9, 22.3 ppm; IR (KBr): ṽmax = 3360, 2123, 1734, 1693, 1398, 1207 cmꢀ1;
HRMS (ESI): m/z calcd for C13H16N2O2Na [M + Na]+: 255.1110; found: 255.1124.
(E)ꢀNꢀCarbamoylꢀ5ꢀmethylhexꢀ2ꢀenamide 3v: Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (60%); white solid (0.019 g, 41% yield);
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mp 174ꢀ176 C. H NMR (600 MHz, d6ꢀDMSO): δ = 10.17 (br. s, 1 H), 7.87 (br. s., 1 H),
7.25 (br. s., 1 H), 6.82 ꢀ 6.87 (m, 1 H), 6.05 (d, J = 15.6 Hz, 1 H), 2.05 (t, J = 7.2 Hz, 2 H),
1.65 ꢀ 1.74 (m, 1 H), 0.86 (s, 3 H), 0.85 ppm (s, 3 H); C{1H} NMR (150 MHz, d6ꢀDMSO):
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δ = 166.5, 154.7, 147.4, 124.5, 41.1, 27.7, 22.6 ppm (2 CH3); IR (KBr): ṽmax = 3377, 2120,
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1703, 1686, 1402, 1107 cmꢀ1; HRMS (ESI): m/z calcd for C8H14N2O2Na [M + Na]+:
193.0953; found: 193.0960.
NꢀCarbamoylbenzamide 3aa:9b,16a Prepared according to the general procedure discussed
above: Rf = 0.3; eluent, EtOAc/nꢀhexane (35%); white solid (0.019 g, 56% yield); mp 213ꢀ
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215 C (lit.9b 210ꢀ211 C). Spectral data are consistent with previously reported values. H
NMR (600 MHz, d6ꢀDMSO): δ = 10.53 (br. s., 1 H), 8.04 (br. s., 1 H), 7.93 (d, J = 7.8 Hz, 2
H), 7.60 (t, J = 7.2 Hz, 1 H), 7.48 (t, J = 7.8 Hz, 2 H), 7.39 ppm (br. s., 1 H); 13C{1H} NMR
(150 MHz, d6ꢀDMSO): δ = 168.6, 154.7, 133.2, 133.1, 129.0 (2 CH), 128.6 (2 CH) ppm.
NꢀCarbamoylꢀ3ꢀmethoxybenzamide 3ab:16g Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (40%); white solid (0.023 g, 64% yield);
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mp 165ꢀ167 C. H NMR (600 MHz, d6ꢀDMSO): δ = 10.54 (br. s., 1 H), 8.03 (br. s., 1 H),
7.52 (d, J = 7.8 Hz, 1 H), 7.49 (br. s., 1 H), 7.37 ꢀ 7.40 (m, 2 H), 7.15 (d, J = 7.8 Hz, 1 H),
3.80 ppm (s, 3 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 168.3, 159.6, 154.6, 134.5,
130.1, 120.9, 119.5, 113.2, 55.8 ppm; IR (KBr): ṽmax = 3366, 3319, 1706, 1667, 1593, 1382,
1233, 1091 cmꢀ1; HRMS (EI): m/z calcd for C9H10N2O3 [M]+: 194.0691; found: 194.0690.
NꢀCarbamoylꢀ4ꢀmethoxybenzamide 3ac:16a Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (50%); white solid (0.0218 g, 61% yield);
mp 214ꢀ216 C (lit.16a 214ꢀ216 C). Spectral data are consistent with previously reported
values. 1H NMR (300 MHz, d6ꢀDMSO): δ = 10.39 (br. s., 1 H), 8.10 (br. s., 1 H), 7.98 (d, J =
9.0 Hz, 2 H), 7.34 (br. s., 1 H), 7.02 (d, J = 8.7 Hz, 2 H), 3.83 ppm (s, 3 H); 13C{1H} NMR
(75 MHz, d6ꢀDMSO): δ = 167.4, 162.8, 154.4, 130.3 (2 CH), 124.6, 113.8 (2 CH), 55.5 ppm.
NꢀCarbamoylꢀ3,4ꢀdimethylbenzamide 3ad: Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (30%); white solid (0.02 g, 56% yield);
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mp 186ꢀ188 C. H NMR (600 MHz, d6ꢀDMSO): δ = 10.37 (br. s., 1 H), 8.06 (br. s., 1 H),
7.77 (s, 1 H), 7.69 (d, J = 6.6 Hz, 1 H), 7.35 (br. s., 1 H), 7.24 (d, J = 7.2 Hz, 1 H), 2.26 (s, 3
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H), 2.25 ppm (s, 3 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 168.5, 154.7, 142.2, 137.0,
130.5, 130.0, 129.6, 126.1, 19.9, 19.8 ppm; IR (KBr): ṽmax = 3373, 3331, 1687, 1600, 1383,
1260, 1106 cmꢀ1; HRMS (EI): m/z calcd for C10H12N2O2 [M]+: 192.0899; found: 192.0888.
NꢀCarbamoylꢀ4ꢀchlorobenzamide 3ae:16c,d Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (35%); white solid (0.014 g, 39% yield);
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mp 231ꢀ233 C (lit16d 252ꢀ253 C). Spectral data are consistent with previously reported
values. 1H NMR (300 MHz, d6ꢀDMSO): δ = 10.64 (br. s., 1 H), 7.98 (br. s., 1 H), 7.97 (d, J =
8.7 Hz, 2 H), 7.58 (d, J = 8.4 Hz, 2 H), 7.44 ppm (br. s., 1 H); 13C{1H} NMR (150 MHz, d6ꢀ
DMSO): δ = 167.6, 154.5, 138.0, 132.0, 130.6 (2 CH), 129.0 (2 CH) ppm.
NꢀCarbamoylꢀ2ꢀnaphthamide 3af:16e,f Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (35%); white solid (0.02 g, 55% yield);
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mp 226ꢀ228 C (lit16f 207ꢀ208 C). H NMR (600 MHz, d6ꢀDMSO): δ = 10.67 (br. s., 1 H),
8.63 (s, 1 H), 8.09 (br. s., 1 H), 8.03 (d, J = 7.8 Hz, 1 H), 7.98 ꢀ 8.01 (m, 2 H), 7.95 ꢀ 7.97 (m,
1 H), 7.65 (t, J = 7.8 Hz, 1 H), 7.60 (t, J = 7.8 Hz, 1 H), 7.44 ppm (br. s., 1 H); 13C{1H} NMR
(150 MHz, d6ꢀDMSO): δ = 168.7, 154.7, 135.2, 132.3, 130.4, 129.7, 129.7, 128.9, 128.6,
128.1, 127.4, 124.7 ppm.
NꢀCarbamoylꢀ[1,1'ꢀbiphenyl]ꢀ4ꢀcarboxamide 3ag: Prepared according to the general
procedure discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (35%); white solid (0.018 g,
48% yield); mp 232ꢀ234 oC. 1H NMR (600 MHz, d6ꢀDMSO): δ = 10.59 (br. s., 1 H), 8.07 (br.
s., 1 H), 8.05 (d, J = 8.4 Hz, 2 H), 7.80 (d, J = 7.8 Hz, 2 H), 7.74 (d, J = 7.8 Hz, 2 H), 7.49 (t,
J = 7.2 Hz, 2 H), 7.41 ppm (t, J = 7.2 Hz, 2 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ =
168.2, 154.7, 144.6, 139.3, 131.9, 129.6 (2 CH), 129.3 (2 CH), 128.8, 127.4 (2 CH), 127.1 (2
CH) ppm; IR (KBr): ṽmax = 3381, 3333, 1702, 1668, 1597, 1385, 1265, 1097 cmꢀ1; HRMS
(EI): m/z calcd for C14H12N2O2 [M]+: 240.0899; found: 240.0895.
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NꢀCarbamoylpivalamide 3ah:17a,c Prepared according to the general procedure discussed
above: Rf = 0.3; eluent, EtOAc/nꢀhexane (30%); white solid (0.0144 g, 44% yield); mp 149ꢀ
151 oC (lit17c 145ꢀ147 oC). 1H NMR (300 MHz, d6ꢀDMSO): δ = 9.68 (br. s., 1 H), 7.90 (br. s.,
1 H), 7.20 (br. s., 1 H), 1.15 ppm (s, 9 H); 13C{1H} NMR (75 MHz, d6ꢀDMSO): δ = 180.0,
154.5, 38.9, 26.4 ppm (3 x CH3).
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NꢀCarbamoylꢀ3ꢀmethylbutanamide 3ai:1b Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (30%); white solid (0.0126 g, 39% yield);
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mp 191ꢀ193 C (lit17d 206ꢀ208 C). H NMR (300 MHz, d6ꢀDMSO): δ = 10.11 (br. s., 1 H),
7.79 (br. s., 1 H), 7.20 (br. s., 1 H), 2.15 (d, J = 7.5 Hz, 2 H), 1.92 ꢀ 2.06 (m, 1 H), 0.88 ppm
(d, J = 6.6 Hz, 6 H); 13C{1H} NMR (75 MHz, d6ꢀDMSO): δ = 174.3, 154.0, 44.8, 25.2 (CH2),
22.2 ppm (2 x CH3).
NꢀCarbamoylꢀ2ꢀmethylbutanamide 3aj:17e Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (40%); white solid (0.0134 g, 41% yield);
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mp 180ꢀ182 C (lit17e 178ꢀ180 C). Spectral data are consistent with previously reported
values. 1H NMR (600 MHz, d6ꢀDMSO): δ = 10.13 (br. s., 1 H), 7.81 (br. s., 1 H), 7.21 (br. s.,
1 H), 2.37 (sxt, J = 6.6 Hz, 1 H), 1.52 (dquin, J = 7.2, 15.0 Hz, 1 H), 1.32 (dquin, J = 7.2,
13.8 Hz, 1 H), 0.99 (d, J = 7.2 Hz, 3 H), 0.79 ppm (t, J = 7.2 Hz, 3 H); 13C{1H} NMR (150
MHz, d6ꢀDMSO): δ = 178.7, 154.5, 41.9, 26.8 (CH2), 17.3, 11.9 ppm.
NꢀCarbamoylbutyramide 3ak:17f Prepared according to the general procedure discussed
above: Rf = 0.3; eluent, EtOAc/nꢀhexane (40%); white solid (0.0117 g, 37% yield); mp 176ꢀ
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178 C (lit17f 173ꢀ174 C). H NMR (600 MHz, d6ꢀDMSO): δ = 10.10 (br. s., 1 H), 7.76 (br.
s., 1 H), 7.19 (br. s., 1 H), 2.22 (t, J = 7.2 Hz, 2 H), 1.51 (sxt, J = 7.2, 14.4 Hz, 2 H), 0.84
ppm (t, J = 7.2 Hz, 3 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 175.2, 154.4, 38.0 (CH2),
18.3 (CH2), 13.9 ppm.
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Cinnamamide 4a:22a Prepared according to the general procedure discussed above: Rf = 0.3;
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eluent, EtOAc/nꢀhexane (60%); white solid (0.032 g, 90% yield); mp 146ꢀ148 C (lit.22a 144
oC). Spectral data are consistent with previously reported values. H NMR (300 MHz, d6ꢀ
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DMSO): δ = 7.55 ꢀ 7.57 (m, 3 H), 7.37 ꢀ 7.45 (m, 4 H), 7.13 (br. s., 1 H), 6.61 ppm (d, J =
15.9 Hz, 1 H); 13C{1H} NMR (75 MHz, d6ꢀDMSO): δ = 166.8, 139.3, 134.9, 129.5, 129.0 (2
CH), 127.6 (2 CH), 122.3 ppm.
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(E)ꢀ3ꢀ(oꢀTolyl)acrylamide 4b:22b Prepared according to the general procedure discussed
above: Rf = 0.3; eluent, EtOAc/nꢀhexane (60%); white solid (0.032 g, 87% yield); mp 172ꢀ
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174 C (lit.22i 176ꢀ178 C). Spectral data are consistent with previously reported values. H
NMR (600 MHz, d6ꢀDMSO): δ = 7.62 (d, J = 16.2 Hz, 1 H), 7.57 (br. s., 1 H), 7.51 (d, J =
7.2 Hz, 1 H), 7.21 ꢀ 7.25 (m, 3 H), 7.13 (br. s., 1 H), 6.49 (d, J = 15.6 Hz, 1 H), 2.35 ppm (s,
3 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 167.2, 137.2, 137.1, 134.1, 131.1, 129.7,
126.8, 126.4, 123.9, 19.9 ppm.
(E)ꢀ3ꢀ(pꢀTolyl)acrylamide 4c:22b Prepared according to the general procedure discussed
above: Rf = 0.3; eluent, EtOAc/nꢀhexane (60%); white solid (0.021 g, 57% yield); mp 190ꢀ
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192 C (lit22j 190ꢀ191 C). Spectral data are consistent with previously reported values. H
NMR (600 MHz, d6ꢀDMSO): δ = 7.49 (br. s., 1 H), 7.43 (d, J = 7.8 Hz, 2 H), 7.36 (d, J =
15.6 Hz, 1 H), 7.20 (d, J = 7.8 Hz, 2 H), 7.06 (br. s., 1 H), 6.53 (d, J = 16.2 Hz, 1 H), 2.30
ppm (s, 3 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 167.3, 139.7, 139.6, 132.6, 130.0 (2
CH), 128.0 (2 CH), 121.7, 21.4 ppm.
(E)ꢀ3ꢀ(3,4ꢀDimethoxyphenyl)acrylamide 4d:22a Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (90%); white solid (0.031 g, 80% yield);
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mp 163ꢀ165 C (lit.22a 166 C). Spectral data are consistent with previously reported values.
1H NMR (600 MHz, d6ꢀDMSO): δ = 7.43 (br. s., 1 H), 7.33 (d, J = 15.6 Hz, 1 H), 7.14 (s, 1
H), 7.08 (d, J = 7.8 Hz, 1 H), 7.00 (br. s., 1 H), 6.96 (d, J = 8.4 Hz, 1 H), 6.47 (d, J = 15.6 Hz,
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1 H), 3.78 (s, 3 H), 3.76 ppm (s, 3 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 167.5,
150.5, 149.3, 139.8, 128.1, 121.9, 120.4, 112.1, 110.3, 56.0, 55.9 ppm.
(E)ꢀ3ꢀ(4ꢀChlorophenyl)acrylamide 4e:22b Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (60%); white solid (0.029 g, 77 % yield);
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mp 207ꢀ209 C (lit22j 210ꢀ211 C); solvent of crystallization: dichloromethane/acetone.
Spectral data are consistent with previously reported values. 1H NMR (600 MHz, d6ꢀDMSO):
δ = 7.57 (d, J = 8.4 Hz, 3 H), 7.45 (d, J = 7.2 Hz, 2 H), 7.38 (d, J = 15.6 Hz, 1 H), 7.14 (br. s.,
1 H), 6.60 ppm (d, J = 15.6 Hz, 1 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 166.9,
138.3, 134.3, 134.3, 129.7 (2 CH), 129.4 (2 CH), 123.6 ppm.
(E)ꢀ3ꢀ(3ꢀChlorophenyl)acrylamide 4f:22c Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (60%); white solid (0.028 g, 74% yield);
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mp 122ꢀ124 C. Spectral data are consistent with previously reported values. H NMR (600
MHz, CDCl3): δ = 7.59 (d, J = 15.6 Hz, 1 H), 7.50 (s, 1 H), 7.37 (d, J = 7.2 Hz, 1 H), 7.29 ꢀ
7.34 (m, 2 H), 6.47 (d, J = 15.6 Hz, 1 H), 5.93 (br. s., 1 H), 5.83 ppm (br. s., 1 H); 13C{1H}
NMR (150 MHz, CDCl3): δ = 167.5, 141.2, 136.3, 134.9, 130.2, 129.9, 127.5, 126.4, 120.8
ppm.
(E)ꢀ3ꢀ(4ꢀBromophenyl)acrylamide 4g:22a Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (60%); white solid (0.025 g, 63% yield);
mp 211ꢀ213 C (lit.22a 214 C). Spectral data are consistent with previously reported values.
1H NMR (300 MHz, d6ꢀDMSO): δ = 7.61 (d, J = 8.4 Hz, 3 H), 7.51 (d, J = 8.4 Hz, 2 H), 7.38
(d, J =15.6 Hz, 1 H), 7.15 (br. s., 1 H), 6.62 ppm (d, J = 16.2 Hz, 1 H); 13C{1H} NMR (75
MHz, d6ꢀDMSO): δ = 166.5, 138.0, 134.2, 131.9 (2 CH), 129.6 (2 CH), 123.2, 122.6 ppm.
(E)ꢀ3ꢀ(2ꢀBromophenyl)acrylamide 4h:22e Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (60%); white solid (0.021 g, 53% yield);
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mp 172ꢀ174 C. Spectral data are consistent with previously reported values. H NMR (600
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MHz, d6ꢀDMSO): δ = 7.68 (d, J = 7.8 Hz, 3 H), 7.63 ꢀ 7.64 (m, 1 H), 7.43 (t, J = 7.8 Hz, 1
H), 7.30 (t, J = 7.8 Hz, 1 H), 7.25 (br. s., 1 H), 6.61 ppm (d, J = 15.6 Hz, 1 H); 13C{1H} NMR
(150 MHz, d6ꢀDMSO): δ = 166.5, 137.6, 134.9, 133.7, 131.6, 128.8, 128.1, 126.0, 124.6
ppm.
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(E)ꢀ3ꢀ(2,5ꢀDibromophenyl)acrylamide 4i: Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (60%); white solid (0.034 g, 81% yield);
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mp 189ꢀ191 C. H NMR (600 MHz, d6ꢀDMSO): δ = 7.84 (d, J = 2.4 Hz, 1 H), 7.63 (d, J =
9.0 Hz, 1 H), 7.56 (br. s., 1 H), 7.55 (d, J = 15.6 Hz, 1 H), 7.49 (dd, J = 1.8, 8.4 Hz, 1 H),
7.31 (br. s., 1 H), 6.68 ppm (d, J = 15.6 Hz, 1 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ =
166.2, 137.2, 136.1, 135.5, 134.0, 130.5, 127.6, 123.4, 121.7 ppm; IR (KBr): ṽmax = 3373,
3177, 1671, 1618, 1389, 1022 cmꢀ1; HRMS (EI): m/z calcd for C9H7Br2NO [M]+: 302.8894;
found: 302.8899.
(E)ꢀ3ꢀ(2,6ꢀDichlorophenyl)acrylamide 4j:22a Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (60%); white solid (0.036 g, 92% yield);
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mp 159ꢀ161 C (lit.22a 164 C). Spectral data are consistent with previously reported values.
1H NMR (600 MHz, CDCl3): δ = 7.74 (d, J = 16.2 Hz, 1 H), 7.35 (d, J = 8.4 Hz, 2 H), 7.18 (t,
J = 7.8 Hz, 1 H), 6.62 (d, J = 16.2 Hz, 1 H), 5.88 (br. s., 1 H), 5.74 ppm (br. s., 1 H); 13C{1H}
NMR (150 MHz, CDCl3): δ = 166.9, 136.1, 135.0, 132.2, 129.7, 128.8 (3 CH), 128.0 ppm.
(E)ꢀ3ꢀ(4ꢀNitrophenyl)acrylamide 4k:22b Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (70%); light yellow solid (0.022 g, 57%
o
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yield); mp 220ꢀ222 C (lit22j 216ꢀ217 C). Spectral data are consistent with previously
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reported values. H NMR (600 MHz, d6ꢀDMSO): δ = 8.24 (d, J = 7.8 Hz, 2 H), 7.82 (d, J =
7.8 Hz, 2 H), 7.68 (br. s., 1 H), 7.50 (d, J = 16.2 Hz, 1 H), 7.29 (br. s., 1 H), 6.78 ppm (d, J =
15.6 Hz, 1 H); 13C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 166.4, 148.0, 142.0, 137.3, 129.1 (2
CH), 127.1, 124.6 (2 CH) ppm.
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(E)ꢀ3ꢀ(4ꢀCyanophenyl)acrylamide 4l:22b Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (60%); white solid (0.029 g, 78% yield);
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mp 182ꢀ184 C. Spectral data are consistent with previously reported values. H NMR (600
MHz, d6ꢀDMSO): δ = 7.86 (d, J = 7.8 Hz, 2 H), 7.73 (d, J = 8.4 Hz, 2 H), 7.63 (br. s., 1 H),
7.45 (d, J = 15.6 Hz, 1 H), 7.24 (br. s., 1 H), 6.73 ppm (d, J = 15.6 Hz, 1 H); 13C{1H} NMR
(150 MHz, d6ꢀDMSO): δ = 166.5, 140.0, 137.8, 133.3 (2 CH), 128.7 (2 CH), 126.3, 119.2,
111.9 ppm.
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(E)ꢀ3ꢀ(Thiophenꢀ2ꢀyl)acrylamide 4m:22b Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (50%); white solid (0.03 g, 83% yield);
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mp 162ꢀ163 C (lit22k 152ꢀ153 C). Spectral data are consistent with previously reported
values. 1H NMR (600 MHz, d6ꢀDMSO): δ = 7.76 (br. s., 1 H), 7.58 (t, J = 4.2 Hz, 1 H), 7.47
(br. s., 1 H), 7.39 (d, J = 15.6 Hz, 1 H), 7.33 (d, J = 4.8 Hz, 1 H), 7.03 (br. s., 1 H), 6.40 ppm
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(d, J = 15.6 Hz, 1 H); C{1H} NMR (150 MHz, d6ꢀDMSO): δ = 167.4, 138.3, 133.7, 128.1,
127.9, 125.6, 122.2 ppm.
(E)ꢀ3ꢀ(Naphthalenꢀ1ꢀyl)acrylamide 4n:22f Prepared according to the general procedure
discussed above: Rf = 0.3; eluent, EtOAc/nꢀhexane (60%); white solid (0.025 g, 65% yield);
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mp 172ꢀ174 C (lit.22f 177 C). Spectral data are consistent with previously reported values.
1H NMR (300 MHz, d6ꢀDMSO): δ = 8.18 ꢀ 8.23 (m, 2 H), 7.97 ꢀ 7.99 (m, 2 H), 7.79 (d, J =
6.9 Hz, 1 H), 7.70 (br. s., 1 H), 7.58 ꢀ 7.65 (m, 2 H), 7.55 (d, J = 7.5 Hz, 1 H), 7.22 (br. s., 1
H), 6.67 ppm (d, J = 15.9 Hz, 1 H); 13C{1H} NMR (75 MHz, d6ꢀDMSO): δ = 167.1, 136.1,
133.8, 132.4, 131.3, 130.0, 129.1, 127.3, 126.7, 126.2, 125.8, 124.9, 123.7 ppm.
(E)ꢀ3ꢀCyclohexylacrylamide 4o:22d Prepared according to the general procedure discussed
above: Rf = 0.3; eluent, EtOAc/nꢀhexane (55%); white solid (0.0207 g, 57% yield); mp 138ꢀ
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140 oC. Spectral data are consistent with previously reported values. H NMR (300 MHz, d6ꢀ
DMSO): δ = 7.34 (br. s., 1 H), 6.88 (br. s., 1 H), 6.55 (dd, J = 6.6, 15.6 Hz, 1 H), 5.80 (dd, J
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= 0.9, 15.6 Hz, 1 H), 2.02 ꢀ 2.12 (m, 1 H), 1.60 ꢀ 1.71 (m, 5 H), 1.01 ꢀ 1.33 ppm (m, 5 H);
13C{1H} NMR (75 MHz, d6ꢀDMSO): δ = 166.9, 148.0, 122.1, 39.2, 31.6 (2 CH2), 25.6 (CH2),
25.3 ppm (2 CH2).
Benzamide 4p:22c Prepared according to the general procedure discussed above: Rf = 0.3;
eluent, EtOAc/nꢀhexane (30%); white solid (0.018 g, 72% yield); mp 122ꢀ124 oC (lit.22c 128ꢀ
129 oC). Spectral data are consistent with previously reported values. 1H NMR (300 MHz, d6ꢀ
DMSO): δ = 7.98 (br. s., 1 H), 7.86 ꢀ 7.88 (m, 2 H), 7.39 ꢀ 7.55 (m, 3 H), 7.37 ppm (br. s., 1
H); 13C{1H} NMR (75 MHz, CDCl3, with few drops of d6ꢀDMSO): δ = 168.9, 133.2, 130.9,
127.6 (2 CH), 126.9 ppm (2 CH).
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4ꢀMethoxybenzamide 4q:22c Prepared according to the general procedure discussed above:
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Rf = 0.3; eluent, EtOAc/nꢀhexane (50%); white solid (0.012 g, 43% yield); mp 164ꢀ166 C
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(lit22c 167ꢀ168 C). Spectral data are consistent with previously reported values. H NMR
(300 MHz, d6ꢀDMSO): δ = 7.84 (d, J = 8.4 Hz, 3 H), 7.18 (br. s., 1 H), 6.97 (d, J = 8.4 Hz, 2
H), 3.80 ppm (s, 3 H); 13C{1H} NMR (75 MHz, CDCl3; with few drops of d6ꢀDMSO): δ =
168.2, 161.4, 128.8 (2 CH), 125.4, 112.7 (2 CH), 54.6 ppm.
4ꢀChlorobenzamide 4r:22c Prepared according to the general procedure discussed above: Rf
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= 0.3; eluent, EtOAc/nꢀhexane (30%); white solid (0.0169 g, 60% yield); mp 180ꢀ182 C
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(lit.22c 178ꢀ179 C). Spectral data are consistent with previously reported values. H NMR
(300 MHz, d6ꢀDMSO): δ = 8.05 (br. s., 1 H), 7.88 (d, J = 8.4 Hz, 2 H), 7.52 (d, J = 8.4 Hz, 2
H), 7.47 ppm (br. s., 1 H); 13C{1H} NMR (75 MHz, CDCl3; with few drops of d6ꢀDMSO): δ
= 167.8, 136.9, 131.7, 128.6 (2 CH), 127.8 ppm (2 CH).
2ꢀNaphthamide 4s:22c Prepared according to the general procedure discussed above: Rf =
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0.3; eluent, EtOAc/nꢀhexane (50%); white solid (0.021 g, 72% yield); mp 200ꢀ202 C (lit.22c
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196ꢀ197 C). Spectral data are consistent with previously reported values. H NMR (300
MHz, d6ꢀDMSO): δ = 8.49 (s, 1 H), 8.15 (br. s., 1 H), 7.97 ꢀ 8.02 (m, 4 H), 7.56 ꢀ 7.63 (m, 2
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