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. 2023 Jan 13;3(2):476–487. doi: 10.1021/jacsau.2c00608

Oxidative Cleavage and Ammoxidation of Unsaturated Hydrocarbons via Heterogeneous Auto-Tandem Catalysis

Bo Chen †, Lei Zhang †, Huihui Luo †, Liang Huang ‡,*, Peipei He †, Gaijun Xue †, Hongliang Liang †, Wen Dai †,*
PMCID: PMC9975833  PMID: 36873692

Abstract

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The oxidative cleavage and functionalization of unsaturated C–C bonds are important processes for synthesis of carbonyl compounds from hydrocarbon feedstocks, yet there has been no report of direct amidation of unsaturated hydrocarbons via an oxidative cleavage of unsaturated C–C bonds with molecular oxygen as an environmentally benign oxidant. Herein, for the first time, we describe a manganese oxide-catalyzed auto-tandem catalysis strategy that enables direct synthesis of amides from unsaturated hydrocarbons by coupling oxidative cleavage with amidation. With oxygen as an oxidant and ammonia as a nitrogen source, a wide range of structurally diverse mono- and multisubstituted activated and unactivated alkenes or alkynes can smoothly undergo unsaturated C–C bond cleavage to deliver one- or multiple-carbon shorter amides. Moreover, a slight modification of the reaction conditions also allows for the direct synthesis of sterically hindered nitriles from alkenes or alkynes. This protocol features excellent functional group tolerance, a broad substrate scope, flexible late-stage functionalization, facile scalability, and a cost-effective and recyclable catalyst. Detailed characterizations reveal that the high activity and selectivity of the manganese oxides are attributed to the large specific surface area, abundant oxygen vacancies, better reducibility, and moderate acid sites. Mechanistic studies and density functional theory calculations indicate that the reaction proceeds through divergent pathways depending on the structure of substrates.

Keywords: oxidative cleavage, heterogeneous catalysis, unsaturated hydrocarbons, amides, nitriles

Introduction

Amides not only represent one of the most privileged moieties in natural products, pharmaceuticals, and agrochemicals but also act as incredibly useful and versatile synthons in organic synthesis.1−3 As such, development of efficient methodologies toward amides continues to be scientifically interesting and attracts the attention of the synthetic community.4 In particular, the focal point is to find or design suitable catalytic protocols that enable delivering amides from readily available and abundant chemical feedstocks. Given that alkenes are a rich and inexpensive source of unsaturated hydrocarbons, direct conversion of alkene feedstocks into amides has long been a hot topic. Among them, hydroaminocarbonylation of alkenes with amines including ammonia and CO represents an attractive strategy for amide synthesis from abundant feedstock chemicals (Figure 1a). Some key advances include the use of Co, Ni, Ru, and Pd complexes as the catalysts.5−7 However, the formation of undesirable formamide byproducts, over-reliance on high-pressure toxic gaseous CO, and/or usage of expensive catalysts still limit most of these reaction classes. Therefore, novel catalytic technologies for efficient amidation of C–C double bonds are still needed to offer a viable pathway toward green, efficient, and economical unsaturated hydrocarbon utilization.

Figure 1.

Figure 1

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Research background.

Oxidative cleavage and functionalization of C=C double bonds is a powerful tool to convert alkenes into carbonyl compounds and has been widely used in the academia and industry. Although numerous homogeneous or heterogeneous catalytic systems have been well-established for the conversion of alkenes to aldehydes, ketones, and acids via C=C double-bond cleavage (Figure 1b),8,9 methods for direct oxidative cleavage and amidation of alkenes remain elusive,10,11 and thus far, none is applicable to a wide range of substrate scope and allows for the use of O2 as a clean and sustainable oxidant. Therefore, developing an environmentally friendly, cost-effective, and widely applicable protocol for direct amidation of alkenes via unsaturated C–C bond cleavage remains an open challenge.

Tandem catalysis, which combines multiple reactions into one synthetic operation, offers many advantages over the traditional step-by-step catalysis, such as minimizing separations, saving operating time and costs, and reducing waste.12−15 More importantly, it also provides tremendous possibilities for driving transformations forward by coupling reactions.16 In this context, we reasoned that the amidation of alkenes might be achieved via tandem oxidative cleavage and ammoxidation. Specifically, the oxidative cleavage of alkenes to oxygenated intermediates such as aldehydes and ketones is generally an endothermic process17 and often restricted by the thermodynamic equilibrium. Rapid transformation of the oxygenated intermediates through ammoxidation could force the first-step oxidation of alkenes to move forward faster and thus break the thermodynamic limitation, as well as suppress the undesired intermolecular oligomerization/polymerization. Taking advantage of the synergistic effect between the two sequential reactions, the corresponding altered reaction pathway can facilitate the overall sequential reactivity. An essential prerequisite for successful execution of this tandem catalysis is the design and synthesis of a catalyst capable of simultaneously promoting oxidative cleavage of alkenes to oxygenated intermediates and rapid ammoxidation of these intermediates in a highly efficient and selective manner.

Manganese oxides have long been of interest as catalysts for epoxidation of alkenes18,19 and ammoxidation of diverse oxygen-containing compounds, such as alcohols20 and aldehydes.21,22 Moreover, Escande et al. demonstrated that sodium manganese oxide enabled the oxidative cleavage of C–C bonds in vicinal diols to aldehydes or ketones with O2 as the terminal oxidant.23 Taking together, we envisioned that manganese oxides might be potential candidates for tandem oxidative cleavage and ammoxidation of C=C double bonds in alkenes. As part of our continued interest in value-added transformation of chemical feedstocks,24,25 herein, for the first time, we report a manganese oxide-catalyzed tandem oxidative cleavage/ammoxidation that enables direct synthesis of amides from unsaturated hydrocarbons (Figure 1c). A diverse set of mono- and multisubstituted aromatic and aliphatic alkenes or alkynes are smoothly converted into amides with O2 as an oxidant and NH3 as a nitrogen source. A slight modification of the reaction conditions also allows for cyanation of sterically hindered alkenes or alkynes to access nitriles. Moreover, the easily prepared MnOx catalyst can be recovered and reused at least eight times without the loss of efficiency. Therefore, the present method not only complements existing protocols for amide and nitrile syntheses but also opens new avenues for direct functionalization of abundant unsaturated hydrocarbons.

Results and Discussion

At the outset, we selected styrene (s1) as the model substrate and performed the reaction using O2 as a green oxidant and NH3 as a nitrogen source. A series of commercial manganese oxides (MnO, Mn3O4, Mn2O3, and MnO2) were screened first, with MnO2 delivering the cleaved and functionalized products benzamide (1) and benzonitrile (1′) in 14 and 15% yields, respectively (Table S1, entries 1–4). Encouraged by this result, we then employed octahedral manganese oxide molecular sieves (OMS-2) as the catalyst since it has shown high activities in many amidation reactions and also can promote the hydration of nitriles into amides.20,21,26 To our delight, the desired product 1 was increased to 30% (entry 5). Notably, MnOx, prepared similarly to OMS-2 but with a less ordered structure (vide infra), displayed the highest activity and gave 1 and 1′ in 77 and 15% yields, respectively (entry 6). Moreover, the yield of 1 can be further improved to 88% by prolonging the reaction time to 24 h (entry 7), indicating that 1′ might be a key intermediate of the reaction. For comparison, the reaction was also performed in an O2 atmosphere, but only 27% conversion with benzoic acid as the main product was obtained (entries 8, and Figure S1). These results imply that the ammoxidation can significantly boost the transformation of styrene by rapidly converting the generated intermediates into benzonitrile and benzamide. When the reaction was performed in the absence of a catalyst, no products were observed (entry 9). KMnO4 and Mn(OAc)2, the precursors for the preparation of MnOx, were also evaluated but showed poor activity toward the reaction (entries 10 and 11). These results highlight the critical role of MnOx in oxidative cleavage and ammoxidation of alkenes. Subsequent variation of the reaction conditions reveals that the temperature and solvents are important for the reaction (entries 12–18). For instance, both conversion and selectivity to 1 were significantly decreased in CH3CN. Thus, we finally chose the optimized conditions in entry 7 (t-amyl alcohol as the solvent, 130 °C, 0.5 MPa O2, 0.5 MPa NH3, 24 h) for the subsequent experiments.

To rationalize the activity of these catalysts, a series of characterizations were performed. X-ray diffraction (XRD) patterns show that all the commercial manganese oxides and OMS-2 exhibit well-defined diffraction peaks, whereas MnOx only displays a broad peak at 37.2°, demonstrating its poor crystalline phase (Figure 2a). N2 sorption experiments disclose that the specific surface areas of MnOx and OMS-2 are 302 and 131 m2 g–1, respectively, which are much higher than that of the commercial manganese oxides (Table S2). In addition, both MnOx and OMS-2 display a typical IV isotherm with H3-type hysteresis loops (Figure 2b), indicating the presence of mesoporous structures with irregular porosity.27 The porous nature of MnOx was further confirmed by scanning electron microscopy and transmission electron microscopy images (Figure S2).

Figure 2.

Figure 2

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XRD patterns (a); N2 adsorption–desorption isotherms (b); Mn 2p (c), Mn 3s (d), and O 1s (e) XPS spectra; O2-TPD (f), H2-TPR (g), and NH3-TPD (h) profiles.

The surface Mn state and oxygen species were investigated by X-ray photoelectron spectroscopy (XPS). As shown in Figure 2c, the Mn 2p spectra of MnOx and OMS-2 are similar to MnO2, but distinct from the other commercial manganese oxides, indicating the oxidation states of Mn in MnOx, and OMS-2 and MnO2 are very similar. To confirm this, the Mn 3s spectra of these oxides were evaluated. As shown in Figure 2d, the Mn 3s spectrum contains a doublet of peaks caused by parallel spin coupling between the electrons in 3s and 3d orbitals. The average oxidation state (AOS) of manganese thus can be calculated according to the following formula: AOS = 8.956 – 1.126 × ΔE, where ΔE is the binding energy difference of the doublet.28 Indeed, the calculated AOS values of manganese for MnOx, OMS-2, and MnO2 are +3.6, +3.7, and +3.8, respectively. Given that the AOS values are relatively lower than the theoretical value of 4.00, structural defects are likely to form, and thus would result in oxygen vacancies.29 Consequently, the surface oxygen species were analyzed using the O 1s spectra. As depicted in Figure 2e, the O 1s spectrum contains two peaks at around 529.8 and 531.5 eV, which can be attributed to lattice oxygen species (named as OL) and surface adsorbed oxygen species or oxygen vacancies (denoted as OV), respectively.28,30 The content of OV is found to be in the order of MnOx > OMS-2 > MnO2, indicating that MnOx has more surface oxygen vacancies than the others. Moreover, the binding energy of OV in MnOx is higher than those in OMS-2 and MnO2 (Table S3), implying that the adsorbed oxygen species can easily accept electrons during the oxidation29 and thus increase the catalytic activity of MnOx.

To further investigate the evolution of oxygen species, oxygen temperature-programed desorption/mass spectrometry (O2-TPD/MS) experiments were performed. As shown in Figure 2f, the desorption peaks located below 400 °C and between 400–600 °C can be attributed to molecular oxygen species adsorbed on oxygen vacancies and surface labile oxygen, respectively.31,32 Compared to OMS-2 and MnO2, MnOx shows a distinct peak below 400 °C, indicating the formation of more oxygen vacancies, which are consistent with the O 1s XPS results. In addition, hydrogen temperature-programed reduction (H2-TPR) experiments were carried out to learn about the reducibility of oxygen species. As shown in Figure 2g, the intensity of the hydrogen consumption peak over MnOx is much stronger than that over the others, and the peak also shifts dramatically to lower temperatures. Based on these results, we may claim that MnOx presents a better oxygen delivery capacity than OMS-2 and MnO2. Finally, NH3-TPD/MS analysis reveals that MnOx and OMS-2 possess more acid sites than the commercial Mn oxides (Figure 2h), which may facilitate the hydrolysis of 1′ into 1 in the present system (Figure S3).21

With the optimized conditions in hand, we first examined the substrate scope of monosubstituted aromatic alkenes (Figure 3). A range of styrenes with both electron-donating (s2–7) and electron-withdrawing groups (s8–17) were all compatible, affording the corresponding benzamides in good to excellent yields. Substitutions at the ortho, meta, and para positions (s4–6 and s10–15) were well-tolerated, although ortho substituents led to lower yields, probably due to the steric hindrance. Notably, the methyl group on the aromatic ring (s4–6) remained intact during the reaction and delivered the methyl-substituted benzamides in high yields, suggesting our current protocol is highly chemoselective.33 In addition, a good yield was obtained when the aryl framework was extended to a naphthalene-derived system (s18). Heterocyclic amides are unique pharmacophores that form an integral part of various drugs or drug-like molecules. In this regard, the cleavage and amidation of alkenyl-substituted heterocycles are of particular interest. Delightfully, alkenes bearing heterocyclic moieties, including pyridine and thiophene (s19–21), were suitable substrates, delivering the desired heterocyclic amides in good to excellent yields.

Figure 3.

Figure 3

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Substrate scope of aromatic alkenes. Yields were determined by GC using nitrobenzene as an internal standard. aIsolated yields. bA total of 68% of nitrile was obtained. c150 °C, 36 h. d110 °C, 36 h. e36 h. f160 °C, 24 h.

Encouraged by the results above, we then sought to determine the generality of the multisubstituted aromatic alkenes. A wide variety of α-methylstyrene and its derivatives (s22–31) were smoothly converted into the desired benzamides in good yields. Due to the steric hindrance, a significant decrease in yields was observed when ortho-substituted α-methylstyrenes were employed (s28, s30). The α-long-chain or branched alkyl-substituted styrenes (s32–36) also showed good performance and yielded the corresponding amides in moderate to good yields. Interestingly, when α-benzyl-substituted styrene (s36) was subjected to the reaction, the yield of the target benzamide was doubled. Next, we turned our attention to β-substituted styrenes. A series of β-methylstyrene derivatives (s37–40) proved to be competent substrates. Impressively, when methyl isoeugenol s38 was subjected to standard conditions, amide 22, the precursors for drugs Itopride,34 can be obtained in good yield. Both trans-stilbene and cis-stilbene (s41, s42) were efficiently cleaved to deliver the desired amide in almost the same yield, demonstrating that the amidation is not sensitive to the configuration of the substrates. Furthermore, trisubstituted alkenes with sterically less accessible C–C double bonds were also investigated. β,β-dimethylstyrene s43, a good example of acyclic trisubstituted alkenes, was a viable substrate and gave the desired product in good yield. It is noteworthy that cyclic trisubstituted alkenes (s44–47) also showed good compatibility. For example, indenes (s45 and s46, Figure S4) and 1,2-dihydronaphthalene (s47) were all selectively cleaved and amidated to furnish the desired phthalimide in acceptable yields, further highlighting the broader adaptability of this protocol.

The discovery of new alkyne transformations through C–C triple bond cleavage is of great value but challenging.8,35 Given the successful amidation of various types of alkenes, we wondered whether the current protocol could be further extended to alkynes. To our delight, the present catalytic system could be well adapted to aromatic alkynes (Figure 4). In the presence of an additional NH4I, a variety of phenylethyne and its derivatives (s48–59) were efficiently cleaved to the corresponding amides in moderate to good yields. Moreover, heterocyclic alkynes (s60–62), as well as disubstituted alkynes (s63–65), were also compatible with this protocol, providing the target products in moderate to excellent yields.

Figure 4.

Figure 4

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Substrate scope of aromatic alkynes. Yields were determined by GC using nitrobenzene as an internal standard. a140 °C, 48 h.

Compared to aromatic alkenes and alkynes, the cleavage and amidation of unactivated aliphatic unsaturated hydrocarbons are generally more challenging. Delightedly, as may be expected, the present catalytic system is well suited for aliphatic unsaturated hydrocarbons. As shown in Figure 5, both phenyl-substituted propene (s66) and butene (s67) can be selectively cleaved to provide benzamide in good yields. Furthermore, the phenyl-substituted aliphatic alkynes (s68 and s69) also proved to be viable substrates to furnish benzamide in satisfactory yields. Finally, attempts were made to realize more inert aliphatic substrates (s70–75). Although the selectivity toward a single product was unsatisfactory, good total yields of one- to four-carbon-shorter amides (26 and 27, Figure S5) can be achieved.

Figure 5.

Figure 5

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Substrate scope of aliphatic alkenes and alkynes. Yields were determined by GC using nitrobenzene as an internal standard.

Nitriles are a ubiquitous class of compounds present in dyes, agrochemicals, pharmaceuticals, and functional materials. Moreover, owing to their unique chemical reactivity, nitriles can also serve as versatile building blocks in organic synthesis.36,37 Traditional cyanation methodologies usually require multiple steps and the utilization of hydrogen cyanide or metal cyanides as a nitrogen source, thus posing a significant safety, environment, and economic concern. Therefore, a sustainable, cyanide-free, and one-step direct synthesis of nitriles remains highly desirable. During the process of optimization, it was found that product selectivity was delicately influenced by reaction conditions. To our delight, a significant increase in selectivity for nitrile formation can be achieved through tuning the reaction conditions. As shown in Figure 6, various ortho-substituted alkenes, as well as alkynes, were effective toward cyanation to deliver the corresponding nitriles in synthetic useful yields.

Figure 6.

Figure 6

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Substrate scope of alkenes and alkynes for the synthesis of nitriles. Yields were determined by GC using nitrobenzene as an internal standard. aIsolated yields. bA magnitude of 0.5 equiv of NH4I was added.

To further establish the generality of this method, a mixture of styrene, α-methylstyrene, and β-methylstyrene was introduced into the reaction. As illustrated in Figure 7a, benzamide was obtained in 81% yield, highlighting the practical utility of this protocol in the direct transformation of unsaturated hydrocarbon mixtures from petroleum or natural gas. In addition, this protocol is applicable to late-stage cyanation of alkenes. For instance, vinyl-containing bioactive molecules, such as (+)-δ-tocopherol (s85), tonalide (s86), and isopulegol (s87), were suitable for this transformation, delivering the desired nitrile products in 51–68% isolated yields (Figure 7b). Moreover, this method can be operationally simple conditions. For instance, the oxidative cleavage and amidation of alkene s1 and alkyne s49 on a gram scale can afford the desired amide in 86 and 75% yields, respectively (Figure 7c). Finally, the reusability of the catalyst was evaluated by recycling experiments. As shown in Figure 7d, the MnOx can be reused at least eight times without an appreciable loss of activity. A hot-filtration experiment showed that no further increase of 1a took place after the catalyst was filtered at the conversion of 36% (Figure S6). These results indicate that the catalyst is stable, and the active species for the reaction is heterogeneous in nature.

Figure 7.

Figure 7

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Practical utility of the present methodology (a–c), and recycling experiments (d).

To gain insights into the reaction mechanism, we performed a series of mechanistic experiments. The time course for the conversion of styrene (s1) under the standard conditions (Figure S7) revealed that styrene was completely consumed after 8 h, with the simultaneous formation of benzonitrile (1′) and benzamide (1). Benzonitrile reached its summit at around 4 h and was gradually converted into benzamide over the rest of the reaction time. Moreover, both benzaldehyde (ii′) and styrene oxide (a) were detected at the initial stage of the reaction by gas chromatography (GC)–MS (Figure 8a). Additionally, the reactions of α-substituted and β-substituted styrenes were also monitored at the initial stage. It was found that epoxides were the main intermediate in the reactions of β-substituted styrenes (Figure 8b and Figure S8), whereas in the case of α-substituted styrenes, acetophenone (ii) was observed as the predominant intermediate (Figure 8c). These results indicate that different kinds of alkenes may proceed through different pathways and thus lead to diverse intermediates.

Figure 8.

Figure 8

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GC–MS spectra of the reaction mixture from various control experiments.

It is well-known that benzaldehyde (ii′) can undergo ammoxidation to produce amides over manganese oxides.21,22 Subsequently, we shifted our attention to epoxides, another common intermediate formed during the reactions of monosubstituted alkenes and β-substituted styrenes. To gain a better understanding of the subsequent pathway of epoxides, the reaction of styrene oxide (a) was performed under standard conditions, but no other new intermediates were detected (Figure S9). Thus, the reaction was also conducted in the absence of O2, and 2-amino-2-phenylethanol (b) was observed (Figure 8d), which was formed through a nucleophilic attack of epoxide by NH3. Furthermore, subjecting b to the reaction conditions, only a trace amount of 2-imino-2-phenylacetic acid (d) was observed (Figure 8e). Interestingly, when the reaction of b was conducted in the absence of NH3, much more d remained (Figure 8f), implying that NH3 can significantly promote the transformation of b. Due to the instability of d, phenylglyoxylic acid, an analogue of d, was subjected to the reaction conditions, and benzamidine (e) was detected (Figure 8g). Taking these results into account, the subsequent transformation of d may involve two pathways (Figure S10): (1) direct decarboxylation into benzonitrile, which undergoes hydrolysis to give the desired amide, and (2) nucleophilic attack by NH3 to form benzamidine, followed by hydrolysis to furnish the target product.

To probe the possible pathway for the conversion of α-substituted styrenes, the reaction of acetophenone (ii), derived from the reactions of α-methylstyrene (s23), was conducted, yielding a small amount of 1-phenylethanimine iii (Figure 8h), which was generated by the condensation of ii with NH3. Notably, when the reaction of ii was performed in the absence of NH3, much more iii was observed (Figure 8i), indicating that the conversion of iii can be accelerated under aerobic conditions. Subsequently, when iii was used as a substrate, d was observed (Figure 8j), which may be derived from tandem oxidation of g. Finally, d can undergo the aforementioned pathway to give the desired amide.

To further demonstrate the reactions of alkenes over MnOx, in situ diffuse reflectance infrared Fourier transform spectroscopy (in situ DRIFTS) experiments with 2-vinylnaphthalene (s18) in flowing O2 at 150 °C were performed under gas-phase conditions (Figure 9a). Initially, the characteristic peaks of =C–H, C=C, and the phenyl ring can be seen at the 3250–3040, 1626, and 1650–1300 cm–1, respectively.38 As the reaction proceeded, the strength of the C=C stretch at 1626 cm–1 gradually decreased, while the absorption band at 1241 cm–1, ascribed to the breathing mode of the oxirane ring, increased significantly. Meanwhile, an additional peak located at 1697 cm–1, which can be assigned to the characteristic absorption peak of the C=O stretching vibration of aldehyde, can also be observed. These results are consistent with the GC–MS analysis, further confirming that both aldehyde and epoxide intermediates are involved in the conversion of monosubstituted alkenes. Subsequently, a small amount of NH3 was injected into the in situ reaction. A distinctive absorption band appeared at 3334 cm–1 instantly, which can be assigned to the stretching vibration of N–H. Moreover, the C=O stretching mode of amide in the region of 1680–1650 cm–1 was gradually intensified, suggesting that the target amide product was increased over time. In addition, due to the formation of nitrile, a new characteristic absorption at 2237 cm–1 can also be observed.

Figure 9.

Figure 9

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In situ DRIFTS spectra of the reaction of 2-vinylnaphthalene (a) and mechanism experiments (b–d).

Next, isotope labeling experiments were conducted to learn the source of oxygen in amides. When the reaction was performed under an 18O2 atmosphere, 74% of benzamide (1) was labeled with 18O (Figure 9b). The percentage of 1 containing 18O was 49% upon the addition of H2O18 (Figure 9c). These results indicate that both dioxygen and water can be the oxygen source of amide products. Then, the effect of different quenchers was investigated to determine the possible reactive oxygen species (Figure 9d). When 2,6-di-tert-butyl-4-methylphenol (BHT) was added to the reaction, the yield of 1 decreased to 55%, indicating that radical intermediates were involved in this catalytic process. Notably, the addition of t-butanol had little effect on the reaction, while the introduction of benzoquinone led to a dramatic decrease of 1, demonstrating that superoxide radicals may be involved in the reaction. Evidence for the generation of the superoxide radical was further confirmed by electron paramagnetic resonance experiments with 5,5-dimethyl 1-pyrroline N-oxide (DMPO) as a radical trapping agent. As shown in Figure S11, six characteristic peaks assigned to the DMPO–•O2– adduct were detected.39 Therefore, we could conclude that superoxide radicals can be identified as the dominant reactive species in the cleavage and ammoxidation of alkenes.

Based on the above results and literature precedents,40 the reaction pathways obtained for the tandem oxidative cleavage and ammoxidation of alkenes are depicted in Figure 10a. In the case of α-substituted styrene (s22), the reaction may proceed via a dioxetane intermediate (i), followed by thermal cleavage to produce ketone ii. Subsequently, the condensation of ii with NH3 would lead to the imine iii, which can be converted into imino acid d through a tandem oxidation. Next, the imino acid d can be transformed via two pathways: nucleophilic attack by NH3 to generate benzamidine (e) and decarboxylation to form benzonitrile (1′). Finally, both e and 1′ are readily converted into benzamide via a hydrolysis process. As for β-substituted styrene (s37), an epoxide intermediate a′ is involved during the reaction. Nucleophilic attack of NH3 to a′ generates amino alcohol b′, which is followed by tandem oxidation to form imino ketone c′. Similar to d, intermediate c′ can be converted into the desired amide through a sequential process. In terms of styrene, since aldehyde ii′, derived from dioxetane i′, and epoxide a intermediates were both engaged, the amide product can be produced via ammoxidation of ii′ and the aforementioned epoxide transformation route.

Figure 10.

Figure 10

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Reaction pathways for different kinds of alkenes (a) and theoretical insights into the oxidation of styrene (b), α-methylstyrene (c), and β, β-dimethylstyrene (d). Mn (purple sphere), O (red sphere), activated O2 (pink sphere), C (gray sphere), N (blue sphere), and H (white sphere).

To certify the above conclusions, density functional theory (DFT) calculations were further performed. As shown in Figures S12 and S13, O2 is first activated at the four-coordinated Mn4c-O sites (i.e., oxygen vacancy) of MnOx. Then, styrene, α-methylstyrene, and β,β-dimethylstyrene can be absorbed nearby the activated O2 with the adsorption energies of −0.14, −0.21, and −0.34 eV, respectively (Figure 10b–d, also see Figure S14). Subsequently, the activated O2 can attack the C=C double bond of the neighboring substrate directly to produce the dioxetane intermediate (red line), or it can approach the β-C atom to form intermediate IM 1, followed by the generation of the epoxide intermediate (blue line). In the case of styrene (Figure 10b), the activation energies of the rate-determining step for both routes are almost equal (0.33 vs 0.32 eV); In terms of α-methylstyrene (Figure 10c), the formation of the dioxetane intermediate is much easier than the generation of the epoxide intermediate (0.29 vs 0.55 eV). As for β,β-dimethylstyrene (Figure 10d), the activation energy barrier of the epoxide route is much lower than that of the dioxetane route (0.27 vs 0.44 eV). These results demonstrate that the reaction pathways are indeed influenced by the structure of alkenes. The underlying reason might be that the charge on α-C or β-C atoms varies with the substituents as the deformation electron density and Mulliken charge analysis41 reveal that the positively charged α-C atom (inset in Figure 10c) is beneficial for the formation of the dioxetane intermediate, while the positively charged β-C atom (inset in Figure 10d) is favorable for epoxide intermediate production.

Conclusions

In conclusion, we have developed a manganese oxide-catalyzed tandem oxidative cleavage/ammoxidation that enables direct synthesis of amides from unsaturated hydrocarbons with O2 as an environmentally benign oxidant and ammonia as a nitrogen source. A wide range of structurally diverse mono- and multisubstituted activated and inactivated alkenes or alkynes can smoothly undergo cleavage of unsaturated C–C bonds to deliver amides. Direct cyanation of unsaturated hydrocarbons to access sterically hindered nitriles can also be achieved through simply tuning the reaction conditions. In addition, this protocol is also applicable for late-stage cyanation of complex bioactive molecules. Detailed characterizations reveal that the high activity and selectivity of the manganese oxides are attributed to the large specific surface area, abundant oxygen vacancies, better reducibility, and moderate acid sites. A combination of experimental and computational mechanistic studies reveal that the reaction proceeds through divergent pathways depending on the structure of substrates. This chemistry represents a significant advancement in developing efficient and sustainable heterogeneous tandem catalysts for value-added transformation of unsaturated hydrocarbons.

Experimental Section

Preparation of MnOx

An aqueous solution of KMnO4 (6.32 g, 100 mL) was added dropwise into a 250 mL aqueous solution of EtOH–H2O (5:1) containing Mn(OAc)2·4H2O (9.8 g). The pH of the mixture was then adjusted to 8 with aq. NH3, and the mixture was stirred at room temperature for 12 h. Finally, a dark brown solid was collected by filtration, washed with distilled water, and dried at 80 °C for 48 h to give the MnOx sample.

General Procedure for Oxidative Cleavage and Amidation of Alkenes

In a typical procedure, MnOx (50 mg), alkene (0.5 mmol), and t-amyl alcohol (1 mL) were added into a glass tube (10 mL volume) with a magnetic stir bar. After being fitted with a PTFE stopper with a pinhole, the tube was placed into an autoclave. Subsequently, the autoclave was flushed with O2 three times and then charged with NH3 (0.5 MPa) and O2 (0.5 MPa). Finally, the autoclave was placed into an oil bath and stirred at 130 °C (bath temperature) for the required time. After the completion of the reaction, the autoclave was cooled to room temperature, and the tube was removed from the autoclave. An internal standard nitrobenzene (60 mg) was added into the tube, and the crude mixture was further diluted with methanol (2 mL), followed by filtration and analysis by GC and GC–MS.

Other Experimental Procedures

See the Supporting Information for details.

Acknowledgments

Financial support from the China Postdoctoral Science Foundation (no. 2022M713082) and Dalian Institute of Chemical Physics is acknowledged. Prof. Huang is acknowledged for the support from the High-Performance Computing Center of Wuhan University of Science and Technology. We also thank Dr. Shuwen Yu from DICP for assistance with in situ DRIFTS experiments.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacsau.2c00608.

  • Catalyst preparation and characterization; reaction details; computational details; and 1H and 13C NMR spectra (PDF)

Author Contributions

§ B.C. and L.Z. contributed equally.

The authors declare no competing financial interest.

Supplementary Material

au2c00608_si_001.pdf (1.9MB, pdf)

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