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Article Cite This: J. Org. Chem. 2018, 83, 2114−2124

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Copper(II)-Catalyzed Reactions of α‑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* Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata, West Bengal 700 032, India S Supporting Information *

ABSTRACT: 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 αketo 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, onestep syntheses of pivaloylurea and isovaleroylurea, displaying anticonvulsant activities, have been carried out.

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Continuing our efforts for the exploration of α-keto 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 N-acylureas, N-cinnamoyl ureas, and N-aroylureas; 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

INTRODUCTION The N-acylurea moiety is a functional group commonly found in a broad spectrum of medicinal and therapeutic agents.1,2 For example, some are known to possess promising anticonvulsant, anti-inflammatory, analgesic, antifungal, antitumor, and antiproliferative activities1 or are used in agriculture as insecticides.2 N-Acylureas are also important building blocks in organic syntheses.3 Various synthetic strategies have been developed for accessing N-acylureas.4−9 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/S-allyl Nacylmonothiocarbamates.5 Other methods starting from ureas include arylboronic acid-catalyzed direct condensation with carboxylic acids6a and acylation with alk-1-en-2-yl esters.6b Recently, the syntheses of N-acylureas have also been accomplished via microwave-assisted Pd-catalyzed carbonylation of aryl or heteroaryl halides with urea nucleophiles using CO gas/Mo(CO)6,7 Rh(III)-catalyzed C−H functionalization of indolines with aryl and alkyl isocyanates,8 or NHCcatalyzed oxidative coupling of aldehydes with N,N′-disubstituted carbodiimides under aerobic conditions.9a Solid-phase synthesis of N-acylureas or cinnamoyl ureas from resin-bound 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 N-acylureas from readily accessible starting materials continues to captivate organic chemists. © 2018 American Chemical Society

Scheme 1. Proposed Synthesis of N-Acylureas 3 and Primary Amides 4 from α-Keto Thioesters and Azides

Received: December 4, 2017 Published: February 2, 2018 2114

DOI: 10.1021/acs.joc.7b03054 J. Org. Chem. 2018, 83, 2114−2124

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The Journal of Organic Chemistry

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 of TMSN3 (entry 13) or 10 mol % of Cu(OAc)2 (entry 14), generating only moderate yields. Different solvents such as DMSO and MeCN were also screened (entries 15 and 16), but without success. The yield of product 3a also decreased when the reaction was conducted at 60 or 100 °C (entries 17 and 18). Only moderate yields were achieved in the absence of any catalyst or solvent, as side reactions were observed (entries 19 and 20). With the optimal reaction conditions (entry 8, Table 1), the substrate scope and generality for this transformation was investigated using various γ-substituted β,γ-unsaturated α-keto methylthioesters 1 and TMSN3 2a, the results of which are given in Table 2. The reaction tolerates a wide range of γsubstituted α-keto methylthioesters. Substrates containing an aromatic ring at the γ-position of thioesters with electron-rich (1b−j) or electron-poor (1k−n) substituents delivered the corresponding substituted cinnamoyl ureas in moderate to good yields (3b−n).9b,13 The p-bromo-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 electron-withdrawing 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 γ-naphthyl substituents yielded the corresponding products (3r,s). Moreover, α-keto thioesters with an alkyl group at the γ-position (1t−v) also furnished the desired products 3t−v in moderate yields. The structures of 3a and 3l were established by singlecrystal X-ray diffraction analysis (Table 2).15 Subsequently, we extended the scope of the reaction with aryl- rather than styryl-substituted α-keto thioesters (Table 3). Under the standard reaction conditions shown in Table 2, substrates containing electron-neutral (1aa), electron-donating (1ab−1ad), and electron-withdrawing (1ae) substituents in the aromatic ring or with a fused aromatic ring (1af) or a biphenyl substituent (1ag) at the α-position of the α-keto thioesters delivered the corresponding N-aroylureas in moderate yields (3aa−ag).9b,16 The synthetic versatility of this developed methodology was established by single-step syntheses of pivaloylurea 3ah, isovaleroylurea 3ai, 2-methylbutanoylurea 3aj, and n-butyrylurea 3ak from the corresponding α-keto thioesters 1ah−1ak (Scheme 2).1b,17 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 sulfur atom of the thioesters, increasing their electrophilicity. Nucleophilic substitution by azide followed by elimination of a 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 a thiolate anion catalyzed by copper, as described in the literature, to yield product 3.19 Alternatively

transformation of the thioester group into a urea moiety via cleavage of the C−C and C−S 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 α-keto thioesters via removal of the thioester group (Scheme 1).

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RESULTS AND DISCUSSION To optimize the reaction conditions for cinnamoyl urea, we initiated model studies with γ-phenyl-substituted β,γ-unsaturated α-keto methylthioesters 1a, different azide sources 2, dry DMF, and 3 Å MS under 30 mol % copper catalysis at 80 °C (Table 1). We were pleased to observe that CuCl could Table 1. Optimization Studies for Accessing Cinnamoyl Urea 3aa,b

entry

azide source

Cu source

time (h)

yield 3a (%)

yield 4a (%)

1 2 3 4 5 6 7 8 9c 10 11c 12 13d 14e 15f 16g 17h 18i 19 20j

TMSN3 TMSN3 TMSN3 TMSN3 TMSN3 TMSN3 TMSN3 TMSN3 TBAA NaN3 TsN3 DPAA TMSN3 TMSN3 TMSN3 TMSN3 TMSN3 TMSN3 TMSN3 TMSN3

CuCl CuBr Cu2O CuCl2 CuBr2 Cu(acac)2 Cu(OTf)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 none Cu(OAc)2

1.5 3 1.5 10 24 1.5 1 1 1.5 4 5 5 1 1 1 5 1.5 2 3 3

66 73 53 trace 48 trace 74 89 nd 28 n.d. nd 77 55 35 nd 42 72 41 55

nd nd nd trace nd trace nd nd nd nd nd 78 nd nd nd nd nd nd nd nd

a

Reaction conditions: 1a (0.03 g, 0.145 mmol), azide 2 (equiv/mmol), and Cu salt (mol %) in 3 Å MS (0.03 g) were heated in 1.0 mL of DMF at 80 °C, employing time as noted. bnd = product not detected. c The starting materials were decomposed. Undetermined byproducts were observed. d3.0 equiv of TMSN3 was used. e10 mol % of Cu(OAc)2 was used. fDMSO was used as a solvent instead of DMF. g MeCN was used as a solvent instead of DMF; starting materials isolated. hThe reaction was conducted at 60 °C. iThe reaction was conducted at 100 °C. jThe reaction was carried out without any solvent. Cu(acac)2 = copper(II) acetylacetonate.

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, CuBr2, Cu(acac)2, and Cu(OTf)2 proved inferior (entries 2−7), utilization of Cu(OAc)2 as a catalyst could significantly improve the yield to 89%, and the reaction proceeded to completion within 1 h (entry 8). Subsequent attempts with commercially available azide sources such as tetrabutylammonium azide (TBAA), NaN3, and ptoluenesulfonyl azide (TsN3) proved discouraging (entries 9− 11). The use of diphenylphosphoryl azide (DPPA) as an azide 2115

DOI: 10.1021/acs.joc.7b03054 J. Org. Chem. 2018, 83, 2114−2124

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The Journal of Organic Chemistry Table 2. Substrate Scope of the Cu(OAc)2/TMSN3Mediated Synthesis of N-Acylureas from γ-Substituted β,γUnsaturated α-Keto Methylthioestersa

Table 3. Substrate Scope of the Cu(OAc)2/TMSN3Mediated Synthesis of N-Aroylureas from α-Keto Thioestersa

a

Unless otherwise noted, all the reactions were carried out under the conditions given in Table 2. Along with the products 3aa−ag, Ph2S2 in 10% yield was isolated in all of the experiments.

Scheme 2. Syntheses of Pivaloylurea, Isovaleroylurea, 2Methylbutanoylurea, and n-Butyrylureaa

a Along with the products, Ph2S2 (10−12% yield) was isolated in all the experiments. bThe reaction was carried out at 70°C.

Scheme 3. Proposed Mechanism for the Formation of NAcylureas from γ-Substituted β,γ-Unsaturated α-Keto Methylthioesters or α-Keto Thioesters

a Reaction conditions: γ-substituted β,γ-unsaturated α-keto methylthioesters 1 (0.05 g, 1 equiv), 3 Å MS (0.05 g), Cu(OAc)2 (30 mol %), and TMSN3 2a (5 equiv/mmol) in dry DMF (2.0 mL) at 80 °C. bThe thermal ellipsoids are shown at a 50% probability level. cThe reaction was carried out at 60 °C. dThe reaction was carried out at 70 °C. e Along with 3v, some inseparable mixtures were present.

(pathway b), IV could react with TMSN3 to produce the carbamoyl azide VIII (a 1,4-adduct), 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 noteworthy that a large excess of TMSN3 (5 equiv) is critical to obtain N-acylureas in moderate to high yields. In order to support our proposed mechanistic model, we next decided to use ESI-HRMS (LTQ Orbitrap) studies as a means of probing the proposed intermediates from the reaction mixtures. α-Keto 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

analyzed by ESI-HRMS (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 2116

DOI: 10.1021/acs.joc.7b03054 J. Org. Chem. 2018, 83, 2114−2124

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The Journal of Organic Chemistry

isolated diphenyl disulfide (Ph2S2) in 10−12% yield during all the reactions discussed above. 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 of TMSN3 and Cu(OAc)2 in DMSO at room temperature, and the reaction was quenched either with MeOH or piperidine after 5 min, and the carbamate 5a or urea 5b derivative was obtained, as expected, along with the desired N-acylurea 3aa. These two parallel experiments support the formation of the intermediate IV. Moreover, the formation of primary amides 4 (Table 6, vide infra) from α-keto thioesters 1 in the presence of water provides direct evidence for the generation of acyl isocyanate IV intermediate via Curtius rearrangement. Furthermore, to clarify the mechanism of the reduction of azide to amine via a nitrene intermediate, carbamoyl azide VIII was prepared independently from the literature precedent19a 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. In parallel, 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 takes place is uncertain at this point, and further investigations are ongoing to find it.19b,c,20 The utility and practical usefulness of the protocol were further investigated by carrying out the reactions on scale-up batches to isolate 3a, 3b, and 3s without any significant decrease in the yields (Table 4).

Figure 1. ESI-HRMS (LTQ Orbitrap) spectrum of the crude reaction mixture after 5 min. Aliquot taken was diluted with MeCN.

Table 4. Scale-Up Batches for N-Acylureasa,b

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 toward 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 the [M − CO + Na] peak of PhCONHCOOAc [derived by the addition of OAc from Cu(OAc)2] to intermediate IV (Figure 1), which indirectly supports the formation of a short-lived 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 ESI-HRMS studies. However, we

a

Unless otherwise noted, all the reactions were carried out under the conditions of Table 2. b15 mL of DMF was used as a solvent.

Scheme 4. Control Experiments

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DOI: 10.1021/acs.joc.7b03054 J. Org. Chem. 2018, 83, 2114−2124

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The Journal of Organic Chemistry Table 5. Optimization Studies for Accessing Cinnamamide 4aa

entry

azide source (equiv)

Cu source (mol %)

solvent

temp (°C)

time (h)

yield 4a (%)

yield 3a (%)

1b,c 2c,d 3c,d 4e 5e 6e 7e

DPPA (5) DPPA (2) DPPA (2) DPPA (2) DPPA (2) DPPA (2) TMSN3 (2)

Cu(OAc)2 (30) Cu(OAc)2 (30) Cu(OTf)2 (30) Cu(OTf)2 (30) Cu(OAc)2 (30) Cu(OTf)2 (10) Cu(OTf)2 (30)

DMF DMF DMF DMF−H2O DMF−H2O DMF−H2O DMF−H2O

80 80 80 100 100 100 100

5.0 6.5 6.5 3.0 3.5 3.5 1.5

78 36 23 90 59 68 51

nd nd nd nd nd nd 44

a Reaction conditions: 1a (0.03 g, 0.145 mmol), azide 2 (equiv/mmol), and Cu salt (mol %) were heated in 1.0 mL of solvent, employing time as noted; nd = not detected. bData were taken from entry 12, Table 1. c0.03 g of 3 Å MS was used. dSome starting materials were recovered. e1 mL of 9.5/0.5 mL (v/v) DMF−H2O 1 mL was used.

Interestingly, during the optimization studies for accessing cinnamoyl urea, we observed that DPPA in the presence of 30 mol % of Cu(OAc)2 provided the cinnamamide in 78% yield (vide supra, Table 1, entry 12). However, the reason behind this unusual behavior of DPPA is not very clear at present. Perhaps the acyl isocyanate intermediate formed via Curtius rearrangement undergoes hydrolysis during a workup 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 of DPPA and 30 mol % of Cu(OTf)2 in DMF/H2O (9.5:0.5) proved to be optimal (entry 4, Table 5). Next, the scope of α-keto thioesters 1 was explored, as shown in Table 6. Various γ-substituted β,γunsaturated α-keto methylthioesters or α-substituted α-keto thioesters were successfully converted to their corresponding primary amides in moderate to good yields (4a−s).22 It is noteworthy that the α-keto thioesters having an alkyl group at the α-position were also found to be compatible under the reaction conditions (4t,u).22h 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.

Table 6. Substrate Scope of the Cu(OTf)2/DPPA-Mediated Synthesis of Primary Amidesa

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CONCLUSIONS In summary, we have developed a new and efficient route to Nacylureas from α-keto thioesters, TMSN3, and catalytic Cu(II). C−C and C−S bond cleavages with retention of the keto group in α-keto 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 the presence of water provides an alternative synthesis of primary amides via removal of the thioester group from αketo 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 ESI-HRMS studies and control experiments. To exhibit the potentiality of the developed method for N-acylureas, singlestep syntheses of pivaloylurea and isovaleroylurea are reported.

Reaction conditions: γ-substituted β,γ-unsaturated α-keto methylthioesters or α-keto thioesters 1 (0.05 g, 1 equiv), Cu(OTf)2 (30 mol %), and DPPA 2b (2 equiv/mmol) in 2 mL of DMF/H2O (v/v 9.5:0.5 mL) at 100 °C. bThe thermal ellipsoids are shown at the 50% probability level. cAlong with 4u, some inseparable mixtures were present. a

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EXPERIMENTAL SECTION

General Information. Melting points were determined in openend capillary tubes and are uncorrected. TLC was performed on silica gel plates (Merck silica gel 60, f254), and the spots were visualized with 2118

DOI: 10.1021/acs.joc.7b03054 J. Org. Chem. 2018, 83, 2114−2124

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The Journal of Organic Chemistry

CH), 134.1, 132.0, 125.9 (2 CH), 120.1, 20.8 (2 × CH3) ppm; IR (KBr) νmax = 3421, 3316, 1679, 1625, 1405, 1192, 1098 cm−1; HRMS (EI) m/z calcd for C12H14N2O2 [M]+ 218.1055; found 218.1056. (E)-N-Carbamoyl-3-(p-tolyl)acrylamide 3d: 13b Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (45%); white solid (0.028 g, 60% yield); mp 219− 221 °C. Spectral data are consistent with previously reported values: 1 H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 166.9, 154.7, 143.4, 140.9, 131.9, 130.1 (2 CH), 128.5 (2 CH), 119.7, 21.5 ppm. (E)-N-Carbamoyl-3-(o-tolyl)acrylamide 3e: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/nhexane (45%); white solid (0.027 g, 58% yield); mp 209−211 °C; 1H NMR (300 MHz, DMSO-d6) 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, DMSO-d6) 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) νmax = 3375, 3322, 1697, 1603, 1388, 1183, 1100 cm−1; HRMS (ESI) m/z calcd for C11H12N2O2Na [M + Na]+ 227.0797; found 227.0799. (E)-N-Carbamoyl-3-(2,3,4-trimethoxyphenyl)acrylamide 3f: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (50%); white solid (0.033 g, 70% yield); mp 190−192 °C; 1H NMR (300 MHz, DMSO-d6) 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, DMSO-d6) 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) νmax = 3428, 3135, 1690, 1572, 1492, 1286, 1176, 1100, 783 cm−1; HRMS (EI) m/z calcd for C13H16N2O5 [M]+ 280.1059; found 280.1049. (E)-N-Carbamoyl-3-(3,4-dimethoxyphenyl)acrylamide 3g: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (50%); white solid (0.029 g, 62% yield); mp 210−212 °C; 1H NMR (300 MHz, DMSO-d6) δ = 10.17 (br s, 1 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 (d, J = 9.0 Hz, 1 H), 6.69 (d, J = 15.6 Hz, 1 H), 3.80 ppm (s, 6 H); 13C{1H} NMR (75 MHz, DMSO-d6) 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) νmax = 3372, 3312, 1668, 1599, 1516, 1262, 1182, 1147 cm−1; HRMS (EI) m/z calcd for C12H14N2O4 [M]+ 250.0954; found 250.0946. (E)-N-Carbamoyl-3-(3-methoxyphenyl)acrylamide 3h: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (50%); white solid (0.031 g, 66% yield); mp 157−159 °C; 1H NMR (300 MHz, DMSO-d6) 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, DMSO-d6) 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) νmax = 3364, 3221, 1680, 1578, 1382, 1255, 1175 cm−1; HRMS (EI) m/z calcd for C11H12N2O3 [M]+ 220.0848; found 220.0842. (E)-N-Carbamoyl-3-(4-hydroxyphenyl)acrylamide 3i: 13c Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (50%); white solid (0.025 g, 54% yield); mp 232−234 °C. Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) 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, DMSO-d6) δ = 166.7, 159.9, 154.4, 143.3, 130.1 (2 CH), 125.2, 116.5, 116.0 (2 CH) ppm. (E)-3-(4-(tert-Butyl)phenyl)-N-carbamoylacrylamide 3j: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (45%); white solid (0.037 g, 79% yield); mp 197−199 °C; 1H NMR (300 MHz, DMSO-d6) 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),

Scheme 5. Proposed Mechanism for the Formation of Primary Amides 4 from γ-Substituted β,γ-Unsaturated αKeto Methylthioesters or α-Keto Thioesters 1

UV light (254 and 365 nm) or by charring the plate dipped in 5% H2SO4−MeOH or vanillin charring solution. 1H and 13C NMR spectra were recorded in CDCl3 or DMSO-d6 solvent using TMS as the internal standard. HRMS (m/z) were measured using EI (magnetic sector, positive ion) and ESI (Q-TOF or LTQ Orbitrap, positive ion) techniques. Infrared (IR) spectra were recorded on Fourier transform infrared spectroscopy, and only intense peaks were reported. 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 flame-dried, two-neck, round-bottomed flask, equipped with a magnetic stirring bar and a condenser, under an argon atmosphere and dried by heating in vacuum. β,γ-Unsaturated α-keto methylthioester or α-keto 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 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/n-hexane] to obtain 3. General Procedure for the Synthesis of 4. A mixture of β,γunsaturated α-keto methylthioesters or α-keto thioester 1 (0.05 g, 1.0 equiv), Cu(OTf)2 (30 mol %), 2 mL of DMF−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/n-hexane] to obtain 4. N-Carbamoylcinnamamide 3a: 9b Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (45%); white solid (0.041 g, 89% yield); mp 204−206 °C (lit.9b 202− 204 °C); solvent of crystallization, dichloromethane/methanol. Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) δ = 10.33 (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, DMSO-d6) δ = 166.3, 154.2, 143.0, 134.2, 130.5, 129.1 (2 CH), 128.1 (2 CH), 120.4 ppm. (E)-N-Carbamoyl-3-(2,4,5-trimethylphenyl)acrylamide 3b: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (45%); white solid (0.039 g, 83% yield); mp 214−216 °C; 1H NMR (600 MHz, DMSO-d6) 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); 13 C{1H} NMR (150 MHz, DMSO-d6) 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) νmax = 3379, 3318, 3223, 1667, 1618, 1417, 1189, 1097 cm−1; HRMS (EI) m/z calcd for C13H16N2O2 [M]+ 232.1212; found 232.1203. (E)-N-Carbamoyl-3-(3,5-dimethylphenyl)acrylamide 3c: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (45%); white solid (0.033 g, 71% yield); mp 213−215 °C; 1H NMR (300 MHz, DMSO-d6) 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); 13 C{1H} NMR (75 MHz, DMSO-d6) δ = 166.3, 154.2, 143.2, 138.1 (2 2119

DOI: 10.1021/acs.joc.7b03054 J. Org. Chem. 2018, 83, 2114−2124

Article

The Journal of Organic Chemistry

205 °C; 1H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 166.5, 154.6, 139.6, 136.4, 133.0, 130.1, 129.1, 119.1 ppm; IR (KBr) νmax = 3378, 3332, 1690, 1613, 1388, 1169, 1105 cm−1; HRMS (EI) m/z calcd for C8H8N2O2S [M]+ 196.0306; found 196.0300. (E)-N-Carbamoyl-3-(naphthalen-2-yl)acrylamide 3r: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (40%); white solid (0.032 g, 68% yield); mp 179− 181 °C; 1H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) 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) νmax = 3386, 3321, 3204, 1684, 1628, 1479, 1180 cm−1; HRMS (EI) m/z calcd for C14H12N2O2 [M]+ 240.0899; found 240.0895. (E)-N-Carbamoyl-3-(naphthalen-1-yl)acrylamide 3s: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (40%); white solid (0.033 g, 70% yield); mp 210− 212 °C; 1H NMR (300 MHz, DMSO-d6) 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, DMSO-d6) δ = 166.2, 154.2, 139.4, 133.4, 131.2, 130.8, 130.6, 128.8, 127.2, 126.4, 125.8, 125.1, 123.3, 123.2 ppm; IR (KBr) νmax = 3373, 1742, 1687, 1585, 1389, 1181, 782 cm−1; HRMS (EI) m/z calcd for C14H12N2O2 [M]+ 240.0899; found 240.0895. (E)-N-Carbamoyl-3-cyclohexylacrylamide 3t: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/ n-hexane (30%); white solid (0.0216 g, 47% yield); mp 189−191 °C; 1 H NMR (300 MHz, DMSO-d6) 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, DMSO-d6) 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) νmax = 3381, 3338, 2925, 2112, 1674, 1616, 1406, 1101 cm−1; HRMS (ESI) m/z calcd for C10H16N2O2Na [M + Na]+ 219.1110; found 219.1130. (E)-N-Carbamoyl-4-methyl-5-phenylpent-2-enamide 3u: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (40%); white solid (0.020 g, 43% yield); mp 140−142 °C; 1H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) 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) νmax = 3360, 2123, 1734, 1693, 1398, 1207 cm−1; HRMS (ESI) m/z calcd for C13H16N2O2Na [M + Na]+ 255.1110; found 255.1124. (E)-N-Carbamoyl-5-methylhex-2-enamide 3v: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (60%); white solid (0.019 g, 41% yield); mp 174− 176 °C; 1H NMR (600 MHz, DMSO-d6) 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); 13C{1H} NMR (150 MHz, DMSO-d6) δ = 166.5, 154.7, 147.4, 124.5, 41.1, 27.7, 22.6 ppm (2 CH3); IR (KBr) νmax = 3377, 2120, 1703, 1686, 1402, 1107 cm−1; HRMS (ESI) m/z calcd for C8H14N2O2Na [M + Na]+ 193.0953; found 193.0960. N-Carbamoylbenzamide 3aa:.9b,16a Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (35%); white solid (0.019 g, 56% yield); mp 213-215 °C (lit.9b 210− 211 °C). Spectral data are consistent with previously reported values: 1 H NMR (600 MHz, DMSO-d6) 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, DMSOd6) δ = 168.6, 154.7, 133.2, 133.1, 129.0 (2 CH), 128.6 (2 CH) ppm.

1.29 ppm (s, 9 H); 13C{1H} NMR (75 MHz, DMSO-d6) 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) νmax = 3386, 2961, 1683, 1579, 1381, 1179 cm−1; HRMS (EI) m/z calcd for C14H18N2O2 [M]+ 246.1368; found 246.1364. (E)-N-Carbamoyl-3-(4-chlorophenyl)acrylamide 3k: 13b Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (45%); white solid (0.027 g, 58% yield); mp 234−236 °C. Spectral data are consistent with previously reported values: 1H NMR (600 MHz, DMSO-d6) 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); 13 C{1H} NMR (150 MHz, DMSO-d6) δ = 166.5, 154.6, 142.0, 135.3, 133.5, 130.2 (2 CH), 129.6 (2 CH), 121.6 ppm. (E)-N-Carbamoyl-3-(3-chlorophenyl)acrylamide 3l: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (45%); white solid (0.037 g, 79% yield); mp 186− 188 °C; solvent of crystallization, dichloromethane/acetone; 1H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 166.4, 154.5, 141.7, 136.9, 134.2, 131.4, 130.5, 128.2, 126.8, 122.6 ppm; IR (KBr) νmax = 3389, 3338, 3209, 1668, 1626, 1418, 1188, 1093 cm−1; HRMS (EI) m/z calcd for C10H9ClN2O2 [M]+ 224.0353; found 224.0349. (E)-N-Carbamoyl-3-(2,5-dichlorophenyl)acrylamide 3m: 13c Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (45%); white solid (0.032 g, 68% yield); mp 209−211 °C. Spectral data are consistent with previously reported values: 1H NMR (600 MHz, DMSO-d6) 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 H), 7.40 (br s, 1 H), 6.88 ppm (d, J = 15.6 Hz, 1 H); 13C{1H} NMR (150 MHz, DMSOd6) δ = 165.9, 154.3, 136.9, 134.3, 132.9, 132.7, 132.3, 131.8, 127.8, 125.7 ppm. (E)-N-Carbamoyl-3-(2,4-dichlorophenyl)acrylamide 3n: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (45%); white solid (0.024 g, 51% yield); mp 200−202 °C; 1H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 166.0, 154.4, 137.1, 135.9, 135.0, 131.5, 130.1, 129.5, 128.7, 124.6 ppm; IR (KBr) νmax = 3392, 3329, 1667, 1622, 1477, 1187, 1098 cm−1; HRMS (ESI) m/z calcd for C10H8Cl2N2O2Na [M + Na]+ 280.9861; found 280.9854. (E)-3-(4-Bromophenyl)-N-carbamoylacrylamide 3o: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (45%); white solid (0.019 g, 40% yield); mp 250− 252 °C; 1H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 166.5, 154.6, 142.1, 133.9, 132.6 (2 CH), 130.4 (2 CH), 124.2, 121.7 ppm; IR (KBr) νmax = 3376, 1739, 1692, 1585, 1397, 1326, 1185 cm−1; HRMS (ESI) m/z calcd for C10H9BrN2O2Na [M + Na]+ 292.9725; found 292.9725. (E)-N-Carbamoyl-3-(3-cyanophenyl)acrylamide 3p: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (50%); white solid (0.019 g, 41% yield); mp 236− 238 °C; 1H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 166.3, 154.5, 141.0, 135.9, 134.0, 132.4 (2 CH), 130.8, 123.3, 118.8, 112.7 ppm; IR (KBr) νmax = 3367, 3330, 3215, 2231, 1665, 1618, 1403, 1184, 1101 cm−1; HRMS (EI) m/z calcd for C11H9N3O2 [M]+ 215.0695; found 215.0689. (E)-N-Carbamoyl-3-(thiophen-2-yl)acrylamide 3q: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (45%); white solid (0.0282 g, 61% yield); mp 203− 2120

DOI: 10.1021/acs.joc.7b03054 J. Org. Chem. 2018, 83, 2114−2124

Article

The Journal of Organic Chemistry N-Carbamoyl-3-methoxybenzamide 3ab: 16g Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/ n-hexane (40%); white solid (0.023 g, 64% yield); mp 165−167 °C; 1 H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 168.3, 159.6, 154.6, 134.5, 130.1, 120.9, 119.5, 113.2, 55.8 ppm; IR (KBr) νmax = 3366, 3319, 1706, 1667, 1593, 1382, 1233, 1091 cm−1; HRMS (EI) m/z calcd for C9H10N2O3 [M]+ 194.0691; found 194.0690. N-Carbamoyl-4-methoxybenzamide 3ac: 16a Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/ n-hexane (50%); white solid (0.0218 g, 61% yield); mp 214−216 °C (lit.16a 214−216 °C). Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) 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, DMSO-d6) δ = 167.4, 162.8, 154.4, 130.3 (2 CH), 124.6, 113.8 (2 CH), 55.5 ppm. N-Carbamoyl-3,4-dimethylbenzamide 3ad: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/ n-hexane (30%); white solid (0.02 g, 56% yield); mp 186−188 °C; 1H NMR (600 MHz, DMSO-d6) 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 H), 2.25 ppm (s, 3 H); 13C{1H} NMR (150 MHz, DMSO-d6) δ = 168.5, 154.7, 142.2, 137.0, 130.5, 130.0, 129.6, 126.1, 19.9, 19.8 ppm; IR (KBr) νmax = 3373, 3331, 1687, 1600, 1383, 1260, 1106 cm−1; HRMS (EI) m/z calcd for C10H12N2O2 [M]+ 192.0899; found 192.0888. N-Carbamoyl-4-chlorobenzamide 3ae:.16c,d Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/ n-hexane (35%); white solid (0.014 g, 39% yield); mp 231−233 °C (lit16d 252−253 °C). Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) 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, DMSO-d6) δ = 167.6, 154.5, 138.0, 132.0, 130.6 (2 CH), 129.0 (2 CH) ppm. N-Carbamoyl-2-naphthamide 3af:.16e,f Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/nhexane (35%); white solid (0.02 g, 55% yield); mp 226−228 °C (lit16f 207−208 °C); 1H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) 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. N-Carbamoyl-[1,1′-biphenyl]-4-carboxamide 3ag: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (35%); white solid (0.018 g, 48% yield); mp 232− 234 °C; 1H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) 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) νmax = 3381, 3333, 1702, 1668, 1597, 1385, 1265, 1097 cm−1; HRMS (EI) m/z calcd for C14H12N2O2 [M]+ 240.0899; found 240.0895. N-Carbamoylpivalamide 3ah:.17a−c Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (30%); white solid (0.0144 g, 44% yield); mp 149−151 °C (lit17c 145−147 °C); 1H NMR (300 MHz, DMSO-d6) 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, DMSO-d6) δ = 180.0, 154.5, 38.9, 26.4 ppm (3 × CH3). N-Carbamoyl-3-methylbutanamide 3ai: 1b Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/nhexane (30%); white solid (0.0126 g, 39% yield); mp 191−193 °C (lit17d 206−208 °C); 1H NMR (300 MHz, DMSO-d6) 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, DMSO-d6) δ = 174.3, 154.0, 44.8, 25.2 (CH2), 22.2 ppm (2 × CH3). N-Carbamoyl-2-methylbutanamide 3aj: 17e Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/nhexane (40%); white solid (0.0134 g, 41% yield); mp 180−182 °C (lit17e 178−180 °C). Spectral data are consistent with previously reported values: 1H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 178.7, 154.5, 41.9, 26.8 (CH2), 17.3, 11.9 ppm. N-Carbamoylbutyramide 3ak: 17f Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (40%); white solid (0.0117 g, 37% yield); mp 176−178 °C (lit17f 173−174 °C); 1H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 175.2, 154.4, 38.0 (CH2), 18.3 (CH2), 13.9 ppm. Cinnamamide 4a: 22a Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (60%); white solid (0.032 g, 90% yield); mp 146−148 °C (lit.22a 144 °C). Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) 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, DMSOd6) δ = 166.8, 139.3, 134.9, 129.5, 129.0 (2 CH), 127.6 (2 CH), 122.3 ppm. (E)-3-(o-Tolyl)acrylamide 4b: 22b Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (60%); white solid (0.032 g, 87% yield); mp 172−174 °C (lit.22i 176− 178 °C). Spectral data are consistent with previously reported values: 1 H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 167.2, 137.2, 137.1, 134.1, 131.1, 129.7, 126.8, 126.4, 123.9, 19.9 ppm. (E)-3-(p-Tolyl)acrylamide 4c: 22b Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (60%); white solid (0.021 g, 57% yield); mp 190−192 °C (lit22j 190− 191 °C). Spectral data are consistent with previously reported values: 1 H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 167.3, 139.7, 139.6, 132.6, 130.0 (2 CH), 128.0 (2 CH), 121.7, 21.4 ppm. (E)-3-(3,4-Dimethoxyphenyl)acrylamide 4d: 22a Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (90%); white solid (0.031 g, 80% yield); mp 163− 165 °C (lit.22a 166 °C). Spectral data are consistent with previously reported values: 1H NMR (600 MHz, DMSO-d6) 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, 1 H), 3.78 (s, 3 H), 3.76 ppm (s, 3 H); 13C{1H} NMR (150 MHz, DMSO-d6) 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)-3-(4-Chlorophenyl)acrylamide 4e: 22b Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/nhexane (60%); white solid (0.029 g, 77% yield); mp 207−209 °C (lit22j 210−211 °C); solvent of crystallization, dichloromethane/ acetone. Spectral data are consistent with previously reported values: 1 H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 166.9, 138.3, 134.3, 134.3, 129.7 (2 CH), 129.4 (2 CH), 123.6 ppm. (E)-3-(3-Chlorophenyl)acrylamide 4f: 22c Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/nhexane (60%); white solid (0.028 g, 74% yield); mp 122−124 °C. Spectral data are consistent with previously reported values: 1H NMR (600 MHz, CDCl3) δ = 7.59 (d, J = 15.6 Hz, 1 H), 7.50 (s, 1 H), 7.37 2121

DOI: 10.1021/acs.joc.7b03054 J. Org. Chem. 2018, 83, 2114−2124

Article

The Journal of Organic Chemistry

hexane (60%); white solid (0.025 g, 65% yield); mp 172−174 °C (lit.22f 177 °C). Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) 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, DMSO-d6) 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)-3-Cyclohexylacrylamide 4o: 22d Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (55%); white solid (0.0207 g, 57% yield); mp 138−140 °C. Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) 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 = 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, DMSO-d6) 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/n-hexane (30%); white solid (0.018 g, 72% yield); mp 122−124 °C (lit.22c 128−129 °C). Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) 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 DMSO-d6) δ = 168.9, 133.2, 130.9, 127.6 (2 CH), 126.9 ppm (2 CH). 4-Methoxybenzamide 4q: 22c Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (50%); white solid (0.012 g, 43% yield); mp 164−166 °C (lit22c 167−168 °C). Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) 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 DMSO-d6) δ = 168.2, 161.4, 128.8 (2 CH), 125.4, 112.7 (2 CH), 54.6 ppm. 4-Chlorobenzamide 4r: 22c Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (30%); white solid (0.0169 g, 60% yield); mp 180−182 °C (lit.22c 178−179 °C). Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) 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 DMSO-d6) δ = 167.8, 136.9, 131.7, 128.6 (2 CH), 127.8 ppm (2 CH). 2-Naphthamide 4s: 22c Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (50%); white solid (0.021 g, 72% yield); mp 200−202 °C (lit.22c 196−197 °C). Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) 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 H), 7.48 ppm (br s, 1 H); 13 C{1H} NMR (75 MHz, DMSO-d6) δ = 168.0, 134.2, 132.2, 131.7, 128.9, 127.9, 127.8, 127.6 (2 CH), 126.7, 124.4 ppm. Pivalamide 4t: 22h Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (50%); white solid (0.015 g, 66% yield); mp 148−150 °C (lit.22h 154−157 °C). Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) δ = 7.01 (br s, 1 H), 6.69 (br s, 1 H), 1.06 ppm (s, 9 H); 13C{1H} NMR (75 MHz, DMSO-d6) δ = 179.9, 37.9, 27.5 ppm (3 × CH3). 2-Methylbutanamide 4u: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n-hexane (50%); white solid (0.0123 g, 54% yield); mp 109−111 °C (lit.17a 112−114 °C). Spectral data are consistent with previously reported values: 1H NMR (600 MHz, DMSO-d6) δ = 7.21 (br s, 1 H), 6.67 (br s, 1 H), 2.07−2.12 (m, 1 H), 1.42−1.49 (m, 1 H), 1.22−1.29 (m, 1 H), 0.94 (d, J = 6.6 Hz, 3 H), 0.79 ppm (t, J = 7.2 Hz, 3 H); 13C{1H} NMR (150 MHz, DMSO-d6) δ = 178.1, 41.5, 27.1 (CH2), 18.0, 12.3 ppm. General Procedure for the Control Experiments. Cu(OAc)2 (0.011 g, 0.062 mmol, 30 mol %) and 3 Å MS (0.05 g) were taken in a 25 mL flame-dried, two-neck, round-bottomed flask, equipped with a magnetic stirring bar, under an argon atmosphere and dried by heating in vacuum. α-Keto thioester 1aa (0.05 g, 0.206 mmol, 1.0 equiv) was added into the mixture. Dry DMSO (2.0 mL) and TMSN3 2a (0.01

(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)-3-(4-Bromophenyl)acrylamide 4g: 22a Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/nhexane (60%); white solid (0.025 g, 63% yield); mp 211−213 °C (lit.22a 214 °C). Spectral data are consistent with previously reported values: 1H NMR (300 MHz, DMSO-d6) 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, DMSO-d6) δ = 166.5, 138.0, 134.2, 131.9 (2 CH), 129.6 (2 CH), 123.2, 122.6 ppm. (E)-3-(2-Bromophenyl)acrylamide 4h: 22e Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/nhexane (60%); white solid (0.021 g, 53% yield); mp 172−174 °C. Spectral data are consistent with previously reported values: 1H NMR (600 MHz, DMSO-d6) 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, DMSOd6) δ = 166.5, 137.6, 134.9, 133.7, 131.6, 128.8, 128.1, 126.0, 124.6 ppm. (E)-3-(2,5-Dibromophenyl)acrylamide 4i: Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/nhexane (60%); white solid (0.034 g, 81% yield); mp 189−191 °C; 1H NMR (600 MHz, DMSO-d6) 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); 13 C{1H} NMR (150 MHz, DMSO-d6) δ = 166.2, 137.2, 136.1, 135.5, 134.0, 130.5, 127.6, 123.4, 121.7 ppm; IR (KBr) νmax = 3373, 3177, 1671, 1618, 1389, 1022 cm−1; HRMS (EI) m/z calcd for C9H7Br2NO [M]+ 302.8894; found 302.8899. (E)-3-(2,6-Dichlorophenyl)acrylamide 4j: 22a Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/ n-hexane (60%); white solid (0.036 g, 92% yield); mp 159−161 °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)-3-(4-Nitrophenyl)acrylamide 4k: 22b Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/nhexane (70%); light yellow solid (0.022 g, 57% yield); mp 220−222 °C (lit22j 216−217 °C). Spectral data are consistent with previously reported values: 1H NMR (600 MHz, DMSO-d6) 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, DMSO-d6) δ = 166.4, 148.0, 142.0, 137.3, 129.1 (2 CH), 127.1, 124.6 (2 CH) ppm. (E)-3-(4-Cyanophenyl)acrylamide 4l: 22b Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/nhexane (60%); white solid (0.029 g, 78% yield); mp 182−184 °C. Spectral data are consistent with previously reported values: 1H NMR (600 MHz, DMSO-d6) 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, DMSOd6) δ = 166.5, 140.0, 137.8, 133.3 (2 CH), 128.7 (2 CH), 126.3, 119.2, 111.9 ppm. (E)-3-(Thiophen-2-yl)acrylamide 4m: 22b Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/nhexane (50%); white solid (0.03 g, 83% yield); mp 162−163 °C (lit22k 152−153 °C). Spectral data are consistent with previously reported values: 1H NMR (600 MHz, DMSO-d6) 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 (d, J = 15.6 Hz, 1 H); 13 C{1H} NMR (150 MHz, DMSO-d6) δ = 167.4, 138.3, 133.7, 128.1, 127.9, 125.6, 122.2 ppm. (E)-3-(Naphthalen-1-yl)acrylamide 4n: 22f Prepared according to the general procedure discussed above; Rf = 0.3; eluent, EtOAc/n2122

DOI: 10.1021/acs.joc.7b03054 J. Org. Chem. 2018, 83, 2114−2124

Article

The Journal of Organic Chemistry mL, 0.62 mmol, 3.0 equiv) were introduced successively, and the resulting reaction mixture was stirred at room temperature. The reaction was quenched after 5 min either with MeOH (0.02 mL, 0.41 mmol, 2.0 equiv) or piperidine (0.04 mL, 0.41 mmol, 2.0 equiv), and stirring was continued for another 30 min at the same temperature. 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/n-hexane] to obtain the products. For MeOH Addition: After purification, we isolated 5a, PhCONHCONH2 3aa (0.010 g, 14%), and trace amounts of Ph2S2 and PhCOCOOMe. The analytical data of 3aa exactly matched with our previously reported values. Methyl benzoylcarbamate 5a:23 Eluent, EtOAc/n-hexane (25%); white solid (0.010 g, 15% yield); mp 118−120 °C (lit.23b 120 °C). Spectral data are consistent with previously reported values: 1H NMR (600 MHz, CDCl3) δ = 8.18 (br s, 1 H), 7.82 (d, J = 7.2 Hz, 2 H), 7.59 (t, J = 7.8 Hz, 1 H), 7.49 (t, J = 7.8 Hz, 2 H), 3.87 ppm (s, 3 H); 13C{1H} NMR (150 MHz, CDCl3) δ = 164.7, 151.7, 133.1, 132.9, 128.9 (2 CH), 127.6 (2 CH), 53.3 ppm. For Piperidine Addition: After purification, we isolated 5b, PhCONHCONH2 3aa (0.010 g, 14%), and trace amounts of Ph2S2 and PhCOCOOMe. The analytical data of 3aa exactly matched with our previously reported values. N-Benzoylpiperidine-1-carboxamide 5b:7 Eluent, EtOAc/n-hexane (25%); white solid (0.014 g, 27% yield); mp 168−170 °C (lit.7 172−174 °C). Spectral data are consistent with previously reported values: 1H NMR (600 MHz, DMSO-d6) δ = 10.93 (br s, 1 H), 8.65 (d, J = 7.8 Hz, 2 H), 8.38 (t, J = 7.8 Hz, 1 H), 8.28 (t, J = 7.2 Hz, 2 H), 4.18 (br s, 4 H), 2.37 (br s, 2 H), 2.30 ppm (br s, 4 H); 13C{1H} NMR (150 MHz, DMSO-d6) δ = 167.3, 153.7, 134.6, 133.4, 129.7 (2 CH), 129.2 (2 CH), 26.8 (2 CH2), 25.1 ppm (3 CH2).

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b03054. Copies of 1H, 13C{1H}, and DEPT-135 NMR spectra (PDF) X-ray data for 3a (CIF) X-ray data for 3l (CIF) X-ray data for 4e (CIF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Indrajit Das: 0000-0002-5731-0232 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS I.D. thanks DST-SERB (EMR/2016/001720) for financial support, and Drs. Basudeb Achari and Ramalingam Natarajan for valuable discussions. R.M. and S.N. thank UGC-India for fellowships.

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REFERENCES

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DOI: 10.1021/acs.joc.7b03054 J. Org. Chem. 2018, 83, 2114−2124