Author Archives: Aron Schwartz

Step Four: Synthesis of (E)-2-chloro-6-(2-(4-(difluoromethoxy)benzylidene)hydrazineyl)-3,5-dimethylpyrazine

Reaction run on 12/8/16

CC1=NC(C)=C(N=C1Cl)N/N=C/C2=CC=C(OC(F)F)C=C2

Procedure:

4-(difluoromethoxy) benzaldehyde (1.5mL) was added to the 2-chloro-6-hydrazineyl-3,5-dimethylpyrazine (0.8g) produced in the last reaction. Ethanol (20mL) was also added with vigorous stirring. The product will be left to stir under an argon atmosphere overnight and TLC will be used to monitor the completeness of the reaction.



Third Step: Synthesis of 2-chloro-6-hydrazineyl-3,5-dimethylpyrazine (HASJK-3-3)

Reaction taken place on 12/5

CC1=NC(C)=C(N=C1Cl)NN

Procedure:

2,6 dichloro-3,5 dimethylpyrazine (0.6g), ethanol (6mL) and hydrazine (0.15 mL) were combined in a round bottom flask and stirred under argon atmosphere. It was then heated in an 80oC oil bath overnight. After, the solvent will be removed under vacuum. Yellow/gold crystals (0.8g) resulted NMR shown below.

 


Second Step: Synthesis of 2,6-dichloro-3,5-dimethylpyrazine Column Chromatography (HASJK-3-2)

Columned on 11/28/16

The product was columned by the Biotage. The fractions 5-7 (high spots) were combined. The product was a white crystal. Fractions 19-30 were also combined (low spot). NMR was run on the high spot. Initial look suggests that the chlorinated dimethyl product was synthesized with traces of starting material. Ran NMR/GCMS on both high and low spots, shown below.

 

Silica gel plates. 50/50 EtoAc/Hexane. Active under UV light.


Second Step: Synthesis of 2,6-dichloro-3,5-dimethylpyrazine (HASJK-3-1)

Date of Reaction: 11/23

CC1=NC(C)=C(N=C1Cl)Cl

 

Procedure:

Excess phosphoryl chloride (5.0mL, 0.0535 mol) was added to the oxidized dimethyl product (1.2g, 0.008 mol). The mixture was stirred and refluxed for 1.5 hours at 70oC. The reaction mixture was then alkalized using 20% NaOH. An extraction was carried out with CHCl3 (3 x 20 mL). Next steps will be to run a column chromatography on that product and then to get NMR data.

 

Table of Reagents (Rxn2) DiMethyl

 
 
 
 
 

Reagent

mass (g)

mols

Molecular Weight (g/mol)

Volume (mL)

Density (g/mL)

Product RxN1

1.200

0.008

158.590

 
 

Phosphoryl Chloride

3.481

0.023

153.333

2.122

1.640

Product RxN2 Dimethyl

1.347

0.008

178.040

 
 
 
 
 
 

*Used 5 mL of POCl3

 

Attached are TLCs 

First Step Synthesis of 2-chloro-3,5-dimethylpyrazine 1-oxide. (HASJK-3-0)

CC1=NC(C)=C(Cl)[N+]([O-])=C1

ImageIMG_9860.JPG

SM/P 

2-chloro-3,5-dimethylpyrazine 

sulfuric acid, conc. 

potassium persulfate 

2-chloro-3,5-dimethylpyrazine 1-oxide 

mw 

142.59 

  

270.31 

158.59 

Equiv 

1.00 

  

1.07 

1.00 

mmol 

14.00 

  

15.00 

14.00 

mg 

2000 

  

4000 

2220 

mL 

  

14.00 

  

  

11/8/2016.  To a 1-neck 14/20 50 mL RB were added 14 mL of concentrated H2SO4, which was cooled to approximately 0 C with ice bath.  The pyrazine was then added, followed by potassium persulfate.  The resulting suspension was allowed to stir with warming to room temperature overnight. 

11/9/16.  The resulting clear solution was poured into a separatory funnel with distilled water and ice and extracted 3 x ~ 90 mL CHCl3.  The combined organic layer was washed with saturated aqueous NaHCO3, water, and brine and dried over MgSO4

11/13/16.  The resulting clear, colorless solution was concentrated with rotary evaporation to afford 2.5 g of a clear, colorless liquid from which a colorless solid formed upon cooling. 

11/14/16.  The Round bottom flask was placed under high vacuum for approximately 1-1.5 hours to afford 1.9 g of a colorless crystalline solid after removal of high vacuum volatiles.  

Crude yield 1900/2200 x 100 = 86%

Synthesis of 3,5-dichloro-2-methylpyrazine (HASJK-2-5)

ClC1=C(C)N=CC(Cl)=N1

November 16th-18th.

Scheme:

 
Procedure:

Add POCl3 (0.064 mol, 6.010 mL) to the product and heat reaction mixture at 70 C for 1 hour. Then, 20% NaOH was added to alkalize the reaction. An extraction was carried out with diethyl ether. The reaction is to be columned. NMR and GC/MS so also be done to characterize. 

 

Table of Reagents (POCl3 Reaction)

 
 
 
 

Reagent

mass (g)

mols

Molecular Weight (g/mol)

Volume (mL)

Density (g/mL)

Product

2.700

0.021

126.000

X

X

Phosphoryl Chloride

9.857

0.064

153.333

6.010

1.640

 
TLC of the product was taken. There appears to be good separation of the product.
 

S= Oxided 2-methylpyrazine Rf = 0.11

C = co-spot Rf = 0.11, 0.33, 0.44, 0.82

P = product-expected to be the product shown above Rf = 0.11, 0.33, 0.44, 0.82

Plate:Silica//Active under:UV//Solvent Hexane/EtOAc: 50/50

Open Source Malaria 2016-11-18 08:41:33

November 16th-18th.

Scheme:

Procedure:

Add POCl3 (0.064 mol, 6.010 mL) to the product and heat reaction mixture at 70 C for 1 hour. Then, 20% NaOH was added to alkalize the reaction. An extraction was carried out with diethyl ether. The reaction is to be columned. NMR and GC/MS so also be done to characterize. 

 

Table of Reagents (POCl3 Reaction)

 
 
 
 

Reagent

mass (g)

mols

Molecular Weight (g/mol)

Volume (mL)

Density (g/mL)

Product

2.700

0.021

126.000

X

X

Phosphoryl Chloride

9.857

0.064

153.333

6.010

1.640

 
TLC of the product was taken. There appears to be good separation of the product.
 

S= Oxided 2-methylpyrazine Rf = 0.11

C = co-spot Rf = 0.11, 0.33, 0.44, 0.82

P = product-expected to be the product shown above Rf = 0.11, 0.33, 0.44, 0.82

Plate:Silica//Active under:UV//Solvent Hexane/EtOAc: 50/50

Synthesis of 3,5-dichloro-2-methylpyrazine (HASJK-10)

ClC1=C(C)N=CC(Cl)=N1

November 16th-18th.

Scheme:

 
Procedure:

Add POCl3 (0.064 mol, 6.010 mL) to the product and heat reaction mixture at 70 C for 1 hour. Then, 20% NaOH was added to alkalize the reaction. An extraction was carried out with diethyl ether. The reaction is to be columned. NMR and GC/MS so also be done to characterize. 

 

Table of Reagents (POCl3 Reaction)

 
 
 
 

Reagent

mass (g)

mols

Molecular Weight (g/mol)

Volume (mL)

Density (g/mL)

Product

2.700

0.021

126.000

X

X

Phosphoryl Chloride

9.857

0.064

153.333

6.010

1.640

 
TLC of the product was taken. There appears to be good separation of the product.
 

S= Oxided 2-methylpyrazine Rf = 0.11

C = co-spot Rf = 0.11, 0.33, 0.44, 0.82

P = product-expected to be the product shown above Rf = 0.11, 0.33, 0.44, 0.82

Plate:Silica//Active under:UV//Solvent Hexane/EtOAc: 50/50