Reaction between isocyanides and salicylic acid or 3-hydroxy-2-naphthoic acid to produce benzo or naphtho-fused 2-(alkylamino)-1,3-dioxin-4-one derivatives

Article abstract of DOI:10.3184/030823408X293215

Protonation of isocyanides by salicylic acid or 3-hydroxy-2-naphthoic acid followed by addition of the conjugate anion of the acid to the resulting nitrilium cation and subsequent cyclisation of the iminoester intermediate formed leads to benzo or naphtho

Full text of DOI:10.3184/030823408X293215

JOURNAL OF CHEMICAL RESEARCH 2008
FEBRUARY, 95–96
RESEARCH PAPER 95
Reaction between isocyanides and salicylic acid or 3-hydroxy-2-naphthoic
acid to produce benzo or naphtho-fused 2-(alkylamino)-1,3-dioxin-4-one
derivatives
Mohammad Anary-Abbasinejad* and Alireza Hassanabadi
Department of Chemistry, Islamic Azad University, Yazd Branch, PO Box 89195-155, Yazd, Iran
Protonation of isocyanides by salicylic acid or 3-hydroxy-2-naphthoic acid followed by addition of the conjugate
anion of the acid to the resulting nitrilium cation and subsequent cyclisation of the iminoester intermediate formed
leads to benzo or naphtho-fused 2-(alkylamino)-1,3-dioxin-4-one derivatives in excellent yields.
Keywords: isocyanides, salicylic acid, 3-hydroxy-2-naphthoic acid, addition reaction
+
.
Isocyanides, as the only class of stable organic compounds
.
C
N
І
R
C
N
R
with a two-valence carbon atom, are very reactive species
and react with many functional groups through different
mechanisms. On the basis of valence-bond theory, isocyanide
functionality can be shown as two resonance forms І and ІІ
(Scheme 1). So, isocyanides have carbenic character on the
basis of the resonance form І and nucleophilic character on the
basis of the form ІІ. In most addition reactions of isocyanides
both the nucleophile and electrophile add to the α-carbon
atom, and no species is added on the nitrogen atom.
The addition reaction of different classes of chemical
compounds to isocyanides has been of particular interest for
many years. For example, the addition of hydrogen halides
to alkyl isocyanides at low temperatures has been reported
to produce N-alkyl formimidoyl halides.1 The addition
of hydrazoic acid to isocyanides was reported to produce
tetrazole derivatives.2,3 The addition of organic CH-acids,
such as Meldrom’s acid4 or 1,1,1-trifluoro pentane-2,3-
diones,5 on isocyanides has also been reported. Isocyanides
have been reported to react with two equivalents of carboxylic
ІІ
Scheme 1
acids to afford the corresponding carboxylic formamides and
carboxylic anhydrides.1 Recently, it has been reported that
the reaction of isocyanides with sulfonic acids leads to the
corresponding sulfonamides.6 A similar reaction was reported
between isocyanides and carboxylic acids in methanol to yield
the corresponding carboxamides.7 In the course of our work
with isocyanides,8-10 we report here that the reaction between
isocyanides and hydroxy carboxylic acids, such as salicylic acid
or 3-hydroxy-2-naphthoic acid, produces benzo or naphtho-
fused 2-(alkylamino)-1,3-dioxin-4-one derivatives in excellent
yields. Thus the reaction between cyclohexyl isocyanide
and salicylic acid in acetone at ambient temperature yields
2-(cyclohexyamino)benzo-1,3-dioxin-4-one in 88% yield.
As shown in Scheme 2, similar products were obtained from
the reaction of 3-hydroxy-2-naphthoic acid with isocyandes.
H
O
O
N
OH
O
X
Y
X
Y
_
C
+
R
+
N
R
O
OH
2
3
1
Entry
1
Substrate
R
Product
Yield%*
90
H
O
N
OH
OH
O
t-Butyl
O
O
3a
3b
O
O
H
N
OH
OH
2
3
Cyclohexyl
t-Butyl
88
87
O
O
H
N
O
OH
O
OH
O
O
O
3c
H
N
OH
4
Cyclohexyl
91
O
OH
O
O
3d
*Isolated yields
Scheme 2
* Correspondent. E-mail: mohammadanary@yahoo.com
PAPER: 08/5020

96 JOURNAL OF CHEMICAL RESEARCH 2008
OH
OH
OH
_
+
+
_
HC N
C N
+
+
O
O
O
4
5
OH
N
3a
O
O
6
Scheme 3
δ 29.03 (3 CH3), 51.67 (C), 83.56 (CH), 112.97, 118.35, 119.62,
130.09, 136.44 and 162.47 (aromatic), 171.89 (C=O).
The structure of compounds 3a–d was deduced from
their elemental analyses and IR, 1H NMR and 13C NMR
spectroscopy. The mass spectra of these compounds displayed
2-(Cyclohexylamino)-1,3-dioxin-4-one (3b): White powder,
m.p. 115–116oC, IR (KBr) (νmax, cm-1): 3260 (NH), 1680 (C=O).
Analyses: Calcd. for C14H17NO3: C, 68.00; H, 6.93; N, 5.66%.
Found: C, 67.7; H, 6.9; N, 5.3%. MS (m/z, %): 247(7). 1H NMR
(500 MHz, CDCl3): δ 1.12–1.96 (10 H, m, 5 CH2 of cyclohexyl), 3.83
(1H, m, CH of cyclohexyl), 5.81 (1H, CH), 6.92–7.83 (4 H, m, 4 CH
aromatic), 10.67(1 H, s, NH). 13C NMR (125.8 MHz, CDCl3): δ 25.14,
25.88, 33.32 (5 CH2 of cyclohexyl), 48.65 (CH of cyclohexyl), 83.25
(CH), 112.94, 118.33, 119.62, 130.15, 136.45 and 162.46(aromatic),
171.75 (C=O).
1
molecular ion peaks at appropriate m/z values. The H NMR
spectrum of 3a exhibited two single sharp lines readily
recognised as arising from tert-butyl (δ = 1.4) and methine (δ
= 5.7) protons, along with signals (δ = 6.9–7.8) for aromatic
protons. A single line was observed at δ = 10.7 which arises
from the NH proton and disappeared by addition of D2O
to the CDCl3 solution of 3a. The 13C NMR spectrum of 3a
showed 10 distinct resonances in agreement with the proposed
structure.
The formation of compound 3a can be rationalised as shown
in Scheme 3. Protonation of t-butyl isocyanide by carboxyl
functionality followed by the nucleophilic addition of the
conjugate anion of salicylic acid 4 on the nitrilium cation 5
leads to iminoester 6 which then cyclises to product 3a.
In summary, we report here that the addition reaction
between isocyanides and salicylic acid or 3-hydroxy-2-
naphthoic acid in acetone affords benzo or naphtho-fused 2-
(alkylamino)-1,3-dioxin-4-one derivatives in excellent yields.
The reaction is carried out under neutral conditions and
starting materials are used without any need for purification
or modification.
2-(Tert-butylamino)naphtho[2, 3-d][1,3]dioxin-4-one (3c): Yellow
powder, m.p. 123–125oC, IR(KBr) (νmax, cm-1): 3395 (NH), 1674
(C=O). Analyses: Calcd. for C16H17NO3: C, 70.83; H, 6.32; N, 5.16%.
1
Found: C, 70.9; H, 6.2; N, 5.4%. MS (m/z, %): 271 (8). H NMR
(500 MHz, CDCl3): δ 1.42 (9 H, s, 3 CH3), 5.81 (1H, s, CH), 7.30–
8.46 (6H, m, 6 CH aromatic), 10.35 (1 H, s, NH). 13C NMR (125.8
MHz, CDCl3): δ 29.06 (3 CH3), 51.76 (C), 83.83 (CH), 112.45,
114.82, 124.57, 126.80, 127.37, 129.53, 129.80, 132.71, 138.48 and
156.92 (aromatic), 171.78 (C=O).
2-(Cyclohexylamino)naphtho[2,3-d][1,3]dioxin-4-one
(3d):
Yellow powder, m.p. 136–138oC, IR (KBr) (νmax, cm-1): 3262 (NH),
1672 (C=O). Analyses: Calcd. for C18H19NO3: C, 72.71; H, 6.44;
N, 4.71%. Found: C, 72.9; H, 6.4; N, 4.4%. MS (m/z, %): 297(6).
1H NMR (500 MHZ, CDCl3): δ 1.19–1.86 (10 H, m, 5 CH2 of cyclohexyl),
3.71 (1H, m, CH of cyclohexyl), 6.13 (1H, s, CH), 7.33–8.59 (6 H, m,
6 CH aromatic), 10.32 (1 H, s, NH). 13C NMR (125.8 MHZ, CDCl3):
δ 24.70, 25.41, 32.84 (5 CH2 of cyclohexyl), 48.84 (CH of cyclohexyl),
83.05 (CH), 111.65, 115.62, 124.44, 126.56, 127.40, 129.56, 129.63,
133.30, 138.08 and 156.76 (aromatic), 170.83 (C=O).
Experimental
Melting points were determined with an electrothermal 9100
apparatus. Elemental analyses were performed using 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 Shimadzu IR-470 spectrometer.
1H, and 13C NMR spectra were recorded on Bruker DRX-500 Avance
spectrometer at solution in CDCl3 using TMS as internal standard.
The chemicals used in this work purchased from fluka (Buchs,
Switzerland) and were used without further purification.
Received 1 January 2008; accepted 5 February 2008
Paper 08/5020
doi: 10.3184/030823408X293215
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General procedure
A solution of acid (2 mmol) and isocyanide (2 mmol) in acetone was
stirred at room temperature for 24 h. The solvent was removed under
reduced pressure and the residue was purified by silica gel (Merck
silica gel 60, 230–400 mesh) column chromatography using hexane–
ethyl acetate mixture as eluent. The solvent was removed under
reduced pressure to afford the product.
2-(tert-butylamino)-1,3-benzodioxin-4-one (3a): White powder,
m.p. 69–70oC, IR (KBr) (νmax, cm-1): 3360 (NH), 1667 (C=O).
Analyses: Calcd. for C12H15NO3: C, 65.14; H, 6.83; N, 6.33%. Found:
C, 65.2; H, 6.6; N, 6.4%. MS (m/z,%): 221 (8). 1H NMR (500 MHz,
CDCl3): δ 1.4 (9 H, s, 3 CH3), 5.77 (1H, s, CH), 6.92–7.82 (4 H, m,
4 CH aromatic), 10.70 (1 H, s, NH). 13C NMR (125.8 MHz, CDCl3):
5
6
7
8
9
10 M. Anary-Abbasinejad, M.H. Mosslemin, S. Tahan and H. Anaraki-
Ardakani, J. Chem. Res., 2006, 170.
PAPER: 08/5020