Ruthenium(ii)-catalyzed decarbonylative and decarboxylative coupling of isatoic anhydrides with salicylaldehydes: access to aryl 2-aminobenzoates

Article abstract of DOI:10.1039/d1ob00027f

A ruthenium(ii)-catalyzed coupling reaction of isatoic anhydrides and salicylaldehydes has been developed for the synthesis of 2-aminobenzoates. This reaction proceeds through metal-catalyzed decarbonylation and decarboxylation to afford good yields of aryl 2-aminobenzoates.

Full text of DOI:10.1039/d1ob00027f

Organic &
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Ruthenium(II)-catalyzed decarbonylative and
decarboxylative coupling of isatoic anhydrides
with salicylaldehydes: access to aryl
2-aminobenzoates†
Cite this: Org. Biomol. Chem., 2021,
19, 2725
Bidisha R. Bora, Rashmi Prakash, Sabera Sultana and Sanjib Gogoi
*
Received 6th January 2021,
Accepted 23rd February 2021
A ruthenium(II)-catalyzed coupling reaction of isatoic anhydrides and salicylaldehydes has been developed
for the synthesis of 2-aminobenzoates. This reaction proceeds through metal-catalyzed decarbonylation
and decarboxylation to afford good yields of aryl 2-aminobenzoates.
DOI: 10.1039/d1ob00027f
rsc.li/obc
The aryl esters of benzoic acids are very important synthons in the presence of the ligand DPEphos for the synthesis of aryl
for the synthesis of various pharmaceutically active com- o-aminobenzoates (Scheme 1, eqn (1)).8 In continuation of our
pounds as well as natural products.1 In photochemistry, aryl work on metal-catalyzed C–H, C–C functionalization reac-
benzoates are used as chemiluminescent indicators.2 Among tions,9 herein, we disclose an unprecedented decarbonylative
the aryl benzoates, particularly, the aryl 2-aminobenzoates and decarboxylative coupling reaction of isatoic anhydrides
have received significant attention because of their utility in and salicylaldehydes for the synthesis of aryl 2-aminobenzo-
the synthesis of bioactive nitrogen containing heterocycles.3 ates (Scheme 1, eqn (2)).
Some of these 2-aminobenzoates have application in fragrance
Initially, the Ru(II)-catalyzed coupling reaction between
and flavor industries owing to their pleasant scent.4 isatoic anhydride (1a) and salicyldehyde (2a) was selected as a
Furthermore, some of the aminobenzoate derivatives exhibit model reaction to find out the optimized reaction conditions
anti-bacterial, anti-fungal and anti-inflammatory activities.5 for the synthesis of the ester 3aa. As shown in Table 1, among
The drug glafenine is a nonsteroidal anti-inflammatory drug all the metal complexes studied for this esterification reaction,
that possesses 2-aminobenzoate as the key skeleton.
only the [{RuCl2(p-cymene)}2] catalyst provided the ester 3aa in
t
These aryl benzoates are traditionally synthesized by esteri- 43% yield using Cu(OAc)2 and AmOH as the additive and
fication, transesterification and Baeyer–Villiger oxidation reac- solvent, respectively. To improve the yield of 3aa, some other
tions.6 However, the highly acidic and basic conditions used in commonly used additives such as CsOAc, AgOAc and KOAc
esterification and transesterification reactions might not be were tested which revealed CsOAc to be the best additive
suitable for some compounds possessing sensitive functional which afforded 58% yield of 3aa (entry 5). Then, further
groups in the molecule. Again, acid-catalyzed esterification of screening of some common solvents proved the aprotic solvent
anthranilic acid to get the ester is a tough reaction owing to
the presence of ortho amino group. This amino group con-
sumes large amount of the acid before esterification with the
alcohol. To overcome these problems, designing of new
method for the synthesis of these esters are very essential. In
recent years, various metal-catalyzed coupling reactions have
been developed for the synthesis of benzoic esters.7 However,
metal-catalyzed reactions for the synthesis of aryl 2-amino-
benzoates are rare. Wu and co-workers reported a Pd2(dba)3-
catalyzed reaction of isatoic anhydrides with arylboronic acids
Applied Organic Chemistry, Chemical Sciences & Technology Division,
CSIR-North East Institute of Science and Technology, Jorhat-785006, AcSIR,
Ghaziabad-201002, India. E-mail: skgogoi1@gmail.com, sanjibgogoi@neist.res.in
†Electronic supplementary information (ESI) available: Copies of 1H NMR, 13C
NMR spectra of the synthesized compounds. See DOI: 10.1039/d1ob00027f
Scheme 1 Metal-catalyzed synthesis of aryl 2-aminobenzoates.
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Table 1 Reaction conditions optimization for 3aaa
Entry
Catalyst
Additive
Solvent
3aab (%)
1
2
3
4
5
6
7
8
Pd(OAc)2
RuCl3·xH2O
[RuCl2(PPh3)3]
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
Cu(OAc)2·H2O
CsOAc
AgOAc
KOAc
CsOAc
CsOAc
CsOAc
CsOAc
tAmOH
tAmOH
tAmOH
tAmOH
tAmOH
tAmOH
tAmOH
MeCN
0
0
0
[{RuCl2(p-cymene)}2]
[{RuCl2(p-cymene)}2]
[{RuCl2(p-cymene)}2]
[{RuCl2(p-cymene)}2]
[{RuCl2(p-cymene)}2]
[{RuCl2(p-cymene)}2]
[{RuCl2(p-cymene)}2]
[{RuCl2(p-cymene)}2]
43
58
27
38
25
42
81
54
9
10
11
DCE
Toluene
Dioxane
a Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), catalyst
(2.5 mol%), additive (0.5 mmol) and solvent (4.0 mL) heated at 95 °C
for 7 h under air. b Isolated yields.
toluene to be the best solvent for the synthesis of the ester 3aa
(81%, entry 10).
Initially the optimized reaction conditions were applied to
study the substrate scope of the isatoic anhydrides (1a–g). As
shown in Scheme 2, isatoic anhydrides substituted with mono-
methyl and di-methyl substituents 1b–c provided 70–78%
yields of the products 3ba–ca. Similarly, isatoic anhydrides
substituted with electron-withdrawing substituents such as
fluoro, chloro and bromo 1d–g, provided good yields (56–68%)
of the products 3da–ga, irrespective of the position of the sub-
stituents on the aromatic ring. Next, the scope of the salicylal-
dehydes 2b–p were studied with 1a for this esterification reac-
tion. As shown in Scheme 2, various salicylaldehydes posses-
sing electron-rich substituents such as methyl, tert-butyl,
methoxy, ethoxy and diethylamino on the phenyl ring of salicy-
laldehyde 2b–g provided 48–80% yields of the esters 3ab–ag.
Similarly, some of the salicylaldehydes substituted with one or
two electron-withdrawing substituents such as fluoro, chloro
and bromo on the phenyl ring of salicylaldehyde 2h–m pro-
vided 64–75% yields of the products 3ah–am. For the products
3ag and 3ai, 4-(diethylamino)-2-hydroxybenzaldehyde (2g) and
4-chloro-2-hydroxybenzaldehyde (2i) were used. The methyl
and chloro group substituted salicylaldehyde 1n also turned
out to be a good substrate for this reaction which provided
71% yield of product 3an. The sensitive allyl group containing
salicylaldehyde 2o provided 44% yield of 3ao. Finally,
Scheme 2 Scope with isatoic anhydrides and salicylaldehydes.
Reaction conditions:
1 (0.5 mmol), 2a (0.5 mmol), Ru(II) catalyst
(2.5 mol%), CsOAc (0.5 mmol) and toluene (4.0 mL) heated at 95 °C for
7 h under air.
Scheme 3 Gram-scale synthesis of ester 3aa.
2-hydroxy-1-naphthaldehyde 2p was tested to afford 50% yield the evaluation of carbon monoxide and carbon dioxide,
of ester 3ap. The reaction of 1a and 3-hydroxy-2-naphthalde- respectively, from the reaction mixture.9b
hyde also provided the same ester 3ap in 53% yield under the
A plausible mechanism for the formation of 3aa is pro-
standard reaction conditions. A gram-scale esterification reac- posed in Scheme 4, based on literature reports.10 As the reac-
tion between 1a and 2a provided 72% yield of 3aa, which tion of 1a, 2a and [{RuCl2(p-cymene)}2] in the absence of the
suggest the practical applicability of this reaction (Scheme 3). additive CsOAc could not provide 3aa in toluene at 95 °C, prob-
The phosphomolybdic acid test and lime water test indicated ably [Ru(OAc)2(p-cymene)] (A) might be the active catalyst.10e
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air for 7 hours. The solvent was removed under vacuum and
the crude reaction mixture was poured into water and extracted
with dichloromethane (25 mL × 2). The dichloromethane layer
was then washed with brine. Finally, it was dried over anhy-
drous Na2SO4 and the solvent was removed under vacuum.
The crude product thus obtained was purified by silica gel
(100–200 mesh) column chromatography using EtOAc/Hexane
as the eluant to afford 3.
Compound characterizations
Phenyl 2-aminobenzoate (3aa).8 Synthesized using GPA from
1a (81 mg,0.5 mmol) and 2a (61 mg, 0.5 mmol). The crude
product was purified by column chromatography using EtOAc/
Hexane (1 : 9) to afford white solid of 3aa (86 mg, 81%). M.p.:
70–72 °C. 1H NMR (500 MHz, CDCl3) δ 8.09 (d, J = 7.9 Hz, 1H),
7.43 (t, J = 7.5 Hz, 2H), 7.36–7.33 (m, 1H), 7.29–7.26 (m, 1H),
7.20–7.18 (m, 2H), 6.74–6.70 (m, 2H), 5.78 (bs, 2H). 13C NMR
(125 MHz, CDCl3) δ 166.7, 151.1, 150.7, 134.8, 131.5, 129.4,
125.7, 122.6, 121.9, 116.7, 116.3, 114.4, 109.5. Anal. Calcd for
C13H11NO2: C, 73.23; H, 5.20; N, 6.57. Found: C, 73.68; H, 5.01;
N, 6.81.
Scheme 4 Possible mechanism.
Phenyl 2-amino-5-methylbenzoate (3ba).8 Synthesized using
GPA from 1b (88 mg, 0.5 mmol) and 2a (61 mg, 0.5 mmol)
which was then purified by column chromatography using
EtOAc/Hexane (1 : 9) to afford white solid (88 mg, 78%). M.p.:
60–62 °C. 1H NMR (500 MHz, CDCl3) δ 7.89 (s, 1H), 7.43 (t, J =
7.5 Hz, 2H), 7.29–7.25 (m, 1H), 7.15–7.20 (m, 3H), 6.64 (d, J =
8.4 Hz, 1H), 5.62 (bs, 2H), 2.28 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 166.8, 150.7, 149.1, 136.0, 131.0, 129.4, 125.7, 125.4,
121.9, 116.8, 109.3, 20.2. Anal. Calcd for C14H13NO2: C, 73.99;
H, 5.77; N, 6.16. Found: C, 74.20; H, 5.83; N, 5.93.
First, the active catalyst A forms Ru(II)-complex B by elimin-
ation of one molecule of acetic acid. This complex B might
exist as tautomer with π-bonded Ru-complex C, which on dec-
arbonylation generates a Ru–CO complex D.10a Then, oxidative
addition of this Ru complex in the C–O bond of 1a followed by
decarboxylation and decarbonylation affords Ru-complex E.
Reductive elimination of the metal initially generates Ru
complex F, which in the presence of acetic acid affords the
active catalyst A and the ester 3aa.
In conclusion, a novel Ru(II)-catalyzed coupling reaction of
isatoic anhydride and salicylaldehyde was developed. This
reaction proceeds through decarboxylation and decarbonyla-
tion to afford good yields of important aryl 2-aminobenzoates.
Phenyl 2-amino-3,5-dimethylbenzoate(3ca). Synthesized
using GPA from 1c (95 mg, 0.5 mmol) and 2a (61 mg,
0.5 mmol) which was then purified by column chromato-
graphy using EtOAc/Hexane (1 : 9) to afford white solid (84 mg,
1
70%). M.p.: 101–103 °C. H NMR (500 MHz, CDCl3) δ 7.81 (s,
1H), 7.43 (t, J = 7.7 Hz, 2H), 7.29–7.25 (m, 1H), 7.18 (d, J =
8.3 Hz, 2H), 7.12 (s, 1H), 5.73 (bs, 2H), 2.27 (s, 3H), 2.18 (s,
3H). 13C NMR (125 MHz, CDCl3) δ 167.2, 150.8, 147.6, 136.9,
129.4, 128.8, 125.6, 124.7, 123.2, 122.0, 108.9, 20.2, 17.3. Anal.
Calcd for C15H15NO2: C, 74.67; H, 6.27; N, 5.81. Found: C,
74.51; H, 6.45; N, 6.09.
Experimentalsections
General information
Melting points were measured with a Buchi B-540 melting
point apparatus. The NMR spectra were recorded on Bruker
Avance III 500 MHz FTNMR spectrometer using tetramethyl-
silane (TMS) as an internal standard. All the commercially
available regents were used as received. All experiments were
monitored by thin layer chromatography (TLC). TLC was per-
formed on Merck TLC Silica gel 60 F254 precoated plates.
Column chromatography was performed on silica gel
(100–200 mesh, Merck). The starting isatoic anhydrides were
synthesized using isatins by following a known procedure.11
Phenyl 2-amino-5-fluorobenzoate(3da).8 Synthesized using
GPA from 1d (90 mg, 0.5 mmol) and 2a (61 mg, 0.5 mmol)
which was then purified by column chromatography using
EtOAc/Hexane (1 : 9) to afford yellow solid of 3da (78 mg, 68%).
M.p.: 110–112 °C. 1H NMR (500 MHz, CDCl3) δ 7.77 (dd, J =
9.6, 3.0 Hz, 1H), 7.47–7.42 (m, 2H), 7.31–7.25 (m, 1H),
7.20–7.16 (m, 2H), 7.09–7.14 (m, 1H), 6.68 (dd, J = 9.1, 4.5 Hz,
1H), 5.65 (bs, 2H). 13C NMR (125 MHz, CDCl3) δ 165.9, 153.7
(d, J = 234 Hz), 150.4, 147.7, 129.4, 125.9, 122.9 (d, J = 23.8 Hz),
121.8, 117.9 (d, J = 7.5 Hz), 116.2 (d, J = 23.8 Hz), 116.14, 109.3
(d, J = 7.5 Hz). Anal. Calcd for C13H10FNO2: C, 67.53; H, 4.36;
General procedure A (GPA)
A mixture of isatoic anhydride (1, 0.5 mmol), salicyaldehyde N, 6.06. Found: C, 67.79; H, 4.30; N, 5.87.
(2, 0.5 mmol), [RuCl2(p-cymene)]2 (2.5 mol%), CsOAc
Phenyl 2-amino-5-chlorobenzoate (3ea).8 Synthesized using
(0.5 mmol) in toluene (4.0 mL) was stirred at 95 °C under open GPA from 1e (98 mg, 0.5 mmol) and 2a (61 mg, 0.5 mmol)
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which was then purified by column chromatography using 8.9 Hz, 2H), 6.94 (d, J = 8.9 Hz, 2H), 6.71 (t, J = 8.1 Hz, 2H),
EtOAc/Hexane (1 : 9) to afford yellow solid of 3ea (75 mg) with 5.77 (bs, 2H), 3.82 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 167.1,
61% yield. M.p.: 100–102 °C. 1H NMR (500 MHz, CDCl3) δ 8.06 157.1, 151.1, 144.1, 134.7, 131.5, 122.6, 116.6, 116.3, 114.4,
(s, 1H), 7.44 (t, J = 8.1 Hz, 2H), 7.30–7.26 (m, 2H), 7.18 (d, J = 109.6, 55.5. Anal. Calcd for C14H13NO3: C, 69.12; H, 5.39; N,
7.6 Hz, 2H), 6.66 (d, J = 8.8 Hz, 1H), 5.79 (bs, 2H). 13C NMR 5.76. Found: C, 68.80; H, 5.27; N, 5.30.
(125 MHz, CDCl3) δ 165.8, 150.4, 149.6, 134.8, 130.6, 129.4,
2-Ethoxyphenyl 2-aminobenzoate (3ae). Synthesized using
125.9, 121.7, 120.7, 118.1, 110.3. Anal. Calcd for C13H10ClNO2: GPA from 1a (81 mg, 0.5 mmol) and 2e (83 mg, 0.5 mmol)
C, 63.04; H, 4.07; N, 5.66. Found: C, 63.27; H, 4.30; N, 5.82.
which was then purified by column chromatography using
Phenyl 2-amino-4-chlorobenzoate (3fa).12 Synthesized using EtOAc/Hexane (1 : 9) to afford white solid of 3ae (78 mg, 61%).
1
GPA from 1f (98 mg, 0.5 mmol) and 2a (61 mg, 0.5 mmol) M.p.: 67–70 °C. H NMR (500 MHz, CDCl3) δ 8.12 (dd, J = 8.3,
which was then purified by column chromatography using 1.6 Hz, 1H), 7.35–7.32 (m, 1H), 7.23–7.19 (m, 1H), 7.15 (dd, J =
EtOAc/Hexane (1 : 9) to afford white solid of 3fa (71 mg, 58%). 7.8, 1.6 Hz, 1H), 7.02–6.97 (m, 2H), 6.74–6.70 (m, 2H), 5.73 (bs,
M.p.: 95–97 °C. 1H NMR (500 MHz, CDCl3) δ 8.01 (d, J = 2H), 4.07 (q, J = 6.9 Hz, 2H), 1.31 (t, J = 7.0 Hz, 3H). 13C NMR
8.6 Hz, 1H), 7.43 (t, J = 7.5 Hz, 2H), 7.29–7.25 (m, 1H), (125 MHz, CDCl3) δ 166.7, 150.9, 150.7, 140.2, 134.5, 131.8,
7.19–7.16 (m, 2H), 6.73–6.66 (m, 2H), 5.86 (bs, 2H). 13C NMR 126.6, 123.1, 120.7, 116.5, 116.3, 113.7, 109.8, 64.4, 14.7. Anal.
(125 MHz, CDCl3) δ 166.2, 151.8, 150.5, 140.8, 132.9, 129.4, Calcd for C15H15NO3: C, 70.02; H, 5.88; N, 5.44. Found: C,
125.8, 121.8, 116.8, 116.0, 108.1. Anal. Calcd for C13H10ClNO2: 70.31; H, 5.94; N, 5.37.
C, 63.04; H, 4.07; N, 5.66. Found: C, 62.86; H, 4.08; N, 5.93.
2-Methoxyphenyl 2-aminobenzoate (3af).8 Synthesized using
Phenyl 2-amino-5-bromobenzoate (3ga). Synthesizedusing GPA from 1a (81 mg, 0.5 mmol) and 2f (76 mg, 0.5 mmol)
GPA from 1g (121 mg, 0.5 mmol) and 2a (61 mg, 0.5 mmol) which was then purified by column chromatography using
which was then purified by column chromatography using EtOAc/Hexane (1 : 9) to afford white solid of 3af (71 mg, 59%).
1
EtOAc/Hexane (1 : 9) to afford white solid of 3ga (82 mg, 56%). M.p.: 111–112 °C. H NMR (500 MHz, CDCl3) δ 8.07 (d, J = 8.4
M.p.: 111–113 °C. 1H NMR (500 MHz, CDCl3) δ 8.19 (s, 1H), Hz, 1H), 7.37–7.29 (m, 2H), 6.84–6.77 (m, 2H), 6.75–6.69 (m,
7.45–7.37 (m, 3H), 7.29–7.24 (m, 1H), 7.17 (d, J = 7.5 Hz, 2H), 3H), 5.77 (bs, 2H), 3.82 (s, 3H). 13C NMR (125 MHz, CDCl3)
6.59 (d, J = 8.8 Hz, 1H), 5.80 (bs, 2H). 13C NMR (125 MHz, δ 166.6, 160.5, 151.7, 151.1, 134.8, 131.5, 129.7, 116.7, 116.3,
CDCl3) δ 165.7, 150.4, 150.0, 137.4, 133.6, 129.4, 125.9, 121.8, 114.1, 111.6, 109.5, 107.8, 55.3. Anal. Calcd for C14H13NO3: C,
118.4, 110.8, 107.3. Anal. Calcd for C13H10BrNO2: C, 53.45; H, 69.12; H, 5.39; N, 5.76. Found: C, 69.26; H, 5.10; N, 5.83.
3.45; N, 4.79. Found: C, 53.46; H, 3.32; N, 4.97.
3-(Diethylamino)phenyl 2-aminobenzoate (3ag). Synthesized
m-Tolyl 2-aminobenzoate (3ab).8 Synthesized using GPA using GPA from 1a (81 mg, 0.5 mmol) and 2g (96 mg,
from 1a (81 mg, 0.5 mmol) and 2b (68 mg, 0.5 mmol) which 0.5 mmol) which was then purified by column chromato-
was then purified by column chromatography using EtOAc/ graphy using EtOAc/Hexane (1 : 9) to afford yellow solid of 3ag
Hexane (1 : 9) to afford colorless oily product of 3ab (91 mg, (68 mg, 48%). M.p.: 43–45 °C. 1H NMR (500 MHz, CDCl3) δ
80%). 1H NMR (500 MHz, CDCl3) δ 8.08 (d, J = 7.7 Hz, 1H), 8.10–8.07 (d, J = 8.0 Hz, 1H), 7.35–7.31 (m, 1H), 7.22 (t, J = 8.1
7.36–7.30 (m, 2H), 7.09 (d, J = 7.6 Hz, 1H), 7.00–6.98 (m, 2H), Hz, 1H), 6.73–6.70 (m, 2H), 6.57–6.55 (m, 1H), 6.45–6.42 (m,
6.73–6.70 (m, 2H), 5.78 (bs, 2H), 2.39 (s, 3H). 13C NMR 2H), 5.78 (bs, 2H), 3.34 (q, J = 7.0 Hz, 4H), 1.16 (t, J = 7.1 Hz,
(125 MHz, CDCl3) δ 166.9, 151.1, 150.6, 139.6, 134.7, 131.5, 6H). 13C NMR (126 MHz, CDCl3) δ 166.9, 152.0, 151.0, 134.5,
129.1, 126.5, 122.5, 118.8, 116.6, 116.3, 109.6, 21.3. Anal. Calcd 131.5, 129.7, 116.6, 116.2, 109.9, 109.0, 108.3, 104.8, 44.3, 12.4.
for C14H13NO2: C, 73.99; H, 5.77; N, 6.16. Found: C, 74.37; H, Anal. Calcd for C17H20N2O2: C, 71.81; H, 7.09; N, 9.85. Found:
5.91; N, 6.39.
C, 71.59; H, 6.90; N, 9.52.
4-(tert-Butyl)phenyl 2-aminobenzoate (3ac). Synthesized
4-Fluorophenyl 2-aminobenzoate (3ah).8 Synthesized using
using GPA from 1a (81 mg, 0.5 mmol) and 2c (89 mg, GPA from 1a (81 mg, 0.5 mmol) and 2h (70 mg, 0.5 mmol)
0.5 mmol) which was then purified by column chromato- which was then purified by column chromatography using
graphy using EtOAc/Hexane (1 : 9) to afford yellow solid of 3ac EtOAc/Hexane (1 : 9) to afford white solid of 3ah (86 mg, 75%).
(87 mg, 65%). M.p.: 119–121 °C. 1H NMR (500 MHz, CDCl3) M.p.: 91–93 °C. 1H NMR (500 MHz, CDCl3) δ 8.06 (d, J = 7.3
δ 8.09 (d, J = 7.1 Hz, 1H), 7.44 (d, J = 8.6 Hz, 2H), 7.36–7.32 (m, Hz, 1H), 7.36–7.33 (m, 1H), 7.16–7.09 (m, 4H), 6.73–6.70 (m,
1H), 7.11 (d, J = 8.6 Hz, 2H), 6.73–6.70 (m, 2H), 5.78 (bs, 2H), 2H), 5.76 (bs, 2H). 13C NMR (125 MHz, CDCl3) δ 166.7, 160.1
1.34 (s, 9H). 13C NMR (125 MHz, CDCl3) δ 167.2, 151.1, 148.5, (d, J = 242.5 Hz), 151.2, 146.5 (d, J = 2.5 Hz), 134.9, 131.4, 123.3
148.2, 134.7, 131.5, 126.3, 121.2, 116.6, 116.3, 109.6, 34.5, 31.6. (d, J = 8.8 Hz), 116.7, 116.3, 116.1 (d, J = 22.5 Hz), 115.9, 109.2.
Anal. Calcd for C17H19NO2: C, 75.81; H, 7.11; N, 5.20. Found: Anal. Calcd for C13H10FNO2: C, 67.53; H, 4.36; N, 6.06. Found:
C, 75.89; H, 7.34; N, 5.52.
C, 67.69; H, 4.67; N, 5.85.
3-Chlorophenyl 2-aminobenzoate (3ai). Synthesized using
4-Methoxyphenyl 2-aminobenzoate (3ad).8 Synthesized
using GPA from 1a (81 mg, 0.5 mmol) and 2d (76 mg, GPA from 1a (81 mg, 0.5 mmol) and 2i (78 mg, 0.5 mmol)
0.5 mmol) which was then purified by column chromato- which was then purified by column chromatography using
graphy using EtOAc/Hexane (1 : 9) to afford white solid of 3ad EtOAc/Hexane (1 : 9) to afford white solid of 3ai (86 mg, 70%).
1
(72 mg, 60%). M.p.: 102–105 °C. 1H NMR (500 MHz, CDCl3) M.p.: 85–87 °C. H NMR (400 MHz, CDCl3) δ 8.05 (dd, J = 8.8,
δ 8.08 (d, J = 8.6 Hz, 1H), 7.34 (t, J = 7.3 Hz, 1H), 7.10 (d, J = 1.6 Hz, 1H), 7.41–7.32 (m, 3H), 7.13 (d, J = 8.8 Hz, 2H),
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6.74–6.70 (m, 2H), 5.76 (bs, 2H). 13C NMR (100 MHz, CDCl3) δ 151.2, 147.8, 135.0, 132.4, 131.4, 131.0, 130.8, 126.8, 123.5,
166.5, 151.3, 149.2, 135.0, 131.5, 131.1, 129.4, 123.3, 116.7, 116.7, 116.4, 109.1, 16.1. Anal. Calcd for C14H12ClNO2: C,
116.4, 109.1. Anal. Calcd for C13H10ClNO2: C, 63.04; H, 4.07; N, 64.25; H, 4.62; N, 5.35. Found: C, 64.13; H, 4.60; N, 5.09.
5.66. Found: C, 63.31; H, 3.88; N, 5.28.
2-Allylphenyl 2-aminobenzoate (3ao). Synthesized using GPA
2,4-Dichlorophenyl 2-aminobenzoate (3aj). Synthesized from 1a (81 mg, 0.5 mmol) and 2o (81 mg, 0.5 mmol) which
using GPA from 1a (81 mg, 0.5 mmol) and 2j (95 mg, was then purified by column chromatography using EtOAc/
0.5 mmol) which was then purified by column chromato- Hexane (1 : 9) to afford white solid of 3ao (55 mg, 44%). M.p.:
graphy using EtOAc/Hexane (1 : 9) to afford white solid of 3aj 45–48 °C. 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.4 Hz, 1H),
(89 mg, 64%). M.p.: 90–93 °C. 1H NMR (500 MHz, CDCl3) 7.37–7.21 (m, 4H), 7.15 (d, J = 8.1 Hz, 1H), 6.75–6.71 (m, 2H),
δ 8.04 (d, J = 7.9 Hz, 1H), 7.43 (s, 1H), 7.29 (t, J = 8.1 Hz, 1H), 5.98–5.88 (m, 1H), 5.78 (bs, 2H), 5.06–5.01 (m, 2H), 3.36 (d, J =
7.23–7.18 (m, 1H), 7.12 (d, J = 8.6 Hz, 1H), 6.65 (t, J = 8.9 Hz, 6.4 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 166.6, 151.2, 148.9,
2H), 5.67 (bs, 2H). 13C NMR (125 MHz, CDCl3) δ 165.4, 151.4, 135.8, 134.8, 132.3, 131.5, 130.3, 127.4, 126.1, 122.6, 116.7,
145.8, 135.3, 131.7, 131.6, 130.0, 128.2, 127.8, 124.9, 116.7, 116.4, 116.3, 109.9, 34.6. Anal. Calcd for C16H15NO2: C, 75.87;
116.5, 108.6. Anal. Calcd for C13H9Cl2NO2: C, 55.35; H, 3.22; N, H, 5.97; N, 5.53. Found: C, 75.60; H, 6.05; N, 5.77.
4.96. Found: C, 55.01; H, 3.07; N, 5.30.
Naphthalen-2-yl 2-aminobenzoate (3ap).8 Synthesized using
4-Bromophenyl 2-aminobenzoate (3ak).8 Synthesized using GPA from 1a (81 mg, 0.5 mmol) and 2p (86 mg, 0.5 mmol)
GPA from 1a (81 mg, 0.5 mmol) and 2k (100 mg, 0.5 mmol) which was then purified by column chromatography using
which was then purified by column chromatography using EtOAc/Hexane (1 : 9) to afford yellow solid of 3ap (65 mg, 50%).
EtOAc/Hexane (1 : 9) to afford white solid of 3ak (97 mg, 67%). M.p.: 121–122 °C. 1H NMR (500 MHz, CDCl3) δ 8.16 (d, J =
M.p.: 77–79 °C. 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 8.0 Hz, 1H), 7.93–7.82 (m, 3H), 7.65 (s, 1H), 7.54–7.47 (m, 2H),
7.4 Hz, 1H), 7.56–7.52 (m, 2H), 7.37–7.32 (m, 1H), 7.08 (d, J = 7.39–7.32 (m, 2H), 6.77–6.71 (m, 2H), 5.80 (bs, 2H). 13C NMR
8.4 Hz, 2H), 6.73–6.69 (m, 2H), 5.77 (bs, 2H). 13C NMR (125 MHz, CDCl3) δ 167.0, 151.2, 148.3, 134.8, 133.7, 131.5,
(100 MHz, CDCl3) δ 166.4, 151.3, 149.7, 135.0, 132.4, 131.4, 131.4, 129.3, 127.7, 127.6, 126.4, 125.6, 121.5, 118.8, 116.7,
130.8, 123.8, 118.8, 116.7, 116.4, 109.1. Anal. Calcd for 116.3, 109.5. Anal. Calcd for C17H13NO2: C, 77.55; H, 4.98; N,
C13H10BrNO2: C, 53.45; H, 3.45; N, 4.79. Found: C, 53.81; H, 5.32. Found: C, 77.84; H, 5.22; N, 5.49.
3.62; N, 4.70.
2-Bromophenyl 2-aminobenzoate (3al).8 Synthesized using
GPA from 1a (81 mg, 0.5 mmol) and 2l (100 mg, 0.5 mmol) Conflicts of interest
which was then purified by column chromatography using
There are no conflicts to declare.
EtOAc/Hexane (1 : 9) to afford colorless oily product of 3al
(101 mg, 70%). H NMR (400 MHz, CDCl3) δ 8.24 (dd, J = 8.0,
1
1.6 Hz, 1H), 7.70 (dd, J = 8.0, 1.6 Hz, 1H), 7.43–7.36 (m, 2H),
Acknowledgements
7.32–7.29 (m, 1H), 7.20–7.16 (m, 1H), 6.71 (d, J = 8.4 Hz, 2H),
5.83 (bs, 2H). 13C NMR (100 MHz, CDCl3) δ 165.5, 151.2, 148.0,
The authors thank SERB and CSIR New Delhi for the financial
support via the GPP-0367 (CRG/2019/001898) and OLP 2038
projects. We thank the Director of CSIR-NEIST for his constant
support. B. R. Bora thanks DST for the INSPIRE-SRF
134.9, 133.0, 131.5, 128.2, 127.0, 123.9, 116.5, 116.3, 116.1,
108.5. Anal. Calcd for C13H10BrNO2: C, 53.45; H, 3.45; N, 4.79.
Found: C, 53.75; H, 3.36; N, 4.98.
2,4-Dibromophenyl 2-aminobenzoate (3am). Synthesized
fellowship.
using GPA from 1a (81 mg, 0.5 mmol) and 2m (139 mg,
0.5 mmol) which was then purified by column chromato-
graphy using EtOAc/Hexane (1 : 9) to afford white solid of 3am
References
(122 mg, 66%). M.p.: 99–101 °C. 1H NMR (500 MHz, CDCl3)
δ 8.13–8.11 (m, 1H), 7.81–7.79 (m, 1H), 7.50–7.48 (m, 1H),
7.37–7.34 (m, 1H), 7.13 (d, J = 8.6 Hz, 1H), 6.74–6.70 (m, 2H),
5.74 (bs, 2H). 13C NMR (125 MHz, CDCl3) δ 165.3, 151.4, 147.6,
135.6, 135.2, 131.7, 131.4, 125.3, 119.3, 117.5, 116.7, 116.5,
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3an (92 mg, 71%). M.p.: 61–64 °C. H NMR (500 MHz, CDCl3)
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