lM TBAF in THF at roon temperature' conditions somewhat nilder than renoval of the SEM group fron pyrrole.3b. In sunmary,. SES-Cl allows high yield fornation.
T etrahed ron Le tters , YoI . 27, No. in Gre at Br it ain P rinte d
19, pp
0040-4039/86 $3.Oo + .OO Ltd. ol986 Pergamon Journals
2O 99- 2 I O 2 , 1 9 8 6
(S E S _C 1 ) :
C H LOR ID E
/ - T RIM ET HYL SIL YIET HANESUI.EONY I
A NEW REAGENT F OR PROTE C TION OF A MIN E S
Steven
M.
We in r e b ,*
Departnent
of
Do n a Id
M.
Ch e n istr y,
Denko,
The
Un ive r sity
and
Pa r k,
s ilane,
The
is
their
title
co n p o u n d ,
a useful
reagent
sulfonanides,
wh ich
Su l f o n a n i d e s it
is
this
c ondit ions
are
re gienerat e
previously
p r o te ctio n
th e
a m in e ca n
u n kn o wn
bv
r n o st
d e tr a cts
1 wh ich
is
( I)
].3
Ie q . be
in
of
steps
fron
pri nary
and
vi nyl tri rnethyl secondary
ani nes
as
i on.
protecti ng
ami ne uti l i ty,
We now
r e a di l y
si nce report
cl eaved
p r e p ared
r e a d ily
tw o
of
th e i r
r e n o va I.2
l essen
U ni versi ty
Raritan, NJ 0886e
fluori de
sta b le
fr o n
fo r
g ir o u p
sulfonarnides
th e cle a ve d
needed
parent
the
Th e s e t he
anong
u s u a l ly
prepared
fo r are
th a t
protecting
s ulf onanid e
and
ar e
stability
e a sily
A,
S tate
P A 16802
ortho pharnaceutr.lr-i.'i..:;l;, A B S T RAC T :
Thonas
P ennsyl vani a
groups.l rather
the by
a pri nary
fron
synthesi s
fl uori de
or
/- tr in e th ylsilyle th a n e sul fonyl
of
i on
a
to
secondary (3),
chl ori de
H ow ever,
extrerne
w hi ch
aml ne we
o\rro Fo
TMS^./-:*,' R e q.
(1)
I
t he
acronyn
S E S- C1 .
viny lt rirue t h y l s i l a n e bi. s ulf it e salt S im ilar
2,
to which overall
as
the
v i n yl
could
SO, * RR'NH
HrC=GH,
R'
I g iv e
TMS-F
-.>
be
y i e J .d s
An e fficie n t sh o wn group
in
syn th e si s Sch e r n e .
ca ta lyze d
d ir e ctly of
th e
SES- Cl
by
co n ve r te d co u ld
t-butyl to
be
of Free
3 w i th
obLai ned
2099
3 has
been
radi cal
perbenzoate
yi el ds
phosphorous vi a
devel oped
addi ti ona
the
free
of
frorn sodi un
sul fonate
pentachl ori de.
5
sul foni c
a.
aci d
2Loo
Schene
NaHSO, -.> PhCO.f-Bu I{eOH/ A 70olo
\
TMS
PCts/CCt1 -;> 60o/o
TMsz1/sQNa 2
3
lo N EXCHANGE
0,0 96
/cctn
TMS
60-?0010
4 prepared
fron
sa lt liq u id
distillable be
purified
by
S u l f o n a n id e s amines and
using
T HF ;
e t h a n o l. (2-3
ca n
T BAF
lM
occasional
in
The
conditions
be
to
stable
a nunber
co r n p a tib le
conditions
th a n
of
with
the
and
( 1 .0 2 and
HzO was
reflux
for
water
was
rotary nethanoL
slo wly 48
h,
r e m o ve d
added. The by
e v a p o r a to r . w h ich
j.n a vacuun
o ve n
Afte r
r e a ctio n
of
fo r
w as
to
afford
w ere
pyrrol e.3b
w i th
w hi ch
are under
i on
fl uori de
(25.96
the
three
g;
ti -nes
soIi d. e
(70?)
0.259
mL of in
100
heated
peroxi desl
ti rnes Thi s
g'
nrol )
rnethanol
w i th
of
100
w as
ni xture
three
a w hi te
0'505
(cauti on:
concentrated
extracted
in
conbi ned
(52.60
conpl ete,
37.0
temperature'
roon
groups.
bi sul fi te
w as
and
pyrrol e-S E S
the
fron
renoved
nol .)
0.005
afford
to h
be
is
ami nes.
fron
sul fonarni des
of
in
procedure sone
TH F at
S E M group
eeui v)
S E S deri vati ves
sal ts
in
cesi un
w i th (3
cl eavage
to
in
B Fg .etherate;
MeC N I yi el ds
sul fon-
6M H C I
TFA ;
refl uxi ng
Interesti ngl y, TB A F
These
base.
V i nyl tri nethyl si l ane
uri xture
so lid
I6
aromati c
converted
functi onal
w as
th e
r e su ltin g
I5 0 ' C
g;
a d d ition
e r a s co n ce n tr a te d at
the
can
sodi un
n ixtu r e
a ze o tr o p in g
The
lM
(2).
te n p e r a tu r e ,
For
the
l atter
fornati on
and
a va r ie ty
p e r b e n zo a te
roon
ani ne' as
TB A F.3I{zO
by the
Tabl e.
yi el d
r e a g e n ts
at
or
been
of
r e n o val
t - b utyl
secondary
good
in
of
co n rneri cal
4 - T r i n e th ylsilyle th a n e su lfo n a te
rnethanol
h,
9-40
and
tetrabutyl arnnoni um
in
h ig h
even
can
pri rnary
refl uxi ng
cl eaved
have
wh ich
a llo ws
by:
in
Li B Fe
d isadvantage
with
n ild e r
SES- Cl
for
sh o wn
are
cle a ve d
s o m e wh a t s u n m a r y,
In
Sodiun
a m in e s
It
of
tri ethyl
preferabl e
untouched
be
se p a r a tin g
in
of
c o u ld
derj.vative
TH F;
n a in
be
are
co u ld 95'C
d ifficu lty va r io u s
a nd
r e flu xin g
DM F a t
in
to
fo u nd
th e y
vari ety
a w i de
D MF contai ni ng
in
w eeks.
for
tenperature
roon
a stabl e,
is
gel .
fron
sta b le
Ho we ve r ,
d e p r o te cte d
subsequently
3
Na H wa s
q u ite
at
silica
prepared
be
S E S -C I
chronatography.
sto r e d
on
ch lo r id e
e q u iv)
Some examples
of
be
a c e to n itr ile .
refluxing
nol)
ca n
a n in e s,
refluxing
quite
wh ich
su lfo n yl
4OZ HF in
an
e xch a n g e
g e n e r a ll.y
are
fluoride
io n
!
h e t e r o c y c l i- c
amides
2 via
ch r o n a to g r a p h y
,/SOzCl
TMS
w i th
nateri al
2 of
)95%
on 250
nL
at )
and
a nL
w as puri tv.
of dri ed
2 101
SFth.Ca lnd CLtvrgc ot $ltonadd.t Sdfomrid.
; V\,-NH
(oY)l^n", 'o-V
I
Clrlvtg. (taYbl4 uml)
I (% Ylrld)
92
82 (29h)
95
80 (22h)
fr'nrx, v,
86 ('l 6h)
93 (40h)
9:t (40h)
8it
(rY'Nnca"
85 (9h )
v
(N},-cooctt'
s tt.snl * -
$*
rY\) \.4r',
oi*",
)l"4i
91 (9h)
89 (24h)
88
fif{sHn;ncr coocH!
87 ('tOh)
v
o.v)
fT-n",
95
90 (40h)
t'tC/-\r-.2\1X,
94
83 (40h)
* N a l l u s e d a s ba se * *Tetrabutyl amnoniurn f luoride
( lM in T I- { F ) used for
cl eavage
2LO 2
in
suspended
was
nol)
0.24?
nL
50
reaction
occurred.
carefully
p ou r e d
extract
was
of
added
The
to
concentrated
p o r tio n s
in
n ixtu r e nL
30
with
sti rred
at
ice
water,
and
NaH C Os (I00
a ye llo w
1.5
(60'C /0.1
di sti l l ed
w as
(5I.3
g'
w as
h,
The
C H zC Iz.
(N azS oa),
dri ed
rnol )
exothermi c
for w i th
extracted
nL),
w as
w hi ch
o i1
an
ti .ne
tenP erature
roon w as
0.08
P entachl ori de
w hi ch
duri ng
wa s of
sa tu r a te d
a ffo r d
ni n,
l5
o ve r
phosphorous
and
g'
(f6.8
2
sal t
S odi un
te tr a ch lo ri de
ca r b o n
in to
wa sh e d
(3).
Ch lo r ide
B - T r i n e t h y l s i l y l e th a n e su lfo n yl
and to
nn)
afford
i0 g ( 60%) o f s E s -c t (3 ). General
P r o c ed u r e
secondary
a nin e
was
treated
nin.
The
and
w i th
e th e r .
c o n c e n t r a te d . YieIds
General
(9-40 The
at
h).
( 0 .5
wa s
was
in
w i th
d ilu te d
wa s
with
p u r ifie d
puri fi ed
the
in d ica te d
nL)
d ilu te d
u su a lly
w as
5 nL by
of
in
1.5
w i th
bri ne,
by
the
g,
1.0
nl
dry
of
D MF at
w ater
0'C 15
D MF over
of
i nto
and
(N azS Oa)'
dri ed
I.96
on
si l i ca
the
ni xture
rnateri al in
concentrated evaporated.
and gel
si l i ca
and
a
and
starti ng
w as
fi l tered,
nrnol )6
D MF, of
ni xture
on
nL
or dry
chrornatography
(0.30
ch r o n a tography
of
TabIe.
C sF
the
ether,
2 nL
poured
di sappearance
and
a d d ed,
in
h'
1.5
for
w ashed
CIeavage.
we r e TLC
w as
nL) mrnol )
2.89
0'C
l i sted
I are
Su l- fo n a n id e
u n til
M e th a n o l
residue
anine
su lfo n a n id e
n n o l)
95'C
at
p hase
p r o d u cts
g,
0.58
stir r e d
o r g a n ic
The
fo r
( 0 .6 1
I
heated
wa s
Cr u d e
Procedure
(3,
SES- CI
p u r ifie d
of
sulfonanide was
with
n ixtu r e
(1.5
ani ne
tr ie thyl
A pri nary
S E S D eri vati ves.
A ni ne
of
and
n n o l)
d r o p wise r e a c tio n
extracted
ge1.
Pr e p a r a tio n
fo r ( 1 .9 3
(see
The
Tabl -e
vacuo. crude
for
yields). A c k n o w l e d g m e n t.
References I.
T h is
and
Greene,
T.
Chem. For
NY,
4,
with
other
liq u id 1974,
Sulfonate
sa lt
U S p a te n t 2 couLd
upon: 5.
Harrnan,
We have
also
sulfuryl 6.
( SEM ) !
A .;
Tsao,
M u ch o wski,
J.
M.;
S o1as,
p r e vio u sly
(Received
in
by
th is
US p a te n t
prepared in is
Wi l ey-Intersci ence:
"
recentl y C .;
and
devel oped
Fuj i no,
J.
M'
is
C hen'
R.
D.
The
S oc',
lCA,
our
al though
h yg r o sco p ic
1986)
and
thl s
appropri ate
(Ti ers'
hands
Iess
G.
than
perbenzoate
is
P 5B 97fl . chl ori de
procedure
C onmun.
and
bi sul fi te
t-butyl 44,
fragnen-
C hen.1984,49,203.
i ni ti ator
In of
Ors.
of C hen.
S oc.,
sodi um
radi cal
use
(I950)
C hen.
J.
from
the
type
a rel ated J.
p tr inethyl si l yl ethyl nagnesi um
5 0 % yie ld ,
Ja n u a r v
J.-H .
P 9527c]).
n ethod.
wa te r .
USA 2 7
as
61,
[C A '
by
removed
prepared
been
2 ,5 0 4 ,4II
3 fr o r n
ve r y
are
Na NOz/N aN Og
(1964)
o b ta in e d
e xclu d e
w as
K i tada,
L.
3 ' 1 4 1 ,8 9 8
D.,
(P MS ) T.;
F u ku d a ,
wh ich
u sin g
f l uo r id e to
S ynthesi s,
groups
has
ch lo r i.d e
Cesiun taken
be
Organi c
Ca r p in o ,
v i n y l t r i r n e t h ylsila n e
of
C A -36023.
2 2 O.
( T EOC)
a) b)
in
g r o up
HF :
N- p r o te ctin g
see:
1978,358.
D',
grant
N IH
1981.
C o mn u n .
tation
by
supported
Gr o u p s
"Pr o te ctive
p - n e t h ylb e n zylsu lfo n a n id e
The
rernovable
3.
wa s
No te s W.
New York, 2.
r e se a r ch
is
more
precauti ons
and
expensi ve. shoul d
be
V.
15% based
