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27th October 2016 @ 14:29

Step 4a.jpg

This procedure was adapted from "Transition-Metal-Free Synthesis of Fluorinated Arenes from Perfluorinated Arenes Coupled with Grignard Reagents" by Sun et. al.

Grignard.pdf

Procedure:

1.2155 g (0.05 mol) of Mg turnings were added to a round bottom with a minimum amount of solid Iodine and THF. The mixture was gently stirred before the liquid was poured out and the resulting activated Mg dried under high vacuum. 100 mL of THF was then added to the turnings and stirred under Ar and the phenethyl bromide was added dropwise. After ~0.5 mL of the halide was added the mixture was heated briefly with a heat gun and allowed to reflux. Once the reaction continued to reflux independently, heat was removed and the remaining halide was added slowly. After a total amount of 4.6265 g (0.025 mol, 3.4144 mL) of the halide had been added the reaction was left to stir for 24 hours. 4.5 g (0.0151 mol) of AAM/AEM 3 was then dissolved in THF under Ar in a round bottom flask. The solution was stirred over ice while all the completed Grignard (still in THF) was added dropwise. The solution was moved off of the ice and allowed to stir for more than 24 hours and until TLC determined that the reaction had produced product. The reaction was then quenched with ~300 mL of water and extracted with ~150 mL portions of ether until a black sludge formed between the aqueous and organic layers. While the sludge most likely still contained product, it was removed with the aqueous layers and only what had gone into the organic layer was kept. This was dried over MgSOand then further purified using an Isolera One automatic column chromatography machine. 

 

 

Data:

Grignard reagent after 24 hours:

 

 

Grignard reaction after completion but before extraction:

 

 

TLC 80% EtOAc in Hexanes after 1 hour of Grignard Reaction:

 

TLC 100% EtOAc after completion of reaction (from top to bottom: product, phenethyl bromide, starting material):

 

 

 

FC(F)OC1=CC=C(C2=NN=C3C=NC=C(C#CC4=CC=CC=C4)N32)C=C1

InChI=1S/C20H12F2N4O/c21-20(22)27-17-10-7-15(8-11-17)19-25-24-18-13-23-12-16(26(18)19)9-6-14-4-2-1-3-5-14/h1-5,7-8,10-13,20H

Attached Files
26th October 2016 @ 23:19

This procedure is based off of AEW 205


Procedure: 

7.5137 g (0.252 mol) of AAM/AEM 2 was added to a round bottom flask with ~125 mL of DCM and stirred until solid was dissolved. 8.1269 g of PhI(OAc)2 was then added to the solution along with another 50 mL of DCM and left to stir overnight under Ar. The reaction was then quenched with NaHCO3 and extracted three times with DCM. The resulting product was purified with a Biotage Isolera One ISO in EtOAc and Hexanes. The solvents were then removed under reduced pressure.


Yield:

4.747 g final yield. 63.21% Yield.

Data:

TLC in 70% EtOAc in Hexanes and visualized under UV

GCMS

Mass Spectrum.pdf

H1 NMR

AAM_AEM_Step3_10_20_16_PROTON_cdcl3_01 - Copy.jpeg

C13 NMR

AAM_AEM_Step3_10_20_16_CARBON_cdcl3_01 - Copy.jpeg

 

 

ClC1=CN=CC(N/N=C/C2=CC=C(OC(F)F)C=C2)=N1 and 

ClC1=CN=CC2=NN=C(C3=CC=C(OC(F)F)C=C3)N21

InChI=1S/C12H9ClF2N4O/c13-10-6-16-7-11(18-10)19-17-5-8-1-3-9(4-2-8)20-12(14)15/h1-7,12H,(H,18,19)/b17-5+

and

InChI=1S/C12H7ClF2N4O/c13-9-5-16-6-10-17-18-11(19(9)10)7-1-3-8(4-2-7)20-12(14)15/h1-6,12H

Attached Files
13th October 2016 @ 23:13

Step 2 scheme

This procedure was adapted from AEW-204


Procedure: 

2-chloro-6-hydrazinylpyrazine (AAM/AEM-1) (3.9043 g, 27.1 mmol) was dissolved in ~200 mL of 200 proof EtOH and stirred for 10 min. To that solution, 4-difluoromethoxy(benzaldehyde) (3.5 mL, 27.1 mmol) was added under argon gas and allowed to stir for 5 min. A yellow precipitate immediately formed. Additional 200 proof EtOh (~200 mL) was added and the reaction was left to sit for ~30 min.

Solvent was removed under reduced pressure.


Yield:

The yield was found to be 7.755 g, with a 95.98% yield.


Images:

Step 2

Above: Reaction after 10 minutes.


Data:

GCMS  (m/z= 297.8769; rt: 13.01 min)

Step 2 GCMS a.png
 
Step 2 GCMS b.png

H1 NMR

Step 2 H1 NMR.jpeg

C13 NMR

AAM_AEM_Step2_10_20_16_CARBON_cdcl3_01.jpeg


Smiles:

ClC1=CN=CC(NN)=N1

and

[H]C(C1=CC=C(OC(F)F)C=C1)=O

to

ClC1=CN=CC(N/N=C/C2=CC=C(OC(F)F)C=C2)=N1

Attached Files
12th October 2016 @ 19:29

Step 1 scheme

This procedure was adapted from AEW-85

Procedure:

2,6-Dichlorpyrazine (6.0 g, 40.5 mmol) was dissolved in ~100 mL EtOH. Hydrazine hydrate (4.96 mL, 60.75 mmol) was then added dropwise and the mixture was heated under reflux at 80°C for 8 hours under argon gas.

The product was then extracted using ethyl acetate and water under standard procedure and then dried with anhydrous magnesium sulfate. The remaining solvent was then removed under pressure.


Yield:

The yield was found to be 4.0388 g, with a 69.2% yield.


Data:

TLC, 30% EtoAc in Hex, UV light, Rf: 0.1 

TLC Step 1.jpg

GCMS, Retention time at 8.09 min, Isotopic m/z= 144 and 146

Step 1 GCMS 1.pdf
 
Step 1 GCMS 2.pdf

H1 NMR

Step 1 H1 NMR.jpeg

C13 NMR

AAM_AEM_Step1_10_20_16_CARBON_cdcl3_01.jpeg
Attached Files
1st September 2016 @ 18:47

This notebook will contain a record of the attempted synthesis of "The Alkyl"--Fully Reduced by Alex Milder and Alexandra Morrison. Proposed synthesis of "The Alkyl"

3-(4-(difluoromethoxy)phenyl)-5-phenethyl-[1,2,4]triazolo[4,3-a]pyrazine

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(CCC4=CC=CC=C4)N32
InChI=1S/C20H16F2N4O/c21-20(22)27-17-10-7-15(8-11-17)19-25-24-18-13-23-12-16(26(18)19)9-6-14-4-2-1-3-5-14/h1-5,7-8,10-13,20H,6,9H2
QKTHSIJWBSHMDZ-UHFFFAOYSA-N