Indian Journal of Chemistry Vol. 50B, August 2011, pp 1123-1127
Note A simple and efficient bromoazidation of alkenes using PTT and TMSN3 in ionic liquid Anil Kumar*, M Sudershan Rao & Vibhor Mehta Chemistry Group, Birla Institute of Technology and Science, Pilani 333 031, India E-mail:
[email protected] Received 18 May 2010; accepted (revised) 8 April 2011 A simple and efficient one-pot method has been described for the bromoazidation of alkenes using phenyltrimethylammonium tribromide (PTT) and TMSN3 in ionic liquid. The bromoazides have been obtained in good to excellent yield from various alkenes such as styrenes, chalcones, and cycloalkenes at room temperature. Keywords: Phenyltrimethylammonium TMSN3, bromoazidation, ionic liquid
tribromide
(PTT),
The functionalization of olefins by addition of two different functional groups in a single step is an important transformation. Haloazidation is one of the most useful reactions for simultaneous introduction of halogen and nitrogen functionality into a carbon skeleton of an olefin. Haloazides can be subjected to further synthetic manipulations to provide a new class of functionalized organic compounds such as vinyl azides1, amines2, aziridines3 and tetrazoles4. There are several methods reported for iodoazidation in the literature, however poor selectivity and instability of iodoazides are the main problems of these methods. There are only a few methods for the preparation of bromoazides such as using Br2/NaN3 (Ref. 5), NBS/NaN3 (Ref. 6), NBS/TMSN3 in the presence of Nafion-H in DME/H2O (Ref. 7) or in the presence of Zn(OTf)2 (Ref. 8) and Yb(OTf)3 (Ref. 9) as catalyst, TMSN3/TsNBr2 (Ref. 10), (diacetoxyiodo)benzene/tetraethylammonium bromide/TMSN3 (Ref. 11). Most of these methods are unsuccessful for the bromoazidation of α,β-unsaturated carbonyl compounds and they require acidic medium, higher temperature, use of organic volatile solvents and take much longer reaction time. Therefore, development of an efficient method for bromoazidation of alkenes remains a challenging task. Phenyltrimethylammonium tribromide (PTT, PhNMe3+Br3-, also known as PTAB) is convenient
source of bromine and has the advantage of high stability, ease of handling and avoids the disadvantage of toxic and corrosive property of bromine12. It has been used as a selective brominating reagent for ketones, ketals or alkenes13-15. It has also been used for aziridation16 and chemoselective conversion of aromatic epoxides and 1,2-diols to 1,3-dioxane derivatives in presence of SbBr3 (Ref. 17). Ionic liquids have been investigated extensively as solvents or catalysts for many important organic reactions because of their unique chemical and physical properties and their potential to enhance reaction rates and selectivity18. Recently, we have developed a onepot procedure for the synthesis of α-azidoketones using PTT and NaN3 in ionic liquid19. In continuation of our interest in ionic liquids as alternative reaction media for various organic transformations20, herein we report an efficient method for one-pot bromoazidation of alkenes using PTT and TMSN3 in ionic liquid (Scheme I). To the best of our knowledge this is the first method using PTT as brominating source and ionic liquid as reaction media for bromoazidation. Results and Discussion Initially, bromoazidation of chalcone 1a was investigated using PTT as the bromine source and NaN3 as the azide source in acetonitrile at RT, but formation of 3-azido-2-bromo-1,3-diphenylpropan-1one 2a was not detected even after 24 hr. The nitrogen source was then changed from NaN3 to TMSN3 and good yield of 2a was obtained after 3 hr. Encouraged with the success of this reaction, the model reaction was performed in other organic solvents such as THF, toluene, [bmim][BF4] and [bmim][PF6] ionic liquid as well as under neat condition. Among the tried solvents, the product 2a was obtained in 90% in [bmim][BF4] and in 82% under neat condition whereas in other organic solvents the yield was less than 60%. In ionic liquid there is an added advantage of purification, where product is separated by simple R'
R
i) PTT ii)TMSN3 [bmim][BF4]
1a-m
Br R'
R N3
2a-m Scheme I
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INDIAN J. CHEM., SEC B, AUGUST 2011
extraction with ethyl acetate/hexane leaving behind phenyltrimethylammonium bromide (PTAB) in ionic liquid. The high yield in ionic liquid may be possibly due to high solubility of PTT in ionic liquid and stabilization of in situ generated bromonium ion from the alkenes. The bromonium ion generated in situ reacts with TMSN3 via substitution mechanism. Presence of ionic liquid is also expected to accelerate this substitution step. Similar effect of ionic liquid has been reported for fluorination by nucleophilic substitution21, nucleophilic substitution of activated aryl halides with secondary amines22 and reactivity of anionic nucleophiles in ionic liquids23. The reaction condition was further optimized by varying amount of PTT, TMSN3, reaction time and ionic liquids. It was found that best yields were obtained by adding 1.2 equivalent of PTT, stirring reaction for 15-20 min followed by addition of 1.2 equivalent of TMSN3 at RT in [bmim][BF4]. Following the success of this procedure for the model reaction, the general scope of the method was examined with number of alkenes 1b-m and the reactions were successful to give corresponding bromoazides 2b-m in high yields (Scheme I, Table I). It is noteworthy to mention that chalcones gave excellent yield (Table I, entry a-i) as compared to low yield reported from these compounds by other methods. The yield of the product is influenced by the electronic effect of substituents present on the aryl groups in chalcones. The presence of electron withdrawing groups in the aryl rings decreased the yield of product and required longer reaction time. The method is efficient, convenient and work-up of product is simple. After extracting the compound from ionic liquid and evaporating the organic solvent under reduced pressure, the crude product was purified by recrystallization in hot ethanol for chalcones, whereas in case of aliphatic alkenes and aromatic alkenes (Table I, entry j-m) the crude product was purified by percolating through a column of silica gel using ethyl acetate/hexane (1:9, v/v) as eluent. The formation of bromoazide was indicated by a characteristic peak of azide group around 2110 cm-1 in IR and two peaks for single proton each at around δ 5.64 and 5.83 for CHBr and CHN3, respectively, in 1H NMR. All the synthesized bromoazides have been characterized by IR, mass and 1H NMR spectroscopic data. The coupling constant values of vicinal protons in 1H NMR analysis showed that the reaction is stereoselective yielding anti-bromoazides. It is also important to mention that formation of dibromo
derivatives was not observed under these experimental conditions. A plausible mechanistic pathway for the regionselective and stereoselective formation of bromoazides is shown in Scheme II. It is expected that a three-membered cyclic bromonium ion intermediate 3a is formed by the reaction of PTT and alkene (chalcone) by electrophilic addition of the Br+ ion generated from PTT onto the double bond. The intermediate 3a is then opened through SN2 mechanism by the azide ion giving anti-bromoazide derivative. The regioselectivity of bromoazides in chalcones and styrenes can be explained on the basis of more electropositive nature of β-carbon in chalcones and αcarbon in styrenes, respectively. In conclusion, an efficient and high yielding onepot method for bromoazidation of alkenes using PTT as bromine source and TMSN3 as azide source in ionic liquid has been developed. This general method works well with all kinds of alkenes including α, βunsaturated carbonyl compounds at RT within short time, without any catalyst under environment friendly conditions. Experimental Section The IR spectra were recorded using KBr pellets on Shimadzu Prestige-21 FTIR spectrophotometer and νmax was expressed in cm-1. The 1H NMR spectra were recorded on a Bruker Heaven Avance 11 400 (400 MHz) spectrometer using TMS as internal standard and CDCl3 as solvent. The chemical shifts are expressed in ppm (δ) and coupling constants (J) in Hz. The mass spectra were recorded on Qstar® Elite LX/MS/MS from Applied Biosystems. The required ionic liquid [bmim][BF4] was prepared according to the reported procedure by alkylation of 1-methylimidazole with 1bromobutane followed by substitution of bromide anion with tetrafluoroborate in dry acetone24. Phenyltrimethylammonium tribromide (PTT) was synthesized by modification of reported procedure from the reaction of N,N-dimethylaniline and methyl bromide followed by addition of bromine9. The solvents and common reagents were purchased from S. D. Fine and Spectrochem, India. Sodium tetrafluoroborate, TMSN3 and 1-methylimidazole were purchased from SigmaAldrich. The products were purified by column chromatography using silica gel (60-120 mesh). The homogeneity of the compounds was determined by TLC on aluminium backed silica gel 60 F254 (Merck) plates and detected by UV light (254 nm) and iodine vapours.
NOTES
1125
Table I — Synthesis of bromoazides using PTT and TMSN3 in ionic liquids.a Sr. No
Alkene
Productb
O
O
Time (hr)
Yield (%)c
2
94
2
93
2
87
2
81
4
73
5
63
2
86
3
85
2
86
2
77
N3
a Br
O
O
N3
b Me
OMe
Br
Me
O
OMe
O
N3
c
MeO
OMe
Br
MeO
O
OMe
O
N3
d
Me
Cl
Br
Me
O
O
Cl
N3
e
O2N
OMe
Br
O2N
OMe
O
O
N3
f MeO
NO2
Br
MeO
O
O
NO2
N3
g
Me
Me
Me
O
Br
Me
O
N3
h
Cl
Cl
F
O
F
Br
F
O
N3
i
H3CO
F
Br
H3CO
N3 j
Br
—Contd
INDIAN J. CHEM., SEC B, AUGUST 2011
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Table I — Synthesis of bromoazides using PTT and TMSN3 in ionic liquids.a—Contd Sr. No
Productb
Alkene
Time (hr)
Yield (%)c
2
86
3
75
3
70
N3 Br
k
H3C
H3C
N3 l
Br N3
m Br
a Reaction condition: Alkene (0.96 mmol), PTT (1.15 mmol), TMSN3 (1.15 mmol) and [bmim][BF4] (2.0 mL), RT; bAll compounds showed satisfactory IR, mass and NMR data; cIsolated yield.
O
PTT
PTAB + Br-
O Br
O
N3
TMSN3 [Bmim][BF4] 1a
N33a Scheme II
Representative procedure To a 10 mL round bottom flask containing ionic liquid [bmim][BF 4] (2.0 mL) was added 1a (200 mg), PTT (433 mg) and the reaction-mixture was stirred at RT for 15 min. TMSN3 (132 mg) was added to the reaction-mixture and stirred for additional 1 hr 45 min at RT. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction-mixture was extracted with hexane/ethyl acetate (2 × 5 mL, 1:1 v/v). The combined organic layer was evaporated under reduced pressure. The residue was recrystallized in hot ethanol to give pure 2a (320 mg, 94%) [In case of aliphatic alkenes product was purified by column chromatography over silica gel 60-120 mesh using hexane-ethyl acetate (95:5 v/v) as eluent]. The obtained 2a was characterized by 1H NMR, IR and mass spectroscopic data. Similarly, other substituted bromoazides 2b-m were prepared by the reaction of corresponding alkenes 1b-m and characterized by IR, 1H NMR and ESI-MS spectroscopic data.
[Bmim][BF4]
Br 2a
Spectral data for selected bromoazides 3-Azido-2-bromo-1,3-diphenylpropan-1-one, 2a: IR (KBr): 3103, 3024, 2106 (N3), 1680 (C=O), 1593, 1579 cm-1; 1H NMR (400 MHz, CDCl3): δ 5.65 (d, J = 11.2 Hz, 1H), 5.84 (d, J = 11.2 Hz, 1H), 7.37-7.44 (m, 4H), 7.52-7.56 (m, 3H), 7.63 (t, J = 7.62 Hz, 1H), 8.10 (d, J = 7.81 Hz, 2H); ESI-MS: m/z 330.0082 (M + H)+, 332.0061 (M + 2 + H)+. 2-Azido-3-bromo-3-(4-methoxyphenyl)-1-p-tolylpropan-1-one, 2b: IR (KBr): 3031, 2107 (N3), 1681 (C=O), 1594 cm-1; 1H NMR (400 MHz, CDCl3): δ 2.46 (s, 3H), 3.85 (s, 3H), 5.68 (d, J = 11.23 Hz, 1H), 5.80 (d, J = 11.22 Hz, 1H), 6.94 (d, J = 8.67 Hz, 2H), 7.35 (d, J = 8.04 Hz, 2H), 7.46 (d, J = 8.64 Hz, 2H), 8.01 (d, J = 8.16 Hz, 2H); ESI-MS: m/z 374.0223 (M + H)+, 376.0203 (M + 2 + H)+. 3-Azido-2-bromo-1,3-bis(4-methoxyphenyl)propan-1-one, 2c: IR (KBr): 3101, 3026, 2106 (N3), 1682 (C=O), 1594, 1576 cm-1; 1H NMR (400 MHz, CDCl3): δ 3.85 (s, 3H), 3.91 (s, 3H), 5.65 (d, J = 11.28 Hz, 1H), 5.80 (d, J = 11.32 Hz, 1H), 6.94 (d, J = 8.68 Hz, 2H), 7.01 (d, J = 8.88 Hz, 2H), 7.45 (d,
NOTES
J = 8.68 Hz, 2H), 8.07 (d, J = 8.88 Hz, 2H); ESI-MS: m/z 390.0163 (M + H)+, 392.0142 (M + 2 + H)+. 3-Azido-2-bromo-1-(4-methoxyphenyl)-3-(4-nitrophenyl)propan-1-one, 2f: IR (KBr): 2907, 2841, 2110 (N3), 1682 (C=O), 1651, 1593, 1514 cm-1; 1H NMR (400 MHz, CDCl3): δ 3.91 (s, 3H), 5.69 (d, J = 11.32 Hz, 1H), 5.77 (d, J = 11.32 Hz, 1H), 7.03 (dd, J = 7.20 Hz, 2.01 Hz, 2H), 7.10 (d, J = 7.20 Hz, 2.01 Hz, 2H), 8.09 (d, J = 7.20 Hz, 2.00 Hz, 2H), 8.29 (d, J = 7.20 Hz, 2.00 Hz, 2H); ESI-MS: m/z 358.0316 (M + H)+, 360.0297 (M + 2 + H)+. 3-Azido-2-bromo-1-(4-chlorophenyl)-3-(2-fluorophenyl)propan-1-one, 2h: IR (KBr): 3064, 3039, 2962, 2102 (N3), 1682, 1587, 1494 cm-1; 1H NMR (400 MHz, CDCl3): δ 5.82 (d, J = 11.2 Hz, 1H), 5.95 (d, J = 11.2 Hz, 1H), 7.12-7.15 (m, 1H), 7.17-7.24 (m, 1H), 7.37-7.52 (m, 2H), 7.53 (d, J = 6.64 Hz, 2H), 8.03 (d, J = 6.64 Hz, 2H); ESI-MS: m/z 381.8974 (M + H)+, 383.8951 (M + 2 + H)+. 3-Azido-2-bromo-3-(2-fluorophenyl)-1-(4-methoxyphenyl)propan-1-one, 2i: IR (KBr): 2193 (N3), 1659 (C=O), 1643, 1591 cm-1; 1H NMR (400 MHz, CDCl3): δ 3.90 (s, 3H), 5.87 (d, J = 11.31 Hz, 1H), 6.05 (d, J = 11.30 Hz, 1H), 6.99 (dd, J = 8.70 Hz, J = 1.89 Hz, 2H), 7.14-7.24 (m, 2H), 7.37-7.39 (m, 1H), 7.64-7.69 (m, 1H), 8.19 (dd, J = 8.94 Hz, J = 1.95 Hz, 2H); ESI-MS: m/z 377.0956 (M + H)+, 379.0935 (M + 2 + H)+. 1-(1-Azido-2-bromoethyl)benzene, 2j: IR (KBr): 3105, 3062, 3026, 2106 (N3), 1494 cm-1; 1H NMR (400 MHz, CDCl3): δ 4.07 (m, 2H), 5.17 (dd, J = 10.24 Hz, J = 5.76 Hz, 1H), 7.32-7.49 (m, 5H); ESIMS: m/z 225.8913 (M + H)+, 227.8890 (M + 2 + H)+. 1-(1-Azido-2-bromoethyl)-4-methylbenzene, 2k: IR (KBr): 3022, 2945, 2920, 2860, 2110 (N3), 1514 cm-1; 1H NMR (400 MHz, CDCl3): δ 2.34 (s, 3H), 3.38-4.08 (m, 2H), 5.13 (dd, J = 10.4 Hz, J = 5.20 Hz, 1H), 7.18 (dd, J = 8.0 Hz, J = 2.40 Hz, 2H), 7.29 (dd, J = 8.0 Hz, J = 2.00 Hz, 2H),; ESI-MS: m/z 239.9769 (M + H)+, 241.9748 (M + 2 + H)+. 1-Azido-2-bromocyclohexane, 2l: IR (KBr): 2924, 2851, 2112 (N3), 1519 cm-1; 1H NMR (400 MHz, CDCl3): δ 1.49-1.51 (m, 2H), 1.78-1.90 (m, 4H), 2.432.26 (m, 2H), 4.40 (m, 2H); ESI-MS: m/z 203.9817 (M + H)+, 205.9796 (M + 2 + H)+. 1-Azido-2-bromocyclooctane, 2m: IR (KBr): 2922, 2850, 2112 (N3) cm-1; 1H NMR (400 MHz, CDCl3): δ 1.62-1.71 (m, 6H), 1.82-1.86 (m, 2H), 2.072.16 (m, 2H), 2.38-2.47 (m, 2H), 4.59 (m, 2H); ESIMS: m/z 232.0286 (M + H)+, 234.0261 (M + 2 + H)+.
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Acknowledgement The financial support by CSIR, New Delhi and UGC-SAP, New Delhi is highly acknowledged. MSR is thankful to BITS, Pilani for institutional fellowships. References 1 Hassner A & Fowler F W, J Org Chem, 33, 1968, 2686. 2 Wasserman H H, Brunner R K, Buynak J D, Carter C G, Oku T & Robinson R P, J Am Chem Soc, 107, 1985, 519. 3 Nguy N-M, Chiu I-C & Kohn H, J Org Chem, 52, 1987, 1649. 4 Moorthy S N & Devaprabakara D, Tetrahedron Lett, 16, 1975, 257. 5 (a) Hassner A & Boerwinkle F, J Am Chem Soc, 90, 1968, 216; (b) Boerwinkle F & Hassner A, Tetrahedron Lett, 8, 1968, 3921; (c) Hassner A & Boerwinkle F, Tetrahedron Lett, 9, 1969, 3309. 6 (a) Van Ende D & Krief A, Angew Chem Int Ed (Engl), 13, 1974, 279; (b) Denis J N & Krief A, Tetrahedron, 35, 1979, 2901. 7 Olah G A, Wang Q, Li X-Y & Prakash G K S, Synlett, 1990, 487. 8 Hajra S, Sinha D & Bhowmick M, Tetrahedron Lett, 47, 2006, 7017. 9 Hajra S, Bhowmick M & Sinha D, J Org Chem, 71, 2006, 9237. 10 Saikia I & Phukan P, Tetrahedron Lett, 50, 2009, 5083. 11 Kirschning A, Hashem M A, Monenschein H, Rose L & Schoning K-U, J Org Chem, 64, 1999, 6522. 12 Jacques J & Marquet A, Org Synth Coll, 6, 1988, 175. 13 Marquet A & Jacques J, Bull Chim Soc Fr, 1962, 90. 14 (a) Johnson W J, Dolf Bass J & Williamson K L, Tetrahedron, 19, 1963, 861; (b) Visweswariah S, Prakash G, Bhushan V & Chandrasekaran S, Synthesis, 1982, 309. 15 Juo W-J, Lee T-H, Liu W-C, Ko S, Chittimalla S K, Rao C P & Liao C-C, J Org Chem, 72, 2007, 7992. 16 Jeong J U, Tao B, Sagasser I, Henniges H & Sharpless K B, J Am Chem Soc, 120, 1998, 6844. 17 Sayama S, Tetrahedron Lett, 47, 2006, 4001. 18 (a) Parvulescu V I & Hardacre C, Chem Rev, 107, 2007, 2615; (b) Jain N, Kumar A, Chauhan S & Chauhan S M S, Tetrahedron, 61, 2005, 1015; (c) Song C E, Chem Commun, 2004, 1033; (d) Dupont J, DeSouza R F & Suarez P A Z, Chem Rev, 102, 2002, 3667. 19 Kumar A, Ahmad I, Rao M S, Patel G & Kumar D, Indian J Chem, 48B, 2009, 611. 20 (a) Kumar A, Rao M S & Kamesvarao V, Aus J Chem, 63, 2010, 135; (b) Kumar A, Ahmad I & Rao M S, J Sulfur Chem, 30, 2009, 570; (c) Kumar D, Patel G, Kumar A & Roy R K, J Heterocyclic Chem, 46, 2009, 791; (d) Rao M S, Ahmad I, Khungar B & Kumar A, Can J Chem, 87, 2009, 714; (e) Kumar, Rao M S, Ahmad I & Khungar B, Aus J Chem, 62, 2009, 322. 21 Kim D W, Soong C E & Chi C Y, J Am Chem Soc, 124, 2002, 10278. 22 (a) Yadav J S, Reddy B V S, Basak A K & Naraiash A V, Tetrahedron Lett, 44, 2003, 2217; (b) Angrish C, Kumar A & Chauhan S M S, Indian J Chem, 44B, 2005, 1515. 23 Betti C, Landini D & Maia A, Tetrahedron, 64, 2008, 1689. 24 Srinivas K A, Kumar A & Chauhan S M S, Chem Commun, 2002, 2456.
