Visible-light-promoted aerobic oxidative cyclization to access 1,3,4-oxadiazoles from aldehydes and acylhydrazides

Tetrahedron Letters 55 (2014) 2065–2069

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Visible-light-promoted aerobic oxidative cyclization to access 1,3,4-oxadiazoles from aldehydes and acylhydrazides Arvind K. Yadav, Lal Dhar S. Yadav ⇑ Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211002, India

a r t i c l e

i n f o

Article history: Received 19 December 2013 Revised 8 February 2014 Accepted 10 February 2014 Available online 21 February 2014 Keywords: Aerobic oxidation Acylhydrazones Eosin Y Oxadiazoles Photoredox catalysis Visible light

a b s t r a c t A novel and practical access to symmetrical and unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles directly from aldehydes and acylhydrazides using visible light irradiation under an air atmosphere in the presence of eosin Y as an organophotoredox catalyst at rt is reported. This is the first example of oxidative cyclization of acylhydrazones employing air and visible light as inexpensive, readily available, non-toxic, and sustainable reagents. Ó 2014 Elsevier Ltd. All rights reserved.

The development of new modes for the catalytic activation of organic molecules is among the fundamental aims in the field of organic synthesis. In this sequence visible light photoredox catalysis has recently received much attention in organic synthesis owing to ready availability, sustainability, non-toxicity, and ease of handling of visible light.1 The pioneer work of the groups of McMillan,2 Yoon,3 and Stephenson4 have reinvigorated the field of visible light photoredox catalysis utilizing ruthenium and iridium complexes as photoredox catalysts. Their ability to engage in singleelectron-transfer (SET) processes with organic substrates upon photoexcitation with visible light is remarkable and has inspired the development of new methodologies in organic synthesis because most of the organic compounds, do not absorb in the visible region (400–800 nm). However, these transition metal based photocatalysts disadvantageously exhibit high cost, potential toxicity, and low sustainability. Recently, metal-free organic dyes such as eosin Y, fluorescein, Rose Bengal, nile red, perylene, and rhodamine B have been used as economically and ecologically superior surrogates for Ru(II) and Ir(II) complexes in visible-light-promoted organic transformations involving SET.5 The five-membered aromatic heterocycles comprise important structural motifs in the field of pharmaceutical chemistry possessing biological activities like antifungal, antiviral, and antibacterial properties.6 Among them, the 2,5-disubstituted

⇑ Corresponding author. Tel.: +91 532 2500652; fax: +91 532 2460533. E-mail address: [email protected] (Lal Dhar S. Yadav). http://dx.doi.org/10.1016/j.tetlet.2014.02.022 0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

1,3,4-oxadiazole motifs are unique due to their optoelectronic properties.7 They also find applications in the field of material science because of their good electron-transporting and hole-blocking abilities.8 To date a plethora of methods have been developed for the synthesis of 1,3,4-oxadiazoles. The most common of them, utilizes oxidative cyclization of acylhydrazones with oxidizing agents such as ceric ammonium nitrate,9 chloramines T,10 Br2,11 KMnO4,12 FeCl3,13 and iodine.6 The major drawbacks associated with them include the use of expensive, hazardous materials, multistep operations and limited substrate scope. In the context of oxidative organic transformations, aerobic oxygen has recently received an upsurge as a hot topic of research.14 It is an ideal source of oxygen, cost effective, oxidant, readily available, and efficiently complies with the principles of green chemistry. To the best of our knowledge, the literature records only one method for the synthesis of 1,3,4oxadiazoles utilizing atmospheric O2 as a terminal oxidant but it employs transition metal catalysis.7 Inspired by organocatalytic visible-light-mediated aerobic oxidative transformations5b,d,g,j,15,16a and our successful efforts for one-pot heterocylization reactions,15b,16 the present oxidative cyclization of acylhydrazones to 1,3,4-oxadiazoles was devised as depicted in Scheme 1. On the basis of earlier observations and properties of organic dyes used as photoredox catalysts,5 eosin Y was chosen as the photocatalyst for the present study. In general, organosulfur/nitrogen compounds have been frequently used as precursors in radical reactions because they form

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A. K. Yadav, Lal Dhar S. Yadav / Tetrahedron Letters 55 (2014) 2065–2069 H N

N R1

R2

iPr

O

H

N

eosin Y, DMF, green LEDs R1

NEt, O2 (air), 12-20 h, rt

2

2,5-disubstituted 1,3,4-oxadiazoles via oxyradicals would extend the substrate scope for visible-light-mediated organic syntheses. In order to work out the envisaged protocol, a key reaction was conducted with acylhydrazone A in DMF containing 2 mol % of eosin Y under an air atmosphere (without air bubbling) by irradiation with visible light (green light-emitting diodes (LEDs), k = 535 nm) at rt. The reaction delivered the desired 2,5-disubstituted 1,3,4-oxadiazole (3a) in 15% isolated yield after 24 h (Table 1, entry 1). Following this experiment, a series of control experiments were performed, which demonstrated that an organic base is essential to give the desired product in a high yield (93%) (Table 1, entry 2) and iPr2NEt was found to be the best base (Table 2, entry 2 vs entries 6, 7, and 9). There was no product formation or it was formed in traces in the absence ( ) of any one of the reagents/catalyst (Table 1, entries 3–5). The reaction did not proceed satisfactorily when a household 18 W fluorescent lamp was used instead of green LEDs (Table 1, entry 6 vs 2). Notably, the same result was obtained on using O2 (balloon) instead of an air atmosphere (Table 1, entry 8 vs 2), while under the degassed condition or under a nitrogen atmosphere no product formation was detected (Table 1, entries 5 and 7). These results establish that visible light, base, photocatalyst, and air are all essential (+) for the reaction and support the photocatalytic model of the reaction. Next, the reaction conditions were optimized with respect to solvents and the catalyst loading. In all the tested solvents (DMF, DMSO, MeOH, and EtOH) the yield of 3a was >50% (Table 2), which indicates that the reaction is not very sensitive to reaction media. DMF was the best solvent in terms of the reaction time and yield (Table 2, entry 1), hence it was used throughout the present work. When the amount of the catalyst was decreased from 2 to 1 mol %, the yield of 3a considerably reduced (Table 2, entry 3), but the use of 3 mol % of the catalyst did not affect the yield (Table 2, entry 1). Under the established reaction conditions in hand, the reaction was tried in a one-pot procedure starting directly from an aldehyde 1a and an acylhydrazide 2a to give the desired product 3a as depicted in Scheme 2. To our delight, it worked well and a number of symmetrical and unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles were successfully synthesized starting directly from various aldehydes 1 and acylhydrazides 2 (Tables 3 and 4). This clearly shows that the reaction is very mild and applicable to aryl, alkyl, heteroaryl, and alicyclic substrates, and tolerates considerable functional group variations like MeO, Br, Cl, and NO2 in the substrates 1 and 2. Regardless of differences in the electronic and steric properties of substrates 1 and 2, they afford the desired product 3 in good to excellent yields (70–96%). However, aldehydes 1 and hydrazides 2 with an electron-donating group on the aromatic ring appear to react faster and afford marginally higher yields in comparison to those bearing an electron-withdrawing group (Table 3, entries 2 and 3 vs entries 4–7; and Table 4, entries 2 and 3 vs entries 4 and 8). On the basis of the above observations and the literature precedents,5,15,16a,17–19 a plausible mechanism involving photoredox catalysis for the oxidative cyclization of acylhydrazones is depicted in Scheme 3. On absorption of visible light, the organophotoredox catalyst eosin Y (EY) is excited to its singlet state 1EY⁄ which through inter system crossing (ISC) comes to its more stable triplet state 3EY⁄ and undergoes a single electron transfer (SET). 3EY⁄ may

N R

O

2

Scheme 1. Visible-light-promoted aerobic oxidative cyclization of acylhydrazones.

Table 1 Screening and control experimentsa

N Ph

A

H N H

Ph

N N

eosin Y (2 mol%), iPr2NEt, air

O

Ph

DMF, visible light, 12-24 h, rt

Ph

O

3a

Entry

Visible light

Eosin Y

Air

Time (h)

Yieldb (%)

1 2 3 4 5 6 7 8 9 10 11

+ +

+ + +

+ + + +

24 12 24 24 24 12 24 12 12 12 12

15c 93 n.r.d n.r. n.r. 49e trace 93 93f 62g 46h

+ + + + + + + +

+ + + + + + +

+ N2 O2 + + +

a Reaction conditions: A (1.0 mmol), eosin Y (2 mol %), iPr2NEt (2.0 equiv), DMF (3 mL), green LEDs 2.6 W, 161 lm irradiation under an air atmosphere at rt. b Isolated yield of the product 3a, n.r. = no reaction. c The reaction was conducted without iPr2NEt base in DMF. d The reaction was carried out in the dark. e The reaction was carried out using 18 W CFL (compact fluorescent lamp). f The reaction was performed with 3.0 equiv of iPr2NEt. g Reaction was performed with 1.0 equiv of iPr2NEt. h Reaction was performed with 1.0 mol % of Eosin Y.

Table 2 Optimization of reaction conditionsa

N Ph

A

H N H

Ph O

N N

eosin Y (mol%), base, air solvent, green LEDs, 12-18 h, rt

Ph

Ph

O

3a

Entry

Eosin Y (mol %)

Base

Solvent

Time (h)

Yieldb (%)

1 2 3 4 5 6 7 8 9

3 2 1 2 2 2 2 2 2

i

DMF DMF DMF MeOH EtOH DMF DMF DMSO DMF

12 12 12 18 18 18 18 12 18

93 93 46 76 65 55 58 85 67

Pr2NEt Pr2NEt i Pr2NEt i Pr2NEt i Pr2NEt DBU DABCO i Pr2NEt Et3N i

a Reaction conditions: A (1.0 mmol), eosin Y (1–3 mol %), solvent (3 mL), base (2.0 equiv), green LEDs 2.6 W, 161 lm irradiation under an air atmosphere at rt. b Isolated yield of the product 3a.

radicals very readily.5f,i,j,15b–d,17 Surprisingly, visible-lightpromoted organic transformations involving oxyradicals as intermediates have been far less extensively studied.4a,b,16b Thus, the present intramolecular cyclization of acylhydrazones to

H PhCHO + H2N N 1a

O 2a

o Ph DMF, 60 C 2-4 h

N Ph

A

H N H

Ph O

N N

eosin Y, green LEDs i

Pr2NEt, O2 (air), 12-20 h, rt

Ph

O

Ph

3a

without isolation

Scheme 2. One-pot sequential reaction for synthesis of 2,5-disubstituted 1,3,4-oxadiazoles directly from aldehydes and acylhydrazides.

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A. K. Yadav, Lal Dhar S. Yadav / Tetrahedron Letters 55 (2014) 2065–2069 Table 3 Scope of aldehydesa

R1CHO + 1

Entry

Aldehydes 1

(i) DMF, 60 oC, 2-4 h

H H2N N 2a

(ii) eosin Y (2 mol%),green LEDs, Pr2NEt, O2 (air), 12-20 h, rt

i

O

Product 3

CHO

O 3a

1a CHO

O 3b

1b

1c

O 3c

O

1d

O 3d

Br

O

Cl

1e

O2N

12

95

12

96

15

84

15

81

20

76

20

86

12

83

12

85

12

89

15

85

15

83

12

85

12

82

16

84

N N

1f

O 3f

O2N

N N

CHO

7

93

3e

Cl

CHO

6

12

N N

CHO

5

Yieldc,d (%)

N N

CHO Br

Timeb (h)

N N

CHO

4

3

N N

2

O

O

N N

1

3

N N R1

O 3g

1g NO2 NO2

N N

CHO 1h

8

O

3h CHO

9

N N

1i

O

3i N N

CHO

10

O

1j

3j CHO

N N

11

O 1k

3k CHO N N

12

O 3l

1l

13

O

14

S

O

CHO O

1m

O

CHO S

1n

CHO

15

a

c d

3n N N

N N

N

O

1o

b

3m N N

N

3o

For the experimental procedure, see Ref. 20. Time required for step (ii). Isolated yield of the products 3. All compounds are known and were characterized by comparison of their mp, IR, NMR, and MS data with those reported in the literature.6–8

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A. K. Yadav, Lal Dhar S. Yadav / Tetrahedron Letters 55 (2014) 2065–2069

Table 4 Scope of acylhydrazidesa H OHC N NH2

R2

2

Entry

R2

(ii) eosin Y (2 mol%), green LEDs, i Pr 2NEt, O2 (air), 12-20 h, rt

+

O

N N

(i) DMF, 60 oC, 2-4 h

1a

Acylhydrazides 2

O 3

Product 3

Timeb (h)

Yieldc,d (%)

12

92

12

93

12

95

20

77

12

87

12

82

16

85

20

70

N N

O NHNH2

1

O 3a

2a O

N N NHNH2

2

O 3b

2b

N N

O NHNH2

3 O

O 3c

O

2c

N N

O NHNH2

4 O2 N

O 3f

O2N

2d

N N

O

5

O

NHNH2

3j

2e

N N

O NHNH2

6

O

3k 2f O

N N

7

NHNH2 N

O N

2g

3o N N

O NHNH2

8 O2N a b c d

O

NO2

2h

NO 2 3p

O2N

For the experimental procedure, see Ref. 20. Time required for step (ii). Isolated yield of the products 3. All compounds are known and were characterized by comparison of their mp, IR, NMR, and MS data with those reported in the literature.6–8

N R1

R2

N H

SET

O R

eosin Y

eosin Y*

C

Photocatalytic cycle of eosin Y

O2 (air) i

visible light O2

eosin Y

O2

N N R1

H

O D

N N

R2

R1 HO2

eosin Y

N R1

3

A

eosin Y

SET

Pr2NEt -H+

vis. light, air

R2

O

Br COOH

Br

H

B

O

O

HO

O

1

Br

Br

R2

N

N

Br

Br HO

H N

R2

Br H

O

O

O Br COOH

eosin Y

Photoredox catalytic cycle of eosin Y Eosin Y (EY)

EY

hv

1

EY*

ISC

3 EY* oxidant

EY reductant

SET

Scheme 3. Photoredox catalytic cycle of eosin Y for the aerobic oxidative cyclization of acylhydrazones to 1,3,4-oxadiazoles.

undergo both reductive15a–c and oxidative5a,b,21 quenching. A SET from B to 3EY⁄ generates acyl radical C, which undergoes intramolecular cyclization (5-endo-trig) to form D followed by attack of O2

to give the product 3, successively. The formation of superoxide radical anion (O2 ) during the reaction was confirmed by the detection of the resulting H2O2 using KI/starch indicator.18

A. K. Yadav, Lal Dhar S. Yadav / Tetrahedron Letters 55 (2014) 2065–2069

In conclusion, we have developed a novel transition metal-free organocatalytic method for the synthesis of 1,3,4-oxadiazoles directly from aldehydes and acylhydrazides in a one-pot procedure in the presence of inexpensive eosin Y as a powerful organophotoredox catalyst at rt. The reaction utilizes visible light, a base, and O2 (air) as reagents. This protocol is a superior alternative to the existing methods for the synthesis of 1,3,4-oxadiazoles with several advantages in terms of green chemistry parameters such as sustainability, eco-friendly reagents, high efficiency, and one-pot simple operation under mild conditions. This methodology widens the scope of substrates for visible light photoredox reactions. Acknowledgments We sincerely thank the SAIF, Punjab University, Chandigarh, for providing spectra. One of us (A.K.Y.) is grateful to the CSIR, New Delhi, for the award of a Senior Research Fellowship. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.02.022. References and notes 1. For selected reviews on visible-light-photoredox catalysis, see: (a) Nicewicz, D. A.; Nguen, T. M. ACS Catal. 2014, 4, 355; (b) Xiea, J.; Jina, H.; Xua, P.; Zhu, C. Tetrahedron Lett. 2014, 55, 36; (c) Lang, X.; Chen, X.; Zhao, J. Chem. Soc. Rev. 2014, 43, 473; (d) Reckenthäler, M.; Griesbeck, A. G. Adv. Synth. Catal. 2013, 355, 2727; (e) Rovelli, D.; Fagnoni, M.; Albini, A. Chem. Soc. Rev. 2013, 42, 97; (f) Hu, J.; Wang, J.; Nguyen, T. H.; Zheng Beilstein J. Org. Chem. 2013, 9, 1977; (g) Xi, Y.; Yia, H.; Lei, A. Org. Biomol. Chem. 2013, 11, 2387; (h) Xuan, J.; Lu, L.-Q.; Chen, J.R.; Xiao, W.-J. Eur. J. Org. Chem. 2013, 6755; (i) Ravelli, D.; Fagnoni, M. ChemCatChem 2012, 4, 169; (j) Xuan, J.; Xiao, W.-J. Angew. Chem., Int. Ed. 2012, 51, 6828; (k) Tucker, J. W.; Stephenson, C. R. J. J. Org. Chem. 2012, 77, 1617; (l) Narayanam, J. M. R.; Stephenson, C. R. J. Chem. Soc. Rev. 2011, 40, 102; (m) Teply, F. Collect. Czech. Chem. Commun. 2011, 76, 859; (n) Yoon, T. P.; Ischay, M. A.; Du, J. N. Nat. Chem. 2010, 2, 527; (o) Zeitler, K. Angew. Chem., Int. Ed. 2009, 48, 9785. 2. Nicewicz, D. A.; MacMillan, D. W. C. Science 2008, 322, 77. 3. Ischay, M. A.; Anzovino, M. E.; Du, J.; Yoon, T. P. J. Am. Chem. Soc. 2008, 130, 12886. 4. (a) Konieczynska, M. D.; Dai, C.; Stephenson, C. R. J. Org. Biomol. Chem. 2012, 10, 4509; (b) Dai, C.; Narayanam, J. M. R.; Stephenson, C. R. J. Nat. Chem. 2011, 3, 140; (c) Narayanam, J. M. R.; Tucker, J. W.; Stephenson, C. R. J. J. Am. Chem. Soc. 2009, 131, 8756. 5. (a) Srivastava, V. P.; Yadav, A. K.; Yadav, L. D. S. Synlett. http://dx.doi.org/ 10.1055/s-0033-1340623.; (b) Yadav, A. K.; Srivastava, V. P.; Yadav, L. D. S. RSC Adv 2014, 4, 4181; (c) Yang, X.-J.; Chen, B.; Zheng, L.-Q.; Wu, L.-Z.; Tung, C.-H. Green Chem. 2014, 16, 1082; (d) Teo, Y. C.; Pan, Y.; Tan, C. H. ChemCatChem 2013, 5, 235; (e) Yang, D.-T.; Meng, Q.-Y.; Zhong, J.-J.; Xiang, M.; Liu, Q.; Wu, L.Z. Eur. J. Org. Chem. 2013, 7528; (f) Hari, D. P.; Hering, T.; König, B. Org. Lett. 2012, 14, 5334; (g) Zou, Y.-Q.; Chen, J.-R.; Liu, X.-P.; Lu, L.-Q.; Davis, R. L.; Jørgensen, K. A.; Xiao, W.-J. Angew. Chem., Int. Ed. 2012, 51, 784; (h) Fidaly, K.; Ceballos, C.; Falguières, A.; Veitia, M. S.-I.; Guy, A.; Ferroud, C. Green Chem. 2012, 14, 1293; (i) Neumann, M.; Füldner, S.; König, B.; Zeitler, K. Angew. Chem., Int. Ed. 2011, 50, 951; (j) Hari, D.; König, P. B. Org. Lett. 2011, 13, 3852.

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