Exp071.JPG

Objective

To synthesize N-Cylohexenylformamide from Cylohexanone and formamide, following the protocol described by Maison, Schlemminger, et.al.

Procedure

Cylohexanone (9.3 ml, 0.1 mol) was dissolved in toluene (50 ml) in a 500 ml round bottom flask. To this solution fomamide (5.61 ml, 0.11 mol) and conc.H2SO4 (0.5 ml) was added. The round bottom flask was connected to a dean-stark apparatus under reflux conditions on a heating mantle for 11.5h. The solution was washed with water (50 mL) and brine (50 mL) and again with water (50ml). The solvent from the organic layer separated was removed under reduced pressure and the crude product obtained was recrystallized from hexanes solvent.

Results

NMR of Reactants
Cyclohexanone HNMR [in CDCl3]
Cyclohexanone CNMR [in CDCl3]
Fomamide HNMR [neat]
Formamide HNMR [in CD3OD]
Formamide CNMR [in CD3OD]

71B HNMR (Brown oil)


71A HNMR (Solid from the aqueous layer) in CD3OD
71A DEPT
71A C-NMR

Discussion

Unfortunately the HNMR of 71B (the organic layer extract) does not look pure, although some amount of formamide may still be in the it.
Since the product was not expected in the aqueous layer, it was not properly treated and was discarded after the recovery of a very small amount of the precipitate.....The product was only obtained in 3.2% yield (to justify this list the peaks that correspond to the published NMR). 71A was insoluble in CDCl3, it was soluble in CD3OD (seems like a formamide property)
There may be some amount of N-Cylohexenylformamide in 71A (HNMR), however is prsumably in an insignicant amount not enought to produce signals in the CNMR.

Conclusion

The experiment was unsuccessful..because the procedure (main protocol) was not followed entirely.

Log

2007-03-18

11:00 : Added cylcohexanone (9.3 ml) to a clean 500ml round bottom flask. Toluene (500 ml) was added to it.
11:05 : Added formamide (5.61 ml) to the r.b. flask.
11:07 : Added conc. H2SO4 (0.5 ml) to the r.b. flask
11:10 : Started heating the r.b.flask connected to a dean-stark apparatus on a heating mantle. (A picture of the setting)
11:15 : Reaction mixture started boil.
10:33 : Almost 3.8 ml water accumulated in the arm of the dean-stark apparatus, more than double of the expected 1.8ml.
10:40 : Stopped heating the solution.

2007-03-19

12:15 : Added distilled water (50ml) to the brown reaction mixture at room temperature. Separated the organic layer from the aqueous using a 500ml separatory funnel.
12:30 : Added brine solution (50ml) to the organic layer, separated the layers and finally washed the organic layer with distilled water (50ml) again. All the aqueous layers were collected together in an erlenmeyer falsk.
12:45 : The organic layer was set on a high vac connected rotovap set at 65C. the MgSO4 step is important here
12:50 : The aqueous layers started forming precipitate.
1:30 : The precipitate in the aqueous layer was filtered through a buchner funnel, the solid collected was washed with ice cold water, dried and weighed 405mg (71A).
2:45 : The organic layer, on the the rotovap after evaporation of the solvent turned in to a thick brown oily liquid (71B).
3:00 : Hexanes (5ml) was added to the brown oil (from the organic layer) and set on a steam bath (did you observe everything going into solution when boiling?). It was removed from the steam bath as it started to boil. The hot solution was cooled to room temperature without being disturbed...It did not develop crystals.
4:00 : The hexanes added 71B was again set on a high vac to remove hexanes...

2007-03-20

17:00 : Obtained HNMR 71A and 71B. The solid product 71A is insoluble in CDCl3 like the parent formamide.


Reference
1.
Main Protocol :Bioorg & Med Chem June 2000, Vol 8 Iss 6 Pages 1343-1360

2. NMR of N-Cylohexenylformamide :J. Am. Chem. Soc.; 1996; 118(11) pp 2574 - 2583;

Tags

Cyclohexanone :InChI=1/C6H10O/c7-6-4-2-1-3-5-6/h1-5H2
Formamide: InChI=1/CH2O/c1-2/h1H2
N-Cylohexenylformamide: InChI=1/C7H11NO/c9-6-8-7-4-2-1-3-5-7/h4,6H,1-3,5H2,(H,8,9)