Convenient synthesis of heterocyclic compounds with dihydropyrano[3,4-b] pyridine scaffold

Article abstract of DOI:10.1080/00397911.2011.616274

A general method for the preparation of various substituted dihydropyrano [3,4-b]pyridines is reported. The formation of pyranopyridine structure was achieved by a Polonovski rearrangement of pyridine N-oxide with acetic anhydride, giving 2-(acetoxymethyl)-pyridine followed by an hydrolyzed and an intramolecular Williamson ether formation.

Full text of DOI:10.1080/00397911.2011.616274

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Convenient Synthesis of Heterocyclic
Compounds with Dihydropyrano[3,4-
b]pyridine Scaffold
Sandrine Pacquelet a , Yves Blache b , Tan Kimny a , Marie-Aleth
Lacaille Dubois a & Nicolas Desbois c
a Laboratoire de chimie Organique et Thérapeutique, Unité de
Molécules d'Intérêt Biologique, Faculté de Pharmacie, Dijon, France
b Laboratoire MAPIEM, UFR Sciences et Techniques, Université du
Sud Toulon-Var, La Garde, France
c Institut National de la Santé et de la Recherche Médicale,
Université de Dijon, Dijon, France
Accepted author version posted online: 27 Feb 2012.Version of
record first published: 21 Feb 2013.
To cite this article: Sandrine Pacquelet , Yves Blache , Tan Kimny , Marie-Aleth Lacaille Dubois &
Nicolas Desbois (2013): Convenient Synthesis of Heterocyclic Compounds with Dihydropyrano[3,4-
b]pyridine Scaffold, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 43:8, 1092-1100
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Synthetic Communications1, 43: 1092–1100, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.616274
CONVENIENT SYNTHESIS OF HETEROCYCLIC
COMPOUNDS WITH DIHYDROPYRANO[3,4-b]PYRIDINE
SCAFFOLD
Sandrine Pacquelet,1 Yves Blache,2 Tan Kimny,1 Marie-Aleth
Lacaille Dubois,1 and Nicolas Desbois3
1
´
´
´
Laboratoire de chimie Organique et Therapeutique, Unite de Molecules
´ ˆ
d’Interet Biologique, Faculte de Pharmacie, Dijon, France
Laboratoire MAPIEM, UFR Sciences et Techniques, Universite du Sud
´
2
´
Toulon-Var, La Garde, France
3
´
Institut National de la Sante et de la Recherche Medicale, Universite de
´
´
Dijon, Dijon, France
GRAPHICAL ABSTRACT
Abstract A general method for the preparation of various substituted dihydropyrano [3,4-
b]pyridines is reported. The formation of pyranopyridine structure was achieved by a Polo-
novski rearrangement of pyridine N-oxide with acetic anhydride, giving 2-(acetoxymethyl)-
pyridine followed by an hydrolyzed and an intramolecular Williamson ether formation.
Keywords m-CPBA; Polonovski rearrangement; pyrano[3,4-b]pyridine; Williamson’s
reaction
INTRODUCTION
Pyrano[3,4-b]pyridines are an interesting class of heterocycles with various bio-
logical activities. Stephaoxocanes alkaloids, for example, Eletifine 1 (extracted from
Cissampelos glaberrima), are used for the treatment of symptoms of asthma and uri-
nary infections.[1] Doxanthrine 2 has improved selectivity for dopamine D1 recep-
tors[2,3] whereas GR218,231 (3) is a highly selective D3 versus D2 receptor
dopamine antagonist (Fig. 1).[4]
Pyrano[3,4-b]pyridines can be prepared, for example, by Friedla¨nder’s reac-
tion[5] or by intramolecular Diels–Alder reactions of pyrazines.[6] Recently, we have
studied the synthesis of pyrano[3,4-b]pyridine-8-one by oxidation of a methyl group
attached to a pyrido system and in situ lactonization.[7]
Received March 1, 2011.
Address correspondence to Nicolas Desbois, Institut National de la Sante et de la Recherche
´
Medicale, Universite de Dijon, CRI-866, Dijon, France. E-mail: nicolas.desbois@u-bourgogne.fr
´
´
1092

OXIDATION OF ALDEHYDES TO ACIDS
1093
Figure 1.
As a part of our research concerning the design of analogs of natural
compounds and evaluation of their antitumor activity, we decided to investigate
the synthesis of new analogs of camptothecin.[8] In this context, we prepared
triazapyrano[b]fluoren-6-one 11.
RESULTS AND DISCUSSION
Preparation of starting material 6 was achieved by treating 3-aminoimi-
dazo[1,2-a]pyridine[9] (4a) with 2-acetylbutyrolactone and a catalytic amount of p-
toluenesulfonic acid to form 5. The resulting enaminone 5 was converted to tricyclic
structure 6 by treatment with phosphorus oxychloride (Scheme 1).
Unfortunately, oxidation of compound 6 with selenium dioxide failed to give
11. Then we turned to a multistep process to prepare the desired lactone. We decided
to convert the methyl group of compound 6 into a hydroxy methyl group via Polo-
novski rearrangement[10] of the pyridine N-oxide. This could lead to the desired lac-
tone 11 after intramolecular cyclization. Oxidation of 6 with 3-chloroperoxybenzoic
acid (m-CPBA) afforded the N-oxide derivative 7 in 63% yield. We noted complete
consumption of 6 could not be obtained despite modification of reaction conditions
(equivalent of m-CPBA, temperature). In fact, compound 6 was recovered and could
be used in further manipulations. Compound 7 was subsequently converted into
alcohol 9. This last step involved Polonovski rearrangement of the 2-methylpyri-
dine-N-oxide derivative 7 to the 2-acetoxymethylpyridine 8 (not isolated) using acetic
anhydride and subsequent deacetylation under acidic conditions to give the alcohol 9
(76%) and the pyrano[3,4-b]pyridine 10a (11%) (Scheme 2).
The structure of the products was confirmed by spectroscopic methods [mass
spectrometry (MS) and 1H and 13C NMR]. Preparation of dihydropyrano[3,4-b]pyri-
dine 10a was optimized by using a solution of 1 N KOH in methanol: the deacetyla-
tion of the intermediary 2-acetoxymethyl 8 and the an intramolecular cyclisation
occurred in one pot (Scheme 3).
Scheme 1.

1094
S. PACQUELET ET AL.
Scheme 2.
In these conditions, only pyranopyridine structure 10a was observed with 55%
yield. We did not observe the classical dehydrohalogenation[11] of intermediate 8.
The Williamson’s reaction should be faster than the formation of the vinyl group.
The use of the tandem Polonovsky rearrangement=Williamson ether synthesis
was attractive because it was possible to achieve, in few steps, a pyrano[3,4-b]pyri-
dine skeleton. In fact, the literature shows that it is generally necessary to use a mul-
tistep procedure to obtain the ortho-2-chloroethyl-hydroxymethyl aromatic
structure contained in compound 9. Then, poor examples are present in literature.[12]
Diols are better candidates for this type of cyclization by intramolecular
dehydration.[13]
The same synthetic route used for compound 10a was applied to different com-
mercial amino aromatic compounds 4b–j to expand the scope of the method. The
results of our investigation are presented in Table 1. The reaction conditions used
for all examples were identical to those for 10a (except for 10f), and on the whole
yields were from moderate to good. All final products were purified by chromato-
1
graphy and were characterized by MS and H and 13C NMR. The synthesis can
be applied to different aromatic rings with various substitution patterns. Contrary
to the isolation of N-oxide 7, all other N-oxides obtained with commercial amino
compounds (4b–4j) (except N-oxide, obtained with 4c) went to good conversions.
In addition, cyclizations with POCl3 were regioselective, giving exclusively angular
products (cf. 10i and 10j). In the case of the formation of 10b and 10e, we also
obtained nucleophilic substitution of 5-chloro by methanol, but if we used 1 N
KOH methanol at room temperature it was possible to eliminate the formation of
5-methoxy compounds. Under these conditions, we obtained 10b and 10e with
81% and 82% of yield respectively. In the case of formation of 10f we observed sim-
ultaneous saponification of ethyl ester.
Scheme 3.

OXIDATION OF ALDEHYDES TO ACIDS
1095
Table 1. 5,6-Dihydro[3,4-b]pyriridines prepared from their
corresponding commercially aromatic substrates
Substrates
Products (yields)a
(Continued )

1096
S. PACQUELET ET AL.
Table 1. Continued
Substrates
Products (yields)a
aOverall yields are for the last step of N-oxide products.
CONCLUSION
In conclusion, we have reported a versatile method for the synthesis of
pyrano[3,4-b]pyridines. To demonstrate its synthetic utility, this methodology has
been successfully applied to produce a range of building blocks for various molecular
constructions.
EXPERIMENTAL
All column chromatography was performed with Merck neutral aluminum
oxide 90 standardized (63–200 mm). All thin-layer chromatography (TLC) was
performed on Fluka aluminum oxide plates (with fluorescent indicator 254 nm).
Melting points were determined on a Reichert–Jung–Koffler apparatus and are
1
not corrected. NMR spectra (300 MHz for H, 75 MHz for 13C) were recorded on
a Bruker Avance 300 instrument using in the solvents indicated. Chemical shifts were
reported in ppm (d). Electrospray ionization–mass spectrometry (ESI-MS) analyses
were performed on a Bruker Esquire 6000 instrument and accurate mass measure-
ments (HR-MS) were carried out using a Bruker microTOF-Q ESI-TOF mass
spectrometer.
Compound 6
This compound was prepared according to the procedure developed in Ref. 7.
Mp: 173–175 ꢀC; C13H11Cl2N3: MS (ESI, m=z) 279; HR-MS (ESI) m=z 302.0213
[M þ Na]þ 302.0222 calcd. for C13H11Cl2N3Na; 1H NMR (CDCl3, 300 MHz) d
8.71 (d, 1H, J ¼ 7 Hz), 7.71 (d, 1H, J ¼ 9 Hz), 7.50 (m, 1H), 6.92 (t, 1H, J ¼ 7 Hz),
3.75 (t, 2H, J ¼ 7 Hz), 3.48 (t, 2H, J ¼ 7 Hz), 2.81 (s, 3H); 13C NMR (CDCl3,
75 MHz) d 151.5, 148.4, 140.1, 134.0, 133.4, 131.3, 127.8, 124.7, 118.3, 111.5, 41.9,
33.2, 23.7.
Procedure for the Synthesis of Compounds 9 and 10a
Compound 6 (0.81 g, 2.90 mmol) was dissolved in dichloromethane (100 mL),
and 70% 3-chloroperoxybenzoic acid (2.17 g, 8.80 mmol) was added. The solution
was stirred and refluxed overnight. The resulting solution was washed with 1 N
sodium hydroxide and water and then dried over Na2SO4. Crude product was

OXIDATION OF ALDEHYDES TO ACIDS
1097
purified on neutral alumina and eluted with dichloromethane to afford 7 and starting
material 6 (20%). Compound 7: yield 63%, mp 191–193 ꢀC; C13H11Cl2N3O: MS (ESI,
m=z) 295; HR-MS (ESI) m=z 318.01741, [M þ Na]þ 318.01714 calcd for
1
C13H11Cl2N3NaO; H NMR (CDCl3, 300 MHz) d 10.01 (d, 1H, J ¼ 7 Hz), 7.86 (d,
1H, J ¼ 9 Hz), 7.66 (m, 1H), 7.06 (t, 1H, J ¼ 7 Hz), 3.79 (t, 2H, J ¼ 7 Hz), 3.54 (t,
2H, J ¼ 7 Hz), 2.84 (s, 3H); 13C NMR (CDCl3, 75 MHz) d 148.0, 143.5, 136.0,
132.2, 130.0, 128.5 (2C), 124.0, 117.3, 111.9, 41.8, 33.5, 14.2.
Protocol A. N-Oxide 7 (0.52 g, 1.76 mmol) and acetic anhydride (4 mL) were
refluxed for 2 h. The solution was evaporated to dryness, and the residue was stirred
in 6 N hydrochloric acid solution (50 mL) at 50 ꢀC for 1 h. The mixture was basified
with a saturated solution of Na2CO3 and extracted with dichloromethane. Organic
layers were dried over sodium sulfate and evaporated in vacuo. The crude product
was purified on neutral alumina and eluted with dichloromethane to afford (in order
of elution) 10a and 9. Compound 10a: yield 11%; mp: 225–227 ꢀC; C13H10ClN3O:
MS (ESI, m=z) 283 (M þ Naþ); HR-MS (ESI) m=z 282.0414 [M þ Na]þ 282.0405
1
calcd. for C13H10ClN3NaO; H NMR (CDCl3, 300 MHz) d 8.68 (d, 1H, J ¼ 7 Hz),
7.76 (d, 1H, J ¼ 9 Hz), 7.54 (m, 1H), 6.95 (t, 1H, J ¼ 7 Hz), 4.94 (s, 2H), 4.09 (t,
2H, J ¼ 7 Hz), 3.10 (t, 2H, J ¼ 7 Hz); 13C NMR (CDCl3, 75 MHz) d 149.0, 148.3,
139.9, 133.2 (2C), 131.9, 125.8, 124.7, 118.2, 111.8, 70.0, 65.0, 26.3. Compound 9:
yield 76%; mp: 193–195 ꢀC; C13H11Cl2N3O: MS (ESI, m=z) 318 (M þ Naþ); HR-MS
1
(ESI) m=z 318.01790 [M þ Na]þ 318.01714 calcd. for C13H11Cl2N3NaO; H NMR
(CDCl3, 300 MHz) d 8.79 (d, 1H, J ¼ 7 Hz), 7.88 (d, 1H, J ¼ 9 Hz), 7.62 (m, 1H),
7.07 (t, 1H, J ¼ 7 Hz), 5.06 (s, 2H), 3. 81 (t, 2H, J ¼ 7 Hz), 3.41 (t, 2H, J ¼ 7 Hz);
13C NMR (CDCl3, 75 MHz) d 151.3, 148.8, 139.5, 135.0, 134.3, 131.7, 126.1,
124.6, 118.5, 112.0, 62.8, 43.0, 31.2.
Protocol B. N-Oxide 7 (0.52 g, 1.76 mmol) and acetic anhydride (4 mL) were
refluxed for 2 h. The solution was evaporated to dryness, and the residue was stirred
in 1 N KOH solution in MeOH (60 mL) at reflux for 30 min. After evaporation of
solvent, water (50 mL) was added, and the mixture was extracted with dichloro-
methane. Organic layers were dried over sodium sulfate and evaporated in vacuo
to give compound 10a, which was purified on neutral alumina and eluted with
dichloromethane: yield 55%.
Synthesis of Compounds 10a to 10j
These compounds were prepared according to the procedure developed for 10a
using basic conditions in the last step (protocol B).
Compound 10b. Mp: 122–124 ꢀC; C12H10ClNO: MS (ESI, m=z) 219; HR-MS
(ESI) m=z 242.0348 [M þ Na]þ 242.0343 calcd. for C12H10ClNNaO; 1H NMR
(CDCl3, 300 MHz) d 8.14 (d, 1H, J ¼ 8.5 Hz), 7.95 (d, 1H, J ¼ 8.5 Hz), 7.68 (t, 1H,
J ¼ 8.5 Hz), 7.55 (t, 1H, J ¼ 8.5 Hz), 4.91 (s, 2H), 4.07 (t, 2H, J ¼ 7 Hz), 3.06 (t,
2H, J ¼ 7 Hz); 13C NMR (CDCl3, 75 MHz) d 156.3, 146.9, 141.6, 129.9, 128.9,
127.0, 125.6 (2C), 123.8, 70.6, 65.1, 26.8. In addition to compound 10b, the following
by-product was observed: 3,4-dihydro-5-methoxy-1H-pyrano[3,4-b]quinoline; yield
(9%); oil brown; C13H13NO2: MS (ESI, m=z) 215; HR-MS (ESI) m=z 238.0814

1098
S. PACQUELET ET AL.
1
[M þ Na]þ 238.0844, calcd. for C13H13NNaO2; H NMR (CDCl3, 300 MHz) d 8.05
(d, 1H, J ¼ 8.5 Hz), 7.99 (d, 1H, J ¼ 8.5 Hz), 7.66 (t, 1H, J ¼ 8.5 Hz), 7.50 (t, 1H,
J ¼ 8.5 Hz), 4.96 (s, 2H), 4.05 (t, 2H, J ¼ 7 Hz), 4.02 (s, 3H), 3.07 (t, 2H, J ¼ 7 Hz);
13C NMR (CDCl3, 75 MHz) d 161.0, 157.5, 148.2, 129.4, 128.6, 125.8, 122.5,
121.7, 118.6, 70.6, 65.1, 61.4, 23.4.
Compound 10c. Mp: 100–102 ꢀC; C13H12ClNO: MS (ESI, m=z) 233, HR-MS
(ESI) m=z 256.0488 [M þ Na]þ, 256.0500 calcd. for C13H12ClNNaO; 1H NMR
(CDCl3, 300 MHz) d 8.04 (d, 1H, J ¼ 8.5 Hz), 7.54 (d, 1H, J ¼ 7 Hz), 7.43 (m, 1H),
4.95 (s, 2H), 4.11 (t, 2H, J ¼ 7 Hz), 3.10 (t, 2H, J ¼ 7 Hz), 2.75 (s, 3H); 13C NMR
(CDCl3, 75 MHz) d 154.9, 146.1, 141.5, 137.1, 129.8, 126.6, 125.5, 125.1, 121.7,
70.8, 65.2, 26.9, 18.1.
Compound 10d. Mp: 143–145 ꢀC; C13H12ClNO2: MS (ESI, m=z) 272
(M þ Naþ); HR-MS (ESI) m=z 272.04361 [M þ Na]þ, 272.04488 calcd. for
1
C13H12ClNNaO2; H NMR (CDCl3, 300 MHz) d 7.87 (d, 1H, J ¼ 9 Hz), 7.41 (d,
1H, J ¼ 3 Hz), 7.35 (dd, 1H, J ¼ 9 Hz, J ¼ 3 Hz), 4.92 (s, 2H), 4.10 (t, 2H, J ¼ 7 Hz),
3.98 (s, 3H), 3.10 (t, 2H, J ¼ 7 Hz); 13C NMR (CDCl3, 75 MHz) d 158.4, 153.4, 142.9,
140.0, 130.4, 126.5, 125.7, 122.7, 101.5, 70.4, 65.1, 55.6, 26.9.
Compound 10e. Mp: 126–128 ꢀC; C12H9BrClNO: MS (ESI, m=z) 297;
HR-MS (ESI) m=z 297.96331 [M þ H]þ, 297.96288 calcd. for C12H10BrClNNaO;
1H NMR (CDCl3, 300 MHz) d 8.36 (d, 1H, J ¼ 2 Hz), 7.85 (d, 1H, J ¼ 9 Hz), 7.77
(dd, 1H, J ¼ 9 Hz, J ¼ 2 Hz), 4.91 (s, 2H), 4.10 (t, 2H, J ¼ 7 Hz), 3.11 (t, 2H,
J ¼ 7 Hz); 13C NMR (CDCl3, 75 MHz) d 156.8, 145.4, 140.4, 133.4, 130.6, 126.7,
126.6, 126.1, 121.3, 70.5, 65.0, 26.9. In addition to compound 10e, the following
by-product was observed: 7-bromo-3,4-dihydro-5-methoxy-1H-pyrano[3,4-b]quino-
line; yield (24%); mp: 117–119 ꢀC; C13H12BrNO2: MS (ESI, m=z) 294; HR-MS
1
(ESI) m=z 294.01308 [M þ H]þ, 294.01242 calcd. for C13H13BrNNaO2; H NMR
(CDCl3, 300 MHz) d 8.19 (d, 1H, J ¼ 2 Hz), 7.82 (d, 1H, J ¼ 9 Hz), 7.71 (dd, 1H,
J ¼ 9 Hz, J ¼ 2 Hz), 4.92 (s, 2H), 4.05 (t, 2H, J ¼ 7 Hz), 4.01 (s, 3H), 3.06 (t, 2H,
J ¼ 7 Hz); 13C NMR (CDCl3, 75 MHz) d 160.0, 158.1, 146.7, 132.9, 130.5, 124.1,
123.8, 119.8, 119.4, 70.6, 64.9, 61.4, 23.5.
Compound 10f. Modification to obtain 10f. N-Oxide intermediate (0.52 g,
1.58 mmol) and acetic anhydride (4 mL) were refluxed for 2 h. The solution was eva-
porated to dryness, and the residue was stirred in 1 N KOH solution in MeOH
(60 mL) at reflux for 30 min. After evaporation of solvent, water (50 mL) was added.
The aqueous layer was washed with dichloromethane, acidified (1 N HCl) to pH 5,
and extracted with dichloromethane. Organic layers were dried over sodium sulfate
and evaporated in vacuo to give compound 10f, which was purified on neutral alu-
mina and eluted with dichloromethane and methanol (96=4, v=v). Mp: 245–247 ꢀC;
C13H10ClNO3: MS (ESI, m=z) 263; HR-MS (ESI) m=z 264.04258 [M þ H]þ,
264.04220 calcd for C13H11ClNNaO3; 1H NMR (CD3OD=CDCl3, 300 MHz) d
8.93 (d, 1H, J ¼ 2 Hz), 8.28 (dd, 1H, J ¼ 9 Hz, J ¼ 3 Hz), 7.98 (d, 1H, J ¼ 9 Hz),
4.91 (s, 2H), 4.12 (t, 2H, J ¼ 7 Hz), 3.13 (t, 2H, J ¼ 7 Hz); 13C NMR (DMSO,
75 MHz) d 166.8, 159.2, 147.8, 141.5, 129.4, 129.3, 127.0, 125.7, 124.8, 124.2, 69.6,
64.1, 26.4.

OXIDATION OF ALDEHYDES TO ACIDS
1099
Compound 10g. Mp: 209–211 ꢀC; C24H18Cl2N2O3: MS (ESI, m=z) 452;
HR-MS (ESI) m=z 475.06091 [M þ Na]þ 475.05867 calcd. for C24H18Cl2N2NaO3;
1H NMR (CDCl3, 300 MHz) d 8.03 (d, 2H, J ¼ 9 Hz), 7.76 (d, 2H, J ¼ 3 Hz), 7.53
(dd, 2H, J ¼ 9 Hz, J ¼ 3 Hz), 4.95 (s, 4H), 4.11 (t, 4H, J ¼ 7 Hz), 3.10 (t, 4H,
J ¼ 7 Hz); 13C NMR (CDCl3, 75 MHz) d 153.3 (4C), 144.0 (2C), 140.6 (2C), 131.3
(2C), 126.6 (2C), 126.3 (2C), 123.6 (2C), 110.7 (2C), 70.5 (2C), 65.0 (2C), 26.9 (2C).
Compound 10h. Mp: 260–262 ꢀC; C24H18Cl2N2O2: MS (ESI, m=z) 436;
HR-MS (ESI) m=z 459.06398 [M þ Na]þ, 459.06375 calcd. for C24H18Cl2N2NaO2;
1H NMR (CDCl3, 300 MHz) d 8.50 (s, 2H), 8.12 (m, 4H), 4.98 (s, 4H), 4.14 (t,
4H, J ¼ 7 Hz), 3.16 (t, 4H, J ¼ 7 Hz); 13C NMR (CDCl3, 75 MHz) d 156.7 (2C),
146.5 (2C), 141.8 (2C), 138.8 (2C), 129.7 (2C), 129.6 (2C), 126.3 (2C), 125.8 (2C),
122.2 (2C), 70.6 (2C), 65.1 (2C), 26.9 (2C).
Compound 10i. (Refluxing Ac2O for 10 min): Mp: 117–119 ꢀC;
C20H17ClN2O: MS (ESI, m=z) 337; HR-MS (ESI) m=z 359.0910 [M þ Na]þ,
1
359.0922 calcd. for C20H17ClN2NaO; H NMR (CDCl3, 300 MHz) d 8.92 (d, 1H,
J ¼ 8.5 Hz), 8.02 (d, 1H, J ¼ 9 Hz), 7.88 (d, 1H, J ¼ 9 Hz), 7.53 (m, 2H), 7.32 (t,
1H, J ¼ 9 Hz), 5.00 (s, 2H), 4.55 (q, 2H, J ¼ 7 Hz), 4.17 (t, 2H, J ¼ 7 Hz), 3.23 (t,
2H, J ¼ 7 Hz), 1.52 (t, 3H, J ¼ 7 Hz); 13C NMR (CDCl3, 75 MHz) d 151.9, 144.5,
139.3, 138.5, 138.1, 128.1, 127.2, 126.0, 124.4, 123.5, 123.0, 118.9, 114.3, 113.2,
109.0, 70.2, 65.4, 37.8, 27.4, 14.3.
Compound 10j. (Refluxing Ac2O for 10 Min): mp: 225–227 ꢀC; C20H14ClNO:
MS (ESI, m=z) 320; HR-MS (ESI) m=z 342.0646 [M þ Na]þ, 342.0656 calcd. for
1
C20H14ClNNaO; H NMR (CDCl3, 300 MHz) d 10.26 (s, 1H), 8.31 (s, 1H), 8.10
(m, 1H), 8.02 (m, 1H), 7.92 (d, 1H, J ¼ 9 Hz), 7.63 (d, 1H, J ¼ 9 Hz), 7.56 (m, 2H),
4.94 (s, 2H), 4.11 (t, 2H, J ¼ 7 Hz), 3.10 (t, 2H, J ¼ 7 Hz); 13C NMR (CDCl3,
75 MHz) d 154.4, 149.1, 141.6, 132.4, 131.6 (2C), 130.8, 129.2, 127.8, 127.6, 127.3,
127.2, 127.1, 126.9, 126.8, 126.1 122.2, 70.0, 65.2, 27.3.
ACKNOWLEDGMENT
´
We are thankful to Marie-Jose Penouilh for the HR-MS mass spectra
(PACSMUB).
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