DOI: 10.1002/chem.201501184
Communication
& Synthetic Methods
Unexpectedly Simple Synthesis of Benzazoles by tBuONaCatalyzed Direct Aerobic Oxidative Cyclocondensation of o-Thio/ Hydroxy/Aminoanilines with Alcohols under Air Xinkang Shi, Junmei Guo, Jianping Liu, Mingde Ye, and Qing Xu*[a] Abstract: tBuONa-catalyzed direct aerobic oxidative cyclocondensation reactions of readily available alcohols and othio/hydroxy/aminoanilines under air have been developed and provide an efficient, practical, and green method for the synthesis of benzazoles. Mechanistic studies revealed that o-substituted anilines promote the initial aerobic alcohol-oxidation step, which explains the high reactivity and success of this unexpectedly simple and practical cyclocondensation method.
Developing efficient methods that use greener, cheaper, and more-readily available substrates and catalysts and avoid mutagenic and waste-producing reagents, unnecessary steps, and energy waste has been a major target in modern sustainable chemistry.[1] For example, constantly improving methods have been developed for the synthesis of benzazoles (benzothiazoles, benzoxazoles, and benzimidazoles),[2–8] which are important building blocks for pharmaceutical agents, bioactive molecules, natural products, agrochemical compounds, and organic materials.[2] Benzazoles are traditionally prepared by condensation of carboxylic acid derivatives (acids, acyl chlorides, esters, nitriles, amides, etc.) with o-thio/hydroxy/aminoanilines (Scheme 1 a), but harsh conditions, such as high temperatures and strong dehydrating reagents, are generally required.[2, 3] Reactions with alkyl polyhalides,[4] oxidative condensation with aldehydes (Scheme 1 a),[5] and intramolecular coupling reactions (Scheme 1 b)[6] were developed later, but these methods have inherent drawbacks such as the utilization of reactive and toxic reagents, less-common substrates, transition-metal (TM) catalysts and ligands, and formation of undesired waste products. Because alcohols are readily available chemical feedstock, frequently used for the preparation of organohalides, aldehydes, and acid derivatives,[9] recently TM-catalyzed anaerobic dehydrogenation methods have also been developed recently (Scheme 1 c).[7] Despite the improvement by using alcohol sub[a] X. Shi, J. Guo, Dr. J. Liu, Prof. M. Ye, Prof. Dr. Q. Xu Zhejiang Key Laboratory of Carbon Materials College of Chemistry and Materials Engineering Wenzhou University Wenzhou, Zhejiang 325035 (P. R. China) E-mail: [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201501184. Chem. Eur. J. 2015, 21, 9988 – 9993
Scheme 1. Methods for the synthesis of benzazoles.
strates, this method still requires high temperatures and expensive TM complexes and ligands because the dehydrogenative process with hydrogen extrusion is a thermodynamically unfavorable process.[9f] More recently, Nguyen and co-workers reported an advantageous redox-neutral Fe/S-catalyzed cyclocondensation of more-readily available heteroarylmethanes and 2-amino/hydroxy nitrobenzenes (Scheme 1 d).[8] This method is incompatible with methylarenes and thionitrobenzenes and is limited to the reactions of heteroarylmethanes to give benzoxazoles and benzimidazoles. Therefore, research into general methods for the efficient and sustainable synthesis of benzazoles, especially benzothiazoles, is still highly desirable. Herein, we report an unexpectedly simple and practical tBuONa-catalyzed[10] direct aerobic oxidative cyclocondensation reaction of alcohols and o-thio/hydroxy/aminoanilines that uses air as the sole oxidant (Scheme 1 e). This reaction provides an efficient, practical, and green method for the synthesis of a diverse range of benzazoles. We recently reported the synthesis of amine, amide,[11] alcohol, ketone,[12] and imine[13] derivatives from alcohols in the presence of air as a promoter or an oxidant. In a continuous study, when benzyl alcohol (1 a; 3 mmol) and 2-aminothiophe-
9988
Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication nol (2 a; 2 mmol) were heated under air with NaOH (50 mol %) Table 1. Optimization of the reaction conditions for benzothiazole synin a 20 mL tube (containing 0.20 mmol O2), cyclized 2-phenyl thesis.[a] benzothiazole (3 a) was obtained in 7 % isolated yield (0.14 mmol, 70 % yield based on O2).[14] According to the reaction scheme (Table 1), this result signified a rather efficient oxidation process in which 70 % O2 uptake occurred from 20 mL Entry Base ([mol %])[b] Additive ([mol %]) Solvent ([mL]) T [oC] 3 a [%][c] of air. Inspired by this result, we envisioned a direct and green 1[d] NaOH (50) – – 150 40 method for benzazole synthesis by aerobic oxidative cyclocon– toluene (1) 150 54 2[d] NaOH (50) densation of alcohols and o-thio/hydroxy/aminoanilines, which, – toluene (2) 100 53 3[d] NaOH (50) 4 NaOH (50) – toluene (2) 100 58 if achieved, can overcome many drawbacks of the known [2–8] 5 tBuONa (50) – toluene (2) 100 82 methods. Next, the reaction of 1 a and 2 a was investigated 6 tBuONa (20) – toluene (2) 100 82 in the presence of greater amounts of air (Table 1). To our de– toluene (2) 100 76 7[e] tBuONa (20) light, the reaction in a 130 mL tube ( 1.3 mmol O2) afforded toluene (2) 100 82 8 tBuONa (20) Co(OAc)2 (5) toluene (2) 100 37 9 tBuONa (20) FeCl3 (5) 3 a in 40 % yield (Table 1, entry 1). Performing the reaction in ·H O (5) toluene (2) 100 55 10 tBuONa (20) Cu(OAc) 2 2 toluene further enhanced the yield of 3 a to 54 % (Table 1, – toluene (2) 100
Communication
& Synthetic Methods
Unexpectedly Simple Synthesis of Benzazoles by tBuONaCatalyzed Direct Aerobic Oxidative Cyclocondensation of o-Thio/ Hydroxy/Aminoanilines with Alcohols under Air Xinkang Shi, Junmei Guo, Jianping Liu, Mingde Ye, and Qing Xu*[a] Abstract: tBuONa-catalyzed direct aerobic oxidative cyclocondensation reactions of readily available alcohols and othio/hydroxy/aminoanilines under air have been developed and provide an efficient, practical, and green method for the synthesis of benzazoles. Mechanistic studies revealed that o-substituted anilines promote the initial aerobic alcohol-oxidation step, which explains the high reactivity and success of this unexpectedly simple and practical cyclocondensation method.
Developing efficient methods that use greener, cheaper, and more-readily available substrates and catalysts and avoid mutagenic and waste-producing reagents, unnecessary steps, and energy waste has been a major target in modern sustainable chemistry.[1] For example, constantly improving methods have been developed for the synthesis of benzazoles (benzothiazoles, benzoxazoles, and benzimidazoles),[2–8] which are important building blocks for pharmaceutical agents, bioactive molecules, natural products, agrochemical compounds, and organic materials.[2] Benzazoles are traditionally prepared by condensation of carboxylic acid derivatives (acids, acyl chlorides, esters, nitriles, amides, etc.) with o-thio/hydroxy/aminoanilines (Scheme 1 a), but harsh conditions, such as high temperatures and strong dehydrating reagents, are generally required.[2, 3] Reactions with alkyl polyhalides,[4] oxidative condensation with aldehydes (Scheme 1 a),[5] and intramolecular coupling reactions (Scheme 1 b)[6] were developed later, but these methods have inherent drawbacks such as the utilization of reactive and toxic reagents, less-common substrates, transition-metal (TM) catalysts and ligands, and formation of undesired waste products. Because alcohols are readily available chemical feedstock, frequently used for the preparation of organohalides, aldehydes, and acid derivatives,[9] recently TM-catalyzed anaerobic dehydrogenation methods have also been developed recently (Scheme 1 c).[7] Despite the improvement by using alcohol sub[a] X. Shi, J. Guo, Dr. J. Liu, Prof. M. Ye, Prof. Dr. Q. Xu Zhejiang Key Laboratory of Carbon Materials College of Chemistry and Materials Engineering Wenzhou University Wenzhou, Zhejiang 325035 (P. R. China) E-mail: [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201501184. Chem. Eur. J. 2015, 21, 9988 – 9993
Scheme 1. Methods for the synthesis of benzazoles.
strates, this method still requires high temperatures and expensive TM complexes and ligands because the dehydrogenative process with hydrogen extrusion is a thermodynamically unfavorable process.[9f] More recently, Nguyen and co-workers reported an advantageous redox-neutral Fe/S-catalyzed cyclocondensation of more-readily available heteroarylmethanes and 2-amino/hydroxy nitrobenzenes (Scheme 1 d).[8] This method is incompatible with methylarenes and thionitrobenzenes and is limited to the reactions of heteroarylmethanes to give benzoxazoles and benzimidazoles. Therefore, research into general methods for the efficient and sustainable synthesis of benzazoles, especially benzothiazoles, is still highly desirable. Herein, we report an unexpectedly simple and practical tBuONa-catalyzed[10] direct aerobic oxidative cyclocondensation reaction of alcohols and o-thio/hydroxy/aminoanilines that uses air as the sole oxidant (Scheme 1 e). This reaction provides an efficient, practical, and green method for the synthesis of a diverse range of benzazoles. We recently reported the synthesis of amine, amide,[11] alcohol, ketone,[12] and imine[13] derivatives from alcohols in the presence of air as a promoter or an oxidant. In a continuous study, when benzyl alcohol (1 a; 3 mmol) and 2-aminothiophe-
9988
Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication nol (2 a; 2 mmol) were heated under air with NaOH (50 mol %) Table 1. Optimization of the reaction conditions for benzothiazole synin a 20 mL tube (containing 0.20 mmol O2), cyclized 2-phenyl thesis.[a] benzothiazole (3 a) was obtained in 7 % isolated yield (0.14 mmol, 70 % yield based on O2).[14] According to the reaction scheme (Table 1), this result signified a rather efficient oxidation process in which 70 % O2 uptake occurred from 20 mL Entry Base ([mol %])[b] Additive ([mol %]) Solvent ([mL]) T [oC] 3 a [%][c] of air. Inspired by this result, we envisioned a direct and green 1[d] NaOH (50) – – 150 40 method for benzazole synthesis by aerobic oxidative cyclocon– toluene (1) 150 54 2[d] NaOH (50) densation of alcohols and o-thio/hydroxy/aminoanilines, which, – toluene (2) 100 53 3[d] NaOH (50) 4 NaOH (50) – toluene (2) 100 58 if achieved, can overcome many drawbacks of the known [2–8] 5 tBuONa (50) – toluene (2) 100 82 methods. Next, the reaction of 1 a and 2 a was investigated 6 tBuONa (20) – toluene (2) 100 82 in the presence of greater amounts of air (Table 1). To our de– toluene (2) 100 76 7[e] tBuONa (20) light, the reaction in a 130 mL tube ( 1.3 mmol O2) afforded toluene (2) 100 82 8 tBuONa (20) Co(OAc)2 (5) toluene (2) 100 37 9 tBuONa (20) FeCl3 (5) 3 a in 40 % yield (Table 1, entry 1). Performing the reaction in ·H O (5) toluene (2) 100 55 10 tBuONa (20) Cu(OAc) 2 2 toluene further enhanced the yield of 3 a to 54 % (Table 1, – toluene (2) 100
