Electrocyclic Ring Opening Sequence between Alkynyl

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Cycloaddition/Electrocyclic Ring Opening Sequence between Alkynyl Sulfides and Azodicarboxylates To Provide N,N‑Dicarbamoyl 2‑Iminothioimidates Chandima J. Narangoda,†,⊥ Tayeb Kakeshpour,§,⊥ Timothy R. Lex,† Brandon K. Redden,∥ Madelyn A. Moore,† Emma M. Frank,† Colin D. McMillen,† Sheryl L. Wiskur,∥ Alex Kitaygorodskiy,† James E. Jackson,*,§ and Daniel C. Whitehead*,†,‡ Downloaded via UNIV OF SOUTHERN INDIANA on July 28, 2019 at 06:08:32 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

†

Department of Chemistry and ‡Eukaryotic Pathogens Innovation Center, Clemson University, Clemson, South Carolina 29634, United States § Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States ∥ Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina 29208, United States S Supporting Information *

ABSTRACT: The α-oxidized thioimidates are useful bidentate ligands and are important motifs in pharmaceuticals, pesticides, and fungicides. Despite their broad utility, a direct route for their synthesis has been elusive. Herein, we describe a one-step synthesis of N,Ndicarbamoyl 2-iminothioimidates from easily accessible thioacetylenes and commercially available azodicarboxylates (20 examples, ≤99% yield). Additionally, the mechanism of the transformation was extensively explored by variable-temperature NMR, in situ IR, and quantum mechanical simulations. These experiments suggest that the reaction commences with a highly asynchronous [2 + 2] cycloaddition, which leads to a four-membered diazacyclobutene intermediate with a barrier consistent with the observed reaction rate. This intermediate was then isolated for subsequent kinetic measurements, which yielded an experimental barrier within 1 kcal/mol of the calculated barrier for a subsequent 4π electrocyclic ring opening leading to the observed iminothioimidate products. This method represents the first direct route to α-oxidized thioimidates from readily accessible starting materials.

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INTRODUCTION

there are no general strategies for their synthesis that appear in the literature. Nevertheless, a few examples of the scaffold are known along with related thioimidates possessing α-oxidation including α-keto (8), α-oximino (9), and α-hydrazono (10) congeners (Figure 1).15−28 Despite the lack of straightforward, general methods to access them from simple building blocks, α-oxidized thioimidates exhibit a broad range of utility and interest including their use as metal-binding ligands,15,16 as dyes,17 as intermediates in the synthesis of rare heterocycles,18−24 pharmaceuticals, pesticides and fungicides,16,25−27 and their occurrence as components of Maillard flavors in cooked food.28 It seems likely that the development of a general route to this class of rare molecules might serve to enhance their utility in a variety of applications. In this report, we describe a straightforward synthesis of N,N-dicarbamoyl 2iminothioimidates (6) and related N,N-dicarbamoyl 2iminoselenoimidates from readily accessible starting materials in one synthetic operation.

Recently, we have reported the synthesis of stable diazacyclobutenes (2) by means of a formal [2 + 2] cycloaddition of 4-phenyl-1,2,4-triazolinedione (PTAD) and electron-rich alkynyl sulfides and selenides (1) (Scheme 1, eq 1).1 Based on similar arguments espoused by Breton et al.,2,3 we surmised that this particular class of bicyclic diazacyclobutenes was more stable than previously studied monocyclic diazacyclobutenes4−10 owing to the unfavorable cis−trans geometry of the imine moieties in the seven-membered heterocycle 3 expected from thermal 4π conrotatory electrocyclic ring opening of the initially formed diazacyclobutene 2. Indeed, the bicyclic diazacyclobutenes 2 exhibit excellent thermal stability up to >200 °C.1 We predicted, however, that use of acyclic azodicarboxylates (4)11−14 in lieu of PTAD might facilitate a straightforward preparation of N,Ndicarbamoyl 2-iminothioimidates 6 via the analogous formal [2 + 2] cycloaddition with 1 to generate monocyclic diazacyclobutenes 5, which could undergo facile 4π electrocyclic ring opening (Scheme 1, eq 2). The results of this study are described herein. 2-Iminothioimidates (i.e., 7, Figure 1) are rarely accessed molecular architectures, and to the best of our knowledge, © XXXX American Chemical Society

Received: June 7, 2019 Published: July 11, 2019 A

DOI: 10.1021/acs.joc.9b01515 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry Scheme 1. Proposed Route to N,N-Dicarbamoyl 2-Iminothioimidates

R1 position. The 2-iminothioimidates 6i and 6j derived from the para-methyl and para-methoxy phenyl substituents at R1 were isolated in excellent yields (88 and 95%, respectively), whereas electron-deficient para-chloro and para-trifluoromethyl aryl groups provided slightly lower yields (i.e., 47% yield for 6k and 69% yield for 6l). Modulating R1 to an alkyl group is also tolerated. Thus, when R1 = n-butyl, the desired 2iminothioimidates 6m (where R2 = Me, 40% yield) and 6n (where R2 = n-Bu, 45% yield) were isolated in lower yields. These particular compounds were also found to be less stable and prone to decomposition after purification. We suspect that the instability of these compounds is likely due to the potential for facile isomerization of the imine moiety to its enamine congeners followed by subsequent decomposition. Additionally, 2-iminothioimidate 6o, where R1 = cyclopropyl, was prepared in 77% yield. This compound, which would less readily isomerize to an enamine tautomer, appears to be comparatively stable, perhaps providing some support to the hypothesis above regarding the instability of the n-alkyl congeners 6m and 6n. We then shifted our focus toward the exploration of other symmetric, acyclic azodicarboxylates. As a result, diisopropyl azodicarboxylate, dibenzyl azodicarboxylate and bis(2,2,2trichloroethyl) azodicarboxylate were reacted with ethyl phenylethynyl sulfide, furnishing the corresponding 2-iminothioimidates in good to excellent yields (i.e., 6p−6r, 79−99% yield). Further, two corresponding alkynyl selenides were reacted with DEAD to furnish the 2-iminoselenoimidates 6s (76%) and 6t (73%) in good yields. Finally, the reaction proceeds well at a larger scale: compound 6b was prepared in 99% yield on a 5 mmol scale (1.67 g 6b), while a 4.61 g sample of 2-iminoselenoimidate 6t was prepared in one operation (73% yield, 14.2 mmol scale). After exploring the substrate scope, we turned to an investigation of the possible mechanism of this reaction by means of variable-temperature NMR, in situ IR, and computational studies. Based on previous studies,2−10 we recognized that this reaction might proceed via the intermediacy of diazacyclobutene intermediates (i.e., 5, Scheme 1). Indeed, after refluxing the mixture of DEAD and ethyl phenylethynyl sulfide for 4 h, the key diazacyclobutene intermediate 5b was isolable by means of preparative thin-layer chromatography. This compound was characterized by 1H and 13 C NMR spectroscopy and then subjected to study over the

Figure 1. α-Oxidized thioimidate scaffolds.

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RESULTS AND DISCUSSION We began our studies by reacting electron-rich phenyl alkynyl sulfides with diethyl azodicarboxylate (DEAD) under otherwise identical conditions to our previous report (i.e., refluxing acetonitrile).1 Thus, we successfully synthesized the first set of N,N-dicarbamoyl 2-iminothioimidates by varying the alkyl chain at the R2 position on the alkynyl sulfide (Scheme 2). Phenyl alkynyl sulfides bearing n-alkyl groups at the R2 position such as methyl, ethyl, n-propyl, and n-butyl generated the corresponding 2-iminothioimidates in good to excellent yields (6a−6d, 73−99% yield), while the substrates bearing nalkyl groups such as n-pentyl (6e) and n-octyl (6f) proceeded in 80 and 73% yields, respectively. Alkynyl sulfides possessing phenyl or benzyl groups at the R2 position also furnished the products 6g and 6h in good yields (i.e., 77 and 83%, respectively). Compound 6g afforded X-ray quality crystals, revealing 1Z,2Z stereochemistry across the thioimidate and imine double bonds (see the Supporting Information for details). The stereochemistry in all other products depicted in Scheme 2 reflects this arrangement by analogy, although all possible stereoisomers of the products are likely readily interconvertible at room temperature (vide infra). This supposition is further confirmed based on the fact that repeated attempts to observe the thioimidate and imine stereochemistry by means of NMR spectroscopy failed to show any discernible NOE enhancements. Next, we tested the reactivity of alkynyl sulfides bearing para-substituted electron-rich and -deficient aryl groups at the B

DOI: 10.1021/acs.joc.9b01515 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry Scheme 2. Substrate Scope (1 mmol Scale)

temperature range of −35 to 64 °C (i.e., 238−337 K) in CD3CN while monitoring the quartet arising from the Smethylene protons (i.e., x and y) of diazacyclobutene 5b and the resulting 2-iminothioimidate 6b (Figure 2). Note that the transformation of 5b to 6b is presented from right to left in Figure 2 so that the compounds coincide with their 1H NMR resonances. These results clearly demonstrated that diazacyclobutene 5b undergoes clean, irreversible electrocyclic ring opening to the 2-iminothioimidate product 6b. Furthermore, we fit the integration data arising from the electrocyclic ring opening of 5b to provide 6b at 373 and 298 K to a first-order decay from which we extracted rate constants k of 7.3(1) × 10−4 and 3(1) × 10−6 s−1, respectively. These data in turn yielded an activation energy Ea of 29 ± 4 kcal/mol for the transformation (see the Supporting Information for details). This value is in reasonable agreement with the calculated barrier of 29.4 kcal/mol for the ring opening event (vide infra). We also attempted to probe the course of the cycloaddition/ electrocyclic ring opening to produce 6b by means of in situ

infrared spectroscopy (see the Supporting Information for details). Having confirmed the intermediacy of the diazacyclobutene in the reaction, we next sought to probe the nuances of the reaction mechanism. Two candidate pathways were identified for the reaction of DEAD with methyl phenylethynyl sulfide (Scheme 3) to form diazacyclobutene 5a and ultimately 2iminothioimidate 6a. In path a, the key intermediate 5a might arise from a stepwise polar mechanism entailing the nucleophilic attack of the thioacetylene onto the azodicarboxylate to form the zwitterionic intermediate 11, which would then undergo ring closure to the observed diazacyclobutene. Alternatively, owing to the potential ketene-like character of the thioacetylene (see resonance form 12, path b), we also entertained the possibility of a concerted, thermal [2 + 2] cycloaddition between the two reactants leading to 5a in one step. We were particularly intrigued by the stepwise path a, as analogous intermediates have been proposed for the related cyclizations of triazolinediones with electron-rich alkenes such as vinyl ethers.29,30 C

DOI: 10.1021/acs.joc.9b01515 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry

(see the Supporting Information for details), we also considered path b, the concerted pericyclic route to 5a. Once arriving at 5a, the two pathways converge on the subsequent thermal, electrocyclic ring opening of the diazacyclobutene intermediate to provide the 2-iminothioimidate product 6a. This step is equally interesting in light of the seemingly clear crystallographic evidence (see the Supporting Information) for the preferred formation of the 1Z,2Z stereochemistry of the dicarbamoyl thioimidate products (cf. 6a). This particular stereochemistry superficially suggests a selective rotatory preference for the ring opening of the diazacyclobutene 5a. Conventional orbital symmetry arguments would point to conrotatory opening of the cis, presumably higher energy, isomer of 5a, implying facile interconversion of the cis and trans stereoisomers with easy ring opening from the cis isomer. Alternatively, electrocyclic ring opening of the more stable trans-5a could occur followed by facile interconversion of the product isomers at room temperature. To probe the merits of the polar mechanism leading to diazacyclobutene 5a versus the pericyclic pathway, we turned to DFT calculations performed using Gaussian 16.31 All geometries were fully optimized at the ωB97X-D/6-31G* level, and the nature of each stationary point was confirmed using vibrational analysis.32−35 Intrinsic reaction coordinate (IRC) calculations were performed to confirm that all transition state structures in fact connect the intermediates (or their readily accessible rotamers) as shown in the free energy diagram (Figure 3). To confirm the use of the lowest energy representatives, conformer sets for each intermediate

Figure 2. Variable-temperature 1H NMR spectra (−35 to 64 °C, CD3CN) of diazacyclobutene 5b transitioning to 2-iminothioimidate 6b.

However, since the in situ IR experiments showed no evidence for intermediates such as 11 en route to diazacyclobutene 5a

Scheme 3. Potential Reaction Mechanisms for the Formation of 2-Iminothioimidates

D

DOI: 10.1021/acs.joc.9b01515 J. Org. Chem. XXXX, XXX, XXX−XXX

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Figure 3. Reaction coordinate diagram for the formation of 2-iminothioimidate 6a calculated at the ωB97X-D/6-31G* level of theory. The inset shows the relative energies of product isomers and their interconversion barriers at the same level of theory.

were generated using Spartan 18,36 and their energies were evaluated as noted above. The ωB97X-D/6-31G* calculations (Figure 3) suggest the stepwise mechanism (path a in Scheme 3), starting with the nucleophilic attack by the alkyne on the DEAD (see TS1 leading to adduct 11). Closure of the four-membered ring is

then almost barrierless (see TS2 leading to trans-5a). In fact, IRC calculations found that some conformers of TS1 directly collapse to the four-membered ring trans-5a with no barrier. Thus, this process is on the borderline between a stepwise and a concerted but highly asynchronous [2 + 2] cycloaddition. In addition, all TS geometries resulting from repeated attempts to E

DOI: 10.1021/acs.joc.9b01515 J. Org. Chem. XXXX, XXX, XXX−XXX

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Figure 4. Calculated relative energies for (left) (Z)-imine, (E)-thioimidate stereoisomer of 6g and (middle) (Z)-imine, (Z)-thioimidate stereoisomer of 6g. (Right) crystal structure (X-ray) of 6g.

which is the most stable zwitterionic species obtained, but still substantially higher in energy than 5a. Calculations suggest that the isomers of 6a interconvert readily at ambient temperature, and hence, the isomer isolated and structurally characterized by X-ray crystallographic analysis may not reflect the actual stereospecificity of the reaction, if indeed any exists. A detailed energy analysis of systematically obtained conformers of the four possible isomers of 6a finds that the (Z)-imine, (E)-thioimidate isomer is the most stable form of 6a (see inset in Figure 3); however, the highest barrier for E to Z inversion is only 14.0 kcal/mol, so all of the possible isomers are readily interconverted at room temperature. We were able to grow single crystals of 6g in which the (Z)imine, (Z)-thioimidate isomer was found. Quantum chemical simulations on systematically generated conformers of all the four possible isomers suggest that, while there is almost no preference for (Z) over (E) configuration at the thioimidate center, the 31 most stable isomers prefer the (Z) configuration at the imine center, which is consistent with the obtained crystal structure. The first (Z)-imine, (Z)-thioimidate isomer appears third on the list with an energy of only +0.3 kcal/mol (cf. the corresponding 1.3 kcal/mol difference in 6b) relative to the most stable (Z)-imine, (E)-thioimidate isomer (Figure 4); this value is much smaller than crystal packing forces for polar compounds like these, so it is not surprising that the crystallized conformer is not the absolute lowest of the calculated structures. Interestingly, the calculations also showed a strong preference for the π stacking of the two phenyl rings; in fact, the first conformer without π stacking was 40th on the energy-sorted list at +2.15 kcal/mol relative to the most stable configuration. In conclusion, we have developed a simple method for the synthesis of the rather rare dicarbamoyl 2-iminothioimidate framework by means of a cycloaddition followed by an electrocyclic ring opening of the intermediate diazacyclobutenes. To the best of our knowledge, this one-step approach represents the first general strategy for the preparation of this unique class of molecules. Further, we have explored potential mechanisms for the transformation by means of variable temperature NMR spectroscopy, in situ IR, and computational quantum chemistry. Future studies are geared toward exploring the potential biological and synthetic utility of this rare class of compounds.

obtain a more symmetric [2 + 2] cycloaddition path ultimately converged to TS1, confirming the preference for polar nucleophilic addition as the first step of the reaction pathway. Significantly, whether formed from trans or cis forms of DEAD, no stable cis-5a minimum could be located; all attempts to optimize such structures fell without the barrier to trans-5a. Interestingly, the calculations also found a triplet state adduct, 14, only 0.4 kcal/mol higher in energy than 11, its singlet state analogue. However, the activation energy for four-membered ring closure of this triplet intermediate, via TS8, was significantly higher than that of the singlet state; it appears unlikely that triplet state species play any role in this chemistry. The barrier to closure of the six-membered heterocycle 15 via the nucleophilic attack by the ester carbonyl (see TS4) was found to be 4.7 kcal/mol higher in energy than that of the fourmembered ring closure via TS2. The barrier to formation of the five-membered ring 17, formed via TS6, is higher than those of four- and six-membered ring closures, consistent with the absence of observed products relevant to this path. Explorations for possible alternative intermediates involved in the reaction pathway turned up two three-membered ring species 16 and 18 (arising from TS7 and TS5, respectively). These, however, have significantly higher formation barriers than that for four-membered ring formation via polar adduct 11. We therefore conclude that such high energy species play no significant role in the observed chemistry. The calculated barrier for the four-membered ring opening, via TS3, is 3.8 kcal/mol higher than that of the addition step, which explains the accumulation (and isolation) of 5a during the reaction. Based on the above analyses, we conclude that the reaction proceeds via an addition step to form trans adduct 11, which falls into the diazacyclobutene 5a with either no or a very low energy barrier. The four-membered ring then opens to the iminothioimidate product 6a, passing over a barrier (i.e., 29.4 kcal/mol) that is higher than that for the initial addition step. This calculated barrier is in good agreement with the barrier that was estimated by means of NMR integration data (see the Supporting Information). In addition to TS1, three other modes of addition originating from the conformational flexibility of DEAD were found, all of which were higher in energy than TS1. While the addition barrier of cis-DEAD (see TS11 in the Supporting Information) was only 3.0 kcal/mol higher in energy than that of TS1, the highly asynchronous transition states TS12 and TS13 were about 10 kcal/mol higher than TS1. TS12 directly leads to the six-membered ring 15, and TS13 leads to the aromatic five-membered ring 20, F

DOI: 10.1021/acs.joc.9b01515 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry

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7.1 Hz, 2H), 4.06 (q, J = 7.1 Hz, 2H), 3.07 (q, J = 7.2 Hz, 2H), 1.69 (sextet, J = 7.3 Hz, 2H), 1.31 (t, J = 7.1 Hz, 3H), 1.13 (t, J = 7.1 Hz, 3H), 0.98 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 175.0, 166.5, 160.7, 159.1, 132.9, 132.5, 128.8, 128.6, 62.9 (2C), 33.3, 21.5, 14.1, 13.8, 13.2; HRMS (ESI+-TOF): calcd for C17H23N2O4S, [M + H]+ 351.1379 found m/z 351.1398. Butyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)-2-phenylethanimidothioate (6d). Colorless liquid; yield: 83% (303 mg); IR (neat): 2958 (w), 2931 (w), 2870 (w), 1716 (s), 1627 (m), 1577 (m), 1446 (m), 1365 (m), 1207 (s), 1091 (m), 1033 (m), 864 (w), 783 (m), 729 (m), 690 (m) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.79 (d, J = 7.2 Hz, 2H), 7.48 (t, J = 7.3 Hz, 1H), 7.38 (t, J = 7.5 Hz, 2H), 4.24 (q, J = 7.1 Hz, 2H), 4.03 (q, J = 7.1 Hz, 2H), 3.06 (t, J = 7.3 Hz, 2H), 1.60 (p, J = 7.3 Hz, 2H), 1.50−1.20 (m, 5H), 1.10 (t, J = 7.1 Hz, 3H), 0.86 (t, J = 7.3 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 174.7, 166.3, 160.6, 159.0, 132.8, 132.5, 128.7, 128.5, 62.8 (2C), 31.1, 29.9, 21.7, 14.0, 13.7, 13.2; HRMS (ESI+-TOF): calcd for C18H25N2O4S, [M + H]+ 365.1535 found m/z 365.1556. Pentyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)-2-phenylethanimidothioate (6e). Colorless liquid; yield: 80% (303 mg); IR (neat): 2954 (w), 2931 (w), 2858 (w), 1720 (s), 1627 (m), 1577 (m), 1446 (m), 1365 (m), 1280 (w), 1207 (s), 1091 (m), 1033 (m), 783 (m), 729 (m), 690 (m) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.76 (d, J = 6.54 Hz, 2H), 7.44 (t, J = 7.3 Hz, 1H), 7.34 (t, J = 7.5 Hz, 2H), 4.20 (q, J = 7.1 Hz, 2H), 4.00 (q, J = 6.90 Hz, 2H), 3.02 (t, J = 7.2 Hz, 2H), 1.58 (p, J = 7.0 Hz, 2H), 1.40−1.15 (m, 7H), 1.05 (t, J = 7.1 Hz, 3H), 0.79 (t, J = 6.9 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 174.6, 166.1, 160.4, 158.8, 132.7, 132.2, 128.5, 128.3, 62.6 (2C), 31.1, 30.4, 27.4, 21.7, 13.8, 13.5, 13.4; HRMS (ESI+TOF): calcd for C19H27N2O4S, [M + H]+ 379.1692 found m/z 379.1710. Octyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)-2-phenylethanimidothioate (6f). Light yellow liquid; yield: 73% (307 mg); IR (neat): 2924 (m), 2854 (w), 1720 (s), 1627 (m), 1577 (m), 1446 (m), 1365 (m), 1207 (s), 1091 (m), 1033 (m), 910 (m), 783 (m), 729 (m), 688 (m) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.77 (d, J = 6.63 Hz, 2H), 7.45 (t, J = 7.3 Hz, 1H), 7.36 (t, J = 7.4 Hz, 2H), 4.21 (q, J = 7.1 Hz, 2H), 4.00 (q, J = 7.0 Hz, 2H), 3.03 (t, J = 7.2 Hz, 2H), 1.59 (p, J = 7.1 Hz, 2H), 1.40−1.12 (m, 13H), 1.07 (t, J = 7.1 Hz, 3H), 0.79 (t, J = 6.4 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 175.0, 166.4, 160.7, 159.1, 132.9, 132.5, 128.8, 128.6, 62.9, 62.8, 31.6, 31.5, 28.9, 28.8, 28.6, 27.9, 22.4, 14.1, 13.9, 13.8; HRMS (ESI+-TOF): calcd for C22H33N2O4S, [M + H]+ 421.2161 found m/z 421.2161. Phenyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)-2-phenylethanimidothioate (6g). Light yellow solid; yield: 77% (296 mg); mp: 70−71 °C; IR (neat): 2981 (w), 1724 (s), 1712 (s), 1631 (m), 1612 (m), 1577 (w), 1477 (m), 1442 (m), 1207 (s), 1095 (w), 1022 (m), 968 (m), 860 (w), 752 (s), 686 (s) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.54 (d, J = 7.4 Hz, 2H), 7.50−7.20 (m, 6H), 7.15 (t, J = 7.5 Hz, 2H), 4.38 (q, J = 7.1 Hz, 2H), 4.28 (broad q, J = 7.1 Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H), 1.35 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ = 173.9, 165.5, 161.3, 159.6, 135.8, 133.2, 132.5, 130.3, 129.0, 128.4, 128.2, 126.1, 63.23, 63.16, 14.2, 14.1; HRMS (ESI+-TOF): calcd for C20H21N2O4S, [M + H]+ 385.1222 found m/z 385.1240. Benzyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)-2-phenylethanimidothioate (6h). Colorless liquid; yield: 83% (330 mg); IR (neat): 2978 (w), 1716 (s), 1627 (w), 1577 (m), 1492 (w), 1450 (w), 1207 (s), 1087 (m), 1026 (m), 910 (w), 729 (w), 690 (w) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.81 (d, J = 6.2 Hz, 2H), 7.51 (t, J = 7.0 Hz, 1H), 7.40 (t, J = 7.7 Hz, 2H), 7.35−7.16 (m, 5H), 4.34 (s, 2H), 4.23 (q, J = 7.1 Hz, 2H), 4.10 (q, J = 7.1 Hz, 2H), 1.27 (t, J = 7.1 Hz, 3H), 1.15 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 174.2, 165.9, 160.6, 158.9, 134.6, 132.9, 132.3, 130.4, 129.1, 128.7, 128.5, 127.7, 62.88, 62.86, 35.8, 14.0, 13.7; HRMS (ESI+TOF): calcd for C21H23N2O4S, [M + H]+ 399.1379 found m/z 399.1391. Methyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)-2-(ptolyl)ethanimidothioate (6i). Colorless liquid; yield: 88% (296 mg); IR (neat): 2978 (w), 2927 (w), 1716 (s), 1627 (m), 1600 (m),

EXPERIMENTAL SECTION

General Information. All reagents were purchased from commercial sources and used without purification. THF and acetonitrile were dried prior to use over sodium/benzophenone and phosphorous pentoxide, respectively. 1H and 13C NMR spectra were collected on Bruker 300 MHz, 500 MHz NMR spectrometers using CDCl3. Chemical shifts are reported in ppm. Spectra are referenced to residual solvent peaks. Infrared spectroscopy data were collected using an IR Affinity-1S instrument (with MIRacle 10 single reflection ATR accessory). A flash silica gel (40−63 μm) was used for column chromatography. All known compounds were characterized by 1H and 13C NMR and are in complete agreement with samples reported elsewhere. All new compounds were characterized by 1H and 13 CNMR, ATR-FTIR, HRMS, XRD, and melting point (where appropriate). HRMS data were collected using an instrument equipped with electrospray ionization in positive mode (ESI+) and a time-of-flight (TOF) detector. Characterization data for the previously known alkynyl sulfides and selenides can be found in earlier reports.1,37 One new seleno-alkyne 1t was synthesized and characterized by 1H and 13C NMR prior to use.

Benzyl(phenyethynyl)selane (1t). Light yellow liquid; yield: 84% (4.46 g); 1H NMR (300 MHz, CDCl3) δ = 7.6−7.28 (m, 10H), 4.16 (s, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ = 137.4, 131.4, 129.0, 128.5, 128.2, 128.1, 127.5, 123.4, 101.2, 71.0, 33.0. General Procedure for Synthesis of N,N-Dicarbamoyl Iminothioimidates. To a flame-dried round-bottom flask equipped with a water-cooled condenser and a stir bar was added a solution of azodicarboxylate (1 mmol, 1 equiv) and 5 mL of dry acetonitrile under nitrogen. To this stirring solution was added dropwise a solution of alkynyl sulfide (1.3 mmol, 1.3 equiv) in 5 mL of dry acetonitrile. The mixture was then refluxed for 24 h. The resultant mixture was concentrated under reduced pressure and purified via flash chromatography with hexanes and ethyl acetate (100% hexanes to 80:20 hexanes/ethyl acetate) to afford the corresponding αimidothioimidate product. Analytical Data for N,N-Dicarbamoyl Iminothioimidates 6a−6t and Diazacyclobutene 5b. Methyl N-(Ethoxycarbonyl)-2((ethoxycarbonyl)imino)-2-phenylethanimidothioate (6a). Colorless liquid; yield: 74% (239 mg); IR (neat): 2981 (w), 2931 (w), 1716 (s), 1627 (m), 1577 (m), 1446 (m), 1365 (m), 1207 (s), 1091 (m), 1033 (m), 864 (w), 690 (m) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.83 (d, J = 6.6 Hz, 2H), 7.52 (t, J = 7.4 Hz, 1H), 7.42 (t, J = 7.3 Hz, 2H), 4.27 (q, J = 7.1 Hz, 2H), 4.08 (q, J = 6.8 Hz, 2H), 2.47 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H), 1.15 (t, J = 7.1 Hz, 3H); 13 C{1H} NMR (75 MHz, CDCl3) δ = 175.6, 166.2, 160.8, 159.2, 133.0, 132.4, 128.7, 128.7, 63.0 (2C, see 2D-HMQC), 14.3, 14.1, 14.0; HRMS (ESI+-TOF): calcd for C15H19N2O4S, [M + H]+ 323.1066 found m/z 323.1087. Ethyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)-2-phenylethanimidothioate (6b). Colorless liquid; yield: 99% (334 mg); IR (neat): 2981 (w), 2931 (w), 2870 (w), 1716 (s), 1627 (m), 1577 (m), 1446 (m), 1365 (m), 1207 (s), 1091 (m), 1033 (m), 864 (m), 690 (m) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.76 (d, J = 6.5 Hz, 2H), 7.44 (t, J = 7.3 Hz, 1H), 7.34 (t, J = 7.4 Hz, 2H), 4.19 (q, J = 7.1 Hz, 2H), 3.99 (q, J = 6.9 Hz, 2H), 3.02 (q, J = 7.3 Hz, 2H), 1.23 (t, J = 7.3 Hz, 6H, see 2D HMQC), 1.05 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 174.6, 166.0, 160.4, 158.8, 132.7, 132.1, 128.5, 128.4, 62.6 (2C), 25.6, 13.8, 13.5, 12.9; HRMS (ESI+-TOF): calcd for C16H21N2O4S, [M + H]+ 337.1222 found m/z 337.1242. Propyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)-2-phenylethanimidothioate (6c). Colorless liquid; yield: 73% (256 mg); IR (neat): 2970 (w), 2931 (w), 1716 (s), 1627 (m), 1577(m), 1446 (w), 1365 (m), 1284 (w), 1207 (s), 1091 (m), 1033 (m), 864 (w), 729 (m), 690 (m) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.82 (d, J = 7.1 Hz, 2H), 7.52 (t, J = 7.3 Hz, 1H), 7.42 (t, J = 7.3 Hz, 2H), 4.27 (q, J = G

DOI: 10.1021/acs.joc.9b01515 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry

δ = 4.25 (q, J = 7.1 Hz, 2H), 4.21 (q, J = 7.1 Hz, 2H), 2.45 (s, 3H), 2.10−1.70 (m, 1H), 1.33 (t, J = 6.3 Hz, 3H), 1.28 (t, J = 6.3 Hz, 3H) 1.26−1.05 (m, 4H); 13C{1H} NMR (75 MHz, CDCl3) δ = 176.1, 175.0, 160.6, 159.3, 63.0, 62.7, 17.2, 13.9 (3C, see 2D-HMQC Analysis in the Supporting Information), 12.4 (2C, see 2D-HMQC Analysis in the Supporting Information); HRMS (ESI+-TOF): calcd for C12H19N2O4S, [M + H]+ 287.1066 found m/z 287.1069. Ethyl N-(Isopropoxycarbonyl)-2-((isopropoxycarbonyl)imino)-2phenylethanimidothioate (6p). Colorless liquid; yield: 99% (361 mg); IR (neat): 2978 (w), 2931 (w), 2873 (w), 1716 (s), 1627 (w), 1577 (m), 1450 (w), 1373 (w), 1215 (s), 1180 (w), 1145 (w), 1099 (s), 983 (m), 937 (w), 786 (w), 729 (m), 686 (m) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.82 (d, J = 5.6 Hz, 2H), 7.55−7.44 (m, 1H), 7.44−7.33 (m, 2H), 5.03 (septet, J = 6.2 Hz, 1H), 4.89−4.66 (bm, 1H), 3.06 (q, J = 7.1 Hz, 2H), 1.41−1.17 (bm, 9H), 1.08 (d, J = 5.6 Hz, 6H); 13C{1H} NMR (75 MHz, CDCl3) δ = 173.8, 165.6, 160.2, 158.5, 132.8, 132.5, 128.7, 128.5, 70.9, 70.8, 25.8, 21.6, 21.3, 13.1; HRMS (ESI+-TOF): calcd for C18H25N2O4S, [M + H]+ 365.1535 found m/z 365.1548. Ethyl N-((Benzyloxy)carbonyl)-2-(((benzyloxy)carbonyl)imino)-2phenylethanimidothioate (6q). Colorless liquid; yield: 79% (364 mg); IR (neat): 2962 (w), 2927 (w), 1716 (s), 1627 (w), 1577 (m), 1450 (m), 1373 (m), 1195 (s), 1095 (m), 1002 (w), 910 (w), 732 (w), 694 (m) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.82 (d, J = 5.6 Hz, 2H), 7.60−7.48 (m, 1H), 7.48−7.20 (m, 12H), 5.26 (s, 2H), 5.03 (s, 2H), 3.04 (q, J = 7.4 Hz, 2H), 1.27 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 175.1, 166.4, 160.5, 158.9, 135.0, 134.9, 133.0, 132.2, 132.1, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 68.6, 68.5, 25.8, 13.0; HRMS (ESI+-TOF): calcd for C26H25N2O4S, [M + H]+ 461.1535 found m/z 461.1545. Methyl 2-Phenyl-N-((2,2,2-trichloroethoxy)carbonyl)-2-(((2,2,2trichloroethoxy)carbonyl)imino)ethanimidothioate (6r). Colorless liquid; yield: 86% (455 mg); IR (neat): 2954 (w), 1732 (s), 1627 (w), 1593 (w), 1577 (w), 1369 (m), 1276 (w), 1176 (s), 1033 (m), 906 (m), 806 (m), 721 (s), 686 (m) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.86 (d, J = 8.0 Hz, 2H), 7.56 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.5 Hz, 2H), 4.84 (s, 2H), 4.66 (s, 2H), 2.53 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 178.0, 167.2, 158.9, 157.3, 133.8, 131.6, 129.0, 128.9, 94.14, 94.07, 75.9, 75.7, 14.7; HRMS (ESI+-TOF): calcd for C15H13N2O4SCl6, [M + H]+ 526.8727 found m/z 526.8739. Methyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)-2-phenylethanimidoselenoate (6s). Light yellow liquid; yield: 76% (280 mg); IR (neat): 2981 (w), 2935 (w), 1716 (s), 1597 (s), 1573 (w), 1446 (w), 1369 (w), 1330 (w), 1292 (w), 1211 (s), 1095 (w), 1026 (m), 898 (w), 864 (w), 771 (w), 732 (w), 690 (m), 528 (w) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.88 (d, J = 7.4 Hz, 2H), 7.60−7.47 (m, 1H), 7.47−7.30 (m, 2H), 4.23 (q, J = 6.9 Hz, 2H), 2.19 (s, 3H), 1.45 (m, 6H); 13C{1H} NMR (75 MHz, CDCl3) δ =179.9, 165.0, 160.8, 160.4, 133.1, 132.3, 128.7, 128.5, 63.1, 62.8, 14.0, 13.9, 8.3; HRMS (ESI+-TOF): calcd for C15H19N2O4Se, [M + H]+ 371.0510 found m/z 371.0528. Benzyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)-2-phenylethanimidoselenoate (6t). Light yellow liquid; yield: 81% (361 mg); IR (neat): 2981 (w), 2931 (w), 1716 (s), 1689 (m), 1627 (m), 1577 (w), 1554 (w), 1494 (m), 1448 (m) 1365 (m), 1207 (s), 1180 (s), 1093 (m), 1024 (s), 970 (w), 904 (m), 732 (m), 694 (s) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.96 (d, J = 6.6 Hz, 2H), 7.70−7.00 (m, 8H), 4.32 (q, J = 7.1 Hz, 2H), 4.27−4.15 (m, 4H), 1.33 (t, J = 7.1 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 179.0, 165.3, 161.0, 160.2, 135.1, 133.1, 132.1, 129.0, 128.7, 128.6, 128.5, 127.3, 63.2, 62.9, 32.3, 14.0, 13.8; HRMS (ESI+-TOF): calcd for C21H23N2O4Se, [M + H]+ 447.0824 found m/z 447.0830. Diethyl 3-(Ethylthio)-4-phenyl-1,2-diazete-1,2-dicarboxylate (5b). Colorless liquid; isolated by prep TLC (2 mg); IR (in CHCl3): 2927 (w), 2849 (w), 1780 (s), 1561 (w), 1463 (s), 1382 (m), 1222 (s), 1095 (m), 1029 (w), 567 (m) cm−1; 1H NMR (500 MHz, CDCl3) δ = 7.85−7.70 (m, 2H), 7.40−7.27 (m, 3H), 4.35 (q, J = 7.1 Hz, 2H), 4.24 (q, J = 7.1 Hz, 2H), 2.93 (q, J = 7.4 Hz, 2H), 1.42−1.34 (m, 6H), 1.26 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ = 154.54, 154.45, 143.7, 128.8, 128.0, 127.0, 124.4,

1462 (w), 1446 (w), 1411 (w), 1388 (w), 1365 (m), 1292 (m), 1207 (s), 1180 (m), 1091 (s), 1033 (s), 914 (m), 821 (w), 775 (w), 729 (s) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.71 (d, J = 7.26 Hz, 2H), 7.21 (d, J = 7.9 Hz, 2H), 4.24 (q, J = 7.1 Hz, 2H), 4.07 (q, J = 6.74 Hz, 2H), 2.44 (s, 3H), 2.35 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H), 1.14 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 175.7, 166.0, 160.8, 159.1, 144.0, 129.6, 129.3, 128.7, 62.79, 62.77, 21.5, 14.2, 14.0, 13.7; HRMS (ESI+-TOF): calcd for C16H21N2O4S, [M + H]+ 337.1222 found m/z 337.1241. Methyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)-2-(4methoxyphenyl)ethanimidothioate (6j). Colorless liquid; yield: 95% (335 mg); IR (neat): 2978 (w), 2931 (w), 2839 (w), 1716 (s), 1593 (s), 1570 (w), 1508 (m), 1462 (w), 1442 (w), 1207 (s), 1168 (s), 1091 (m), 1026 (s), 910 (m), 840 (m), 729 (s) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.77 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 8.9 Hz, 2H), 4.22 (q, J = 7.1 Hz, 2H), 4.06 (q, J = 7.0 Hz, 2H), 3.79 (s, 3H), 2.42 (s, 3H), 1.27 (t, J = 7.1 Hz, 3H), 1.13 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 175.6, 165.3, 163.6, 160.9, 159.1, 130.9, 124.7, 114.0, 62.8, 62.7, 55.3, 14.1, 14.0, 13.7; HRMS (ESI+-TOF): calcd for C16H21N2O5S, [M + H]+ 353.1171 found m/z 353.1185. Methyl 2-(4-Chlorophenyl)-N-(ethoxycarbonyl)-2((ethoxycarbonyl)imino)ethanimidothioate (6k). Colorless liquid; yield: 47% (168 mg); IR (neat): 2978 (w), 2927 (w), 1716 (s), 1627 (m), 1589 (m), 1400 (w), 1365 (w), 1207 (s), 1087 (s), 1029 (s), 864 (w), 783 (w), 725 (m) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.77 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.6 Hz, 2H), 4.26 (q, J = 7.1 Hz, 2H), 4.10 (q, J = 7.1 Hz, 2H), 2.47 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H), 1.17 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 175.4, 165.4, 160.6, 159.0, 139.5, 130.9, 130.0, 129.0, 63.1 (2C), 14.3, 14.1, 13.8; HRMS (ESI+-TOF): calcd for C15H18ClN2O4S, [M + H]+ 357.0676 found m/z 357.0686. Methyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)-2-(4(trifluoromethyl)phenyl)ethanimidothioate (6l). Colorless liquid; yield: 69% (270 mg); IR (neat): 2981 (w), 1724 (s), 1631 (w), 1577 (w), 1411 (w), 1323 (s), 1211 (s), 1168 (m), 1126 (m), 1064 (s), 1033 (w), 1014 (w), 848 (m), 771 (w), 748 (w) cm−1; 1H NMR (300 MHz, CDCl3) δ = 7.95 (d, J = 7.4 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H), 4.27 (q, J = 7.1 Hz, 2H), 4.09 (q, J = 6.9 Hz, 2H), 2.49 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H), 1.16 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 175.5, 165.5, 160.4, 159.1, 135.8, 134.3 (q, 2JCF = 32.8 Hz), 129.1, 125.7 (q, 3JCF = 3.7 Hz), 123.5 (q, 1JCF = 272.7 Hz), 63.33, 63.25, 14.3, 14.1, 13.9; HRMS (ESI+-TOF): calcd for C16H18F3N2O4S, [M + H]+ 391.0939 found m/z 391.0963. Methyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)hexanimidothioate (6m). Light yellow liquid; yield: 40% (121 mg); IR (neat): 2958 (w), 2931 (w), 1716 (s), 1662 (w), 1608 (w), 1500 (w), 1465 (w), 1365 (w), 1215 (s), 1095 (w), 1033 (m), 948 (w), 914 (w), 732 (m) cm−1; 1H NMR (300 MHz, CDCl3) δ = 4.40− 4.10 (m, 4H), 2.48 (t, J = 7.8 Hz, 2H), 2.41 (s, 3H), 1.56 (p, J = 7.6 Hz, 2H), 1.40−1.23 (m, 8H), 0.86 (t, J = 7.3 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ = 171.2, 161.7, 160.6, 159.7, 62.9, 62.8, 27.8, 23.3, 15.1, 14.1, 14.0, 13.7, 13.5; HRMS (ESI+-TOF): calcd for C13H22N2O4SNa, [M + Na]+ 325.1198 found m/z 325.1210. Butyl N-(Ethoxycarbonyl)-2-((ethoxycarbonyl)imino)hexanimidothioate (6n). Light yellow liquid; yield: 45% (155 mg); IR (neat): 2958 (w), 2931 (w), 2870 (w), 1724 (s), 1662 (w), 1604 (m), 1462 (w), 1365 (w), 1215 (s), 1095 (w), 1037 (m), 948 (w), 914 (w), 779 (w), 732 (w) cm−1; 1H NMR (300 MHz, CDCl3) δ = 4.19 (m, 4H), 2.99 (t, J = 7.3 Hz, 2H), 2.47 (t, J = 7.6 Hz, 2H), 1.7− 1.48 (m, 4H), 1.48−1.22 (m, 10H), 1.00−0.80 (m, 6H); 13C{1H} NMR (75 MHz, CDCl3) δ = 171.4, 161.0, 160.5, 159.8, 62.8, 62.7, 30.6, 30.0, 29.5, 27.7, 22.3, 21.8, 14.1, 14.0, 13.4, 13.3; HRMS (ESI+TOF): calcd for C16H29N2O4S, [M + H]+ 345.1848 found m/z 345.1862. Methyl 2-Cyclopropyl-N-(ethoxycarbonyl)-2-((ethoxycarbonyl)imino)ethanimidothioate (6o). Colorless liquid; yield: 77% (220 mg); IR (neat): 2981 (w), 2931 (w), 1716 (s), 1651 (m), 1583 (m), 1444 (w), 1382 (w), 1365 (m), 1219 (s), 1193 (s), 1028 (s), 995 (m), 862 (m), 775 (m) 731 (m) cm−1; 1H NMR (300 MHz, CDCl3) H

DOI: 10.1021/acs.joc.9b01515 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry 63.4, 63.1, 29.8, 29.7, 14.9, 14.4, 14.1. Note that compound 5b was insufficiently stable for HRMS analysis.

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(9) Jursic, B. S. Study of ring opening of 1,2-diformyl-1,2diazacyclobutene by ab initio and density functional Gaussian-typeorbital approach. J. Mol. Struct.: THEOCHEM 1995, 357, 243−253. (10) Bachrach, S. M.; Liu, M. Ab initio study of the conrotatory ring opening of phospha- and azacyclobutenes. 2. Diphospha- and diazacyclobutenes. J. Org. Chem. 1992, 57, 2040−2047. (11) Nair, V.; Biju, A. T.; Mathew, S. C.; Babu, B. P. Carbonnitrogen bond-forming reactions of dialkyl azodicarboxylate: A promising synthetic strategy. Chem. − Asian J. 2008, 3, 810−820. (12) Vallribera, A.; Maria Sebastian, R.; Shafir, A. Azodicarboxylates as electrophilic aminating reagents. Curr. Org. Chem. 2011, 15, 1539− 1577. (13) Zhirov, A. M.; Aksenov, A. V. Azodicarboxylates: synthesis and functionalization of organic compounds. Russ. Chem. Rev. 2014, 83, 502−522. (14) Swamy, K. C. K.; Bhuvan Kumar, N. N.; Balaraman, E.; Kumar, K. V. P. P. Mitsunobu and related reactions: advances and applications. Chem. Rev. 2009, 109, 2551−2651. (15) Viñuelas-Zahínos, E.; Maldonado-Rogado, M. A.; Luna-Giles, F.; Barros-García, F. J. Coordination behaviour of Schiff base 2-acetyl2-thiazoline hydrazone (ATH) towards cobalt(II), nickel(II), and copper(II). Polyhedron 2008, 27, 879−886. (16) Viñ uelas-Zahínos, E.; Luna-Giles, F.; Torres-García, P.; Rodríguez, A. B.; Bernalte-García, A. Effects of a derivative thiazoline/thiazolidine azine ligand and its cadmium complexes on phagocytic activity by human neutrophils. Inorg. Chim. Acta 2011, 366, 373−379. (17) MacKenzie, N. E.; Thomson, R. H.; Greenhalgh, C. W. New dyes based on 3-aryl-benzo- and -naphtho-1,4-thiazines. J. Chem. Soc., Perkin Trans. 1 1980, 2923−2932. (18) Coustard, J.-M. 1-Arylamino-1-methylthio-2-nitroethene in superacids: NMR study and reactivity of the formed hydroxynitrilium lons. Tetrahedron 1996, 52, 9509−9520. (19) Cousson, A.; Coustard, J.-M. X-ray structure determination of products resulting from trapping of hydroxynitrilium ions. Tetrahedron 1998, 54, 6523−6528. (20) Bamba, F.; Soro, Y.; Siaka, S.; Marrot, J.; Coustard, J. M. A new way for synthetizing (E)-methyl methylsulfanyl(phenylamino)methylene carbamates via Beckmann transposition in triflic acid. Bull. Chem. Soc. Ethiop. 2015, 29, 291−298. (21) Elghandour, A. H. H.; Ibrahim, M. K. A.; El-badry, B.; Waly, H. K. Utility of hydrazidoyl halides in heterocycles: A new route for the synthesis of alkylmercaptoheterocyclic compounds. Phosphorus, Sulfur Silicon Relat. Elem. 1994, 88, 147−153. (22) Joule, J. A.; Kearney, T.; Jackson, A. Synthesis of 2-methylthio3H-indol-3-one 3-oximes from 1-(N-arylamino)-1-methylthio-2-nitroethenes. Heterocycles 1992, 33, 757−762. (23) Deryabina, T. G.; Bel’skaya, N. P.; Kodess, M. I.; Bakulev, V. A. Reaction of 2-arylhydrazono-2-cyano-N-cyclohexylthioacetamides with halocarbonyl compounds. Chem. Heterocycl. Compd. 2007, 43, 18−27. (24) Bel’skaya, N. P.; Koksharov, A. V.; Deyabina, T. G.; Bakulev, V. A. Intramolecular cyclization of 1-[1-alkylsulfanyl-2-phenyl- 2(phenylhydrazono) ethylidene]-pyrrolidinium salts. Chem. Heterocycl. Compd. 2010, 46, 1156−1157. (25) Stetter, J.; Führer, W.; Brandes, W. Hydroximic acid esters, their preparation and their use as fungicides, E.P. Appl. EP0056161A2, January 13, 1981. (26) Bayer, H.; Sauter, H.; Benoit, R.; Müller, R.; Ammerman, E.; Lorenz, G. Thioimidates, Their Preparation and Their Use, Canadian Patent Appl. 2137018, June 4, 1995. (27) Clark, R.; Takemura, A.; Watanabe, N.; Asano, O.; Nagakura, T.; Tabata, K. 2,3-dihydro-iminoisoindole derivatives, U.S. Patent Appl. US 2009/0270433 A1, October 29, 2009. (28) Fuganti, C.; Gatti, F. G.; Serra, S. A general method for the synthesis of the most powerful naturally occurring Maillard flavors. Tetrahedron 2007, 63, 4762−4767. Clark, R.; Matsuura, F.; Shinoda, M.; Hirota, S.; Kira, K.; Azuma, H.; Takemura, A.; Yasui, S.; Kusano,

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.9b01515. Kinetic analysis of diazacyclobutene ring opening, in situ IR data and discussion, 1H and 13C NMR spectra, X-ray crystallography data for 6g (PDF) Computational coordinates for all calculated structures and transition states (PDF) Computational data for all calculated structures and transition states (XLSX) Molecular descriptions of all calculated structures and transition states (XYZ) Molecular descriptions of 6g (XYZ) Crystallography data for 6g (CIF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (J.E.J.). *E-mail: [email protected] (D.C.W.). ORCID

Daniel C. Whitehead: 0000-0001-6881-2628 Author Contributions ⊥

C.J.N. and T.K. contributed equally.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was facilitated by a National Science Foundation Major Research Instrumentation grant (CHE-1725919) for a 500 MHz Bruker NEO NMR spectrometer with a Prodigy (R) cryoprobe. Computational resources were provided by the Institute of Cyber-Enabled Research (iCER) at Michigan State University.

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REFERENCES

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