Phenylacetic Acid → 2-Benzylisonicotinonitrile

HRID 660033Notes

Reaction equation

[C:1]([C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1)#[N:2].[C:9]1([CH2:15]C(O)=O)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.FC(F)(F)C(O)=O.[OH-].[Na+]>[N+]([O-])([O-])=O.[Ag+].ClC1C=CC=CC=1.O>[CH2:15]([C:5]1[CH:4]=[C:3]([C:1]#[N:2])[CH:8]=[CH:7][N:6]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

Conditions

Temperature: 50 °C

Procedure

p-cyanopyridine (4.00 g, 38.4 mmol) was added to a 1:1 mixture of chlorobenzene/water (750 mL) in a 1 L round-bottom flask. Phenylacetic acid (14.6 g, 107.5 mmol), (NH4)2S2O8 (17.1 g, 74.9 mmol), trifluoroacetic acid (4.38 g, 38.4 mmol) and AgNO3 (0.510 g, 3.0 mmol) were added and the heterogeneous mixture was vigorously stirred at 50° C. for 2 h. The reaction was cooled down to 0° C. and 8 M NaOH was added slowly until pH 9-10. The mixture was filtered through Celite and extracted with EtOAc (×3). The combined organic extracts were dried with MgSO4 and the solvent removed in vacuo. The dark-brown oil was purified via flash chromatography (1:5 EtOAc/Hexane) to give a brown oil (4.480 g, 61%); 1H NMR (400 MHz, CDCl3): δ 4.19 (s, 2H), 7.23-7.35 (m, 7H), 8.68 (d, J=5.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 44.4, 120.8, 122.7, 124.6, 126.9, 128.5, 128.9, 129.1, 137.9, 150.2, 162.7; HRMS-EI (m/z): [M+H+] calcd for [C13HN11N2]+, 195.0922. found, 195.0917.

Workup

temperatureThe reaction was cooled down to 0° C.
filtrationThe mixture was filtered through Celite
extractionextracted with EtOAc (×3)
dry with materialThe combined organic extracts were dried with MgSO4
customthe solvent removed in vacuo
customThe dark-brown oil was purified via flash chromatography (1:5 EtOAc/Hexane)

Sources & evidence

ORD record: ord-075c62eb5be047b49aafec28ed5a27da
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08084471B2

Reaction notes

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