Potassium Hydroxide Catalyzed Addition of Arylamines to Styrenes

Abstract

Potassium hydroxide is a competent and cheap catalyst for the intermolecular addition of arylamines to styrenes. The reactions are performed in nontoxic dimethyl sulfoxide and can be used for the large-scale synthesis of β-phenylethylamines.

alkenes - amines - styrenes - potassium hydroxide - base-catalyzed hydroamination - β-phenylethylamines

References and Notes

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2 For a review on base-catalyzed hydroaminations, see: Seayad J. Tillack A. Hartung CG. Beller M. Adv. Synth. Catal.  2002,  344:  795 

For selected examples of base-catalyzed intermolecular hydroaminations, see:

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6

Gaylord Chemical Company, L.L.C. http://www.gaylordchemical.com/bulletins/Bulletin102B/Bulletin102B.pdf (accessed Jan 28, 2011).

7

General Procedure Exemplified by the Reaction of Styrene (1) with p -Toluidine (2)
An oven-dried Schlenk tube equipped with a Teflon stopcock and a magnetic stirring bar was transferred to a nitrogen-filled glove box and charged with p-toluidine (343 mg, 3.2 mmol), styrene (208 mg, 2.0 mmol), dry DMSO (1.0 mL), and KOH (99.99% from Sigma-Aldrich, 6 mg, 0.1 mmol, 5 mol%). The tube was sealed, and the resulting mixture was heated to 70 ˚C for 4 h. After the tube had been cooled to r.t. the reaction mixture was poured into an aq NaOH solution (1 M, 10 mL) and extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were dried (MgSO₄) and concentrated under vacuum in the presence of Celite^®. Finally, the crude product was purified by flash chromatography (light PE-EtOAc, 20:1) to give amine 3a (359 mg, 1.7 mmol, 85%) as a pale yellow oil. ^¹H NMR (500 MHz, CDCl₃): δ = 2.22 (s, 3 H), 2.86 (t, J _H,H = 7.1 Hz, 2 H), 3.33 (t, J _H,H = 7.1 Hz, 2 H), 3.46 (s, 1 H, NH), 6.51 (d, J _H,H = 8.2 Hz, 2 H), 6.97 (d, J _H,H = 8.0 Hz, 2 H), 7.16-7.23 (m, 3 H), 7.26-7.31 (m, 2 H) ppm. ^¹³C NMR (126 MHz, DEPT, CDCl₃): δ = 20.3 (CH₃), 35.4 (CH₂), 45.3 (CH₂), 113.1 (CH), 126.3 (CH), 126.5 (C), 128.5 (CH), 128.7 (CH), 129.7 (CH), 139.3 (C), 145.7 (C) ppm. IR (neat): ν = 3404, 3025, 2918, 2861, 1615, 1519, 1318, 1259, 1182, 1080, 1031, 808, 699 cm^-¹. HRMS (70 eV): m/z calcd for C₁₅H₁₇N: 211.1361; found: 211.1365.

8

Under comparable conditions, much lower yields were obtained with toluene (<5%), 1,4-dioxane (<5%), THF (9%), and DME (9%).

9 A base-catalyzed addition of the DMSO anion to styrene has been reported: Walling C. Bollyky L. J. Org. Chem.  1964,  29:  2699 

10 Azeotropic data of H₂O-hexane: T_Az = 61.6 ˚C, P_Az = 101.33 kPa; y_water = 0.2110. See: Lide DR. Handbook of Chemistry and Physics   87th ed.:  CRC Press; Boca Raton: 2006.  p.6-161