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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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15th September 2016 @ 17:26

TLC Plate one illustrates the reaction of  2,6-dichloropyrazine (Molecule 1) to 2-(6-chloropyrazin-2(1H)-ylidene)malononitrile, which is product 2. The starting material is very concentrated in lane 1 and the co-spot, but is not present in lane 2. This means the reaction went to completion.

Product 3, Methyl 6-chloropyrazine-2-carboxylate, had been left stirring overnight since 9/12/16. On 9/13/16, the solution was milky white. The filtrate from the reaction was dried in vacuo, then partitioned between H2O (8 mL) and CHCl3 (8 mL). The organic phase was dried over MgSO4, instead of Na2SO4, which is what was used in the literature. The literature also noted to filter the solution through a short plug of silica, but instead we used cotton at the bottom of a glass funnel. Lastly, volatiles were removed in vacuo, yeilding Methyl 6-chloropyrazine-2-carboxylate (Product 3). The compound was a pale yellow oil that crystallized in about 30 minutes. The reaction is illustrated by TLC plate 2. Since we did not filter through the plug of silica, this might be why product 3 is unpure. However, none of the starting material (product 2)  is seen on the plate in lane 3, which is confirmation that the reaction went until completion.

TLC Plate 1:

eluant: 90% ethyle acetate and 10% methanol

Lane 1: Molecule 1, 2,6-dichloropyrazine (See reaction scheme) Rf: .792

Lane 2: Co-spot

Lane 3: Product, faint yellow spots (2-(6-chloropyrazin-2(1H)-ylidene)malononitrile)

Rf: .458

TLC Plate 2:

eluant: chloroform

Lane 1: Product 2, (2-(6-chloropyrazin-2(1H)-ylidene)malononitrile)

Rf: 0. Product 2 did not travel up the silica at all.

Lane 2: Co-spot
Lane 3: Product 3, Methyl 6-chloropyrazine-2-carboxylate. Rf: .600


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. .

Attached Files
tlc plate 1.png