Closed KlementineJBS closed 1 year ago
Reaction had turned black overnight.
Product appears to still be a combination of mono/bis propargylated hexadiamine. Probably need to column manually to determine percentage yield.
Peaks at both 377.24 [M+Na] (mono product) and 415.26 [M+Na] (bis product).
Performed a manual column to isolate mono and bis products. Used ~ 10 cm silica (possibly too much) and accidentally disturbed column bed part of the way through, possibly disrupting flow.
Column conditions: 50 mL 5:95 EtOAc/pet benzine 75 mL 6.7:93.3 EtOAc/pet benzine 100 mL 10:90 EtOAc/pet benzine 200 mL 20:80 EtOAc/pet benzine 50 mL 30:70 EtOAc/pet benzine
TLC's indicated bis product in fractions 18, 19, 20 and 22, 23, 24. Mono product appeared to be in fractions 26 - 35 but some SM was evident from fraction 29 onwards.
Note that M and D refer to references standards of mono-substituted and double-substituted products respectively, obtained from Nick Smith
Collected fractions 18 - 20 and 22 - 24 (believed to be bis product).
Empty vial: 16.1803 Full vial: 16.2002 g Mass: 19.9 mg
1H NMR (300 MHz, CDCl3) δ 4.02 (4H), 3.30 (4H), 2.18 (2H), 1.54 (4H), 1.47 (18H), 1.31 (4H).
Mysterious peak at 9.16 - seems like solvent (clean singlet, integrates to 0.43). There also appears to be water in the sample resulting in an increased integral at 1.54 (should be 4H but shows up as ~ 7H).
During the column, very faint signs of product could be seen in some fractions before F18. These weren't collected as the signal was so faint, however, collecting them may increase yield.
Link to HIRAC, original method and master page.
Last attempt is #22.
KBS17 Generic propargylation of 1,n-diamine.docx
Reaction scheme
Outcome
20 mg (0.0510 mmol), 10%
Overall, it does not seem to be worth attempting to "re-react" the mono product to obtain more of the bis product, as the yield was so poor. In future, the reaction will simply be uspcaled, though optimisation of solvents etc will still be attempted.