2-cyanoacetic acid (Sigma Aldrich)

Isobutyl alcohol (Sigma Aldrich)

Sulfuric acid (Vetec)

Dichloromethane (Sigma Aldrich)

2-Cyano acetic acid (80 mmol) & Isobutanol (360 mmol) was added to a 1Lt, 4 necked flask carrying mechanical stirrer, addition flask and condenser. Concentrated sulfuric acid (98%, 94 mmol) was charged to addition flask and added drop wise at room temperature. The temperature of the reaction mixture was maintained between 80-85°C for 16–18 hours. Then the reaction mixture was allowed to cool at room temperature and poured into 20% sodium carbonate solution. The reaction mass was extracted with dichloromethane (CH2Cl2). The combined organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure to obtain product with (60-70%) yield.

 We observed interesting esterification and Ritter reaction product. When isobutyl alcohol is reacted with 2-cyanoacetic acid it gave interesting isobuty ester and tert-butyl amino Ritter product in moderate yield.

To the best of our knowledge and available literature, this is the first example of Ritter reaction of an unactivated alcohol.

IR(cm-1): 3292.49 ([NH]), 1741.72 ([ester]), 1651.67([NH]).

1H NMR (400 MHz, CDCl3): 4.14 (t, 2H, (OCH2) ), 3.97-3.90( m, 1H, CH), 3.29 (s, 2H,CO-CH2), 1.67-1.60 ( m, 2H, CH2), 1.53-1.43 (m, 2H, CH2), 1.41-1.33 (m, 2H, CH3),1.25 (s, 1H, NH), 1.13(s, 2H, CH2), 0.95-0.89 (m, 3H, CH3).

13C NMR (100 MHz,CDCl3) :169.8, 164.2, 65.3, 46.7, 41.2, 30.4, 29.4, 20.2, 19.0, 13.6, 10.2.

HRMS : calc. For C13H14O4Na (M-NH3) :257.0790. Found: 257.0797 (M-NH3).

“A One-Pot Esterification and Amide formation via Acid-Catalyzed Dehydration and Ritter Reactions” Pankaj Dawar, M. Bhagavan Raju, Ramesha A. Ramakrishna. Synth. Commun., 2014, 44, 836–846.

“One-pot esterification and Ritter reaction: chemo- and regioselectivity from tertbutyl methyl ether” Pankaj Dawar, M. Bhagavan Raju, Ramesha A. Ramakrishna. Tetrahedron let., 2011, 52, 4262-4265.