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20th November 2014 @ 11:34

Note: See Synthesis of (E)-4-((2-(6-chloropyridin-2-yl)hydrazono)methyl)benzonitrile (JS 6-1) for previous problems trying to synthesise the desired E isomer . 


Reaction Scheme 

Experimental Procedure 

JS 4-1 [see - Synthesis of 2-chloro-6-hydrazinylpyradine (JS 4-1) ] (1.005 g, 7 mmol) was stirred into a solution of ethanol (100 mL). 4-cyanobenzaldehyde (0.92 g, 7 mmol) was added and the reaction was stirred at refux for 2 hours.

TLC (Hexane/EtOAc - 70/30) indicated that the reaction was complete. 

The solvents were removed in vacuo and the crude was used in the next reaction (1.88 g, 104 % ) 

Risk Assessment 

JS 10-1.docx

SMILES 

 

ClC1=CC=CC(NN)=N1 

and

[H]C(C1=CC=C(C#N)C=C1)=O

to

ClC1=CC=CC(N/N=C/C2=CC=C(C#N)C=C2)=N1

 

InChI Strings 

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

and

InChI=1S/C8H5NO/c9-5-7-1-3-8(6-10)4-2-7/h1-4,6H

to

InChI=1S/C13H9ClN4/c14-12-2-1-3-13(17-12)18-16-9-11-6-4-10(8-15)5-7-11/h1-7,9H,(H,17,18)/b16-9+


NMR 

JS 10-1 .png
Linked Posts
Attached Files
19th November 2014 @ 06:17

19 November 2014 @ 16:51

Synthesis of SGS 4-1 (AEW 198-1)

http://malaria.ourexperiment.org/triazolopyrazine_se/11058/Synthesis_of_E2chloro62pyridin2ylmethylenehydrazinylpyrazine_AEW_1982.html

Reaction performed by Jason Chami and Mackenzie Shaw.

SGS 1-1 (1.06 g, 7.33 mmol) was stirred into MeCN (15 mL). 2-Pyridinecarboxaldehyde (0.77 g, 7.2 mmol) and AcOH (0.4 mL) were added to the mixture.  This reaction mixture was then stirred at room temperature overnight.

TLC: 

TLC SGS 4-1

Synthesis of SGS 4-1

SMILES

ClC1=CN=CC(NN)=N1

and

O=C([H])C1=CC=CC=N1

to

ClC1=CN=CC(N/N=C/C2=NC=CC=C2)=N1

 

InchI Strings

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

and

InChI=1S/C6H5NO/c8-5-6-3-1-2-4-7-6/h1-5H

to


InChI=S/C10H8ClN5/c11-9-6-12-7-10(15-9)16-14-5-8-3-1-2-4-13-8/h1-7H,(H,15,16)/b14-5+

15th November 2014 @ 13:45

Reaction Scheme: 


Experimental Procedure: 

 see Synthesis of (E)-4-((2-(6-chloropyridin-2-yl)hydrazono)methyl)benzonitrile (JS 6-1) 

To a solution of JS 6-1 (100 mg, 0.39 mmol, crude) stirred in dry THF (8 mL) was added chloramine-T (97.8 mg, 0.43 mmol). The reaction was stirred at room temperature over the weekend. 

No change in TLC. The solvent was removed in vacuo and then the solid re-dissolved in 2-MeTHF. This was refluxed overnight to no avail. The reaction has not proceeded at all due to the possibility that the starting material is the incorrect isomer (the Z isomer). 

 

Risk Assessment :

JS 9-1.docx

SMILES 

ClC1=CC=CC(N/N=C/C2=CC=C(C#N)C=C2)=N1

to

ClC1=CC=CC2=NN=C(C3=CC=C(C#N)C=C3)N21

 

InchI Strings

InChI=1S/C13H9ClN4/c14-12-2-1-3-13(17-12)18-16-9-11-6-4-10(8-15)5-7-11/h1-7,9H,(H,17,18)/b16-9+

to

InChI=1S/C13H7ClN4/c14-11-2-1-3-12-16-17-13(18(11)12)10-6-4-9(8-15)5-7-10/h1-7H

Attached Files
15th November 2014 @ 13:40

Optimising Reaction conditions to avoid side product synthesis 


Reaction Scheme 


Experimental Procedure 

Compound 3 (0.1 g, ) was treated with  Hydrazine hydrate - 64 % weight in H2O - (0.019 mL, 10 equivs) in EtOH (1.2 ml) . The resulting mixture was stirred overnight at reflux. TLC of the resulting mixture in two different solvent systems will be performed performed (100% EtOAc and 10/90 EtOAc/Hexane). After 24 hours The TLC indicted the reaction was not complete . TLC after 48 hours showed the reaction was still not complete but more product had formed.  An NMR was taken at this stage and showed the product was  present in a ratio of 2:1 with the starting material.These conditions favour synthesis of the product faster than conditions in (JS 5-5). 

RISK ASSESSMENT 

JS 5-2.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

15th November 2014 @ 13:38

Optimising Reaction conditions to avoid side product synthesis 


Reaction Scheme 


Experimental Procedure 

Compound 3 (0.1 g, ) was treated with  Hydrazine hydrate - 64 % weight in H2O - (0.03 mL, 2 equivs) in EtOH (1.2 ml) . The resulting mixture was stirred overnight at reflux. TLC of the resulting mixture in two different solvent systems will be performed performed (100% EtOAc and 10/90 EtOAc/Hexane). After 24 hours The TLC indicted the reaction was not complete . TLC after 48 hours showed the reaction was still not complete but more product had formed.  An NMR was taken at this stage and showed the starting material was still present in a ratio of 2:1 with the desired product. 

RISK ASSESSMENT 

JS 5-2.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