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Oxidative synthesis of benzamides from toluenes and DMF
Tetrahedron Letters 55 (2014) 5082–5084
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Oxidative synthesis of benzamides from toluenes and DMF Jian-Bo Feng a, Duo Wei a, Jin-Long Gong a, Xinxin Qi a, Xiao-Feng Wu a,b,⇑ a b
Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou, Zhejiang Province 310018, People’s Republic of China Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
a r t i c l e
i n f o
Article history: Received 19 June 2014 Revised 17 July 2014 Accepted 22 July 2014 Available online 29 July 2014
a b s t r a c t An interesting oxidative procedure for the synthesis of benzamides has been developed through the cleavage of sp3 CAH bond of methyl arenes with N-substituted formamides. Various benzamides were prepared in low to moderate yields. Even though the yields are moderate in general, this new synthetic procedure provides another option for benzamide synthesis. Ó 2014 Elsevier Ltd. All rights reserved.
Keywords: Benzamide Oxidation Toluene Formamide tert-Butyl hydrogen peroxide
The development of novel chemical approach to improve the synthetic efficiency, atom economy, and benign environmental impact is still the main issue in current organic synthesis. Under this background, the CAH activation of methyl arenes has attracted a great deal of interest in both academic and industrial research.1 Among these, the oxidative cleavage of sp3 CAH bond and subsequent coupling has emerged as an efficient strategy to access amides, esters, and other carbonyl compounds.2 In the known procedures, transition-metal-catalyzed CAH bond functionalization approach has made a profound progress, including copper,3 manganese,4 palladium,5 and so on. On the other hand, the oxidation system with cheap catalyst or without transition-metal salts is considered as attractive methodology in organic synthesis and more and more organic chemists are putting their efforts in this area. Recently, iodine or tetrabutylammonium iodide (TBAI)-based catalytic system has drawn much attention for they can avoid the usage of transition-metal catalysts.6 Furthermore, the combination of TBAI and tert-butyl hydroperoxide (TBHP) was proven to be more efficient in oxidation reaction, especially in CAH activation.7 The amide is one of the most widely used functional groups in chemistry and plays a significant role in natural products, biomolecules, pharmaceuticals, and agrochemicals.8 In general, amides are synthesized by the reaction of carboxylic acids or their active derivatives, such as acid anhydrides, acyl halides, aldehydes, and esters with corresponding amine.9 Other alternative methods include acylation of amines with aldehydes or alcohols,10 ⇑ Corresponding author. E-mail address: [email protected] (X.-F. Wu). http://dx.doi.org/10.1016/j.tetlet.2014.07.083 0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
cross-coupling of formamides with organohalides,11 hydration of nitriles,12 modified Staudinger reaction,13 rearrangement of oximes,14 transamidation,15 and so on. Although many methodologies of amide synthesis have been published these years, more economic, environmentally friendly, and efficient strategies still need to be explored. Herein, we wish to report the development of an oxidation system for the benzamide synthesis via sp3 CAH bond activation of methyl arenes with N-substituted formamides. We employed toluene 1a and N,N-dimethylformamide (DMF) 2a as the initial substrates in the presence of 20 mol % TBAI and 4 equiv TBHP at 80 °C. Fortunately, we got N,N-dimethylbenzamide 3aa in 5% GC yield (Table 1, entry 1). Encouraged by this result, we proceeded to optimize the reaction conditions. We found that by decreasing the amount of TBAI to 10 mol %, the yield of amide product 3aa was raised (Table 1, entry 2). While increasing the amount of TBHP to 6 equiv or 8 equiv, the 6 equiv gave better yield (Table 1, entries 3 and 4). The yield has no significant change when changing the reaction temperature to 100 or 60 °C (Table 1, entries 5 and 6). However, replacing TBHP with a series of oxidants including di-tert-butyl peroxide (DTBP), H2O2, meta-chloroperoxybenzoic acid (mCPBA), benzoyl peroxide (BPO), and O2 (Table 1, entries 7–11), the yields were decreased. While employing I2 or KI as the catalyst, only trace amount of product was found (Table 1, entries 12 and 13). Notably, when 10 mol % Zn(OAc)2, ZnI2, ZnBr2, ZnCl2 was used as additive, higher conversions were obtained (Table 1, entries 14–17). We were delighted to find that 20 mol % ZnBr2 afforded 3aa in the highest yield (Table 1, entry 18). Furthermore, several typical solvents were screened subsequently and acetonitrile was found to be the optimal solvent for our oxidation
5083
J.-B. Feng et al. / Tetrahedron Letters 55 (2014) 5082–5084 Table 1 Reaction optimizationsa
O
O + 1a
a b c
H
Conditions
N
N
2a
3aa
Entry
Catalyst (mol %)
Oxidant (equiv)
Additives (mol %)
Temp. (°C)
Yieldb (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
TBAI (20) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10) I2 (25) KI (20) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10)
TBHP (4) TBHP (4) TBHP (6) TBHP (8) TBHP (6) TBHP (6) DTBP (6) H2O2 (6) mCPBA (6) O2 (1 atm) BPO (6) TBHP (6) TBHP (6) TBHP (6) TBHP (6) TBHP (6) TBHP (6) TBHP (6)
/ / / / / / / / / / / / / Zn(OAc)2 (10) ZnI2 (10) ZnBr2 (10) ZnCl2 (10) ZnBr2 (20)
80 80 80 80 100 60 80 80 80 80 80 80 80 80 80 80 80 80
5 15 17 13 12 16 Trace Trace Trace Trace 18 Trace Trace 14 21 21 20 53c
Reaction conditions: 1a (10 mmol), 2a (1 mmol), catalyst, oxidant, additive, solvent (2 mL) for 16 h. GC yield. Isolated yield.
system. In the tested cases, benzaldehyde could be detected as byproduct and the rest of toluene was intact. With the optimized reaction conditions in our hand, we started to investigate the substrate generality and limitation for this amide formation procedure (Table 2). DMF was chosen as the amino source and a variety of methyl arenes were studied. para-Halide substituted methyl arenes afforded the amide products in 50–55% yields (3ba–3da). It was noted that those with para- and meta-substituents worked better than ortho-substituted one due to the steric effect (3da, 3fa vs 3ea). Substrates with the strong electron-withdrawing group decreased the yield (3ga). Electrondonating methyl arenes such as methyl/methoxy-substituted toluene provided the corresponding product in 12–48% yields (3ha–3ja). The reaction proceeded not very well with the biphenyl group (3ka, 3la). Furthermore, naphthalene substituents were also investigated, resulting in poor yield (3ma, 3na). Notably, 66% of demethylated product 3ia0 was isolated when 4-methylanisole was applied as substrate. We also studied the scope of amino source. Under the standard reaction conditions, N-ethylbenzamide 3ab was obtained from the reaction of N,N-diethylformamide and toluene too, probably due to the steric hindrance or the self-decompose of the Et2Nradical. Furthermore, N-methylformamide 2c and N-phenylformamide 2d reacted with toluene give 3ac and 3ad in 47% and 40% yields (see Scheme 1). Based on these results and previous studies, a plausible mechanism is proposed in Scheme 2. 7 First, benzylic radical was generated by the cleavage of benzylic CAH bond of methyl arene under catalysis of TBAI/TBHP. Benzylic radical was then oxidized to benzylic alcohol and further to benzaldehyde, which subsequently converted to benzoyl radical catalyzed by tert-butoxyl radical. Meanwhile, the tert-butoxyl radical traps the H of DMF, followed by the elimination of CO to form the aminyl radical. Finally, the benzoyl radical coupled with the aminyl radical to provide the benzamide product.7c In summary, we have described the development of a new catalytic method for the benzamide formation under oxidative
Table 2 Synthesis of N,N-dimethylbenzamides from methyl arenes and DMFa,b
O
O +
TBAI/TBHP/ZnBr2 H
N
80 °C, 16 h
N
R 1
R
2a O
3 O
O N
N F
3a a (53 %)
N Br 3ca ( 55%)
3ba (50%) O
O
O Cl
N
N
Cl 3ea (34%)
Cl 3da (50%) O
N
3fa (48%)
O
O
N
N
N
O2N
O 3ga (3 0%)
3 ha (48% )
O
O
N H
O
3ia (12%) O
N
O
N Ph
3ia' ( 66%)
3 ja (37%)
3k a (53 %)
O O
N
N
O N
Ph 3la (35 %)
3ma (39% )
3na (3 3%)
a
Reaction conditions: 1a–n (10 mmol), 2a (1 mmol), TBAI (10 mol %), TBHP (6 equiv), ZnBr2 (20 mol %), CH3CN (2 mL) at 80 °C for 16 h. b Isolated yield.
5084
J.-B. Feng et al. / Tetrahedron Letters 55 (2014) 5082–5084
O
O +
H
N
R1
TBAI/TBHP/ZnBr 2 80 °C, 16 h
N H
R1
2.
R2 1a
2
3 3ab R 1 = R 2 = Et 3ac R 1 = Me, R 2 = H 3ad R 1 = Ph, R 2 = H
3.
31% 47% 40%
4.
Scheme 1. Formation of N-substituted benzamides.
tBuOOH
tBuOOH
O
tBuOOH
tBuO O
O t BuO
tBuOH
O N
O CO H
7.
OH
OH
tBuOOH
tBuOH
OH
1/2 I 2
t BuOO
t BuO
6.
tBuO
I H2 O
5.
8.
N
N 9. Scheme 2. Proposed reaction mechanism.
reaction conditions. Toluenes and DMF were applied as substrates; the desired benzamides were formed in moderate yields in a decarbonylative manner. To the best of our knowledge, this is the first oxidative coupling via sp3 CAH bond activation of methyl arenes and N-substituted formamides.
10.
Acknowledgments
11.
The authors thank for the financial support from Zhejiang Sci-Tech University (1206838-Y). X.-F. Wu appreciates the general support from Professor Matthias Beller in LIKAT.
12.
Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2014. 07.083. References and notes 1. (a) Shilov, A. E.; Shul’pin, G. B. Chem. Rev. 1997, 97, 2879–2932; (b) Ackermann, L. Chem. Rev. 2011, 111, 1315–1345; (c) Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.Q. Acc. Chem. Res. 2012, 45, 788–802; (d) Yamaguchi, J.; Yamaguchi, A. D.; Itami, K. Angew. Chem. Int. Ed. 2012, 51, 8960–9009; (e) Kuhl, N.; Hopkinson, M. N.; Wencel-Delord, J.; Glorius, F. Angew. Chem. Int. Ed. 2012, 51, 10236–10254; (f) Wencel-Delord, J.; Glorius, F. Nat. Chem. 2013, 5, 369–375; (g) Ackermann, L.
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Commun. 2012, 48, 12240–12242; (h) Li, X.; Xu, X.; Tang, Y. Org. Biomol. Chem. 2013, 11, 1739–1742; (i) Li, X.; Xu, X.; Hu, P.; Xiao, X.; Zhou, C. J. Org. Chem. 2013, 78, 7343–7348; (j) Gao, Y.; Song, Q.; Cheng, G.; Cui, X. Org. Biomol. Chem. 2014, 12, 1044–1047; (k) Zhang, J.; Jiang, J.; Li, Y.; Wan, X. J. Org. Chem. 2013, 78, 11366–11372. (a) Humphrey, J. M.; Chamberlin, A. R. Chem. Rev. 1997, 97, 2243–2266; (b) Sood, A.; Panchagnula, R. Chem. Rev. 2001, 101, 3275–3304; (c) Constable, D. J. C.; Dunn, P. J.; Hayler, J. D.; Humphrey, G. R.; Leazer, J. L., Jr.; Linderman, R. J.; Lorenz, K.; Manley, J.; Pearlman, B. A.; Wells, A.; Zaks, A.; Zhang, T. Y. Green Chem. 2007, 9, 411–420. (a) Srinivas, K. V.; Das, B. J. J. Org. Chem. 2003, 68, 1165–1167; (b) Al-Zoubi, R. M.; Marion, O.; Hall, D. G. Angew. Chem., Int. Ed. 2008, 47, 2876–2879; (c) Valeur, E.; Bradley, M. Chem. Soc. Rev. 2009, 38, 606–631; (d) Donets, J. R.; Xiang, Y.; Baldwin, A.; Ringling, J. Org. 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Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Oxidative synthesis of benzamides from toluenes and DMF Jian-Bo Feng a, Duo Wei a, Jin-Long Gong a, Xinxin Qi a, Xiao-Feng Wu a,b,⇑ a b
Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou, Zhejiang Province 310018, People’s Republic of China Leibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
a r t i c l e
i n f o
Article history: Received 19 June 2014 Revised 17 July 2014 Accepted 22 July 2014 Available online 29 July 2014
a b s t r a c t An interesting oxidative procedure for the synthesis of benzamides has been developed through the cleavage of sp3 CAH bond of methyl arenes with N-substituted formamides. Various benzamides were prepared in low to moderate yields. Even though the yields are moderate in general, this new synthetic procedure provides another option for benzamide synthesis. Ó 2014 Elsevier Ltd. All rights reserved.
Keywords: Benzamide Oxidation Toluene Formamide tert-Butyl hydrogen peroxide
The development of novel chemical approach to improve the synthetic efficiency, atom economy, and benign environmental impact is still the main issue in current organic synthesis. Under this background, the CAH activation of methyl arenes has attracted a great deal of interest in both academic and industrial research.1 Among these, the oxidative cleavage of sp3 CAH bond and subsequent coupling has emerged as an efficient strategy to access amides, esters, and other carbonyl compounds.2 In the known procedures, transition-metal-catalyzed CAH bond functionalization approach has made a profound progress, including copper,3 manganese,4 palladium,5 and so on. On the other hand, the oxidation system with cheap catalyst or without transition-metal salts is considered as attractive methodology in organic synthesis and more and more organic chemists are putting their efforts in this area. Recently, iodine or tetrabutylammonium iodide (TBAI)-based catalytic system has drawn much attention for they can avoid the usage of transition-metal catalysts.6 Furthermore, the combination of TBAI and tert-butyl hydroperoxide (TBHP) was proven to be more efficient in oxidation reaction, especially in CAH activation.7 The amide is one of the most widely used functional groups in chemistry and plays a significant role in natural products, biomolecules, pharmaceuticals, and agrochemicals.8 In general, amides are synthesized by the reaction of carboxylic acids or their active derivatives, such as acid anhydrides, acyl halides, aldehydes, and esters with corresponding amine.9 Other alternative methods include acylation of amines with aldehydes or alcohols,10 ⇑ Corresponding author. E-mail address: [email protected] (X.-F. Wu). http://dx.doi.org/10.1016/j.tetlet.2014.07.083 0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
cross-coupling of formamides with organohalides,11 hydration of nitriles,12 modified Staudinger reaction,13 rearrangement of oximes,14 transamidation,15 and so on. Although many methodologies of amide synthesis have been published these years, more economic, environmentally friendly, and efficient strategies still need to be explored. Herein, we wish to report the development of an oxidation system for the benzamide synthesis via sp3 CAH bond activation of methyl arenes with N-substituted formamides. We employed toluene 1a and N,N-dimethylformamide (DMF) 2a as the initial substrates in the presence of 20 mol % TBAI and 4 equiv TBHP at 80 °C. Fortunately, we got N,N-dimethylbenzamide 3aa in 5% GC yield (Table 1, entry 1). Encouraged by this result, we proceeded to optimize the reaction conditions. We found that by decreasing the amount of TBAI to 10 mol %, the yield of amide product 3aa was raised (Table 1, entry 2). While increasing the amount of TBHP to 6 equiv or 8 equiv, the 6 equiv gave better yield (Table 1, entries 3 and 4). The yield has no significant change when changing the reaction temperature to 100 or 60 °C (Table 1, entries 5 and 6). However, replacing TBHP with a series of oxidants including di-tert-butyl peroxide (DTBP), H2O2, meta-chloroperoxybenzoic acid (mCPBA), benzoyl peroxide (BPO), and O2 (Table 1, entries 7–11), the yields were decreased. While employing I2 or KI as the catalyst, only trace amount of product was found (Table 1, entries 12 and 13). Notably, when 10 mol % Zn(OAc)2, ZnI2, ZnBr2, ZnCl2 was used as additive, higher conversions were obtained (Table 1, entries 14–17). We were delighted to find that 20 mol % ZnBr2 afforded 3aa in the highest yield (Table 1, entry 18). Furthermore, several typical solvents were screened subsequently and acetonitrile was found to be the optimal solvent for our oxidation
5083
J.-B. Feng et al. / Tetrahedron Letters 55 (2014) 5082–5084 Table 1 Reaction optimizationsa
O
O + 1a
a b c
H
Conditions
N
N
2a
3aa
Entry
Catalyst (mol %)
Oxidant (equiv)
Additives (mol %)
Temp. (°C)
Yieldb (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
TBAI (20) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10) I2 (25) KI (20) TBAI (10) TBAI (10) TBAI (10) TBAI (10) TBAI (10)
TBHP (4) TBHP (4) TBHP (6) TBHP (8) TBHP (6) TBHP (6) DTBP (6) H2O2 (6) mCPBA (6) O2 (1 atm) BPO (6) TBHP (6) TBHP (6) TBHP (6) TBHP (6) TBHP (6) TBHP (6) TBHP (6)
/ / / / / / / / / / / / / Zn(OAc)2 (10) ZnI2 (10) ZnBr2 (10) ZnCl2 (10) ZnBr2 (20)
80 80 80 80 100 60 80 80 80 80 80 80 80 80 80 80 80 80
5 15 17 13 12 16 Trace Trace Trace Trace 18 Trace Trace 14 21 21 20 53c
Reaction conditions: 1a (10 mmol), 2a (1 mmol), catalyst, oxidant, additive, solvent (2 mL) for 16 h. GC yield. Isolated yield.
system. In the tested cases, benzaldehyde could be detected as byproduct and the rest of toluene was intact. With the optimized reaction conditions in our hand, we started to investigate the substrate generality and limitation for this amide formation procedure (Table 2). DMF was chosen as the amino source and a variety of methyl arenes were studied. para-Halide substituted methyl arenes afforded the amide products in 50–55% yields (3ba–3da). It was noted that those with para- and meta-substituents worked better than ortho-substituted one due to the steric effect (3da, 3fa vs 3ea). Substrates with the strong electron-withdrawing group decreased the yield (3ga). Electrondonating methyl arenes such as methyl/methoxy-substituted toluene provided the corresponding product in 12–48% yields (3ha–3ja). The reaction proceeded not very well with the biphenyl group (3ka, 3la). Furthermore, naphthalene substituents were also investigated, resulting in poor yield (3ma, 3na). Notably, 66% of demethylated product 3ia0 was isolated when 4-methylanisole was applied as substrate. We also studied the scope of amino source. Under the standard reaction conditions, N-ethylbenzamide 3ab was obtained from the reaction of N,N-diethylformamide and toluene too, probably due to the steric hindrance or the self-decompose of the Et2Nradical. Furthermore, N-methylformamide 2c and N-phenylformamide 2d reacted with toluene give 3ac and 3ad in 47% and 40% yields (see Scheme 1). Based on these results and previous studies, a plausible mechanism is proposed in Scheme 2. 7 First, benzylic radical was generated by the cleavage of benzylic CAH bond of methyl arene under catalysis of TBAI/TBHP. Benzylic radical was then oxidized to benzylic alcohol and further to benzaldehyde, which subsequently converted to benzoyl radical catalyzed by tert-butoxyl radical. Meanwhile, the tert-butoxyl radical traps the H of DMF, followed by the elimination of CO to form the aminyl radical. Finally, the benzoyl radical coupled with the aminyl radical to provide the benzamide product.7c In summary, we have described the development of a new catalytic method for the benzamide formation under oxidative
Table 2 Synthesis of N,N-dimethylbenzamides from methyl arenes and DMFa,b
O
O +
TBAI/TBHP/ZnBr2 H
N
80 °C, 16 h
N
R 1
R
2a O
3 O
O N
N F
3a a (53 %)
N Br 3ca ( 55%)
3ba (50%) O
O
O Cl
N
N
Cl 3ea (34%)
Cl 3da (50%) O
N
3fa (48%)
O
O
N
N
N
O2N
O 3ga (3 0%)
3 ha (48% )
O
O
N H
O
3ia (12%) O
N
O
N Ph
3ia' ( 66%)
3 ja (37%)
3k a (53 %)
O O
N
N
O N
Ph 3la (35 %)
3ma (39% )
3na (3 3%)
a
Reaction conditions: 1a–n (10 mmol), 2a (1 mmol), TBAI (10 mol %), TBHP (6 equiv), ZnBr2 (20 mol %), CH3CN (2 mL) at 80 °C for 16 h. b Isolated yield.
5084
J.-B. Feng et al. / Tetrahedron Letters 55 (2014) 5082–5084
O
O +
H
N
R1
TBAI/TBHP/ZnBr 2 80 °C, 16 h
N H
R1
2.
R2 1a
2
3 3ab R 1 = R 2 = Et 3ac R 1 = Me, R 2 = H 3ad R 1 = Ph, R 2 = H
3.
31% 47% 40%
4.
Scheme 1. Formation of N-substituted benzamides.
tBuOOH
tBuOOH
O
tBuOOH
tBuO O
O t BuO
tBuOH
O N
O CO H
7.
OH
OH
tBuOOH
tBuOH
OH
1/2 I 2
t BuOO
t BuO
6.
tBuO
I H2 O
5.
8.
N
N 9. Scheme 2. Proposed reaction mechanism.
reaction conditions. Toluenes and DMF were applied as substrates; the desired benzamides were formed in moderate yields in a decarbonylative manner. To the best of our knowledge, this is the first oxidative coupling via sp3 CAH bond activation of methyl arenes and N-substituted formamides.
10.
Acknowledgments
11.
The authors thank for the financial support from Zhejiang Sci-Tech University (1206838-Y). X.-F. Wu appreciates the general support from Professor Matthias Beller in LIKAT.
12.
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