Further Rearrangement of Meisenheimer Products of Allyl Aryl Amine Oxides

Full text of DOI:10.1021/jo960647v

1506
J . Org. Chem. 1997, 62, 1506-1508
Sch em e 1
F u r th er Rea r r a n gem en t of Meisen h eim er
P r od u cts of Allyl Ar yl Am in e Oxid es†
Me
N
Me
NH
X
K2CO3–Me2CO
65–80%
Krishna C. Majumdar* and Gour H. J ana
R1
R1
+
Department of Chemistry, University of Kalyani,
Kalyani 741 235, West Bengal, India
R2
R2
1
2, X = Br or Cl
3
R1
R2
R1
R2
Received April 8, 1996
Thyagarajan and co-workers have studied the molec-
ular reorganization of arylpropynyl sulfoxides1 and aryl-
propynylamine oxides.2 It has been proposed that the
[2s,3s] sigmatropic shift is followed by a [3s,3s] shift,
enolization, ketol formation, etc., to give a five-membered
ring in benzo[b]thiophenes and indoles in almost quan-
titative yields. The formation of indoles occurs readily
in one step by simply stirring a solution of arylpropyn-
ylamine with 1 equiv of m-CPBA at room temperature.
More recently,3 this methodology has been successfully
applied to form fused heterocyclic rings in different
heterocycles. The initial step in the reorganization of
arylpropynyl sulfoxides and arylpropynylamine oxides is
a [2s,3s] sigmatropic rearrangement analogous to the
[2s,3s] shift in allylarylamine oxides4 in the case of the
Meisenheimer rearrangement. Recently, we have ob-
served a [1a,3s] sigmatropic shift during thermal re-
arrangement of [(aryloxy)methyl]coumarins.5 This ob-
servation prompted us to study the Meisenheimer re-
arrangement of different allylic substrates and also the
subsequent thermal rearrangement of the initial Meisen-
heimer products. Here we report the results of our
investigation.
CH3
CH3
3a,
d,
CH2O
CH2O
CH3
H
H
H
e,
f,
CH3
b,
c,
H
H
CH2O
Cl
Ph
Sch em e 2
Me
Me
O–
+
N
N
[2,3] shift
84–95%
O
m-CPBA
CHCl3
R1
3a–f
R1
R2
R2
5
4
R1
R2
R1
R2
CH3
CH3
5a,
d,
e,
f,
CH2O
CH2O
CH3
H
H
H
CH3
b,
c,
H
H
CH2O
Cl
Ph
Sch em e 3
Me
The allylic tertiary amines 3a -f were prepared by the
reaction of N-methylaniline (1) with appropriate allylic
halides 2a -f in refluxing acetone in the presence of
anhydrous potassium carbonate (Scheme 1) in 65-80%
yields.
O
N
DMF, ∆
60–80%
5a–e
R1
R2
6
R1
R2
R1
R2
Resu lts a n d Discu ssion
CH3
CH3
CH3
6a,
d,
e,
f,
CH2O
CH2O
CH3
H
When N-methyl-N-phenyl-N-[1-((E)-3-methylbut-2-
enyl)]amine (3a ) was treated with 1 equiv of m-CPBA in
chloroform at 0-5 °C, within 10 min formation of a highly
polar N-oxide was observed as indicated by TLC. If this
reaction mixture was kept at rt for 8-10 h a new product
5a , characterized as O-[2-(2-methylbut-3-enyl)]-N-meth-
yl-N-phenylhydroxylamine was obtained in excellent
yield.
On similar treatment substrates 3b-e furnished the
corresponding products 5b-e also in nearly quantitative
yields. These products turned reddish brown on standing
in air. Interestingly, a different product was isolated
b,
c,
H
H
H
H
CH2O
Cl
Ph
from the reaction of 3f and characterized as O-[1-((E)-3-
phenylprop-2-enyl)]-N-methyl-N-phenylhydroxylamine (6f).
Presumably, 6f was produced from the rearrangement
of 5f under the reaction conditions.
Meisenheimer product 5a in C6H5Cl remained un-
affected at 100 °C (3 h). However, a new product O-[1-
((E)-3-methylbut-2-enyl)]-N-methyl-N-phenylhydroxyl-
amine (6a ) was obtained in 70% yield when heated at
120-130 °C for 4 h. Further heating gradually decom-
poses the product to N-methylaniline. The reaction was
also studied in o-dichlorobenzene, and the results were
about the same. However, the same product 6a was
obtained in slightly higher yield (80%) in a shorter
reaction time (2 h) in DMF at 120 °C. Similar treatment
of Meisenheimer products 5b-e led to products 6b-e in
60-72% yields.
† Dedicated to Professor B. S. Thyagarajan of the University of Texas
at San Antonio on the occasion of his 65th birthday.
(1) (a) Majumdar, K. C.; Thyagarajan, B. S. J . Chem. Soc., Chem.
Commun. 1972, 83. (b) Majumdar, K. C.; Thyagarajan, B. S. Int. J .
Sulfur Chem., Part A 1972, 2, 93.
(2) (a) Thyagarajan, B. S.; Hillard, J . B.; Reddy, K. V.; Majumdar,
K. C. Tetrahedron Lett. 1974, 1999. (b) Hillard, J . B.; Reddy, K. V.;
Majumdar, K. C.; Thyagarajan, B. S. J . Heterocycl. Chem. 1974, 11,
369.
(3) (a) Majumdar, K. C.; Chattopadhyay, S. K. J . Chem. Soc., Chem.
Commun. 1987, 524. (b) Majumdar, K. C.; Chattopadhyay, S. K.;
Khan, A. T. J . Chem. Soc., Perkin Trans. 1 1989, 1285. (c) Majumdar,
K. C.; Ghosh, S. K. J . Chem. Soc., Perkin Trans. 1 1994, 2889.
(4) Kleinschmidt, R. F.; Cope, A. C. J . Am. Chem. Soc. 1944, 66,
1929.
The formation of products 6a -e from 5a -e may be
explained by a concerted [1,3] shift (Scheme 3). Steric
effects are likely to limit the generality of [1,3] shifts,
(5) Majumdar, K. C.; Saha, S.; De, R. N.; Ghosh, S. K. J . Chem.
Soc., Perkin Trans. 1 1993, 715.
S0022-3263(96)00647-0 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 5, 1997 1507
(M+). Anal. Calcd for C17H19NO: C, 80.63; H, 7.51; N, 5.53.
Found: C, 80.90; H, 7.38; N, 5.48.
and examples of thermal [1,3] shifts are rare.6 The
formation of products 6a -e is unaffected when a radical
scavenger (e.g., hydroquinone) is added to the reaction
mixture. On the other hand, the reaction also does not
take place at 100 °C in the presence of a radical initiator
(AIBN). As the formation of 6a -e from 5a -e is un-
affected in the presence of a radical inhibitor as well as
radical initiator it seems that migration of the less
crowded neutral oxygen heteroatom to a carbon atom is
facilitated through a concerted low energy transition
state.
In the case of the amine oxide rearrangement of
arylprop-2-ynylamine oxide, the [2, 3] sigmatropic shift
(i.e., Meisenheimer rearrangement) is followed by a [3,3]
shift, but in the present work it is interesting to note that
initial Meisenheimer rearrangement products undergo
[1,3] shifts of the oxygen heteroatom to carbon on further
heating.
N -Me t h yl-N -p h e n yl-N -[1-((E )-3-p h e n ylp r op -2-e n yl)]-
a m in e (3f): yield 72%; viscous liquid; UV λmax 251 (log ꢀ 3.05),
1
265 (log ꢀ 2.77); IR (thin film) 3060, 1600, 1210 cm-1; H NMR
(CDCl3, 100 MHz) δ 2.96 (s, 3H), 4.06 (d, J ) 5 Hz, 2H), 6.22
(dt, J ) 16, 5 Hz, 1H), 6.52 (d, J ) 16 Hz, 1H), 6.60-7.60 (m,
10H); MS m/z 223 (M+). Anal. Calcd for C16H17N: C, 86.09; H,
7.62; N, 6.28. Found: C, 86.40; H, 7.54; N, 6.54.
Gen er a l P r oced u r e for Oxid a tion a n d Meisen h eim er
R ea r r a n gem en t of Ter t ia r y Am in es 3a -f. m-(Chloro-
peroxy)benzoic acid (0.010 mol, 3.44 g, 50%) in CHCl3 (50 mL)
was added to a well-stirred solution of the appropriate tertiary
amine (0.010 mol) in CHCl3 (50 mL), at 0-5 °C over a period of
20 min. The reaction mixture was stirred for 10 h longer. The
reaction mixture was washed with an aqueous solution of K2CO3
and dried (Na2SO4). The solvent was removed, and the crude
mass was purified by column chromatography over silica gel.
Compounds 5a -e and 6f were obtained when the column was
eluted with pet. ether.
O-[2-(2-Met h ylb u t -3-en yl)]-N-m et h yl-N-p h en ylh yd r ox-
yla m in e (5a ): yield 89%; viscous liquid; UV λmax 235 (log ꢀ 2.71),
1
279 (log ꢀ 2.22); IR (thin film) 2980, 1600, 1260 cm-1; H NMR
Exp er im en ta l Section
(CDCl3, 100 MHz) δ 1.40 (s, 6H), 3.08 (s, 3H), 5.04-5.32 (m,
2H), 5.96-6.28 (m, 1H), 6.92-7.44 (m, 5H); MS m/z 191 (M+).
Anal. Calcd for C12H17NO: C, 75.39; H, 8.90; N, 7.33. Found:
C, 75.62; H, 8.66; N, 7.08.
Gen er a l Meth od s. UV absorption spectra were recorded in
ethanol. IR spectra were run as thin films. 1H-NMR spectra
were performed at the IICB, Calcutta. Elemental analyses and
mass spectra were determined at CDRI, Lucknow. Silica gel
60-120 mesh was used for chromatographic separation. Pet.
ether indicates petroleum ether (60-80 °C).
O-[2-(Bu t-3-en yl)]-N-m eth yl-N-ph en ylh ydr oxylam in e (5b):
yield 95%; viscous liquid; UV λmax 241 (log ꢀ 3.13), 279 (log ꢀ
2.57); IR (thin film) 3060, 1590, 1260 cm-1 1H NMR (CDCl3,
;
100 MHz) δ 1.36 (d, J ) 7 Hz, 3H), 3.08 (s, 3H), 4.32 (m, 1H),
5.16 (br d, J ) 10 Hz, 1H), 5.24 (br d, J ) 18 Hz, 1H), 5.80-
6.20 (m, 1H), 6.92-7.52 (m, 5H), MS m/z 177 (M+). Anal. Calcd
for C11H15NO: C, 74.57; H, 8.47; N, 7.90. Found: C, 74.30; H,
8.69; N, 7.72.
Gen er a l P r oced u r e for th e P r ep a r a tion of Ter tia r y
Am in es 3a -f. A mixture of N-methylaniline (1) (2.14 g, 0.020
mol) and the appropriate allylic halides 2a -f (0.022 mol) was
refluxed in dry acetone (100 mL) in the presence of anhyd K2CO3
(2 g) for 4-10 h. Progress of the reaction was monitored by TLC.
The reaction mixture was cooled and filtered. The solvent was
removed from the filtrate in vacuo, and the crude mass was
chromatographed over silica gel to provide the pure products
3a -f.
O-[2-[1-(4′-Ch lor op h e n oxy)b u t -3-e n yl]]-N -m e t h yl-N -
p h en ylh yd r oxyla m in e (5c): yield 91%; viscous liquid; UV λmax
226 (log ꢀ 3.28), 250 (log ꢀ 2.30), 264 (log ꢀ 3.05); IR (thin film)
3060, 1590, 1260 cm-1 1H NMR (CDCl3, 100 MHz) δ 3.08 (s,
;
3H), 4.14 (d, J ) 4 Hz, 2H), 4.44-4.68 (dt, J ) 7, 4 Hz, 1H),
5.33 (dt, J ) 10, 1.2 Hz, 1H), 5.43 (dt, J ) 16, 1.2 Hz, 1H), 5.88-
6.28 (m, 1H), 6.80-7.64 (m, 9H); MS m/z 303, 305 (M+). Anal.
Calcd for C12H17ClNO2: C, 67.22; H, 5.93; N, 4.61. Found: C,
67.50; H, 5.76; N, 4.84.
N -Me t h y l-N -p h e n y l-N -[1-((E )-3-m e t h y lb u t -2-e n y l)]-
a m in e (3a ): yield 85%, viscous liquid; UV λmax 251 (log ꢀ 3.00),
300 (log ꢀ 2.54); IR (thin film) 2980, 1600 cm-1; 1H NMR (CDCl3,
100 MHz) δ 1.76 (s, 6H), 2.92 (s, 3H), 3.92 (d, J ) 7 Hz, 2H),
5.26 (t, J ) 7 Hz, 1H), 6.68-6.80 (m, 3H), 7.16-7.36 (m, 2H);
MS m/z 175 (M+). Anal. Calcd for C12H17N: C, 82.29; H, 9.71;
N, 8.00. Found: C, 82.00; H, 9.48; N, 8.29.
O-[2-[1-(4′-Me t h ylp h e n oxy)b u t -3-e n yl]]-N -m e t h yl-N -
p h en ylh yd r oxyla m in e (5d ): yield 85%; viscous liquid; UV λmax
226 (log ꢀ 3.28), 279 (log ꢀ 2.70); IR (thin film) 3000, 1600, 1230
N-Meth yl-N-ph en yl-N-[1-((E)-bu t-2-en yl)]am in e (3b): yield
81%; viscous liquid; UV λmax 251 (log ꢀ 2.86), 300 (log ꢀ 2.24); IR
cm-1 1H NMR (CDCl3, 100 MHz) δ 2.28 (s, 3H), 3.12 (s, 3H),
;
1
(thin film) 3000, 1590 cm-1; H NMR (CDCl3, 100 MHz) δ 1.70
4.16 (d, J ) 4 Hz, 2H), 4.48-4.72 (dt, J ) 7, 4 Hz, 1H), 5.34 (br
d, J ) 10 Hz, 1H), 5.43 (br d, J ) 17 Hz, 1H), 5.88-6.28 (m,
1H), 6.80-7.60 (m, 9H); MS m/z 283 (M+). Anal. Calcd for
(d, J ) 5 Hz, 3H), 2.90 (s, 3H), 3.84-4.08 (m, 2H), 5.34-5.60
(m, 1H), 5.64 (dt, J ) 16, 5 Hz, 1H), 6.68-6.80 (m, 3H), 7.16-
7.40 (m, 2H); MS m/z 161 (M+). Anal. Calcd for C11H15N: C,
81.99; H, 9.32; N, 8.69. Found: C, 81.72; H, 9.00; N, 8.42.
N-Meth yl-N-p h en yl-N-[1-[(E)-4-(4′-ch lor op h en oxy)bu t-2-
en yl]]a m in e (3c): yield 80%; viscous liquid; UV λmax 251 (log ꢀ
C
18H21NO2: C, 76.32; H, 7.42; N, 4.94. Found: C, 76.09; H, 7.29;
N, 5.36.
O-[2-(1-P h en oxybu t-3-en yl)]-N-m eth yl-N-p h en ylh yd r ox-
yla m in e (5e): yield 84%; viscous liquid; UV λmax 225 (log ꢀ 3.32),
1
3.13), 300 (log ꢀ 2.42); IR (thin film) 3000, 1600, 1230 cm-1; H
250 (log ꢀ 3.30), 264 (log ꢀ 3.01); IR (thin film) 3000, 1600, 1230
1
cm-1; H NMR (CDCl3, 100 MHz) δ 3.04 (s, 3H), 4.10 (d, J ) 4
NMR (CDCl3, 100 MHz) δ 2.96 (s, 3H), 3.96-4.16 (m, 2H), 4.48-
4.68 (m, 2H), 5.80 (dt, J ) 16, 5 Hz, 1H), 5.92 (dt, J ) 16, 5 Hz,
1H), 6.68-7.44 (m, 9H); MS m/z 287, 289 (M+). Anal. Calcd
for C17H18ClNO: C, 70.96; H, 6.26; N, 4.86. Found: C, 70.66;
H, 6.58; N, 4.57.
Hz, 2H), 4.40-4.64 (dt, J ) 7, 4 Hz, 1H), 5.20-5.56 (m, 2H),
5.84-6.20 (m, 1H), 6.76-7.52 (m, 10H); MS m/z 269 (M+). Anal.
Calcd for C17H19NO2: C, 75.84; H, 7.06; N, 5.20. Found: C,
75.62; H, 6.66; N, 5.28.
N-Met h yl-N-p h en yl-[1-[(E)-4-(4′-m et h ylp h en oxy)b u t -2-
en yl]]a m in e (3d ): yield 65%; viscous liquid; UV λmax 251 (log ꢀ
R ea r r a n gem en t of Meisen h eim er P r od u ct s 5a -f in
DMF . A mixture of 5a -e (4 mmol) and DMF (3 mL) was heated
on an oil bath at 120-130 °C for 30 min to 2 h. The reaction
was monitored by TLC. The reaction was cooled and then
subjected to column chromatography over silica gel. Compounds
6a -e were obtained when the column was eluted with pet. ether.
Starting material (15-20%) was recovered in each case except
in the case of 5a .
1
3.01), 300 (log ꢀ 2.30); IR (thin film) 3020, 1590, 1280 cm-1; H
NMR (CDCl3, 100 MHz) δ 2.30 (s, 3H), 2.96 (s, 3H), 3.92-4.12
(m, 2H), 4.48-4.72 (m, 2H), 5.76 (dt, J ) 16, 5 Hz, 1H), 5.90
(dt, J ) 16, 5 Hz, 1H), 6.68-7.40 (m, 9H); MS m/z 267 (M+).
Anal. Calcd for C18H21NO: C, 80.89; H, 7.86; N, 5.24. Found:
C, 80.59; H, 7.58; N, 5.00.
N -Me t h yl-N -p h e n yl-N -[1-((E )-4-p h e n oxyb u t -2-e n yl)]-
a m in e (3e): yield 83%; viscous liquid; UV λmax 251 (log ꢀ 3.08),
O-[1-(3-Met h ylb u t -2-en yl)]-N-m et h yl-N-p h en ylh yd r ox-
yla m in e (6a ): yield 80%; viscous liquid; UV λmax 241 (log ꢀ 3.28),
1
1
300 (log ꢀ 2.38); IR (thin film) 3000, 1600, 1230 cm-1; H NMR
263 (log ꢀ 2.69); IR (thin film) 2900, 1660, 1270 cm-1; H NMR
(CDCl3, 100 MHz) δ 2.92 (s, 3H), 3.94-4.16 (m, 2H), 4.50-4.70
(CDCl3, 100 MHz) δ 1.74 (d, J ) 4 Hz, 6H), 3.08 (s, 3H), 4.32 (d,
J ) 6 Hz, 2H), 5.46 (t, J ) 6 Hz, 1H), 6.88-7.44 (m, 5H); MS
m/z 191 (M+). Anal. Calcd for C12H17NO: C, 75.39; H, 8.90; N,
7.33. Found: C, 75.22; H, 8.60; N, 7.10.
O-[1-((E )-B u t -2-e n y l)]-N -m e t h y l-N -p h e n y lh yd r ox yl-
a m in e (6b): yield 60%; viscous liquid; UV λmax 248 (log ꢀ 3.25),
(m, 2H), 5.80-5.96 (m, 2H), 6.68-7.46 (m, 10H); MS m/z 253
(6) (a) Gill, G. B.; Wills, M. R. In Pericyclic Reactions; Chapman &
Hall: London, 1974; p 181. (b) Berson, J . A.; Nelson, G. L.; J . Am.
Chem. Soc. 1967, 89, 5503; 1970, 92, 1096.

1508 J . Org. Chem., Vol. 62, No. 5, 1997
Notes
1
302 (log ꢀ 2.69); IR (thin film) 2960, 1600, 1260 cm-1; H NMR
(CDCl3, 100 MHz) δ 1.74 (d, J ) 4 Hz, 3H), 3.08 (s, 3H), 4.25-
4.52 (m, 2H), 5.52-5.76 (m, 1H), 5.90 (dt, J ) 16, 5 Hz, 1H),
O-[1-((E )-4-P h e n oxyb u t -2-e n yl)]-N -m e t h yl-N -p h e n yl-
h yd r oxyla m in e (6e): yield 62%; viscous liquid; UV λmax 230
(log ꢀ 3.09), 277 (log ꢀ 2.58); IR (thin film) 3010, 1600, 1230 cm-1
;
6.92-7.48 (m, 5H); MS m/z 177 (M+). Anal. Calcd for C11H15
NO: C, 74.57; H, 8.47; N, 7.90. Found: C, 74.80; H, 8.33; N,
7.74.
-
1H NMR (CDCl3, 100 MHz) δ 3.08 (s, 3H), 4.42 (d, J ) 4.5 Hz,
2H), 4.54 (d, J ) 4.5 Hz, 2H), 5.96 (dt, J ) 16, 5 Hz, 1H), 6.08
(dt, J ) 16, 5 Hz, 1H), 6.72-7.48 (m, 10H); MS m/z 269 (M+).
Anal. Calcd for C17H19NO2: C, 75.84; H, 7.06; N, 5.20. Found:
C, 75.62; H, 6.66; N, 5.08.
O-[1-[(E)-4-(4′-Ch lor op h en oxy)bu t-2-en yl]]-N-m eth yl-N-
p h en ylh yd r oxyla m in e (6c): yield 72%; viscous liquid; UV λmax
226 (log ꢀ 3.26), 278 (log ꢀ 2.64); IR (thin film) 2900, 1600, 1230
O-[1-((E )-3-P h e n ylp r op -2-e n yl)]-N -m e t h yl-N -p h e n yl-
h yd r oxyla m in e (6f): yield 48%; viscous liquid; UV λmax 265 (log
cm-1; H NMR (CDCl3, 100 MHz) δ 3.08 (s, 3H), 4.36 (d, J ) 4
1
1
Hz, 2H), 4.52 (d, J ) 4 Hz, 2H), 5.96 (dt, J ) 16, 4 Hz, 1H), 6.08
(dt, J ) 16, 4 Hz, 1H), 6.72-7.44 (m, 9H); MS m/z 303, 305 (M+).
Anal. Calcd for C17H18ClNO2: C, 67.22; H, 5.93; N, 4.61.
Found: C, 67.08; H, 5.77; N, 4.37.
ꢀ 2.91); IR (thin film) 3010, 1600, 1230 cm-1; H NMR (CDCl3,
100 MHz) δ 3.08 (s, 3H), 4.50 (d, J ) 5 Hz, 2H), 6.38 (dt, J ) 16,
5 Hz, 1H), 6.68 (d, J ) 16 Hz, 1H), 6.96-7.68 (m, 10H); MS m/z
239 (M+). Anal. Calcd for C16H17NO: C, 80.33; H, 7.11; N, 5.85.
Found: C, 80.12; H, 7.00; N, 5.60.
O-[1-[(E)-4-(4′-Meth ylp h en oxy)bu t-2-en yl]]-N-m eth yl-N-
p h en ylh yd r oxyla m in e (6d ): yield 61%; viscous liquid; UV λmax
226 (log ꢀ 3.25), 277 (log ꢀ 2.63); IR (thin film) 3010, 1600, 1230
Ack n ow led gm en t. We thank the CSIR (New Delhi)
for financial assistance and Dr. S. Sengupta, Depart-
ment of Chemistry, J adavpur University, Calcutta, for
some infrared spectral data.
cm-1 1H NMR (CDCl3, 100 MHz) δ 2.20 (s, 3H), 3.00 (s, 3H),
;
4.30 (d, J ) 4 Hz, 2H), 4.42 (br s, 2H), 5.92 (dt, J ) 16, 4 Hz,
1H), 6.04 (dt, J ) 16, 4 Hz, 1H), 6.62-7.40 (m, 9H); MS m/z 283
(M+). Anal. Calcd for C18H21NO2: C, 76.32; H, 7.4; N, 4.97.
Found: C, 76.10; H, 7.77; N, 4.70.
J O960647V