An organocatalytic rearrangement of 2-(N-alkyl-/aryl-)amino-4-oxo-4H-1- benzopyran-3-carbaldehyde

Article abstract of DOI:10.1016/j.tetlet.2011.02.053

2-(Arylamino)-4-oxo-4H-1-benzopyran-3-carbaldehyde rearranges to 4-oxo-4H-1-benzopyran-3-carbanilide when treated with glycine in the presence of formalin, but under similar conditions 2-(alkylamino)-4-oxo-4H-1-benzopyran-3- carbaldehyde rearranges to 3-a

Full text of DOI:10.1016/j.tetlet.2011.02.053

Tetrahedron Letters 52 (2011) 1946–1948
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An organocatalytic rearrangement of 2-(N-alkyl-/aryl-)amino-4-oxo-
4H-1-benzopyran-3-carbaldehyde
⇑
Sourav Maiti, Suman Kalyan Panja, Chandrakanta Bandyopadhyay
Department of Chemistry, R. K. Mission Vivekananda Centenary College, Rahara, Kolkata 700 118, West Bengal, India
a r t i c l e i n f o
a b s t r a c t
Article history:
2-(Arylamino)-4-oxo-4H-1-benzopyran-3-carbaldehyde rearranges to 4-oxo-4H-1-benzopyran-3-carban-
ilide when treated with glycine in the presence of formalin, but under similar conditions 2-(alkylamino)-4-
oxo-4H-1-benzopyran-3-carbaldehyde rearranges to 3-alkylaminomethylenechroman-2,4-dione.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 21 January 2011
Revised 10 February 2011
Accepted 12 February 2011
Available online 17 February 2011
Keywords:
Rearrangement
Organocatalysis
Chromone-3-carbanilide
2-Aminochromone-3-carbaldehyde
Chroman-2,4-dione
1-Benzopyran
1. Introduction
work-up, the reaction mixture produced a white solid, which was
found to be 4a (Table 1, entry 1). The structure of the compound
Organocatalysis reaction is a rapidly growing area in the field of
synthetic organic chemistry. The advantage is that metal is ex-
cluded which often causes toxicity. Iminium ion catalysed organic
reactions and rearrangements have gained significance in the last
decade.1 Isomerisation of retinals which are the key reactions in
vision can be catalysed by iminium ion.2 It also catalyses asymmet-
was established on the basis of 1H NMR and mass spectral analysis
and finally confirmed by comparing with an authentic sample.11
Similar results were obtained from the reactions of 1b–d (entries
2–4). The structure of 4 clearly rules out the possibility of incorpo-
ration of formaldehyde and glycine in the product,12 but in their
absence no change was observed when 1 was heated in methanol
for 15 h. As 1°-amine reacts with 1 to produce 3,9 catalytic activity
of either CH2O or combined effect of formalin and 1°-amine was
examined. Compound 1 was heated with formalin alone in metha-
nol for 16 h, but no change in 1 was observed (entry 5). To check
the combined effect of CH2O and 1°-amine, glycine was substituted
by alanine and compound 1a produced 4a in good yield (entry 6).
Assuming amine moiety of aminoacid to be responsible for the
rearrangement, an equimolar amount of 1a and ethyl amine was
heated in methanol in the presence of excess formalin. Surpris-
ingly, the same transformation takes place although in lower yield
(entry 7). Methyl amine or benzyl amine was also employed, but
yields are poor compared to that of glycine (entries 8 and 9). It
should be mentioned that the above rearrangement does not take
place in the presence of formaldehyde and liquor ammonia (entry
10). When the amine component is changed from aliphatic to aro-
matic, no rearranged product was isolated even after heating for
18 h (entry 11). Use of paraformaldehyde in place of formalin takes
a longer reaction time and gives a poor yield (entry 12).
ric vinylogous a
-ketol rearrangements.3 Conversion of O-allylated
salicylaldehyde to chromanone using thiazolidine salt as organo-
catalyst has been accomplished.4 Recently, a study has been made
on asymmetric organocatalytic rearrangement reactions.5
2-Alkyl/arylaminochromone-3-carbaldehyde (1) has been re-
ported to be a very good building block for the synthesis of various
heterocycles.6 It has been synthesized by selective rearrangement
of nitrone 2.7 Compound 1 reacts with formalin and secondary
amine to produce 3,30-methylenebis(2-alkyl/arylaminochromone)
using deformylative Mannich reaction.8 Primary amines (both ali-
phatic and aromatic) convert 1 to 3.9 We report herein a rearrange-
ment reaction of 1 catalysed by the combined action of formalin
and primary amine.
In continuation of our earlier studies on double deformylative
Mannich reaction on 3-formylchromone using formalin and gly-
cine as the reagent to form N,N-di(chromon-3-ylmethyl)glycines,10
compound 1a was heated in methanol with equimolar amount of
glycine in the presence of excess formalin for 10 h. After usual
To verify the extent of catalytic activity of the amine compo-
nent, glycine was used in the reaction mixture in varying amounts
keeping formalin in excess (Table 2). It was observed that the
⇑
Corresponding author.
E-mail address: kantachandra@rediffmail.com (C. Bandyopadhyay).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.02.053

S. Maiti et al. / Tetrahedron Letters 52 (2011) 1946–1948
1947
Table 1
Table 2
Rearrangement of 1 using a primary amine and formalin
Catalytic effect of glycine on the rearrangement of 1 to 4
Entry R1
R2
Amine
component
Additive Time Product
Mp (°C)
Entry
R1
R2
Glycine (mol%)
Time (h)
Product
Yield (%)
(h)
(% yield)
1
2
3
4
5
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
100
40
26
12
6
7
4b
4b
4b
4b
4b
72
72
72
60
40
1
H
Ph
Glycine
CH2O
8
4a (70)
214–216
(215–
14
14
24
40
217)11
2
Me Ph
Glycine
CH2O
CH2O
CH2O
CH2O
CH2O
CH2O
CH2O
CH2O
CH2O
CH2O
(CH2O)n
CH2O
7
8
4b (72)
4c (70)
4d (74)
188–190
220–222
218–220
3
4
H
Ara Glycine
Me Ara Glycine
10
16
10
10
10
14
15
18
13
8
5
6
7
8
H
H
H
H
Ph
Ph
Ph
Ph
––
Alanine
EtNH2
MeNH2
PhCH2NH2
NH4OH
PhNH2
Glycine
85% recovery of 1a
4a (72)
4a (40)
4a (35)
4b (60)
70% recovery of 1a
60% recovery of 1a
4b (40)
5e (55)
(E/Z:1/2)
5f (52)
(E/Z:2/5)
5g (60)
(E/Z:2/5)
214–216
214–216
214–216
188–190
The reaction was then extended using 2-(alkylamino)-4-oxo-
4H-1-benzopyran-3-carbaldehyde 1 (R2 = alkyl). When 1e–g was
heated with equimolar amounts glycine in methanol in the pres-
ence of excess formalin for 7–10 h, it produced 5 (Table 1, entries
13–15). Compound 5 appeared as a diastereomeric mixture of E
and Z forms.7
The above observations may be rationalized as follows: initial
formation of iminium ion from 1°-amine and CH2O catalyses the
intramolecular attack of NHR2 group of 1 on the CHO function to
form 6, where 1,3-H shift takes place to produce 7. Electrocyclic
ring opening of 7 (R2 = aryl) (path a) leads to 8, which forms 4 with
the expulsion of iminium ion. But in 7 when R2 = alkyl, NR2 group
becomes more nucleophilic and facilitates the pyran ring opening
to 9 (path b), which recyclises to 10. Expulsion of iminium ion from
10 leads to the opening of azetinium ring to form 11, which finally
tautomerises to 5 (Scheme 1).
9
Me Ph
10
11
12
13
H
H
Ph
Ph
Me Ph
H
188–190
198–200
(194–96)7
184–186
Me Glycine
14
15
Me Et
Glycine
Glycine
CH2O
CH2O
10
10
H
Et
184–186
16
17
H
H
Ph
Ph
AlCl3 in benzene
BF3 in CH2Cl2
5
6
65% recovery of 1a
60% recovery of 1a
a
Ar stands for 4-MeC6H4.
reaction time increases with decrease in the concentration of gly-
cine (Table 2, entries 1–5). Use of 26 mol% of glycine gives 72%
yield in 14 h (entry 3), on further decreasing the concentration of
glycine, the yield decreases even with longer reaction hours.
It may be predicted that the formation of iminium ion is respon-
sible in catalysing the reaction. Among the different amines used in
the rearrangement, aminoacids have the highest and the aromatic
amine has the lowest tendency to form the iminium ion. The yields
NR2
NHR2
CHO
O
O
O
R3NH2
O-
CH N+
R1
R1
R1
CH
NR3
R2
O
2
O
1
O
H
3
CH2=N+HR
CH2O + RNH2
For 1-11
1
2
a
O
O
: R = H; R = Ph
1
O
NR2
2
b
: R = Me; R = Ph
NHR2
c: R1 = H; R2 = p-C6H4Me
d: R1 = Me; R2 = p-C6H4Me
e: R1 = H; R2 = Me
C
H
O
R1
R1
CH2NHR
O
6
O
5
f: R1 = Me; R2 = Et
g: R1 = H; R2 = Et
b
H
O
O
O
O
NR2
Path a
R2 = Aryl
NR2
a
NR2
C
O
R1
R1
R1
CH2NHR
O
H
O
11
O
O
7
CH2
8
NHR
R2 = Alkyl
Path b
-CH2=N+HR
NHR
CH2
O
O
O-
O
N+R2
N+R2
CH
NHR2
C
O
R1
R1
R1
CH2NHR
O
O
4
O
9
O
10
Scheme 1. Rearrangement of 1–4 and 5 using a primary amine and formalin.

1948
S. Maiti et al. / Tetrahedron Letters 52 (2011) 1946–1948
3. Zhang, E.; Fan, C. A.; Tu, Y. Q.; Zhang, F. M.; Song, Y. L. J. Am. Chem. Soc. 2009,
131, 14626–14627.
4. (a) Enders, D.; Breuer, K.; Runsink, J. Helv. Chim. Acta 1996, 79, 1899–1902; (b)
Aupoix, A.; Vo-Thanh, G. Synlett 2009, 1915–1920.
of rearrangement products also corroborate the above prediction.
It is to be mentioned here that anhydrous AlCl3 or BF3 failed to car-
ry out this rearrangement (entries 16 and 17).
5. Moyano, A.; El-Hamdouni, N.; Atlamsani, A. Chem. Eur. J. 2010, 16, 5260–5273.
6. (a) Singh, G.; Singh, L.; Ishar, M. P. S. Tetrahedron 2002, 58, 7883–7890; (b)
Sattofattori, E.; Anzaldi, M.; Balbi, A.; Artali, R.; Bombieri, G. Helv. Chim. Acta
2002, 85, 1698–1705; (c) Singh, G.; Singh, G.; Ishar, M. P. S. Synlett 2003, 256–
258; (d) Singh, G.; Singh, G.; Ishar, M. P. S. Helv. Chim. Acta 2003, 86, 169–180.
7. Ghosh, T.; Bandyopadhyay, C. Tetrahedron Lett. 2004, 45, 6169–6172.
8. Maiti, S.; Panja, S. K.; Bandyopadhyay, C. Tetrahedron Lett. 2009, 50, 3966–3969.
9. Maiti, S.; Panja, S. K.; Bandyopadhyay, C. Indian J. Chem. 2009, 48B, 1447–1452.
10. Panja, S. K.; Maiti, S.; Drew, M. G. B.; Bandyopadhyay, C. Tetrahedron 2009, 65,
1276–1280.
In conclusion, we have reported a combined organocatalytic
effect of formaldehyde and glycine in the rearrangement of
2-(N-alkyl-/aryl-)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde
(1). The differential effect of alkyl and aryl group in the amine func-
tion of 1 in this rearrangement has also been rationalized.
Acknowledgements
11. Klutchko, S.; Cohen, M. P.; Shavel, Jr. J.; von Strandtmann, M. J. Heterocycl.
Chem. 1974, 11, 183–188.
We gratefully acknowledge Department of Biotechnology
(DBT), India (No. BT/PR8217/Med/14/1239/2006) for financial
assistance; IICB, Jadavpur for spectral analysis and finally the col-
lege authorities for providing research facilities.
12. General procedure for the rearrangement of 1: To a solution of 1b (140 mg,
0.5 mmol) in methanol (5 mL), formalin (0.3 mL) and glycine (10 mg,
0.13 mmol, 26 mol%) were added. The resulting mixture was heated under
reflux. A solid began to separate after 4.5 h and heating was continued for 14 h
when the absence of 1b was observed by TLC. The reaction mixture was cooled
and deposited solid was filtered out. The solid was further crystallized from
benzene–light petroleum to afford 4b (100 mg, 72%) as a white crystalline
References and notes
solid. IR (KBr) m ;
max: 3124, 3048, 2758, 1678, 1615, 1558 cmꢀ1 1H NMR (CDCl3)
d: 2.51 (3 H, s, CH3), 7.14 (1 H, br t, J = 7.5 Hz, ArH), 7.34–7.39 (2 H, m, ArH),
7.47 (1 H, d, J = 8.4 Hz, 8-H), 7.57 (1 H, br d, J = 8.4 Hz, 7-H), 7.73 (2 H, br d,
J = 7.8 Hz, ArH), 8.09 (1 H, br s, 5-H), 9.04 (1 H, s, 2-H), 11.44 (1 H, br s,
exchangeable, NH); mass m/z: 280 (M++H), 302 (M++Na).
1. Erkkila, A.; Majander, I.; Pihko, P. M. Chem. Rev. 2007, 107, 5416–5470.
2. (a) Ouellet, S. G.; Tuttle, J. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127,
32–33; (b) Yang, J. W.; Hechavarria Fonseca, M. T.; Vignola, N.; List, B. Angew.
Chem., Int. Ed. 2005, 44, 108–110.