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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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8th September 2016 @ 21:40

We will be performing this reaction on the 1 gram scale, so we weighed out 1.025 g of 2-6 dichloropyrazine [molecuel #1], mw 148.97 g/mol, for 6.881 mmol, 1 equiv. We then weighted out approx 2 equiv, 0.876 g of malononitrile, mw 66.06g/mol, 13.26 mmol. The malononitrile was dissolved in approx 85 mL dry THF in a 3 neck round bottomed flask full of argon. Note: for this procedure, we stick to a reaction under argon. To the stirring solution of malononitrile in THF, we added approx 2 equiv, 13.43 mmol, 0.45 g of NaH (60% in mineral oil) SLOWLY, venting as needed. After all the NaH was added we allowed this to stir unperturbed for a half hour. This solution appeared pale and dull yellow, transparent.

We added our sample of 2-6 dichloropyrazine to a round bottom flask, flushed it with argon, and capped it with a rubber septum. We then disolved it in approx 25 mL dry THF. After the half hour, we added this solution in little squirts to the solution of malononitrile using a needle through the septum to avoid air contamination. After all of the 2-6 dichloropyrazine had been added, the combined solution stirring looked more yellow and towards translucent. 

We attempted to set up a reflux at this point, but there were two errors: our rubber tubing was too wide and water sprayed the outside of our flask. We do not think at this time that any segnificant ammount of water entered the closed system. Also, while looking for more tubing, the mixture came to a boil, and bubbling hot solution flowed up the refluxing condenser into our argon balloon. The quick attachment of rubber tubing and cold water through the refluxing condenser remedied this problem.


We then left the mixture for a 20h reflux


This procedure is following that laid out in the article :

Nikishkin, Nicolai I. et al. "Pyrazine-Functionalized Calix[4]Arenes: Synthesis By Palladium-Catalyzed Cross-Coupling With Phosphorus Pronucleophiles And Metal Ion Extraction Properties". New J. Chem. 37.2 (2013): 391-402. Web. 4 Sept. 2016. .