protection of tertiary amine while epoxidize an alkene.

1. use NaHSO3 to reduce the amine oxide.

tert-amine can be oxidized by mcpba to amine oxide. by using NaHSO3, the oxide can be reduced to tert-amine again. So use 2 eq. mcpba , then treated with NaHSO3.

2. TFA protection.
use TFA to convert the tert-amine to TFA salt which prevented oxidation.
after mcpba, use K2CO3 to remove TFA.
this method is not good to acid sensitive compound.

preparation of methanoli HCl

very expensive if you buy it from aldrich.
easy to make.
you need HCl gas cylinder or you can prepare it from con. sulfuric acid and NaCl ( add sulfuric acid into NaCl and stirring).

then you bubble HCl gas to MeOH. heat will be generated so an ice bath can be used.
by weighing the MeOH before and after, the concentration can be easily calculated.
In my case, I can easily reach 6N .

Once again, another lab accident.

This time it is a sealed tube reaction.
solvent is methanolic HCl (about 3-6 M, 10 ml). ace galssware 50 ml seal tube (max. 60 psi) with teflon cap.
temp is only 80-90 C. magnetic stirring.
after about 5 hr, somehow, the teflon cap was unscrewed (by itself !) and popped up to the ceiling of the fume hood along with all the solvents and reactants.

the reaction was not supposed to generate any gas.
the solution was green, which was not observed in a previous run.
the magnetic stir bar was broken after the explosion. magnetic metal inside can be seen.
Luckily, nobody get injured because of a protection shield we have.
Also nothing got broken. the seal tube is still intact and looks ok.

what is going on?
I guess the defective magnetic stir bar was the reason, which generated H2 gas in the presence of HCl. this is also explained why the color is green.

What is interesting is I still can not image how the tight teflon cap managed to unscrew itself.
In an early similar accident I had half a year ago, the sealed tube was just destroyed by the inside pressure.

Another lab accident .

Here is the detail:
I put about 30 g NaH in mineral oil in a 1000ml rbf. 500 ml of DMF added at rt.
Then ethyl acrylate 50 ml added at once. The temperature remained the same. No bubbling at all.
Then I went to the balance to weight something.
After about 15 min, the mixture became very hot. At the same time, a lot of gas was released. The reaction is so violent that it didn't stop until almost half of the orange colored mixture was pushed out of the rbf. What a big fountain!

Luckily nothing got hurt.
What happened?
the gas released during the accident was H2(trapped in a balloon which went upward showing the gas has lower density than air).
The smell of acrylate disappeared.

My conclusion is anionic polymerization.
The real question is
Did NaH deprotonate the a-proton of acrylate and initiated the reacion?

puting on THP protecting group.

tetrahydropyrane is stable to basic conditions. easily removed under acidic conditions.

To protect an indole ( N-H):

dihydropyrane + camphor sulfornic acid in DCM. rt.
8hr.

Curtius rearrangement

converts acid to carboxylic azides (use DPPA or acid chloride then NaN3) then upon heating rearrange to an isocyanate.

Then the isocyanate can be trapped by alcohol to form a carbamate.

related rxn: Hofmann Rearrangement, Schmidt Reaction.

Condition I used (to amine):

toluene, dppa, tea, 80C 2h,

then water added, 80C, overnight.

turned out the above transformation is not high yielding.
seems trapping the isocyanate by water is not a good idea.

generally, t-BuOH or BnOH was used to make a carbamate. then remove the carbamate by acid or hydrogenation.

2nd condition I used to make amine:
1. toluene, oxalyl chloride 60C. then concentrated invacuo.
2. acid chloride made in step 1 was dissolved in acetone, then added into NaN3 in water at zero degree. then rt. excess water was used to precipitate the product.
3. heated in toluene to 80C for 2 hr.
4. BnOH added. heated for another 2 hr.
isolate product by column.
5. MeOH, acoh, water + pd/c + H2. rt.
2 hr, then celite filtration.
K2CO3 solution was used to neutralize acoh and make free amine( pH>9). then extract the amine to DCM. the crude product is very clean. no column needed.

FIsher indole synthesis

Condition I used:
40% aquous H2SO4 + toluene
80 C, 4 hr.
phenylhydrazine + 2-methyl-1,3-cyclohexanedione.

2nd generation condition:
1. phenylhydrazine + ketone in EtOH at rt. orange colored hydrazone will be formed in 15 min.
2. remove EtOH invacuo, then add 10%H2SO4 aqueous solution. Turned blue immidiately. heated to reflux for 2-4 hr will decolorize the blue solution. Then simply collect the product by filtration after cooling down.