Iodine-catalyzed ammoxidation of methyl arenes

ChemComm COMMUNICATION Iodine-catalyzed ammoxidation of methyl arenes† Cite this: Chem. Commun., 2015, 51, 5085

Songjin Guo,a Gen Wan,a Song Sun,a Yan Jiang,a Jin-Tao Yua and Jiang Cheng*ab

Received 3rd February 2015, Accepted 15th February 2015 DOI: 10.1039/c5cc01024a www.rsc.org/chemcomm

The development of organic transformation using cheap and readily available substrates under mild conditions will be pivotal for green and sustainable synthetic organic chemistry. Concerning our continued interest in the cyanation reaction, a metal-free direct ammoxidation of readily available methyl arenes leading to nitriles was established under mild conditions. A series of aryl methanes especially heteroaryl methanes (30 examples) were applicable in moderate to good yields with good functionality tolerance.

The methyl group is one of the most common groups in smallmolecule organic compounds.1 Therefore, the transformation of aromatic methyl as a potential functional group into other target molecules is of great importance.2 In comparison with the well-developed transition-metal catalyzed cyanation of aryl halides3 and C–H cyanation reactions,4 the ammoxidation of methyl arenes that are abundant starting materials is almost the most straightforward and simplest procedure leading to aryl nitriles in the large industrial scale, which are not only useful intermediates5 but also potential pharmaceutical and biological active molecules.6 This ammoxidation procedure represents an ideal process using O2 as a clean oxidant (eqn (1), Scheme 1).7 However, it suffers from high reaction temperature on a laboratory scale. To circumvent this drawback, Jiao et al. reported CuSO4-catalyzed conversion of methyl arenes to nitriles utilizing excess amounts of toxic NaN3 as the nitrogen source and expensive (diacetoxyiodo)-benzene (DIB) as the oxidant (eqn (2), Scheme 1).8 Subsequently, Togo developed a one-pot two-step procedure for the transformation of methyl arenes into nitriles by treatment with N-bromosuccinimide (NBS), 1,3-dibromo-5,5dimethylhydantoin (DBDMH) or HBr followed by I2 and aqueous a

School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, and Jiangsu Province Key Laboratory of Fine Petrochemical Engineering, Changzhou University, 1 Gehu Road, Changzhou, 213164, P. R. China. E-mail: [email protected] b State Key Laboratory of Coordination Chemistry, Nanjing University, 22 Hankou Road, Nanjing, 210093, P. R. China † Electronic supplementary information (ESI) available: Detailed synthetic procedures and characterization of new compounds. See DOI: 10.1039/c5cc01024a

This journal is © The Royal Society of Chemistry 2015

Scheme 1

Direct transformation of methyl arenes into nitriles.

ammonium (eqn (3), Scheme 1).9 Wang described palladium(II)catalyzed direct conversion of methyl arenes into aromatic nitriles with tert-butyl nitrite as the N source (eqn (4), Scheme 1).10 Nevertheless, these reported protocols either required transition metals and toxic additives, or suffered from multisteps. Moreover, metal-free oxidative C–H activation via a radical approach has received growing attention and has become a powerful tool for organic synthesis due to the eco-friendly conditions.11 Our interest in cyanation12 and metal-free C–H activation13 spurred us to explore the more environmentally friendly methods. Herein, we explored a useful system by the combination of I2/TBHP for the transformation of methyl arenes into nitriles with cheap and readily available ammonium salts as the N atom source (eqn (5), Scheme 1). This procedure features: (1) a metal-free procedure with mild reaction conditions; (2) no expensive catalysts or toxic additives were required. Our study was initialized by evaluation of the direct ammoxidation of 1-methylnaphthalene under oxidative conditions. To our delight, in the presence of (NH4)2CO3, the combination of I2 and TBHP provided the nitrile product 2a in 29% yield in DMSO at 70 1C (Table 1, entry 1). The yield increased to 58% by replacing (NH4)2CO3 with NH4OAc (Table 1, entry 2). However, under similar

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Communication Table 1

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The optimization of reaction conditionsa

Entry

Ammonium

Catalyst

Oxidant

Solvent

Yieldb (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

(NH4)2CO3 NH4OAc NH3H2O NH4Br NH4Cl NH4F NH4F NH4F NH4F NH4F NH4F NH4F NH4F NH4F NH4F NH4F NH4F NH4F NH4F NH4F NH4F

I2 I2 I2 I2 I2 I2 KI CuI Bu4NI I2 I2 I2 I2 I2 I2 I2 I2 I2 I2 I2 I2

TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP DTBP TBPB H 2 O2 Oxone NaIO4 TBHP TBHP TBHP TBHP TBHP TBHP TBHP

DMSO DMSO DMSO DMSO DMSO DMSO DMSO DMSO DMSO DMSO DMSO DMSO DMSO DMSO CH3NO2 DCE EtOH PC HMPA DMAc CH3CN

29 58 o5 o5 14 80(68)c (71)d (75)e (65)f (60)g (71)h (0)i 60 36 56 0 0 0 0 o5 0 o5 0 o5 o5 9 47

a Reaction conditions: 1a (0.2 mmol), catalyst (20 mol%), ammonium (0.8 mmol), oxidant (2.4 mmol), solvent (0.5 mL), at 70 1C under O2 for 48 h, sealed tube. TBHP (70% in water). b Isolated yields. c TBHP (1.2 mmol). d TBHP (1.6 mmol). e TBHP (2.0 mmol). f N2. g 24 h. h 36 h. i Without I2 or TBHP. (TBHP = tert-butyl hydroperoxide, DTBP = di-tert-butyl peroxide, TBPB = tert-butyl peroxybenzoate, PC = propylene carbonate, HMPA = hexamethylphosphoramide, DMAc = dimethyl acetamide).

reaction conditions, NH3H2O, NH4Cl and NH4Br failed to promote this transformation (Table 1, entries 3 and 5). At last, NH4F was found to be the best choice and 80% of 1-cyanonaphthalene was isolated (Table 1, entry 6). The reaction eﬃciency decreased with less amount of TBHP, shorter reaction time or under N2 (Table 1, entry 6). The blank experiment confirmed that no reaction took place in the absence of TBHP or I2. Other iodide species such as KI, CuI or Bu4NI could also catalyze this transformation giving moderate yields (Table 1, entries 7–9). To our surprise, replacing TBHP with DTBP, TBPB, H2O2, oxone or NaIO4 resulted in no reaction at all (Table 1, entries 10–14). Further studies revealed that the solvent played a key role in this procedure as no reaction took place in solvents except DMSO and CH3CN (Table 1, entries 15–21). With the optimized conditions in hand, the scope and limitation of the methyl arenes were studied, as shown in Fig. 1. Generally, substrates bearing electron-donating groups as well as 1- and 2-methyl naphthalenes provided the cyanation products in good to excellent yields. For example, 2f, 2j and 2k were isolated in 71%, 81% and 83% yields, respectively. For 1,4-xylene and 1,3,5-mesitylene, mono-cyanated compounds were obtained as the major products (2g and 2h) and only a trace amount of the di-cyanated compound was detected by GC-MS. However, for the substrates possessing electron-withdrawing groups, moderate yields were obtained. Notably, the chloro, bromo and iodo groups survived well through this procedure although with elongated time, which provided a potential handle for further functionalization. To further evaluate the practicability of this procedure, the reactions

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Fig. 1 The ammoxidation of methyl arenes to nitriles. Reaction conditions: 1 (0.2 mmol), I2 (20 mol%), NH4F (0.8 mmol), TBHP (70% in water, 2.4 mmol), DMSO (0.5 mL), at 70 1C under O2 for 48 h, sealed tube. Isolated yields. a 10 mmol scale. b 60 h.

were conducted on a 10 mmol scale, and the desired products 2a, 2f and 2p were obtained in comparable yields. Next, the scope of heteroaromatic substrates was investigated, as shown in Fig. 2. To our delight, the methyl in quinoline and


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Communication

Scheme 2

Mechanism studies.

Scheme 3

Proposed mechanism.

Fig. 2 The ammoxidation of methyl hetero-arenes to nitriles. Reaction conditions: 1 (0.2 mmol), I2 (20 mol%), NH4F (0.8 mmol), TBHP (70% in water, 2.4 mmol), DMSO (0.5 mL), at 70 1C under O2 for 48 h, sealed tube. Isolated yields. a 1 (0.2 mmol), KI (20 mol%), NH4F (0.8 mmol), TBHP (2.0 mmol), DMSO (1.0 mL), at 70 1C under O2 for 12 h. b 48 h. c 60 h. d 112 h. e DMSO 1.0 mL. f 10 mmol scale.

isoquinoline reacted smoothly using the standard procedure. For 2,6-dimethyl quinoline, the mono-ammoxidation product 3i was selectively isolated in 49% yield, where the 6-methyl remained intact. Particularly, methyl quinoxaline provided the cyanation product 3f in 56% yield. Notably, benzoxazole and benzothiophene were appropriate reaction partners, albeit the cyanation products 3k and 3l were isolated in moderate yields. Meanwhile, 6-methyl-2,3-dihydrobenzo[b][1,4]dioxine worked well, providing the cyanation product 3m in 58% yield. More experiments were conducted to gain some insights into the mechanism. Firstly, the addition of 2.0 equivalents of TEMPO (2,2,6,6-tetramethylpiperidinyloxy) inhibited the reaction, indicating that a radical intermediate might be involved in this transformation (eqn (1), Scheme 2). Secondly, some potential intermediates were subjected to the standard procedure. Amide provided no cyanation product, ruling out the possibility of serving as the intermediate (eqn (2), Scheme 2). However, benzyl amine, alcohol and iodide as well as aromatic aldehyde all reacted smoothly to produce the nitrile in good yields (eqn (2), Scheme 2). Based upon these experimental facts, a plausible mechanism was outlined (Scheme 3). The reaction may contain two catalytic cycles. In cycle 2, firstly, the tert-butoxy radical was produced by the single electron transfer between I and TBHP. Subsequently, the formed tert-butoxy radical abstracts one H-atom from methyl to form the benzyl radical, which may be oxidized by I2 to produce the benzylic carbocation along with one equivalent of I to finish cycle 2. Secondly, the reaction between the benzylic carbocation and I produces benzyl iodide, which takes part in a Kornblum oxidation using DMSO


to form aromatic aldehyde. Meanwhile, I is regenerated to finish cycle 1. Finally, the reaction between ammonium and aldehyde aﬀords nitrile. However, benzyl amine and benzyl alcohol may be formed via the nucleophilic attack of ammonia or water on the benzylic carbocation. They can convert to the target cyanation product as confirmed in eqn (2), Scheme 2.14 In conclusion, we have developed a mild method for the direct conversion of methyl arenes into nitriles. The procedure did not require expensive catalysts or toxic additives. In combination with the ubiquity of methyl groups, it represents a facile and green methodology leading to nitriles. We thank the National Natural Science Foundation of China (no. 21272028 and 21202013), ‘‘Innovation & Entrepreneurship Talents’’ Introduction Plan of Jiangsu Province, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology (BM2012110), State Key Laboratory of Coordination Chemistry of Nanjing University, Jiangsu Province Key Laboratory of Fine Petrochemical Engineering, and the Priority Academic Program Development of Jiangsu Higher Education Institutions for financial support.

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