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Dihydro azoles and free radicals
oo4Mom/a7 33 al + .oo Pergamon JcumakLtd.
Tecruhedmn Vol. 43. No 3. pp 625 IO 630, 1987 Printed in Great Bnmn.
DIHYDRO AZOLES AND FREE RADICALS. Part I. I-ARYL-4-METHYLENE+MORPHOLXNO-v-TRXAZOLINESAND HALOMETHYL RADICALS: FRA~MEN3ATION OF TRIAZOLINIC RADICAL SIGMA COMPLEXES. NICOLETTA ALMIRANTE',, STEFANO CICARDI', CATERINA NAPOLETANO' and MARCO SERRAVALLE* 1 Istituto di Chimica Organica, Facolta di Farmacia, Universita degli Studi, V. Venezian,21, 20133 MILANO, ITALY 2. Dipartimento di Chimica, Politecnico di Milano, V. Colgi, 39, MILANO, ITALY (Received m UK 3 Nooember 1986)
1 were Abstract - I-Aryl-4-methylene-5-morpholino-v-triazolines reacted with halomethyl radicals generated by reaction of=halo methanes 2 with benzoyl peroxide or copper(I)chlori In theformer case the corresponding I-aryl-4-trihaloethyl-v-triazoles 1 and I-aryl-4-halomethyl-v-triazoles4 were formed. In the second case v-triazoles
the corresponding
l-aryl-4-trihaloethyl-5-morpholino
5 accompanied by triatoles 4 = were obtained. Reaction mechanisms a;e discussed.
The readily accessible 1-aryl-4-methylcne-4,5-dihydro-5-mor~~ol~no-v-tria~oles 1' = have been shown to react with nucleophiles through addition or addition-elimination 2.3
processes
producing
v-triazolines
Much work has been done also Recently cyclic
double
As a part radical
we reported bond of of
an
on their
derivatives,
reactivity
respectively.
in cycloaddition
H-NMR study evidencing 5 1. = program on v-triatolines
4
reactions.
the electronic
features
of
the exo
substrates
our research
chemistry
1
or v-triazole
we have now studied
and owing
the reaction
of
to our interest
substrates 1 with
in
halomethyl
radicals.
RESULTS
The reaction of == la-e WIW haiornethanes22-e was performed by heating the v-triazo 5 lines in excess halomethrne,acting both as reactant and solvent, in presence of an equimofar amount of purified benzoyl
peroxide.
R’
Rz
H
CFs
NOz COoEt He Cl H
H Ii H
Y-cx,
NO2
2 625
X
Cl H H Br Br
Cl Br Cl Cl Br
--I-2s b
Ii
Y
: e
N.
626 The reaction
mixture
bromotrichloromethane $$;
2$,42
a single
product,
were readily
i.e.
identified singlet
2.5-5
a mixture
et al.
h. When carbon of
Starting
was obtained.
and /or
a typical
for
2i were used
respectively)
were separated ing
was refluxed
ALMIRANTE
products with
tetrachloride
1~ and
2 and 4 (zz,$$;
chloroform
zz,$J;
22,
$2 and bromoform
EL
In all cases the reaction products ga.b,d,f-h, == 5 = = = was formed. purified by column chromatography. Both compounds 2 and 4 1 H-NMR spectra, show by their analytical data and by their in the 6 4.0-5.0 Table 1
region
- Reactional
which
is
associated
with
the
CH2 group.
data forprcducts 3 and 4
FTcdlJcts
xarting!zanpxd
3
Yield X
la
2a
3a
31
4
Yield X
4a
ta
2b
3b
62
la
2c
3a
33
la
2d
3a
26
4b
lb
2d
x
27
4c
lb
2b
3d
61
1c
2a
3e
35
1c
2b
3f
58
ld
2b
Js
51
le
2b
3h
55
4d
Table 2 - Reactional data for pr0dwX.s4 and 5 Products
Starting cm
2a
4s
13
5a
37
2e
4b
15
5b
22
1c
2a
4d
37
5c
30
1c
2e
4d
21
5d
15
le
2a
4a
30
5e
25
le
2e
4s
20
5f
18
If
2a
4f
43
50
18
If
2e
4f
34
5h
20
to a singlet
in the expected
yields
of
proaucts
.aed in
3-5X yield
2 were obtained. only.In
all
was found.
T.le yields
3 and 4 are
radical with
products
data of
of
generator.
la,c,e,f, == = = =
2 aid
the radical
in
Carbon presence
Instead,
cases
and some tarry material
The course
Yield X
5
la
rise
troscopical
Yield X
la
H-5 gives
of
4
Idebctant
the
when present,
starting
listed
in Table
tetrachloride CuC1.M
of
in Table substrates
fair
! reacted
completely
foe
were present.
Physical,
analytical
and spec
3. 1
$2 and carbon the former
to
f were
products 1.
Moderate
by products
triazoline
definite
reaction
6
of 6 S-8.5.
No other
4 aze collticted
of
range
case
was
also
studied
with
CuCl as
tetrabromide
‘22 were reacted
the reaction
was
performed
at
Dihydrostoles and freeradicals-l the refluxing
temperature
In the
case
second
tetrachloride tor
column their is
and the
was used
formed
in a 2.5:1
in any case.
a large
reactants
reaction ratio
mixture
of
in products
of
listed
the CH2 group
was heated
respect
to
in Table
2.
showing
and is
2 and the multiplets
22 as reactant ratio
and solvent.
were dissolved
to reflux.The
=. A mixture 1
the products.which
and ‘H-NMR spectra with
excess
1 and 2~ in a 1:2
with
The yields
chromatography,are analytical
associated
signals
both
by using
621
of
CuCl radical triazoles
were separated
in good centered
with
at about
region
R2 CF3 CF3
X Cl Br
H
Cl
H H H H H
Br cl Br Br Br
6 3.1-3.2
and
I-
c COOEt d COOEt e Cl fC1 g h
H H
by which
the corresponding
Ph’ or PhCOO*
R' 3a H b H c NO2 dN& e COOEt f COOEt gFk hC1
by
identified
in the 6 4.0-5.0
agreement
genera
4 ana 2 was
and purified
Compounds 2 were easily a singlet
in carbon
NH H H NO2 N&
Cl Br Cl Br Cl Br
63.6-3.7
N.
628 typical
of
scopical
the morpholino
data
for
ALMIMNTB et al.
substituent.
compounds
2 are
In Table
3 physical,
analytical
and SPeCtrg
listed. DISCUSSION
According bond of being
to the
compounds
normally
foregoing
1 shows a good
completed
within
red even when relatively bed to
the
thermal
the presence
of
results
it
unstability
with
four
of
of
side
established
reactivity about
low yields
competing
is
halomethyl
hours.
products
substrates
reactions
that
the exocyclic
double
radicals,
reaction
No starting were obtained.
1 and,
which,
perhaps
howeuer,
the
compound was recove This
is
to be ascri
to a greater
do not
extent,to
produce
definite
compounds. By considering obtained
only
three
de attacks
when
compounds
a radical
triazole
by interaction
of
radical
the reaction noalkyl
group of
is
tack,
addition
are equally
by the
and hence
is
an amino radical
attempts When tion
of
for
the
to
trap
stituent which
affords both
nit
system
in this
species.
case.the
in turn
e
0 complexes
through
radical
structure.
of
not
Cases
of
formed
a S-ami
be expected
prefer
to give,
when the
knowledge.
ad
On the whole
should
substrates
ointermediates,
radical
used
with
material
While here
through
is
the
failed
leaving
substitution
by radical
formed.
a complex
at-
not
electron-transfer
is
to the
is
trend
deprotonated latter
is
the
acquainting
intermediate
z from which of
hydra
the
basic
oxidation
of
to z.g preferred
to be exceedingly produces
by abstrac
both
former,
both labile
a stabilized
to
be expla
Unfortunately,
assistance
oxidation
the
should
produced
triazoline
the
expected
that
trend
character
now.
the electron-transfer
7 which = be acceptable,
and is
expected
Two mechanisms,
intramolecular
aromatic
aromatization.
till
producing is
is
radical
According
the
it
has not
the observed
the attacking
oxidation
could
isolated
produced
2 which
such processes,
starting
great,
possibility
the cationic
compound f was not cause,
is
mechanisms
to give
radical,
by fragmentation
alkene
feature
products.
fragmentation
to our
by radicals.
the morpholinyl
Another
this
a In fact
the
not
the
eliminated,
at C-5.
While
of
a ligand-transfer
is
followed
peroxi
radical
radical
as usually,
to an alkene
known that
has the
a Y’
known7 that
formed,
through
the Y atom from 2 = and Cu(I1) of = 5, are possible.
2 undergoes
not
view
formation
gen chloride
$ which
a morpholinyl
and form aromatic
precedented
that
is
copper(I)chlor
from 1 and benzoyl
the o complex
is
1 are
picture
However, in the case of substrates L, the formation of o canplex
attacked
gain
of
systems
fact
eliminate
by the energy
It
addition
being
are not
unknown.
readily
is
reactions.
on aromatic
is made possible
ined
point
process,
an amino one,
amino groups
2.
products
mechanistic
and concurrently,
species
to a radical
Under this
halomethanes,
looses
to 1 yielding
forming
the u complex
produced
compound but by addition
as the more favourable with
it
and that
following
intermediate
to this,
a radical
corresponds
radical.
the
‘CX3 radical
adds
PhCOC’ and 1,
to an aromatic
can be formed
present,
=. Similarly 3
product
case
products are
the radical
According
to eliminate
In the present dition
1 producing
a morpholinyl
show a trend
of
II 1 ions
Scheme the
acomplex.
the aromatic liminates
kinds
copper(
As shown in the
arises. of
that
sub 6 = because
and be catio
all
Dihydroazolcsand freeradicals-l The formation but is
not
of
4, in presence
accompanied
pholino-v-triarole This
points
by the
which
out
that
its
Scheme , a possibility CuXg which
is
ted by the very of
the yield
quick
4,. This of
offered
of
the
reaction
process
products
..p,
of
by reaction should
in relatively of
ring.
70
p with
As
group
c‘C I
l
s cnp 4.25
n-NNR
0.30
3c
170-172
4.30
0.25
s
30.45
2.0
133.35)
I2.06)
27.05
1.6 (1.5
de0
4.70
2.2
0.29
3c
133-134
4.75
0.15
38
163-105
4.60
0.20
3h
150-150
4.05
0.25
)
3.45)
12.05)
)
2.6 2.5
4.00
0.25
4.65
0.15
162-154
4.a5
0.30
4d
113-114
4.bO
0.15
4.
134-135
4.00
b.15
4r
100-102
4.00
0.25
2.7 2.3
)
2.5
I ) 1
116-117
4.25
3.15-3.70
bb
130-131
4.60
3.20-3.75
(41.9 32.2 131.9
5c
149-150
4.25
3.15-3.70
47.0
5d
15b-160
4.60
3.15-3.70
5a
153-155
4.25
3.15-3.70
bf
172-174
)
50
lb7-lbb
4.25
3.10-3.70
5h
103-lb4
4.60
3.20-3.75
I
b
All
.p.ctr.
‘R.qu1r.d
in vmluam
CDC13 in
from .xe.pt
3d
)
lb.0
)
I
1
(, 23.5 13.0 ( 13.0
I
(
9.951
I
)
I 9.8 ( 9.9 1
(13.0
14.10 (14.15)
2.6 (2.65)
41.15
3.50
10.7 (10.6 (17.2 )
(13.0
Ct12C12/n-pent*n*.
(DNSO).
Othar
albnalk
w.r,
round
in
expected
r.nb...
bracketa,
EXPERIMENTAL Meltin& points are uncorrected end were taken on a Tottoll lnetrument. corded on a Varisn EM 390 spectrometer, chemical
shifts
being
given
ln
1
13.25
3.0’. (2.0
)
17.05
0.45)
31.45
I 1
13.0
0,551
31.6
)
1 10.15
3.5
01.75)
I
15.65 15.0
(3.4
1
19.5
3.55
(31.15) eryst~llI;~d
13.7
lb.2 lb.4 23.5
(4.4
(41.351
compounds
13.0 )
4.3
42.35
3.15-3.75
4.60
1e.051
3.1 3.1 2.90
(2.5
36.25
(42.4
16.05
1
4.55)
2.95) 3.1 3.2 2.65
(47.05)
(36.0
9.25
4.4
145.3 41.05
5a
0.451
2.6
53.05 (54.25) 47.3 (47.4 45.25
1
2.45 1
30.15 (30.2
1
2.65 1
lb.65 (39.2
4lT
1.6
1
1
I 10.0 5.5 1
1.7
45.5 (45.9
77-73
2.4
26.05
)
a.5 0.5
)
2.4
01.15)
74-76
17.4
11.0
31.45
(27.0
17.65 )
3.45
32.45 (32.4
( 0.a I
17.3
(44.0
4.30
I
12.3
)
1
0.75
1.55)
26.55 (26.4 45.05
117-lib
12.15 (12.2
1.6
0.26
3a
N
2.15
37.65 (37.35)
200-205
c
Ii
C
morpholtno
(27.6bl
'All
lowers
All4lY~l4
0.25
4.05
4b
high
which
b
s n3
112-113
44
suppof
2.
Jb
3d
from
the copper
affording
reaction
in the
group
is strongly
1 with CuCl 2 In acetonitrile = side
to
Species.
shown
to the CH?
hypothesis
an unavoidable
amount
a cupric
be different. leaving
This
high
4-halomethyl-5-mo:
halogen-transfer
the morpholino
triazole of
occurs
the corresponding
mechanism
represents
105-107
34
ions
of
by ionic
1 Product4
copper
be formed
by binding
atom and aromatization yields
should
formation
is
assisted
of
formation
629
1 H-NMR spectra were rc
ppm from Me4Si.
Ready-to-
1
630
ALMUUNTE et al,
N.
use silica
gel
Materials pitatinp
plates
were employed for
- Bensoyl
peroxide
with methanol.
TLC.
was purchased
Copper(I)chlor
and purified
was freshly
by dissolving
prepared
la,b,c,d,e have been described E= = w e = by analogous procedure (m.p. 118-12O’C
before
4-methylene-v-triazolines
previously
lf was preparated r=
dec.).
in chloroform
and reprccl
each reaction. 5-Morpholino4 1 5 (la , == lb , lc-e 1. Compound =_z == =
Reactions
of la-e with CX Y and benzoyl peroxide - The triszoline reactant 1 (3.3 mm011 was dis w= D -3 = or suspended in the solvent reactant 2 (10 ml) and the solution was brought to reflux. =
solved
Then, benzoyl pearance was cooled layer
peroxide
of bensoyl
and basified
was separated,
residue
Reactions dissolved
(TLC benzene/ethyl
by adding an aqueous
washed twice
data for of la,c.e,f
temperature
for
four
tographed
ted in Tables Reactions dissolved
hours.
and refluxing
4:l)
(about
are listed
over sodium sulphate.
in Tables
gel
The residue
acetate/cyclohexane
(1:9).
(1.5
reactant
evaporation
the
(4:ll.
Yields
1 (3.3
mmol) was
mixture
on a silica
and physical
=
was heated
at78V.
was stirred
g1 was added
was charged
Yields
After
1 and 3.
(10 ml) and the mixture
chromatography
disae
mixture
The organic
acetate
and CC_14- The trlazoline
for
pressure.
until
The reaction
of’ sodium hydrogencarbonate,
mm011 was added and the reaction
Silica
was continued
3-5 h).
column with cyclohexane/ethyl
tetrachloride
(8.25
at reduced
with ethyl
gel
products
in carbon
copper(I)chlor
re was evaporated
solution
with copper(I)chlor
PZ = = f
acetate
with water and dried
on a silica
the isolated
or suspended
prepared
and gel
data for
Freshly
at the same mixtu
the
column and chroma
the products
are lia
2 and 3.
of
la,c,e,f with copper(I)chlor z= = = =
or suspen prepared
ted as described Tables
mm011 was added in one portion
was chromatographed
and physical
freshly
(3.3
peroxide
sd in a solution
copper(I)chlor above for
and CBr_4- The triazoline
of CBr4 (6.6 (8.25
Ccl4 alone.
mm011 in Ccl4
mmol) was added.
Yields
The reaction
and physical
reactant
(10 ml).
data for
After
1 (3.3 = heating
was performed
the products
mm011 was at ?OoC
and elabora
are listed
in
2 and 3.
Reactionof
la with copper(II)chlo ==
(5 ml) and solid
copper(II)chlo
ture was charged
on a silica
yielding
- The triazoline (1 mmol) was added.
gel
la (1 mmol) was dissolved == After
column and chromatographed
stirring
for
5 min
with cyclohexane/ethyl
in acetonitrile the reaction acetate
mis
(4:l)
pure 4a. == REFERENCES
.
i P. Della Croce, D. Pocar, R. Stradi and P. Trimarco, J. Chem. Sot., Perkin Trans I, 141, (19801 2 S. Cilloni, D. Pocar, L.M. Rossi and P. Trimarco, J. Chem. Res., (S), 14, (1980) 3 G. Bolis, D. Pocar, R. Stradi and P. Trimarco, J. Chem. Sot., Perkin Trans I, 2365, (19771 4 therein E. Erba, M.L. Gelmi, D. Pocar and P. Trimarco, Chem. Ber., 119, 1083, (1986) and references =z= 5 N. Almirante, M. Ballabio, G. Bianchetti, A. Cambiaghi and D. Pocar. J. Chum. Res.(Sl, 132, (19861 6 Vol 5 Katritzky and C.W. Rees eds., H. Uamhoff in “Comprehensive Hetsrocyclic Chemistry” , A.R. K.T. Potts ed., Pergamon Press, Oxford, 1984, p. 678 7 M. Tiecco, Act. Chem. Res., 13, 51, (1980) z= 8 See for example M.S. Kharasch, Otto Reinmuth and W.H.
Urry,
J. Am. Chem. Sot.,
69,
1105,
(1947)
and references therein 9 Cambridge University Press, 1974, p. 308 D.C. Nonhebel exi J.C. Walton, “Free Radical Chemistry”. 10 Bromo derivatives were formed in lower yield with respect to chloro compounds preventing their isolation
in many cases.
Tecruhedmn Vol. 43. No 3. pp 625 IO 630, 1987 Printed in Great Bnmn.
DIHYDRO AZOLES AND FREE RADICALS. Part I. I-ARYL-4-METHYLENE+MORPHOLXNO-v-TRXAZOLINESAND HALOMETHYL RADICALS: FRA~MEN3ATION OF TRIAZOLINIC RADICAL SIGMA COMPLEXES. NICOLETTA ALMIRANTE',, STEFANO CICARDI', CATERINA NAPOLETANO' and MARCO SERRAVALLE* 1 Istituto di Chimica Organica, Facolta di Farmacia, Universita degli Studi, V. Venezian,21, 20133 MILANO, ITALY 2. Dipartimento di Chimica, Politecnico di Milano, V. Colgi, 39, MILANO, ITALY (Received m UK 3 Nooember 1986)
1 were Abstract - I-Aryl-4-methylene-5-morpholino-v-triazolines reacted with halomethyl radicals generated by reaction of=halo methanes 2 with benzoyl peroxide or copper(I)chlori In theformer case the corresponding I-aryl-4-trihaloethyl-v-triazoles 1 and I-aryl-4-halomethyl-v-triazoles4 were formed. In the second case v-triazoles
the corresponding
l-aryl-4-trihaloethyl-5-morpholino
5 accompanied by triatoles 4 = were obtained. Reaction mechanisms a;e discussed.
The readily accessible 1-aryl-4-methylcne-4,5-dihydro-5-mor~~ol~no-v-tria~oles 1' = have been shown to react with nucleophiles through addition or addition-elimination 2.3
processes
producing
v-triazolines
Much work has been done also Recently cyclic
double
As a part radical
we reported bond of of
an
on their
derivatives,
reactivity
respectively.
in cycloaddition
H-NMR study evidencing 5 1. = program on v-triatolines
4
reactions.
the electronic
features
of
the exo
substrates
our research
chemistry
1
or v-triazole
we have now studied
and owing
the reaction
of
to our interest
substrates 1 with
in
halomethyl
radicals.
RESULTS
The reaction of == la-e WIW haiornethanes22-e was performed by heating the v-triazo 5 lines in excess halomethrne,acting both as reactant and solvent, in presence of an equimofar amount of purified benzoyl
peroxide.
R’
Rz
H
CFs
NOz COoEt He Cl H
H Ii H
Y-cx,
NO2
2 625
X
Cl H H Br Br
Cl Br Cl Cl Br
--I-2s b
Ii
Y
: e
N.
626 The reaction
mixture
bromotrichloromethane $$;
2$,42
a single
product,
were readily
i.e.
identified singlet
2.5-5
a mixture
et al.
h. When carbon of
Starting
was obtained.
and /or
a typical
for
2i were used
respectively)
were separated ing
was refluxed
ALMIRANTE
products with
tetrachloride
1~ and
2 and 4 (zz,$$;
chloroform
zz,$J;
22,
$2 and bromoform
EL
In all cases the reaction products ga.b,d,f-h, == 5 = = = was formed. purified by column chromatography. Both compounds 2 and 4 1 H-NMR spectra, show by their analytical data and by their in the 6 4.0-5.0 Table 1
region
- Reactional
which
is
associated
with
the
CH2 group.
data forprcducts 3 and 4
FTcdlJcts
xarting!zanpxd
3
Yield X
la
2a
3a
31
4
Yield X
4a
ta
2b
3b
62
la
2c
3a
33
la
2d
3a
26
4b
lb
2d
x
27
4c
lb
2b
3d
61
1c
2a
3e
35
1c
2b
3f
58
ld
2b
Js
51
le
2b
3h
55
4d
Table 2 - Reactional data for pr0dwX.s4 and 5 Products
Starting cm
2a
4s
13
5a
37
2e
4b
15
5b
22
1c
2a
4d
37
5c
30
1c
2e
4d
21
5d
15
le
2a
4a
30
5e
25
le
2e
4s
20
5f
18
If
2a
4f
43
50
18
If
2e
4f
34
5h
20
to a singlet
in the expected
yields
of
proaucts
.aed in
3-5X yield
2 were obtained. only.In
all
was found.
T.le yields
3 and 4 are
radical with
products
data of
of
generator.
la,c,e,f, == = = =
2 aid
the radical
in
Carbon presence
Instead,
cases
and some tarry material
The course
Yield X
5
la
rise
troscopical
Yield X
la
H-5 gives
of
4
Idebctant
the
when present,
starting
listed
in Table
tetrachloride CuC1.M
of
in Table substrates
fair
! reacted
completely
foe
were present.
Physical,
analytical
and spec
3. 1
$2 and carbon the former
to
f were
products 1.
Moderate
by products
triazoline
definite
reaction
6
of 6 S-8.5.
No other
4 aze collticted
of
range
case
was
also
studied
with
CuCl as
tetrabromide
‘22 were reacted
the reaction
was
performed
at
Dihydrostoles and freeradicals-l the refluxing
temperature
In the
case
second
tetrachloride tor
column their is
and the
was used
formed
in a 2.5:1
in any case.
a large
reactants
reaction ratio
mixture
of
in products
of
listed
the CH2 group
was heated
respect
to
in Table
2.
showing
and is
2 and the multiplets
22 as reactant ratio
and solvent.
were dissolved
to reflux.The
=. A mixture 1
the products.which
and ‘H-NMR spectra with
excess
1 and 2~ in a 1:2
with
The yields
chromatography,are analytical
associated
signals
both
by using
621
of
CuCl radical triazoles
were separated
in good centered
with
at about
region
R2 CF3 CF3
X Cl Br
H
Cl
H H H H H
Br cl Br Br Br
6 3.1-3.2
and
I-
c COOEt d COOEt e Cl fC1 g h
H H
by which
the corresponding
Ph’ or PhCOO*
R' 3a H b H c NO2 dN& e COOEt f COOEt gFk hC1
by
identified
in the 6 4.0-5.0
agreement
genera
4 ana 2 was
and purified
Compounds 2 were easily a singlet
in carbon
NH H H NO2 N&
Cl Br Cl Br Cl Br
63.6-3.7
N.
628 typical
of
scopical
the morpholino
data
for
ALMIMNTB et al.
substituent.
compounds
2 are
In Table
3 physical,
analytical
and SPeCtrg
listed. DISCUSSION
According bond of being
to the
compounds
normally
foregoing
1 shows a good
completed
within
red even when relatively bed to
the
thermal
the presence
of
results
it
unstability
with
four
of
of
side
established
reactivity about
low yields
competing
is
halomethyl
hours.
products
substrates
reactions
that
the exocyclic
double
radicals,
reaction
No starting were obtained.
1 and,
which,
perhaps
howeuer,
the
compound was recove This
is
to be ascri
to a greater
do not
extent,to
produce
definite
compounds. By considering obtained
only
three
de attacks
when
compounds
a radical
triazole
by interaction
of
radical
the reaction noalkyl
group of
is
tack,
addition
are equally
by the
and hence
is
an amino radical
attempts When tion
of
for
the
to
trap
stituent which
affords both
nit
system
in this
species.
case.the
in turn
e
0 complexes
through
radical
structure.
of
not
Cases
of
formed
a S-ami
be expected
prefer
to give,
when the
knowledge.
ad
On the whole
should
substrates
ointermediates,
radical
used
with
material
While here
through
is
the
failed
leaving
substitution
by radical
formed.
a complex
at-
not
electron-transfer
is
to the
is
trend
deprotonated latter
is
the
acquainting
intermediate
z from which of
hydra
the
basic
oxidation
of
to z.g preferred
to be exceedingly produces
by abstrac
both
former,
both labile
a stabilized
to
be expla
Unfortunately,
assistance
oxidation
the
should
produced
triazoline
the
expected
that
trend
character
now.
the electron-transfer
7 which = be acceptable,
and is
expected
Two mechanisms,
intramolecular
aromatic
aromatization.
till
producing is
is
radical
According
the
it
has not
the observed
the attacking
oxidation
could
isolated
produced
2 which
such processes,
starting
great,
possibility
the cationic
compound f was not cause,
is
mechanisms
to give
radical,
by fragmentation
alkene
feature
products.
fragmentation
to our
by radicals.
the morpholinyl
Another
this
a In fact
the
not
the
eliminated,
at C-5.
While
of
a ligand-transfer
is
followed
peroxi
radical
radical
as usually,
to an alkene
known that
has the
a Y’
known7 that
formed,
through
the Y atom from 2 = and Cu(I1) of = 5, are possible.
2 undergoes
not
view
formation
gen chloride
$ which
a morpholinyl
and form aromatic
precedented
that
is
copper(I)chlor
from 1 and benzoyl
the o complex
is
1 are
picture
However, in the case of substrates L, the formation of o canplex
attacked
gain
of
systems
fact
eliminate
by the energy
It
addition
being
are not
unknown.
readily
is
reactions.
on aromatic
is made possible
ined
point
process,
an amino one,
amino groups
2.
products
mechanistic
and concurrently,
species
to a radical
Under this
halomethanes,
looses
to 1 yielding
forming
the u complex
produced
compound but by addition
as the more favourable with
it
and that
following
intermediate
to this,
a radical
corresponds
radical.
the
‘CX3 radical
adds
PhCOC’ and 1,
to an aromatic
can be formed
present,
=. Similarly 3
product
case
products are
the radical
According
to eliminate
In the present dition
1 producing
a morpholinyl
show a trend
of
II 1 ions
Scheme the
acomplex.
the aromatic liminates
kinds
copper(
As shown in the
arises. of
that
sub 6 = because
and be catio
all
Dihydroazolcsand freeradicals-l The formation but is
not
of
4, in presence
accompanied
pholino-v-triarole This
points
by the
which
out
that
its
Scheme , a possibility CuXg which
is
ted by the very of
the yield
quick
4,. This of
offered
of
the
reaction
process
products
..p,
of
by reaction should
in relatively of
ring.
70
p with
As
group
c‘C I
l
s cnp 4.25
n-NNR
0.30
3c
170-172
4.30
0.25
s
30.45
2.0
133.35)
I2.06)
27.05
1.6 (1.5
de0
4.70
2.2
0.29
3c
133-134
4.75
0.15
38
163-105
4.60
0.20
3h
150-150
4.05
0.25
)
3.45)
12.05)
)
2.6 2.5
4.00
0.25
4.65
0.15
162-154
4.a5
0.30
4d
113-114
4.bO
0.15
4.
134-135
4.00
b.15
4r
100-102
4.00
0.25
2.7 2.3
)
2.5
I ) 1
116-117
4.25
3.15-3.70
bb
130-131
4.60
3.20-3.75
(41.9 32.2 131.9
5c
149-150
4.25
3.15-3.70
47.0
5d
15b-160
4.60
3.15-3.70
5a
153-155
4.25
3.15-3.70
bf
172-174
)
50
lb7-lbb
4.25
3.10-3.70
5h
103-lb4
4.60
3.20-3.75
I
b
All
.p.ctr.
‘R.qu1r.d
in vmluam
CDC13 in
from .xe.pt
3d
)
lb.0
)
I
1
(, 23.5 13.0 ( 13.0
I
(
9.951
I
)
I 9.8 ( 9.9 1
(13.0
14.10 (14.15)
2.6 (2.65)
41.15
3.50
10.7 (10.6 (17.2 )
(13.0
Ct12C12/n-pent*n*.
(DNSO).
Othar
albnalk
w.r,
round
in
expected
r.nb...
bracketa,
EXPERIMENTAL Meltin& points are uncorrected end were taken on a Tottoll lnetrument. corded on a Varisn EM 390 spectrometer, chemical
shifts
being
given
ln
1
13.25
3.0’. (2.0
)
17.05
0.45)
31.45
I 1
13.0
0,551
31.6
)
1 10.15
3.5
01.75)
I
15.65 15.0
(3.4
1
19.5
3.55
(31.15) eryst~llI;~d
13.7
lb.2 lb.4 23.5
(4.4
(41.351
compounds
13.0 )
4.3
42.35
3.15-3.75
4.60
1e.051
3.1 3.1 2.90
(2.5
36.25
(42.4
16.05
1
4.55)
2.95) 3.1 3.2 2.65
(47.05)
(36.0
9.25
4.4
145.3 41.05
5a
0.451
2.6
53.05 (54.25) 47.3 (47.4 45.25
1
2.45 1
30.15 (30.2
1
2.65 1
lb.65 (39.2
4lT
1.6
1
1
I 10.0 5.5 1
1.7
45.5 (45.9
77-73
2.4
26.05
)
a.5 0.5
)
2.4
01.15)
74-76
17.4
11.0
31.45
(27.0
17.65 )
3.45
32.45 (32.4
( 0.a I
17.3
(44.0
4.30
I
12.3
)
1
0.75
1.55)
26.55 (26.4 45.05
117-lib
12.15 (12.2
1.6
0.26
3a
N
2.15
37.65 (37.35)
200-205
c
Ii
C
morpholtno
(27.6bl
'All
lowers
All4lY~l4
0.25
4.05
4b
high
which
b
s n3
112-113
44
suppof
2.
Jb
3d
from
the copper
affording
reaction
in the
group
is strongly
1 with CuCl 2 In acetonitrile = side
to
Species.
shown
to the CH?
hypothesis
an unavoidable
amount
a cupric
be different. leaving
This
high
4-halomethyl-5-mo:
halogen-transfer
the morpholino
triazole of
occurs
the corresponding
mechanism
represents
105-107
34
ions
of
by ionic
1 Product4
copper
be formed
by binding
atom and aromatization yields
should
formation
is
assisted
of
formation
629
1 H-NMR spectra were rc
ppm from Me4Si.
Ready-to-
1
630
ALMUUNTE et al,
N.
use silica
gel
Materials pitatinp
plates
were employed for
- Bensoyl
peroxide
with methanol.
TLC.
was purchased
Copper(I)chlor
and purified
was freshly
by dissolving
prepared
la,b,c,d,e have been described E= = w e = by analogous procedure (m.p. 118-12O’C
before
4-methylene-v-triazolines
previously
lf was preparated r=
dec.).
in chloroform
and reprccl
each reaction. 5-Morpholino4 1 5 (la , == lb , lc-e 1. Compound =_z == =
Reactions
of la-e with CX Y and benzoyl peroxide - The triszoline reactant 1 (3.3 mm011 was dis w= D -3 = or suspended in the solvent reactant 2 (10 ml) and the solution was brought to reflux. =
solved
Then, benzoyl pearance was cooled layer
peroxide
of bensoyl
and basified
was separated,
residue
Reactions dissolved
(TLC benzene/ethyl
by adding an aqueous
washed twice
data for of la,c.e,f
temperature
for
four
tographed
ted in Tables Reactions dissolved
hours.
and refluxing
4:l)
(about
are listed
over sodium sulphate.
in Tables
gel
The residue
acetate/cyclohexane
(1:9).
(1.5
reactant
evaporation
the
(4:ll.
Yields
1 (3.3
mmol) was
mixture
on a silica
and physical
=
was heated
at78V.
was stirred
g1 was added
was charged
Yields
After
1 and 3.
(10 ml) and the mixture
chromatography
disae
mixture
The organic
acetate
and CC_14- The trlazoline
for
pressure.
until
The reaction
of’ sodium hydrogencarbonate,
mm011 was added and the reaction
Silica
was continued
3-5 h).
column with cyclohexane/ethyl
tetrachloride
(8.25
at reduced
with ethyl
gel
products
in carbon
copper(I)chlor
re was evaporated
solution
with copper(I)chlor
PZ = = f
acetate
with water and dried
on a silica
the isolated
or suspended
prepared
and gel
data for
Freshly
at the same mixtu
the
column and chroma
the products
are lia
2 and 3.
of
la,c,e,f with copper(I)chlor z= = = =
or suspen prepared
ted as described Tables
mm011 was added in one portion
was chromatographed
and physical
freshly
(3.3
peroxide
sd in a solution
copper(I)chlor above for
and CBr_4- The triazoline
of CBr4 (6.6 (8.25
Ccl4 alone.
mm011 in Ccl4
mmol) was added.
Yields
The reaction
and physical
reactant
(10 ml).
data for
After
1 (3.3 = heating
was performed
the products
mm011 was at ?OoC
and elabora
are listed
in
2 and 3.
Reactionof
la with copper(II)chlo ==
(5 ml) and solid
copper(II)chlo
ture was charged
on a silica
yielding
- The triazoline (1 mmol) was added.
gel
la (1 mmol) was dissolved == After
column and chromatographed
stirring
for
5 min
with cyclohexane/ethyl
in acetonitrile the reaction acetate
mis
(4:l)
pure 4a. == REFERENCES
.
i P. Della Croce, D. Pocar, R. Stradi and P. Trimarco, J. Chem. Sot., Perkin Trans I, 141, (19801 2 S. Cilloni, D. Pocar, L.M. Rossi and P. Trimarco, J. Chem. Res., (S), 14, (1980) 3 G. Bolis, D. Pocar, R. Stradi and P. Trimarco, J. Chem. Sot., Perkin Trans I, 2365, (19771 4 therein E. Erba, M.L. Gelmi, D. Pocar and P. Trimarco, Chem. Ber., 119, 1083, (1986) and references =z= 5 N. Almirante, M. Ballabio, G. Bianchetti, A. Cambiaghi and D. Pocar. J. Chum. Res.(Sl, 132, (19861 6 Vol 5 Katritzky and C.W. Rees eds., H. Uamhoff in “Comprehensive Hetsrocyclic Chemistry” , A.R. K.T. Potts ed., Pergamon Press, Oxford, 1984, p. 678 7 M. Tiecco, Act. Chem. Res., 13, 51, (1980) z= 8 See for example M.S. Kharasch, Otto Reinmuth and W.H.
Urry,
J. Am. Chem. Sot.,
69,
1105,
(1947)
and references therein 9 Cambridge University Press, 1974, p. 308 D.C. Nonhebel exi J.C. Walton, “Free Radical Chemistry”. 10 Bromo derivatives were formed in lower yield with respect to chloro compounds preventing their isolation
in many cases.