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25th March 2014 @ 01:11

This reaction is a model reaction to test if previously trialled conditions in JU 4-1 will work on the triazolopyrazine. JU 6-1 which used the exact conditions seems to have broken up the triazolopyrazine so this reaction will alter the temperature.

Literature reference: 10.1021/jo901707x

GitHub link: #165

Reaction Scheme

Procedure

Started 1:40pm

Phenethyl alcohol (0.06 mL, 60 mg, 0.5 mmol, 1.2 equiv) was added to 1 mL toluene along with JU 3-6 (96 mg, 0.38 mmol, 1 equiv), potassium hydroxide (69 mg, 1.2 mmol, 3.2 equiv) and 18-crown-6 (10 mg, 0.04 mmol, 0.1 equiv). The reaction mixture turned a dark red-brown on addition of the 18-crown-6. Analysis by TLC at the beginning of the reaction showed a spot which looked like product, but also plenty of starting material remaining.

TLC JU 6-2 EtOAc:Hex 70:30 start.jpg
TLC JU 6-2 EtOAc:Hex 70:30 start vanillin.jpg

The reaction was stirred at room temp for 1 h. Analysis by TLC showed no change.

TLC JU 6-2 EtOAc:Hex 70:30 1 h.jpg
TLC JU 6-2 EtOAc:Hex 70:30 1 h vanillin.jpg

The reaction was heated to 40oC and stirred for a further 1 h. Analysis by TLC showed all of the JU 3-6 starting material was gone.

TLC JU 6-2 EtOAc:Hex 70:30 2 h.jpg
TLC JU 6-2 EtOAc:Hex 70:30 2 h vanillin.jpg

The sample was cooled to room temperature and diluted with 4 mL of water. The mixture was extracted with EtOAc (4 x 3 mL). The aqueous layer was extracted with DCM (4 x 3 mL). Each  organic layer was separately washed with water (2 x 4 mL) until the aqueous layer became neutral followed by brine (3 mL) and dried over Na2SO4. They were filtered and dried under reduced pressure and in vacuo. The EtOAc layer yielded a dark red brown oil (180 mg, x % crude yield) that was analysed by 1H NMR. The DCM layer yielded a yellow brown solid (5 mg) that was analysed by 1H NMR.

1H NMR, crude EtOAc layer, DMSO, 200 MHz

JU 6-2 crude EtOAc layer DMSO 200 MHz.pdf
JU 6-2 crude EtOAc layer.zip

1H NMR, crude DCM layer, DMSO, 200 MHz

JU 6-2 crude DCM layer DMSO 200 MHz.pdf
JU 6-2 crude DCM layer.zip

The DCM layer doesn't appear to conatin any product. The EtOAc layer however does contain the product. The EtOAc layer was purified by flash column chromatography over silica. The column was first eluted with 50:50 EtOAc and Pet Benzine followed by 70:30 EtOAc:PB, 80:20 EtOAc:PB 90:10 EtOAc:PB and 100% EtOAC. The pure product was a brown oil which crystallised out overnight into light brown crystals (33 mg, 26% yield).

1H NMR, pure, CDCl3, 200 MHz

JU 6-2 pure CDCl3 200 MHz.pdf
JU 6-2 pure CDCl3.zip

13C NMR, pure, CDCl3, 300 MHz

JU 6-2 13C pure CDCl3 300 MHz.pdf
JU 6-2 pure CDCl3.zip

IR data

JU 6-2.pdf
 

HIRAC

See JU 6-1

InChI strings

InChI=1S/C12H6ClN5/c13-10-6-15-7-11-16-17-12(18(10)11)9-3-1-8(5-14)2-4-9/h1-4,6-7H

and

InChI=1S/C8H10O/c9-7-6-8-4-2-1-3-5-8/h1-5,9H,6-7H2

to

InChI=1S/C20H15N5O/c21-12-16-6-8-17(9-7-16)20-24-23-18-13-22-14-19(25(18)20)26-11-10-15-4-2-1-3-5-15/h1-9,13-14H,10-11H2

SMILES

N#CC(C=C1)=CC=C1C2=NN=C3C=NC=C(Cl)N32

and

OCCC1=CC=CC=C1

to

N#CC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4=CC=CC=C4)N32


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Attached Files
Reaction Scheme JU 6-1.png
TLC JU 6-2 EtOAc:Hex 70:30 start.jpg
TLC JU 6-2 EtOAc:Hex 70:30 start vanillin.jpg
TLC JU 6-2 EtOAc:Hex 70:30 1 h vanillin.jpg
TLC JU 6-2 EtOAc:Hex 70:30 1 h.jpg
TLC JU 6-2 EtOAc:Hex 70:30 2 h.jpg
TLC JU 6-2 EtOAc:Hex 70:30 2 h vanillin.jpg
JU 6-2 crude EtOAc layer DMSO 200 MHz.pdf
JU 6-2 crude EtOAc layer.zip
JU 6-2 crude DCM layer DMSO 200 MHz.pdf
JU 6-2 crude DCM layer.zip
JU 6-2 pure CDCl3.zip
JU 6-2 pure CDCl3 200 MHz.pdf
JU 6-2 pure CDCl3 200 MHz.pdf
JU 6-2 13C pure CDCl3 300 MHz.pdf
JU 6-2 pure CDCl3.zip
JU 6-2.pdf