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09-06-2016, First step in synthesis of the hetero-oxadiazole, reaction of 2-6 dichloropyrazine with malononitrile, following procedure from Nikishkin et al (2013)
09-11-2016, Work up of the second attempt at step 1
09-23-2016. Step 1 redo, on 5 gram scale
09-24-2016. Work up of 09-23-2016
09-29-2016, work up and purification of [4]
09/28/2016 Step 4, on a larger scale this time. Conversion of methyl 6-chloropyrazine-2-carboxylate [3] to methyl 6-hydrazineylpyrazine-2-carboxylate [4] using hydrazine according to AEW 85-5
10/07/2016 GC mass spec characterization of rxn from [4]->[5]
10/18/16: Trial work up of reaction of 6-chloropyrazinecarbonitrile and hydrazine
10/4/16: Trial of Step 4:Product [4] to Product [5]
10/6/16: Trial Synthesis of 6-hydrazinelypyrazine-2-carbonitrile and from 6- hydrazinelypyrazine-2-carboximidhydrazide from chloropyrazinecarbonitrile
9/12/16 Step 2 in synthesis. Going from [2]->[3]
9/13/16: Work-up of product [3] and TLC plates
9/15/16: Second Synthesis of Methyl 6-chloropyrazine-2-carboxylate [product 3]
9/18/16-9/20/16: Trial Synthesis of Methyl 6-hydrazineylpyrazine-2-carboxylate (Product 4)
9/22/16: Inconclusive Trial Synthesis of Methyl 6-hydrazineylpyrazine-2-carboxylate (Product 4)
9/25/16-9/27/16: Synthesis of Product 3, methyl 6-chloropyrazine-2-carboxylate
9/27/2016 Late Night
9/29/2016 HNMR of product 4, and HNMR of product 4 after D2O exchange 01/10/2016
9/8/16-Continued Synthesis of 2-(6-chloropyrazin-2(1H)-ylidene)malononitrile
CNMR so far
HNMR so far, of all relevant compounds
The Synthetic scheme of Hetero-oxadiazole Synthesis
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6th October 2016 @ 17:07

After the purification of product [4], we were left with 0.06g (.357 mmol, yield=1.8%) due to the mistaken spilling of the percipitate prior to washing it like we had planned. The NMR spectra was not as clean as we had hoped, but we decided to try to push forward. Product [4] was dissolved in ethanol, and 0.10g of 4-(difluoromethoxy)benzaldehyde was added The solution was stirred for an hour and a half.The solution became more translucent, and a solid began to form in the yellow solution.  It was believed that the solid was product [5].

TLC was preformed to evaluate the reaction. The eluent was 7:1 EtOAc and hexanes. On the TLC plate labeled "immine formation," Lane 1 was spotted with product [4], lane 2 was a cospot, and lane 3 was the solution after the reaction with 4-(difluoromethoxy)benzaldehyde. Since the starting material was not entirely present in lane 3, we believed a reaction did occur. When comparing the solution with  4-(difluoromethoxy)benzaldehyde, our product from the reaction had a slightly different rf than the pure 4-(difluoromethoxy)benzaldehyde, which was promising. This TLC plate is named "aldehyde comparison," the eluent was 3:1 EtOAc and Hexane, lane 1 was diluted 4-difluoromethoxy)benzaldehyde, lane 2 was a cospot, and lane 3 was the reaction solution.

However, once the solution was filtered by vacuum filtration, there was only a very tiny amount of product left on the filter paper, and we were not able to isolate it. Therefore, dichloromethane was poured over the filter paper in hopes of redissolving the solid. The solution was concentrated under reduced pressure. The solid that remains is believed to be excess (difluoromethoxy)benzaldehyde. We will use NMR to confirm this suspicion. 

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