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27th July 2017 @ 17:10

Reaction Scheme:

Step3ReactionScheme.png

Compound

MW (g/mol)

Mol (mmol)

Mass (g)

Density (g/mL)

Volume (mL)

Equiv

5-chloro-[1,2,4]triazolo[4,3-a]pyrazine

154

1.69

0.26

 

 

1

NBS

177.98

1.52

0.281

 

 

0.9

Chloroform

 

 

 

 

15

 

3-bromo-5-chloro-[1,2,4]triazolo[4,3-a]pyrazine

231.92

1.69

0.392

 

 

1

 

Procedure:

6/14/17 NBS was recrystallized before the reaction. Water (35 ml) was added to NBS (3 g). The mixture was stirred and heated at 100 celsius degree until NBS was dissolved to make a yellow solution. The solution was cooled to room temperature. White crystals formed. The crystals were filtered out and washed with ice water. The crystals were placed on the high vac in a dessicator over P2O5 to dry overnight.

7/5/17 5-chloro-[1,2,4]triazolo[4,3-a]pyrazine (0.26 g, 2 mmol) and N-bromosuccinimide (0.281 g, 1.6 mmol, 0.9equiv.) were placed in chloroform (50 mL) and refluxed for 44 h. Reflux started at 10:30 am.

7/6/17 TLC showed that there was still starting material. Another 0.5 equivalents of NBS were added to the reaction. TLC at 2:00 pm still showed a lot of starting material.

7/7/17 TLC still showed mostly starting material. There seems to be a faint product spot. Another 0.5 equivalents of NBS were added, but TLC at the end of the day was still the same, so reaction was stopped. Flask was kept covered with aluminum foil to block light.

BrClfinalTLC.png

7/19/17 Solvent removed under reduced pressure. NMR showed that some product had formed, but there was still unreacted starting material.

NMRcrudeBrCl.png

7/21/17 Product was purified by column chromatography using 70:30 EtOAc: Hexanes. The NBS came off first, followed by the product. Solvent was removed under reduced pressure to yield a yellow solid (0.37 g, 1.6 mmol, 94% yield). NMR obtained.

BrClFinalNMR.png
Attached Files
27th July 2017 @ 16:00

Reaction Scheme:

Screen Shot 2017-07-27 at 11.39.36 AM.png

Compound 

MW (g/mol) 

Mol (mmol) 

Mass (g) 

Density (g/mL) 

Volume (mL) 

Equiv

2-chloro-6-hydrazinylpyrazine 

144.56 

3.14 

0.454 

 

 

1 

Toluene  

 

 

 

 

10 

 

Triethyl Orthoformate 

148.2 

6.28 

0.931 

0.891 

1.04 

2.0 

TsOH 

190.22 

0.157 

0.03 

 

 

0.05 

Product 

154 

 

 

 

 

1 

Procedure:

6/28/17 Hydrazinylpyrazine (0.454 g, 3.14 mmol, 1 equiv.) triethyl orthoformate (0.931 g 1.04 ml, 6.28 mmol, 2 equiv.), and tosylic acid (0.0299 mg, 0.157  mmol, 0.05 equiv.) were dissolved in toluene (10 ml) and heated at  reflux for about 24 hours 

TsOH placed on high vac in a dessicator under P2Oovernight. Reaction started at 3:30. Hydrazinylpyrazine was dissolved in toluene first. It dissolved around 65 degrees. Triethyl Orthoformate and TsOH were then added. The temperature was turned up to 95 degrees, and reaction was left overnight. TLC was taken in 30:70 EtOAc: Hexanes at 5:00 pm and indicated that some starting material remained. 

6/29/17 Reaction removed from reflux at 10:30 am. TLC in 50:20 EtOAc: Hexanes showed starting material was gone and one of the intermediates had disappeared. We think that the spot just below the starting material is probably the product. Reaction mixture turned very dark brown. Solvent removed under reduced pressure to yield a reddish brown solid (0.523 g, 3.40 mmol, 108% yield). 

6/30/17 Column ran with 70:30 EtOAc: Hexanes as the starting eluent. Gradient ran up to 100% EtOAc. The bottom spot on our TLC, which we assumed to be the product was fluorescent blue on the bottom half of the spot and dark brown on the top. The blue and brown eluted separately from the column (blue followed by brown).  

Fractions 27-59 (brown spot) and Fractions 61-80 were collected. Solvents was removed under reduced pressure. NMR of both fractions were obtained.  

NMR indicated that the product was in fractions 27-59 (0.31 g, 2.0 mmol, 64 % yield) 

TLC: 

6/28/17 5:00pm

Solvent System( on left):TLC in 30:70 EtOAc: Hexanes

Solvent system( on right): 50:20  EtOAc: Hexanes

Screen Shot 2017-07-27 at 11.47.25 AM.png

NMR:

Screen Shot 2017-07-27 at 11.51.26 AM.png

Screen Shot 2017-07-27 at 11.51.35 AM.png
Attached Files
27th July 2017 @ 15:31

Reaction Scheme: 

Reaction Scheme.png

Compound 

MW (g/mol) 

Mol (mmol) 

Mass (g) 

Density (g/mL) 

Volume (mL) 

Equiv 

2,6-Dichloropyrazine 

148.98 

13.4 

2 

 

 

1 

Hydrazine hydrate  

50.06 

13.4 

0.680 

1.02 

0.66 

1 

EtOH 

 

 

 

 

20 

 

Product: 2-chloro-6-hydrazinylpyrazine 

144.56 

13.4 

 

 

 

1 

Procedure: 

6/19/17 2,6-Dichloropyrazine (2 g, 13.4 mmol) was stirred in ethanol (20 mL) and hydrazine hydrate (0.66 mL, 680 mg, 13.4 mmol) was added. The mixture was heated at 80˚C for 12 h. 

Reflux started at 3 pm.  

6/20/17 Reaction was removed from the heat at 9:30 am. TLC showed a small amount of starting material, but most of it was gone.  

Br:ClS1TLC.png

The solvent was removed under reduced pressure to yield a yellow solid. The solid was dissolved in 30mL water and 40 mL ethyl acetate. The aqueous layer was extracted with 3x20mL etoac. The organic layers were combined and washed with 20 mL brine, and then dried over MgSO4. Solvent was removed under reduced pressure to yield yellow solid (1.05 g, 7.26 mmol, 54% yield)

S1GCMS.png


Attached Files