niobium
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Hydroxylated 2C-B/I
Hi all.
recently swin has been making some 2ci. swins using the method of varma and kabalaka using BF3xEt2O+catalytic amounts NaBH4 in THF (Tetrahedron
46(21), 7443-7457 (1990)) to reduce nitrostyrenes to amines. upon looking at the nice article again, and going thru pihkal again, swin noticed that
making the hydroxylamines from the styrenes using BF3/NaBH4 would be much easier and much milder (1hour reaction time in room temp).
So swin wanted to ask a few questions -
1. would the 2,5-dimethoxyphenylhydroxylamine withstand iodination with KI/Oxone?
2. would the 2,5-dimethoxyphenylhydroxylamine withstand bromination with KBr/H2O2?
3. How could swin iodinate/brominate the benzaldehyde? since that would be much nicer...
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niobium
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DMSN reduciton to hydroxyls Success
Alright. let me report something.
Swin has went on and reduced his DMNS (1 spot on tlc, purity is supposed to be high), with BF3xEt2O and NaBH4. Swin used 10g of DMNS.
Swins procedure was the following :
5.7g NaBH4 (0.1505 mol) was dropped in a 3neck RBF equipped with a reflux condenser sitting in an ice bath and added a bit of thf to it. Then 27.14g
BF3xEt2O (01919 mol) was added along with some more thf in sequential additions (meaning a bit BF# a bit thf a bit BF3 a bit THF etc...), till all was
in the flask. argon was pumped thru. Then ice ath was removed and the mixture was allowed to stir for 15 minutes.
After those 15 minutes a solution of 8.5g DMNS (0.0478 mol) in 40-60ml THF (not all dissolved, since swin was impatient, but it DOES dissolve
completly) was added slowly to the reaction mixture. Stirring was continued, and the flask was left to react for 1 full hour. During which time the
color of the reaction mixture went from dark yellow to bright yellow.
Then ice was added SLOWLY(!!) and a little volcano apeared was was controlled easily. when all nabh4 and BF3 reacted with the ice and decomposed
(evident by no bubling after ice addition) the reaction mixture was transfered to a vacuum flask, and vacuum was applied with slight heat to evaporate
all ether and most of THF. When it apeared to be anough, the mixture was acidifed with diluted HCl to about ph 2, and then heated on an oil bath for 2
hours at 80-90degC.
While it was heating and all THF disapeared, xtals of fluffy orange material apeared, which are thouhgt to be unreacted DMNS (will try to decide later
via tlc).
all in all there was collceted by filteration 3.5g unreacted styrene, which leaves us with about 5g of reacted DMNS.
So the now styrene free solution was washed with ether 3 times untill yellow color disapeared and a greyish pinkish hue was obtained and ether washes
came back clear. Then the mixture was basified with NaOH to ph 12, and extracted twice with ether. ether was washed onec with water, and dried with
MgSO4.
after which it was evaporated in vacuum and slight heating to produce 2.56g of fluffy whitish greyish powder which is though to be
2,5-dimethoxy-phenethylhydroxylamine.
2.56g equated to 54% yield of 5g styrene. this is a nice yield for a first time reaction. If calculated on all the DMNS used it is probably around
25-35%, but since styrene was saved it will be re reduced later.
This is a confirmation of Varma and Kabalka's paper on hydroxylamines in the article refrences int he last post.
Now, swin knows he made few mistkaes. First of all, the reduction solution should first be yellow (which it was) and gradually turn back white. This
should take 1hour according to varma and kabalka but apperently it isnt so. swin believes if he waits longer next time till white color is achived all
the styrene will react.
note : When swin used a similair procedure to reduce DMNS to the striaght amine, it wsa done via BF3/NaBH4 but with slight molar differences, elevated
temps (hot reflux) and longer reaction time (5.5 hours). When it was done swin reports that white color was achived after 30 minutes or so.
This leads swin to believe that when no heat is applied a longer reaction time is needed then 1 hour to achive full reduction!
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niobium
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Perfection of the method at hand
Hello boys and girls!
This time swin was set out to prove the yields can be boosted, and the styrene can be reacted completly without leaving styrene leftovers from the
reaction, and scaling up :
In an ice bath, a 1000ml earlenmayer flask was charged with argon and fitted with a reflux condesner. 11.81g (0.312mol) of NaBH4 was placed in the
flask, and charged in sequential addition 200ml THF and 56.15g (0.3956mol, 50ml) BF3xEt2O (while removing on and off the condesner). When addition was
complete the ice bath was removed and the contents were left to stir at room temp for 20 minutes.
after those minutes 20.7g (0.0989mol) DMNS in 150ml THF was added slowly to the reaction mixture and the reflux column was replaced quickly. The
contents were left to stir at room temp for 3.5 hours. It was hypothesized that the yellow color of the solution will go white, but it did not.
After 35 hours the heat was turned on for 20 minutes trying to get the yellow out, but to no avial, so the flask was cooled in an ice bath, and slowly
ice was added. The mixture fizzed for quite a bit, and required the help of the ice bath to control the fizzing (Strongly recommended to add the ice
*SLOWLY* and let each small cube react completly before adding more). When the fizzing was ahlted a bit more ice was added to ensure full reaciton
between H2O and the borons.
When it was certain it reacted completly the mixture was poured into a vacuum bottle, and sucked till most of the thf was gone. It was then acidifed
with HCl to the point of ph 2, and was then heated for 2 more hours on the oil bath at a temp of 80-90degC. This caused complete disappearence of the
non polar layer and the color went from yellow to yellow orange.
It was then washed 3 times with ether which took most of the color from the solution and swin was left with a nearly yelowless solution.
Then the solution was basified to ph 11-12 (during which the solution went milky white, at ph 5-7, and was slightly less milky at the higvher ph). It
was then extracted 1 time with ether which was then purple greyish in color. Then it was washed once with chloroform which came out clear, and then
another ether wash which came out also clear.
Now swin had to go and wash and dry his flasks for reuse, so he left the etheral solution untouched. when he came back xtals were allready apperent
(it is known that hydroxylated amines for freebase xtals). the solution was very very concentrated (maybe 20-50ml of ether all togather), and it is
hypothesized that it was simply saturated and the xtals fell out of solution. It was quickly removed to the small vacuum bottle and sucked as dry as
possible. When it was sufficiently dry alot of xtals were there in the color of light purple greyish.
total xtals collected - 11.01g
total yield calculated from styrene is 56.4%
this is happily the best yield so far from this method, which not only offers new compounds, but it also offers the ease of freebase spontaneous
xtalization, which eliminates the need for pesky acidification tekniqs!
TAKE CARE!
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