All Notebooks | Help | Support | About
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             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. [data]20305[/data] 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. [data]20301[/data] 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         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. [data]20305[/data] 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. [data]20301[/data] 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. [data]20297[/data] 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. [data]20291[/data] 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. [data]20303[/data] 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: 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
Comments