Three-component reaction between 3-hydroxy-2-naphthoic acid, aromatic aldehydes and acetonitrile in the presence of chlorosulfonic acid: Synthesis of 4-(acetylaminoarylmethyl)-3-hydroxy-2-naphthoic acid

Article abstract of DOI:10.3184/030823408X293224

The one-pot, three-component reaction between 3-hydroxy-2-naphthoic acid, aromatic aldehydes and acetonitrile in the presence of chlorosulfonic acid leads to 4-(acetylaminoarylmethyl)-3-hydroxy-2-naphthoic acids in excellent yields.

Full text of DOI:10.3184/030823408X293224

JOURNAL OF CHEMICAL RESEARCH 2008
FEBRUARY, 107–108
RESEARCH PAPER 107
Three-component reaction between 3-hydroxy-2-naphthoic acid,
aromatic aldehydes and acetonitrile in the presence of chlorosulfonic
acid: synthesis of 4-(acetylaminoarylmethyl)-3-hydroxy-2-naphthoic acid
Mohammad Anary-Abbasinejad*, Alireza Hassanabadi, Fatemeh Ghanee and Nahid Tahmasbnia
Department of Chemistry, Islamic Azad University, Yazd Branch, PO Box 89195-155, Yazd, Iran
The one-pot, three-component reaction between 3-hydroxy-2-naphthoic acid, aromatic aldehydes and acetonitrile in
the presence of chlorosulfonic acid leads to 4-(acetylaminoarylmethyl)-3-hydroxy-2-naphthoic acids in excellent yields.
Keywords: chlorosulfonic acid, 3-hydroxy-2-naphthoic acid, three-component reaction, aryl aldehydes
O
Multi-component reactions (MCR) have been examined
because they can be employed for the rapid assembly of
a
Ar
N
series of diverse structures.1-6 The three–component
H
reaction between an enolic system such as, acetophenone or
β-dicarbonyl compounds, an aryl aldehyde and acetonitrile
has been recently used to synthesise β-acetamidoketones.
This reaction is usually carried out in the presence of
excess acetyl chloride and is catalysed by an acid.7 A three-
component reaction between acetophenone or β-ketoesters,
aryl aldehydes and acetonitrile was also carried out in the
presence of excess trimethylchlorosilane and catalysed by
heteropoly acids.8 Recently we reported that a similar reaction
can be carried out between other enolic systems such as 4-
hydroxycoumarin9 or 2-naphthol,10 aromatic aldehydes and
acetonitrile in the presence of chlorosulfonic acid without the
need to use any other catalyst or activator. In continuation of
our work, we now report that the three-component reaction
between 3-hydroxy-2-naphthoic acid aromatic aldehydes and
acetonitrile can be carried out in the presence of chlorosulfonic
acid. Thus, when a mixture of 3-hydroxy-2-naphthoic acid
and 4-chlorobenzaldehyde was stirred in boiling acetonitrile
in the presence of two equivalents of chlorosulfonic acid,
a clean reaction took place and was complete within 1 h
(determined by TLC). After pouring the reaction mixture into
ice-water 4-(acetylamino4-chlorophenylmethyl)-3-hydroxy-
2-naphthoic acid 3a was obtained as a white powder which
was pure on the basis of NMR spectral data. It could be
further purified by recrystallisation from an ethyl acetate–
hexane mixture. As shown in Scheme 1, this reaction can
be carried out with different aromatic aldehydes to yield
OH
OH
ClSO3H
CH3CN, reflux
ArCHO
+
CO2H
CO2H
2
1
3
Yield*
/%
Ar
3
a
4-ClC6H4
95
b
c
3-ClC6H4
2-ClC6H4
95
95
90
90
94
4-CH3C6H4
4-NO2C6H4
d
e
3-NO2C6H4
4-BrC6H4
f
g
h
90
90
3-CH3OC6H4
i
2-CH3OC6H4
95
*Isolated yield.
Scheme 1
was converted to a singlet. The protons of the hydroxy groups
resonate in the range of 12.00–13.00 ppm as a very broad
signal which in some cases were broadened and were not
observed. The 13C NMR spectrum of compound 3a showed
18 distinct signals consistent with the proposed structure.
A reasonable mechanism for the formation of compounds
3a–i is presented in Scheme 2. Acetonitrile attacks to
condensation product of 3-hydroxy-2-naphthoic acid and the
aldehyde in the presence of chlorosulfonic acid to afford the
cation 5 which is hydrolysed to from product 3.
In summary, we report a simple and efficient one-pot
synthesis of 4-(arylacetylaminomethyl)-3-hydroxy-2-naphthoic
acids by a one-pot, three-component reaction between 3-
hydroxy-2-naphthoic acid, aromatic aldehydes and acetonitrile
in the presence of chlorosulfonic acid, in excellent yields.
The advantages of this method are readily available starting
materials, short reaction times, easy and clean work-up and
excellent yields.
4-(acetylaminoarylmethyl)-3-hydroxy-2-naphthoic
acid
derivatives 3a–i in excellent yields.
Compounds 3a–i were new and their structures were
deduced by elemental and spectroscopic analysis. The 1H NMR
spectrum of 3a exhibited a sharp line at δ = 1.9 ppm for the
protons of the methyl group. The methine and NH protons
coupled to each other and two doublets were observed for
1
them at 7.1 and 8.7 ppm, respectively. When the H NMR
spectrum was recorded after the addition of some D2O to the
d6-DMSO solution of 3a the doublet related to NH proton
was disappeared and the doublet related to methine proton
_
CH3
:
N C CH3 - Cl
+
OH2
HO2C
O
Cl S OH
O
C
N
3
HO2C
_
HCl
O
Ar
- H2SO4
Ar
O
O
4
S
HO
O
5
Scheme 2
* Correspondent. E-mail: mohammadanary@yahoo.com
PAPER: 07/5072

108 JOURNAL OF CHEMICAL RESEARCH 2008
8.72 (1 H, d, 3JHH = 8 Hz, NH), 11.76(2 H, broad s, 2OH). 13C NMR
(125.8 MHz, d6-DMSO): δ 22.88 (CH3), 47.96 (CH), 120.05, 123.38,
123.77, 124.20, 127.43., 130.25, 131.05, 133.83, 135.23 and 155.00
(naphthol moiety), 114.92, 127.56, 146.47 and 150.85 (phenyl
moiety), 170.28,172.66 (2C=O).
Experimental
Melting points were determined with an Electrothermal 9100
apparatus. Elemental analyses were performed using a Heraeus CHN-
O-Rapid analyser. Mass spectra were recorded on a FINNIGAN-
MAT 8430 mass spectrometer operating at an ionisation potential of
70 eV. IR spectra were recorded on a Shimadzu IR-470 spectrometer.
1H and 13C NMR spectra were recorded on Bruker DRX-500 Avance
spectrometer for solutions in d6-DMSO using TMS as internal
standard. The chemicals used in this work purchased from Fluka
(Buchs, Switzerland) and were used without further purification.
4-[Acetylamino(3-nitrophenyl)methyl]-3-hydroxy-2-naphthoicacid
(3f): Yellow powder, m.p. 250–252oC, 94%; IR (KBr) (νmax cm-1):
3385, 3136–2527, 1723, 1672. Analyses: Calcd. for C20H16 N2O6: C,
63.16; H, 4.24; N, 7.36. Found: C, 63.20; H, 4.30; N, 7.40%. MS
1
(m/z, %): 380 (7). H NMR (500 MHz, d6-DMSO): δ 2.01 (3 H, s,
CH3), 7.24–8.65 (10 H, m, aromatic and NCH), 8.77 (1 H, d, 3JHH
= 8 Hz, NH), 11.74(2 H, broad s, 2OH). 13C NMR (125.8 MHz,
d6-DMSO): δ 22.92 (CH3), 47.70 (CH), 119.10, 120.81, 121.92,
123.32, 124.25, 130.17, 130.33, 133.85, 135.20 and 155.38 (naphthol
moiety), 114.91, 127.25, 131.07, 133.25, 145.08 and 148.22 (phenyl
moiety),170.28,172.65 (2C=O).
General procedure
To a magnetically stirred solution of 3-hydroxy-2-naphthoic acid
(3 mmol) and aldehyde (3 mmol) in acetonitrile (15 ml) was added
chlorosulfonic acid (6 mmol) at room temperature. The reaction
mixture was then refluxed for 1 h. The reaction mixture was poured
into 50 ml ice-water. The solid product was filtered, washed with ice-
water and recrystallised from ethyl acetate/n-hexane to give the pure
product.
4-[Acetylamino(4-chlorophenyl)methyl]-3-hydroxy-2-naphthoic
acid (3a): Yellow powder, m.p. 262–264oC, IR (KBr) (νmax cm-1):
3350, 3125–2605, 1725, 1669. Analyses: Calcd. for C20H16ClNO4:
C, 64.96; H, 4.36; N, 3.79. Found: C, 65.00; H, 4.28; N, 3.85%. MS
4-[Acetylamino(4-bromophenyl)methyl]-3-hydroxy-2-naphthoic
acid (3g):Yellow powder, m.p. 235–237oC, 90%; IR (KBr) (νmax cm-1):
3385, 3150–2590, 1740, 1663. Analyses: Calcd. for C20H16BrNO4:
C, 57.99; H, 3.89; N, 3.38. Found: C, 58.06; H, 3.95; N, 3.40%.
MS (m/z, %): 414 (9). 1H NMR (500 MHz, d6-DMSO): δ 1.99 (3 H, s,
CH3), 7.01 (1 H, d, 3JHH = 8 HZ, NCH), 7.31–8.61 (9 H, m, aromatic),
8.72 (1 H, d, 3JHH = 8 Hz, NH), 11.70(2 H, broad s, 2OH). 13C NMR
(125.8 MHz, d6-DMSO): δ 22.97(CH3), 47.55 (CH), 119.77, 120.53,
124.27, 126.40, 128.70, 129.49, 129.70, 131.40, 132.99 and 156.50
(naphthol moiety), 115.67, 127.10, 137.68 and 141.97 (phenyl
moiety), 170.03,172.05 (2C=O).
1
(m/z, %): 369 (11). H NMR (500 MHz, d6-DMSO): δ 1.98 (3 H, s,
CH3), 7.11 (1 H, d, 3JHH = 8 HZ, NCH), 7.25–8.62 (9 H, m, aromatic),
8.76 (1 H, d, 3JHH = 8 Hz, NH), 11.74 (2 H, broad s, 2 OH). 13C
NMR (125.8 MHz, d6-DMSO): δ 22.97 (CH3), 47.48 (CH), 120.58,
124.08, 128.32, 128.50, 129.17, 129.35, 130.99, 131.29, 133.50 and
153.06 (naphthol moiety), 114.82, 127.41, 135.27 and 141.52 (phenyl
moiety), 169.98,172.71 (2C=O).
4-[Acetylamino(3-methoxyphenyl)methyl]-3-hydroxy-2-naphthoic
acid (3h): Yellow powder, m.p. 224–226oC, IR (KBr) (νmax cm-1):
3385, 3118–2521, 1732, 1664. Analyses: Calcd. for C21H19NO5:
C, 69.03; H, 5.24; N, 3.83. Found: C, 69.10; H, 5.30; N, 3.80%. MS
4-[Acetylamino(3-chlorophenyl)methyl]-3-hydroxy-2-naphthoic
acid(3b):Yellowpowder, m.p. 258–260oC, 95%;IR(KBr)(νmax cm-1):
3385, 3155–2615, 1708, 1668. Analyses: Calcd. for C20H16ClNO4:
C, 64.96; H, 4.36; N, 3.79. Found: C, 65.00; H, 4.28; N, 3.85%. MS
1
(m/z, %): 365 (11). H NMR (500 MHz, d6-DMSO): δ 1.98 (3 H, s,
3
CH3), 3.66 (3 H, s, OCH3), 6.70 (1 H, d, JHH = 8 HZ, NCH), 7.11–
8.61 (9 H, m, aromatic), 8.70 (1 H, d, 3JHH = 8 Hz, NH), 11.75 (2 H,
broad s, 2OH). 13C NMR (125.8 MHz, d6-DMSO): δ 22.99 (CH3),
47.81 (CH), 55.35 (OCH3), 118.86, 119.75, 121.05, 124.00, 127.37,
129.69, 130.92, 133.29, 135.40, and 154.80 (naphthol moiety),
111.33, 112.95, 114.75, 129.88, 144.06 and 159.64 (phenyl moiety),
169.81,172.75 (2C=O).
1
(m/z, %): 369 (8). H NMR (500 MHz, d6-DMSO): δ 1.99 (3 H, s,
CH3), 7.01 (1 H, d, 3JHH = 8 HZ, NCH), 7.27–8.63 (9 H, m, aromatic),
8.71 (1 H, d, 3JHH = 8 Hz, NH), 11.73(2 H, broad s, 2OH). 13C NMR
(125.8 MHz, d6-DMSO): δ 22.95 (CH3), 47.60 (CH), 120.41, 123.51,
124.13, 125.23, 126.11, 126.78, 130.10, 130.49, 133.59 and 154.92
(naphthol moiety), 114.87, 127.39, 131.01, 133.42, 135.26 and
145.16 (phenyl moiety), 170.07,172.70 (2C=O).
4-[Acetylamino(2-methoxyphenyl)methyl]-3-hydroxy-2-naphthoic
acid (3i): Yellow powder, m.p. 244–246oC, IR (KBr) (νmax cm-1):
3395, 3130–2570, 1703, 1669. Analyses: Calcd. for C21H19NO5:
C, 69.03; H, 5.24; N, 3.83. Found: C, 69.10; H, 5.30; N, 3.80%. MS
4-[Acetylamino(2-chlorophenyl)methyl]-3-hydroxy-2-naphthoic
acid (3c):Yellow powder, m.p. 246–248oC, 95%; IR (KBr) (νmax cm-1):
3390, 3130–2580, 1729, 1667. Analyses: Calcd. for C20H16ClNO4:
C, 64.96; H, 4.36; N, 3.79. Found: C, 65.00; H, 4.28; N, 3.85%. MS
1
(m/z, %): 365 (9). H NMR (500 MHz, d6-DMSO): δ 1.93 (3 H, s,
CH3), 3.58 (3 H, s, OCH3), 7.12–8.61 (10 H, m, aromatic and NCH),
8.74 (1 H, d, 3JHH = 8 Hz, NH), 11.64 (2 H, broad s, 2OH). 13C NMR
(125.8 MHz, d6-DMSO): δ 22.76 (CH3), 47.75 (CH), 53.75 (OCH3),
119.33, 123.34, 123.93, 126.95, 128.84, 129.75, 129.87, 130.21,
132.65 and 155.37 (naphthol moiety), 114.64, 127.24, 131.01, 133.55,
135.80 and 139.57 (phenyl moiety), 169.27, 172.83 (2C=O).
1
(m/z, %): 369 (10). H NMR (500 MHz, d6-DMSO): δ 1.94 (3 H, s,
CH3), 7.15 (1 H, d, 3JHH = 8 HZ, NCH), 7.23–8.62 (9 H, m, aromatic),
8.74 (1 H, d, 3JHH = 8 Hz, NH), 11.63 (2 H, broad s, 2OH). 13C NMR
(125.8 MHz, d6-DMSO): δ 22.76 (CH3), 47.76 (CH), 119.34, 123.35,
123.93, 126.95, 128.84, 129.75, 129.86, 130.21, 132.66 and 155.38
(naphthol moiety), 114.65, 127.25, 131.01, 133.55, 135.81 and
139.57 (phenyl moiety), 169.29,172.84 (2C=O).
Received 5 February 2008; accepted 24 February 2008
4-[Acetylamino(4-methylphenyl)methyl]-3-hydroxy-2-naphthoic
acid (3d): White powder, m.p. 228–230oC, IR (KBr) (νmax cm-1):
3350, 3182–2630, 1721, 1669. Analyses: Calcd. for C21H19NO4: C,
72.19; H, 5.48; N, 4.01. Found: C, 72.34; H, 5.40; N, 4.05%. MS
Paper 08/5072
doi: 10.3184/030823408X293224
References
1
(m/z, %): 349 (10). H NMR (500 MHz, d6-DMSO): δ 1.97 (3 H, s,
1
2
3
4
5
6
7
P. Eibracht and A. Schimdt, Chem. Rev., 1999, 99, 3329.
I. Ugi, Pure Appl. Chem., 2001, 77, 187.
CH3), 2.22 (3 H, s, CH3), 6.95 (1 H, d, 3JHH = 8 HZ, NCH), 7.21–8.61
(9 H, m, aromatic), 8.75 (1 H, d, 3JHH = 8 Hz, NH), 11.73(2 H, broad
s, 2OH). 13C NMR (125.8 MHz, d6-DMSO): δ 20.99 and 23.03
(2 CH3), 47.71 (CH), 121.24, 123.96, 126.41, 127.12, 129.13, 129.78,
130.90, 133.21, 135.41 and 154.80 (naphthol moiety), 114.75, 127.39,
135.73 and 139.32 (phenyl moiety), 169.75,172.78 (2C=O).
M.C. Bagley, J.W. Cale and J. Bower, Chem. Commun., 2002, 1682.
U. Bora, A. Saikia and R.C. Boruah, Org. Lett., 2003, 5, 435.
I. Ugi, B. Werner and A. Domling, Molecules, 2003, 8, 53.
A. Domling, Curr. Opin. Chem. Biol., 2000, 4, 318.
A.T. Khan, L.H. Choudhury, T. Parvin and M. Asif Ali, Tetrahedron Lett.,
2006, 47, 8137.
4-[Acetylamino(4-nitrophenyl)methyl]-3-hydroxy-2-naphthoicacid
(3e): Yellow powder, m.p. 253–255oC, 90%; IR (KBr) (νmax cm-1):
3380, 3134–2580,1729, 1671. Analyses: Calcd. for C20H16 N2O6: C,
63.16; H, 4.24; N, 7.36. Found: C, 63.20; H, 4.30; N, 7.40%. MS
8
9
M.M. Heravi, L. Ranjbar, F. Derikvand and F.F. Bamoharram, J. Mol.
Cat. A, 2007, 271, 28.
M. Anary-Abbasinejad, H. Anaraki-Ardakani, A. Saidipoor and M. Shojaee,
J. Chem. Res., 2007, 537.
1
(m/z, %): 380 (8). H NMR (500 MHz, d6-DMSO): δ 1.96 (3 H, s,
10 M. Anary-Abbasinejad, A. Hassanabadi, M. Kamali-Gharamaleki,
CH3), 7.12 (1 H, d, 3JHH = 8 HZ, NCH), 7.25–8.65 (9 H, m, aromatic),
A. Saidipoor and H. Anaraki-Ardakani, J. Chem. Res., 2007, 644.
PAPER: 07/5072