(Diacetoxyiodo)benzene-Lithium Bromide as a Convenient Electrophilic Br⁺ Source

Abstract

A mild and versatile procedure for the bromination of olefins and activated arenes by in situ generation of ‘Br⁺’ using (diacetoxyiodo)benzene and lithium bromide is presented. The reactions were carried out in open vessels at room temperature and were typically complete in 30 minutes. The brominated products were isolated by column chromatography, which also allowed for the isolation of the iodobenzene by-product for recycle.

electrophilic aromatic substitution - electrophilic addition - bromine - alkenes - hypervalent iodine

References

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For recent contributions see:

7a Roy SC. Guin C. Rana KK. Maiti G. Tetrahedron Lett.  2001,  42:  6941 

7b Tamhankar BV. Desai UV. Mane RB. Wadgaonkar PP. Bedekar AV. Synth. Commum.  2001,  31:  2021 

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16

A Typical Procedure for DIB-LiBr Bromination: To a solution of substrate (5 mmol) and LiBr (0.48 g, 5.5 mmol) stirring in anhyd THF at r.t. in an open vessel DIB was added portionwise over 5 min (1.77 g, 5.5 mmol). The suspension was stirred for a further 25 min, water added (10 mL) and the reaction mixture extracted with CH₂Cl₂ (20 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over MgSO₄ and concentrated in vacuo, and chromatographed (isooctane-Et₂O) to give the brominated product.

17

4-Bromanisole (Table [1] , entry 1): Yield: 88%; colourless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.36 (d, J = 9.0 Hz, 2 H, ArH), 6.76 (d, J = 9.0 Hz, 2 H, ArH), 3.76 (s, 3 H, CH₃). ¹³C NMR (68 MHz, CDCl₃): δ = 158.7, 132.4, 115.8, 112.9, 55.4. MS (EI): m/z = 186, 188 [M⁺·]. HRMS: m/z calcd for C₇H₇O⁷⁹Br: 185.9680; found: 185.9697. 6-Bromo-2,3-dihydrobenzo[1,4]dioxine (Table [1] , entry 2): Yield: 74%; Yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.00 (d, J = 2.4 Hz, 1 H, ArH), 6.91 (dd, J = 8.8, 2.4 Hz, 1 H, ArH), 6.72 (d, J = 8.8 Hz, 1 H, ArH), 4.20 (br s, 4 H, CH ₂CH ₂). ¹³C NMR (100 MHz, CDCl₃): δ = 144.4, 142.9, 124.3, 120.3, 118.6, 112.8, 64.3, 64.2. MS (EI): m/z = 214, 216 [M⁺·]. HRMS: m/z calcd for C₈H₇O₂ ⁷⁹Br: 213.9629; found: 213.9628. 5-Bromobenzo[1,3]dioxole (Table [1] , entry 3): Yield: 71%; colourless oil. ¹H NMR (400 MHz, CDCl₃): δ = 6.92 (m, 2 H, ArH), 6.66 (d, J = 8.8 Hz, 1 H, ArH), 5.95 (s, 2 H, CH₂). ¹³C NMR (100 MHz, CDCl₃): δ = 148.6, 147.0, 124.3, 113.1, 112.3, 109.6, 101.7. MS (EI): m/z = 200, 202 [M⁺·]. HRMS: m/z calcd for C₇H₅O₂ ⁷⁹Br: 199.9473; found: 199.9473. 4-Bromo- N , N -dimethylaniline (Table, entry 4): Yield: 73%; colourless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.27 (d, J = 8.7 Hz, 2 H, ArH), 6.55 (d, J = 8.7 Hz, 2 H, ArH), 2.89 (s, 6 H, CH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 149.5, 131.7, 114.1, 108.5, 40.6. MS (ES): m/z = 200, 202 [MH⁺]. HRMS: m/z calcd for C₈H₁₁NBr: 200.0075; found: 200.0084. 2-Bromo-5-methylthiophene (Table [1] , entry 5): Yield: 88%; colourless oil. ¹H NMR (400 MHz, CDCl₃): δ = 6.83 (d, J = 3.7 Hz, 1 H, ArH), 6.51 (d, J = 3.7 Hz, 1 H, ArH), 2.42 (s, 3 H, CH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 141.4, 129.6, 125.5, 108.5, 15.5. MS (EI): m/z = 176, 178 [M⁺·]. HRMS: m/z calcd for C₅H₅S⁷⁹Br: 175.9295; found: 175.9336. 3-Bromo-benzo[ b ]thiophene (Table [1] , entry 6): Yield: 79%; colourless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.74-7.80 (m, 2 H, ArH), 7.40 (t, J = 7.4 Hz, 1 H, ArH), 7.35-7.32 (m, 2 H, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 138.7, 137.6, 127.6, 125.1, 123.6, 123.2, 122.8, 107.8. MS (EI): m/z = 212, 214 [M⁺·]. HRMS: m/z calcd for C₈H₅S⁷⁹Br: 211.9295; found: 211.9285. 4-Bromo-2,4,6-tri- tert -butylcyclohexa-2,5-dienone (Table [1] , entry 9): Yield: 87%; orange crystalline solid; mp 71-73 °C [lit. [22] 80.5-81.5 °C]. IR (CH₂Cl₂): 1656, 1636 cm^-1. ¹H NMR (400 MHz, CDCl₃):
δ = 6.92 (s, 2 H, ArH), 1.25 [s, 18 H, 2- and 6-C(CH₃)₃], 1.14 [s, 9 H, C(CH₃)₃)]. ¹³C NMR (100 MHz, CDCl₃): δ = 189.0, 145.2, 139.9, 72.5, 40.0, 35.0, 29.4, 26.5. MS (CI⁺): 341, 343 [MH⁺]. HRMS: m/z calcd for C₁₈H₃₀O⁷⁹Br: 341.1480; found: 341.1472. 5-Bromomethyl-γ-butyrolactone (Table, 1 entry 10): Yield: 89%; colourless oil. IR (thin film; NaCl): 1777 cm^-1. ¹H NMR (270 MHz, CDCl₃): δ = 4.71 (m, 1 H, OCH), 3.51 (d, J = 5.1 Hz, 2 H, CH₂Br), 2.70-2.32 (m, 3 H, CHHCH ₂ ), 2.17-1.96 (m, 1 H, CHH). ¹³C NMR (68 MHz, CDCl₃): δ = 176.4, 78.0, 34.5, 28.5, 26.2. MS (CI⁺): m/z = 196, 198 [M + NH₄ ⁺]. MS (CI^-): 79, 81 [Br]. HRMS: m/z calcd for C₅H₁₁ ⁷⁹BrNO₂: 195.9973; found: 195.9971. (2,3-Dibromopropoxy)benzene (Table [1] , entry 11): Yield: 87%; colourless oil. ¹H NMR (270 MHz, CDCl₃): δ = 7.37 (dt, J = 7.6, 0.9 Hz, 2 H, ArH), 7.07 (t, J = 7.6 Hz, 1 H, ArH), 6.99 (d, J = 7.6, 2 H, ArH), 4.49-4.32 (m, 3 H), 4.02-3.91 (m, 2 H). ¹³C NMR (68 MHz, CDCl₃): δ = 158.1, 129.6, 121.9, 115.0, 69.2, 48.0, 33.1. MS (EI): m/z = 292, 294, 296 [M]. HRMS: m/z calcd for C₅H₁₁ ⁷⁹Br₂NO₂: 291.9098; found: 291.9092. Methyl 2,3-Dibromopropionate (Table [1] , entry 12): Yield: 80%; orange oil. ¹H NMR (270 MHz, CDCl₃):
δ = 4.40 (dd, J = 11.2, 4.4 Hz, 1 H), 3.87 (dd, J = 11.2, 9.9 Hz, 1 H), 3.79 (s, 3 H, CH₃), 3.63 (dd, J = 9.9, 4.4 Hz, 1 H). ¹³C NMR (68 MHz, CDCl₃): δ = 168.2, 53.5, 40.8, 29.7.

18 Drake MD. Bateman MA. Detty MR. Organometallics  2003,  22:  4158 

19

However, ¹H NMR studies of LiBr-DIB in THF-d ₈ failed to detect any new species: only PhI(OAc)₂ and PhI could be observed.

20a Beebe TR. Wolfe JW. J. Org. Chem.  1970,  35:  2056 

20b

This reagent was prepared in situ, and its activity confirmed by conversion of cis-cyclooctene to trans-1-bromo-2-acetoxy-cyclooctane.

21 See for example: Stang PJ. Zadankin VV. Chem. Rev.  1996,  96:  1123 

22 Baciocchi E. Illuminati G. J. Am. Chem. Soc.  1967,  89:  4017