search

KlementineJBS / USYD_PhD_ELN

This repository forms the electronic laboratory notebook (ELN)for Klementine Burrell-Sander's PhD's
2 stars 0 forks source link

KBS17-10 - Propargylation of 1,6-diaminohexane #50

Closed KlementineJBS closed 1 year ago

KlementineJBS commented 1 year ago

Link to HIRAC, original method and master page.

Last attempt is #45.

KBS17 Generic propargylation of 1,n-diamine.docx

Reaction Scheme

KBS17 hexadiamine

Changes to make

KlementineJBS commented 1 year ago

29.11.22

  1. Added NaH (163.5 mg of 60% dispersion in mineral oil, 4.09 mmol, 2.90 equiv.) to a dry flask
  2. Washed with pet. benz. (3 x 5 mL)
  3. Added KBS3-3 (447.7 mg, 1.41 mmol) dissolved in dry DMF (10 mL)
  4. Left stirring at rt from 10.30 am

TLC indicated "activation step" (deprotonation by NaH) was complete at 1.45 pm.

Reaction at 1.45 pm

  1. Cooled to 0 C
  2. Added propargyl bromide (0.5 mL, 80% in toluene, 6.60 mmol, 4.7 equiv.)

Reaction went black instantly upon addition of propargyl bromide.

TLC at 4.45 pm indicated formation of mono and bis product already, but SM remained.

KlementineJBS commented 1 year ago

30.11.22

TLC at 9.30 am indicated formation of mono and bis products.

20% ethyl acetate/pet. benz.; from left to right: 17-10, 17-10/starting material co spot, starting material, 17-11/starting material cospot, 17-11

KlementineJBS commented 1 year ago

01.12.22

TLC at 10 am.

Decided to work up despite SM remaining (~ 48 hours reaction time).

  1. Quenched with NH4Cl (20 mL)
  2. Extracted with toluene (4 x 50 mL)
  3. Washed with water (5 x 100 mL)
  4. Washed with brine (125 mL)
  5. Dried over mag sulphate and rotovapped.

Reaction after quenching

Reaction after brine wash

Empty vial: 15.8697 Full vial: 16.3023 Mass: 432.6 mg

KlementineJBS commented 1 year ago

8.12.22

Column

Ethyl acetate/pet. benz.

100 mL - 5% 250 mL - 10% 200 mL - 20% 100 mL - 50% 100 mL - 100%

Label Fractions Vial weight (g) Vial weight (full) Mass (mg) Moles (mmol) Yield
B 10-12 15.7548 - - - -
C 13-22 15.7553 15.8522 96.9 0.247 18%
D 23-24 15.4883 15.5064 18.1 0.046 3%
E 25-29 15.5235 15.6196 96.1 0.271 19%
F 30-34 15.9494 15.9747 25.3 0.071 5%
G 35+
KlementineJBS commented 1 year ago

07.12.22

Column TLCs.

KlementineJBS commented 1 year ago

20.12.22

LRMS

KBS-17-10_2-A,6_1_693-1.pdf KBS-17-10_2-A,6_1_693.pdf

Evidence of mono product (377.26) and bis product (415.29) in a ratio of roughly 77:100 i.e. mono = 44%, bis = 56%.