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28th October 2014 @ 15:22

Reaction Scheme 


Experimental Procedure 

Compound 3 (0.2 g, 0.74 mmol) was treated with  Hydrazine hydrate - 64 % weight in H2O - (0.4 mL,  6 equivs) in EtOH (0.5 mL) . The resulting mixture was stirred overnight at reflux. TLC of the resulting mixture in two different solvent systems was performed (100% EtOAc and 10/90 EtOAc/Hexane). The results showed that most of the starting material had gone and that there were several products from the reaction. 

NMR analysis of the crude mixture revealed that the major product was the desired one. The rest of the peaks were due to impurities which have yet to be assigned. 

 

RISK ASSESSMENT 


JS 5-1.docx


InChI strings

InChI=1S/C12H8Cl2N2O/c13-8-3-1-4-9(7-8)15-12(17)10-5-2-6-11(14)16-10/h1-7H,(H,15,17)

to

InChI=1S/C12H11ClN4O/c13-8-3-1-4-9(7-8)15-12(18)10-5-2-6-11(16-10)17-14/h1-7H,14H2,(H,15,18)(H,16,17)

SMILES

ClC1=NC(C(NC2=CC=CC(Cl)=C2)=O)=CC=C1

to

O=C(NC1=CC=CC(Cl)=C1)C2=CC=CC(NN)=N2

 

TLC

JS 5-1.JPG

 

NMR

JS 5-1 crude.pdf


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Attached Files
23rd October 2014 @ 09:29

Conclusion: Using more concentrated hydrazine is very beneficial for speeding up the reaction. Recrystallization from water is very efficient, removing all impurities and water traces on NMR. 


Reaction Scheme 

 

Procedure 

2,6-Dichloropyridine (Aldrich, 5 g, 33.75 mmol) was teated with neat Hydrazine hydrate - 64 % weight in H2O - (10 mL, 204 mmol) . The resulting mixture was stirred overnight at 60C. TLC analysis showed that little starting material had been formed. White crystals had crashed out of solution overnight - TLC revealed this to be starting material. EtOH (10 mL) was added to the solution to dissolve the starting material and the reaction was allowed to stir over the weekend at reflux. 

Upon removing from heat and then removing the solvents in vacuo the resulting solid was sent for NMR analysis. This revealed some slight impurities in the solid and also some contaminating water. The solid was recrystallized from water to yield the titled compound as a pure blonde needle like crystal ( 2.7g, 18.8 mmol, 58% yield). 

Hazard & Risk Assessment

see Synthesis of 2-chloro-6-hydrazinylpyradine (JS 3-1)

JS 2-2.docx


InChI strings

InChI=1S/C5H3Cl2N/c6-4-2-1-3-5(7)8-4/h1-3H

to

InChI=1S/C5H6ClN3/c6-4-2-1-3-5(8-4)9-7/h1-3H,7H2,(H,8,9)

SMILES

ClC1=CC=CC(Cl)=N1

to

ClC1=CC=CC(NN)=N1

 NMR 

JS 4-1.pdf

Pure Compound NMR 

4-1 after recrystal.pdf

 

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Attached Files
23rd October 2014 @ 06:50


2-Chloropyrazine (1.8 g, 15.7 mmol) was dissolved in EtOH (15 mL), and hydrazine hydrate (1.6 mL, 31.4 mmol, 2 eq) added. The mixture was refluxed for 8 hours.

The solvent was removed under reduced pressure to give a pale yellow solid. Water (~30 mL) and EtOAc (~20m L) were added, and the mixture was shaken in an attempt to dissolve all solid. The organic layer was removed, the aqueous layer extracted with EtOAc (3 x 15 mL), and the combined organic layers washed with brine (~15 mL) before being concentrated under reduced pressure to yield a brown orange mixture (~381 mg).

Comment: Very poor yield and strange NMR - no NMR from TM 62-1 Was work up performed (?) as TM 65-1 suggests that at least 1.5 g was synthesised from 3 g. Crude to be used in AEW 209-1 regardless.

Data:

AEW 207-1 crude 300 proton.pdf
AEW 207-1 work up.zip

Hazard and Risk Assessment:

See Preparation of 2-hydrazinylpyrazine (TM 62-1)

Strings:

InChI=1S/C4H3ClN2/c5-4-3-6-1-2-7-4/h1-3H

to

InChI=1S/C4H6N4/c5-8-4-3-6-1-2-7-4/h1-3H,5H2,(H,7,8)

 

ClC1=NC=CN=C1

to

NNC1=NC=CN=C1

Attached Files
22nd October 2014 @ 07:50

5-chloro-[1,2,4]triazolo[4,3-a]pyrazine (1 g, 6.5 mmol) was combined with N-bromosuccinimide (1.96 g, 7.2 mmol, 1.1 eq) in chloroform (50 mL), and refluxed from 4 pm.


N-bromosuccinamide was freshly purified by recrystalliation in water:

20 g in 200 mL, heated to 95 ˚C until all solid dissolved and then left to cool at rt until white crystals formed. Then cooled to 0 ˚C for 30 minutes, filtered washed with cold water to yield a white solid (15 g).

Hazard and Risk Assessment:

See Synthesis of 3-bromo-5-chloro-[1,2,4]triazolo[4,3-a]pyrazine (TM 57-1)

 

Strings:

InChI=1S/C5H3ClN4/c6-4-1-7-2-5-9-8-3-10(4)5/h1-3H

to

InChI=1S/C5H2BrClN4/c6-5-10-9-4-2-8-1-3(7)11(4)5/h1-2H

ClC1=CN=CC2=NN=CN21

to 

ClC1=CN=CC2=NN=C(Br)N21

Attached Files
21st October 2014 @ 01:24

 

Repeat of Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-1), see also Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-2) and Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-3)

 

2,6-dichloropyrazine (21 g, 141 mmol) was dissolved in EtOH (100 mL), and hydrazine hydrate (13.5 mL, 270 mmol, 2 eq) added. The reaction mixture was stirred at reflux for 6 hours, 


The solvent was removed under reduced pressure to give a pale yellow solid. Water (~150 mL) and EtOAc (~200 mL) were added, and the mixture was shaken in an attempt to dissolve all solid. The organic layer was removed, the aqueous layer extracted with EtOAc (3 x 100 mL), and the combined organic layers washed with brine (~30 mL) before being concentrated under reduced pressure to yield 

 

Data:

Hazard and Risk Assessment:

See Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-1)

InChi Strings:

InChI=1S/C4H2Cl2N2/c5-3-1-7-2-4(6)8-3/h1-2H

to

InChI=1S/C4H5ClN4/c5-3-1-7-2-4(8-3)9-6/h1-2H,6H2,(H,8,9)

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