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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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20th October 2016 @ 19:46

The first steps in our proposed synthesis are very time consuming (See scheme 1). Also, our reaction that turns product 3 into product 4 had a very low yield (1.8%). Therefore, we began to experiment a new way to get to product 4 (See scheme 2). We based our new synthesis on an article by Foks. et al (see attachment Foks_scheme). Although we did not want to copy their synthesis exactly, we think that their chemistry could be mirrored with different reagents in efforts to create product 4. This entry details our trial of step 1.2 in scheme 2 (see attached file: scheme 3). We are not positive what the products of this reaction will be, but in scheme 3 we illustrate 2 probable ones. 

 

Scheme3.png

In a 50 mL round-bottom flask, 0.56 grams of 6-chloropyrazinecarbonitrile (MW 139g/mol, 4.01 mmol) was combined with 7 mL of ethanol. 10 mL hydrazine hydrate (~80% in H2O) was added to the round-bottom flask. The solution started off clear, then turned yellow, then subsequently red. The solution was refluxed for 5 hours. After, the round bottom flask was covered with parafilm and left in the hood.

Foks, H. et. al. (1974) Pyrazine derivatives. III. Synthesis and tuberculostatic activity of 6-(N-methylamino)-pyrazine-2-carboxylic acid derivatives Polish journal of pharmacology and pharmacy. 26(5). 537-543.

Attached Files
Foks_scheme.png
Scheme1_Hetero Oxadiazole synthesis.png
Scheme2.png
Scheme3.png