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6th December 2016 @ 11:38

AT-1-023 #2

Synthesis of (E)-2-chloro-6-(2-(4(pyrrolindin-1-yl)benzylidene)hydrazine)pyrazine from 4-(pyrrolindin-1-yl)benzaldehyde and 2-chloro-6-hydrazinylpyrazine in a condensation reaction #2

 

Both Reactions were carried out using a microscale to minimalize waste of intermediate product used as reactant.

Reaction 1: Repeat of original condensation reaction

 

 

reaction scheme 

 

 

 

Reagent

Eq

Mw

mmol

w/vol

2-chloro-6-hydrazinylpyrazine

1

144.56

0.2853

41mg

4-(pyrrolindin-1-yl)benzaldehyde

1

175.23

0.2853

50mg

ethanol

~

46.07

~

4ml

 

Experimental Procedure

2-chloro-6-hydrazinylpyrazine (41mg, 0.2853mmol) and 4-(pyrrolindin-1-yl)benzaldehyde (50mg, 0.2853mmol) were added to ethanol (4ml) in a glass vial. The glass vial had a lid put on it and shaken and left to react for 4 hours.

produt.png

TLC analysis (70:30, Pet. Ether/ EtOAc and the final TLC was 1:1 Pet. Ether/ EtOAc) was taken after two hours, showing it hadn’t gone to completion. After 4 hours TLC analysis showed it had.

tlcs.png

In the TLC, on the spots for the product, several isomers had the same r.f. value so it is impossible to tell them apart from TLC. Crude NMR taken and shown to be the same as reaction 2, so the crude products (78.6mg) were combined to column together.

Reaction 2: Acetonitrile and acetic acid

 

 reaction scheme

 

 

Reagent

Eq

Mw

mmol

w/vol

2-chloro-6-hydrazinylpyrazine

1

144.56

0.2853

41mg

4-(pyrrolindin-1-yl)benzaldehyde

1

175.23

0.2853

50mg

Acetonitrile

1

41.05

~

1ml

Glacial acetic acid

~

60.05

~

0.045ml

Experimental Procedure

2-chloro-6-hydrazinylpyrazine (41mg, 0.2853mmol) and 4-(pyrrolindin-1-yl)benzaldehyde (50mg, 0.2853mmol) were added to acetonitrile (1ml) and glacial acetic acid (0.045ml in a glass vial. The glass vial had a lid put on it and shaken and left to react for 4 hours.

produt.png

TLC analysis (70:30, Pet. Ether/ EtOAc and the final TLC was 1:1 Pet. Ether/ EtOAc) was taken after two hours, showing it hadn’t gone to completion. After 4 hours TLC analysis showed it had.

tlcs.png

In the TLC, on the spots for the product, several isomers had the same r.f. value so it is impossible to tell them apart from TLC. Crude NMR taken and shown to be the same as reaction 2, so the crude products (75.5mg) were combined to column together.

Mixed reactions for isomer separation

The acetonitrile (75.5mg) and ethanol (78.6mg) crude products were mixed together (154.1mg). The crude NMR’s had shown the same product produced for both reactions, which contained the correct isomer. The products were dissolved in DCM and TLC systems for the best separation was tested. TLC tank A contained 80:20 Pet. Ether: EtOAc and tank B contained 90:10 Pet. Ether: EtOAc.

Tank C contained 80:20 Pet. Ether: diethyl ether and tank D contained 70:30 Pet. Ether: Diethyl ether.

Finally Tank E contained 70:30 Toluene: acetone.

tlc.png

The best tank for the separation of my crude product was a mixture between tank A and B, with 85:15 Pet. Ether and EtOAc. The crude product was purified via flash chromatography and 50 vials were taken off.

column tlc.png

A single product was present between vials 5-7, 8-12 had a mixture of isomers and 13-48 had a mixture of at least 2 isomers. The pure product betweek vials 5-7 was mostly clean but still contained some water, EtOAc and Pet. Ether. The correct isomer was not isolated however. It was still contained within the mass between vials 13-48.

fractions.png

Due to the very close r.f. values it was very difficult to separate out the isomers (all yellow solids), which meant that this step could not be moved forward because the correct product was not isolated.

 Reference:

  1. Open source malaria: our experiment, http://malaria.ourexperiment.org/triazolopyrazine_se/9268/Synthesis_of_E2chloro62naphthalen2ylmethylenehydrazinylpyrazine_TY_21.html ,date accessed: 04/11/16

 

Attached Files
column tlc.png
reaction with ethanol.png
tlc.png
tlcs.png
fractions.png
produt.png
acetonitrile.png
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