Objective

To synthesize three Ugi adducts from in methanol using Ugi 4CR following Explan005. If solid products are obtained, the experiment will serve as a template for an automated run. This experiment is similar to Exp185 expect for the higher concentrations of the reagents used.

Procedure

To two one dram vials, charged with methanol (1mL), 4- (trifluoromethyl benzaldehyde (2mmol), respective amines (2mmol), methactrylic acid (2mmol) and t-butyl isocyanide (2mmol) was added in that order. After each addition, the resulting solution was vortexed for 15 seconds and confirmed that a homogeneous solution had been obtained. The vial was capped tight and left at room temperature. Once a solid precipitate was obtained, excess solvent was decanted and the residue was washed with methanol (3x1ml), each time centrifuging it to obtain a residue. The product was then dried under high vac.

187-2A: N-benzyl-N-[2-(tert-butylamino)-2-oxo-1-[4-(trifluoromethyl)pheny​l]ethyl]-2-methyl-prop-2-enamide; C24H27F3N2O2; White solid; M.Pt: 136-138 C; 1H NMR (external image delta.gif ppm, CDCl3) 1.29 (s, 9H), 1.93 (s, 3H), 4.54(d, 1H), 4.78 (bs, 1H), 5.22 (bs, 1H), 5.23 (s, 1H) 5.53 (s,1H), 5.78 (s, 1H) 6.96-7.53 (aromatics, 9H) 13C NMR (external image delta.gif ppm, CDCl3), ; HRMS (FAB,m-nitrobenzyl alcohol): m/z calcd for C24H28F3N2O2, 433.210287 (M+H) found 433.210447

Sample ID
Aldehyde
Amine
Acid
Isocyanide
Ppt (Y/N) & Yield
187-1
4- (trifluoromethyl) benzaldehyde
(2mmol-273.1uL)
5-Methylfurfurylamine
(2mmol-222.9uL)
Methacrylic acid
(2mmol-168.6uL)
t-butylisocyanide
(2mmol-226.2uL)
N
187-2
4- (trifluoromethyl) benzaldehyde
(2mmol-273.1uL)
Benzylamine
(2mmol-218.4uL)
Methacrylic acid
(2mmol-168.6uL)
t-butylisocyanide
(2mmol-226.2uL)
Y
187-3
4- (trifluoromethyl) benzaldehyde
(2mmol-273.1uL)
t-butylamine
(2mmol- 210.1uL)
Methacrylic acid
(2mmol-168.6uL)
t-butylisocyanide
(2mmol-226.2uL)
N

Results


Exp ID
Day1
Day-2
Final
Analytical data
187-1
187-1.JPG
187-1day2.JPG

N/A
187-2
187-2.JPG
Day 1
187-2day2.JPG
Day 2
187-2_day5.JPG
Day 5
187-2A
Amt - 36 mg
M P - 136-138C
IR - ATR
HNMR (500MHz)
Labile H Exchange(500MHz)
Labile H Exchange(300MHz)
HNMR Overlay (500MHz)
CNMR(500MHz)
CNMR (300MHz)
FAB - Nominal Mass
FAB - Exact Mass
187-3
187-3.JPG
187-3day2.JPG

N/A

Discussion

In the sequence of experiments with same reagents, (Exp185, Exp187 and Exp188) and variable reagent concentrations, only 187-2 precipitated out. Exp187 was done at the highest concentration of the reactants in the sequence of the experiments. In the previous experiments Ugi products precipitated out when a concentration of 0.5mmol/1ml methanol had been used.

Log


2008-05-08

20:00 Added methanol (1mL) to three small vials labelled 187-1, 187-2 and 187-3. Then added 4- (trifluoromethyl) benzaldehyde (273.1uL) to each vial, vortexed for 15s each. This was followed by the addition of respective amines (from the table above) to each vial, vortexed for 15s..then added methacrylic acid (168.6uL) to each, vortexed 15s each and finally t-butyl isocyanide (226.2uL) was added to the vials..vortexed for 15s.
20:30 Obtained pictures of the vials. (series - Day 1)

2008-05-09

18:15 Obtained pictures of the vials. (series - Day 2)

2008-05-12

18:20 Observed crystals in 187-2 (day 5)

2008-05-14

14:00 Decanted excess solvent from the precipitate in 187-2 in another bigger vial, added methanol (1mL) to the residue, vortexed it for 30s, centrifuged it and collected the residue. The obtained residue was similarly washed, vortexed, centrifuged and decanted a further of one more time. It was observed that the product was very soluble in methanol. After the second wash there was hardly any solid left in the methanol wash, therefore the solvent had to be evaporated by blowing over compressed Nitrogen. After evaporating methanol (the methanol from which washes?) , a small amount of white residue obtained.
15:00 The residue was set under a high vac in a desiccator.
20:30 Removed from the high vac and obtained 36mg of a dry white solid now renamed 187-2A
21:00 Obtained a melting point of the 187-2A and an IR on Perkin Elmer FTIR
21:20 Obtained HNMR of 187-2A in CDCl3 on a Varian Inova 500MHz instrument.

Tags


Chemical
Inchi
Inchikey
4- (trifluoromethyl benzaldehyde
InChI=1/C8H5F3O/c9-8(10,11)7-3-1-6(5-12)2-4-7/h1-5H
BEOBZEOPTQQELP-UHFFFAOYAG
5-Methylfurfurylamine
InChI=1/C6H9NO/c1-5-2-3-6(4-7)8-5/h2-3H,4,7H2,1H3
YSEAGSCGERFGBL-UHFFFAOYAH
Benzylamine
InChI=1/C7H9N/c8-6-7-4-2-1-3-5-7/h1-5H,6,8H2
WGQKYBSKWIADBV-UHFFFAOYAL
tert-butylamine
InChI=1/C4H11N/c1-4(2,3)5/h5H2,1-3H3
YBRBMKDOPFTVDT-UHFFFAOYAT
Methacrylic acid
InChI=1/C4H6O2/c1-3(2)4(5)6/h1H2,2H3,(H,5,6)
CERQOIWHTDAKMF-UHFFFAOYAE
t-butyl isocyanide
InChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3
FAGLEPBREOXSAC-UHFFFAOYAL
187-2
InChI=1/C24H27F3N2O2/c1-16(2)22(31)29(15-17-9-7-6-8-10-17)20(21(3 ​0)28-23(3,4)5)18-11-13-19(14-12-18)24(25,26)27/h6-14,20H,1,15H2,2​ -5H3,(H,28,30)
KPGSTEQWODPHDS-UHFFFAOYAL
187-1
InChI=1/C23H27F3N2O3/c1-14(2)21(30)28(13-18-12-7-15(3)31-18)19(20 ​(29)27-22(4,5)6)16-8-10-17(11-9-16)23(24,25)26/h7-12,19H,1,13H2,2​ -6H3,(H,27,29)
SAWKKHAHHFXDJA-UHFFFAOYAY
187-3
InChI=1/C21H29F3N2O2/c1-13(2)18(28)26(20(6,7)8)16(17(27)25-19(3,4 ​)5)14-9-11-15(12-10-14)21(22,23)24/h9-12,16H,1H2,2-8H3,(H,25,27)
NIWFYVBPVKUUFJ-UHFFFAOYAT