Reaction of resorcinol with mesityl oxide: Synthesis of 2,2-dimethyl-4-formyl-7-methoxy-(2H)-1-benzopyran

Article abstract of DOI:10.1081/SCC-120015811

Synthesis of 2,2-dimethyl-4-formyl-7-methoxy-(2H)-1-benzopyran has been achieved by a three step reaction sequence, wherein the key step has been the preparation of 7-hydroxy-2,2,4-trimethyl-(2H)-1-benzopyran by a novel condensation reaction between resor

Full text of DOI:10.1081/SCC-120015811

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Reaction of Resorcinol with Mesityl Oxide:
Synthesis of 2,2-Dimethyl-4-formyl- 7-methoxy-(2 H
)-1-benzopyran
A. K. Tripathi , K. R. Khan & S. C. Taneja
To cite this article: A. K. Tripathi , K. R. Khan & S. C. Taneja (2003) Reaction of Resorcinol with
Mesityl Oxide: Synthesis of 2,2-Dimethyl-4-formyl- 7-methoxy-(2 H )-1-benzopyran, Synthetic
Communications, 33:4, 579-585, DOI: 10.1081/SCC-120015811
To link to this article: http://dx.doi.org/10.1081/SCC-120015811
Published online: 16 Aug 2006.
Submit your article to this journal
Article views: 45
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [Central Michigan University]
Date: 14 October 2015, At: 18:07

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 4, pp. 579–585, 2003
Reaction of Resorcinol with Mesityl Oxide:
Synthesis of 2,2-Dimethyl-4-formyl-
7-methoxy-(2H )-1-benzopyran#
A. K. Tripathi,1 K. R. Khan,2 and S. C. Taneja1,
*
1Regional Research Laboratory (CSIR),
Jammu Tawi, India
2Barkatulla University, Bhopal, M.P., India
ABSTRACT
Synthesis of 2,2-dimethyl-4-formyl-7-methoxy-(2H )-1-benzopyran
has been achieved by a three step reaction sequence, wherein the key
step has been the preparation of 7-hydroxy-2,2,4-trimethyl-(2H )-1-
benzopyran by a novel condensation reaction between resorcinol and
mesityl oxide in presence of polyphosphoric acid (PPA).
Key Words: Resorcinol; Mesityl oxide; Polyphosphoric acid; 2,2-
dimethyl-4-formyl-7-methoxy-(2H)-1-benzopyran.
#R.R.L. (Jammu) communication no. 2348
*
Correspondence: S. C. Taneja, Regional Research Laboratory (CSIR), Canal
Road, Jammu Tawi, India; Fax: (0191) 548607; E-mail: sc_taneja@rediffmail.
com..
579
DOI: 10.1081/SCC-120015811
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
580
Tripathi, Khan, and Taneja
Benzopyrans or chromenes are the versatile intermediates used in
the preparation of biologically important natural as well as synthetic
molecules. One of the most commonly used methods of their preparation
is based on acid or base catalysed condensation reaction between phenols
and a,b-unsaturated carbonyl compounds.[1] Our requirement of 2,2-
dimethyl-4-formyl-7-methoxy-(2H)-1-benzopyran 9 for the preparation
of biologically active compounds directed us to search for the prepara-
tion of 7-hydroxy-2,2,4-trimethyl-(2H)-1-benzopyran 1 as one of the
possible precursors. For the preparation of 7-hydroxy-2,2,4-trimethyl-
(2H)-1-benzopyran 1 we envisaged resorcinol and mesityl oxide condensa-
tion reaction as one of the probable routes to its synthesis.
On reviewingthe literature it was noted that there is no prior
report on formation of compound 1 duringthe condensation reaction
between resorcinol and mesityl oxide or acetone, though theoretically its
formation alongwith the isomeric structure 2 is a distinct possibility. The
condensation reaction between resorcinol and mesityl oxide has been the
subject of some interestingstudies in the past and a variety of product
formation has been reported. An earlier work reports the formation
of 4-aryl benzopyran 3 as the major product.[2] The patent filed by
Mitsubishi Petrochemicals, Japan claimed the formation of 2,2,4-
trimethyl-5-hydroxy-(2H)-1-benzopyran 5 as the product in basic
conditions.[3] Similarly formation of two spiro products 4 and 6 have
also been reported.[4,5] One another patent[6] claimed flavan 7 as the
major product, which has also been corroborated in a recent publication
by Livant et al.[7] In a detailed study of acid catalysed condensation reac-
tion of mesityl oxide with resorcinol, they confirmed the formation of
flavan 7 as the major product when resorcinol was used in excess (Sch. 1).[7]
In view of absence of any report on the formation of the 1 from
resorcinol and mesityl oxide which is a reasonably possible product,
it was proposed to explore in detail the possibility of its preparation by
acid catalysed condensation reactions.
RESULTS AND DISCUSSION
Our initial attempts to obtain the desired chromene 1 usingdilute
hydrochloric acid[6] and one mole each of the reactants under varied
conditions of temperature and concentrations of acid resulted mostly in
the formation of 7 as the major product alongwith some unidentified
polymeric compounds. Similar product formation was also observed when
dilute sulphuric acid or acetic acid is used as catalyst. Orthophosphoric
acid catalysed condensation however gave an indication of different

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Reaction of Resorcinol with Mesityl Oxide
581
Scheme 1.
Scheme 2.
product profile. Alongwith the formation of 7, another minor compound
was also detected which is identified as 1. Therefore use of polyphosphoric
acid (PPA) was envisaged for improvement of its yield. After several
attempts with PPA as catalyst and optimisation of the experimental
conditions, formation of 1 upto 60% was achieved after purification
with column chromatography (Sch. 2). Its identification was carried out
on the basis of spectral and chemical data. Concentrated sulphuric acid
catalysed reaction at room temperature also showed the formation of
compound 1, though over all yield was low. Results of the above experi-
ments are summarized in Table 1.
For the preparation of desired formyl analogue 9, methyl ether 8
was prepared from 1 and subjected to oxidation with selenium dioxide

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
582
Tripathi, Khan, and Taneja
Table 1.
Catalyst
Entry
Product (%)
1
2
3
4
5
6
HCl (10%)[8]
HCl (conc.)[9]
H2SO4 (10%)[8]
H2SO4 (conc.)[9]
PPA[9]
7 (63)
7 (47)
7 (65)
1 (22)
1 (60)
7 (55)
Acetic acid[10]
Scheme 3.
in dioxane, which resulted in facile conversion to 2,2-dimethyl-4-formyl-
7-methoxy-(2H)-1-benzopyran 9 structure of which was cofirmed by
spectral data (Sch. 3).
In conclusion the reaction of mesityl oxide with resorcinol in
presence of PPA produces 2,2,4-trimethyl-7-hydroxy-(2H)-1-benzopyran
1 in moderate yield. The methyl ether of 1 can easily be oxidised to its
4-formyl analogue 9 usingselenium dioxide.
EXPERIMENTAL
Solvents and the reagents were mostly LR grade, distilled and dried
whenever required. NMR spectra were recorded as ꢀ values at 60 and
200 MHz usingTMS as an internal standard. Infrared spectra were
recorded on HITACHI model 270-30 instrument and mass spectrum
on JEOL-MS-300 spectrometer.
Preparation of 7-Hydroxy-2,2,4-trimethyl-(2H )-1-benzopyran
A vigorously stirred suspension of resorcinol (11 g, 0.1 mol) and
freshly prepared polyphsphoric acid (PPA, 60 mL) was treated dropwise

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Reaction of Resorcinol with Mesityl Oxide
583
with mesityl oxide (10.8 g, 0.11 mol). The initial light coloured reaction
mixture turned dark red after some time at room temperature. The
stirringis further continued for six hours and mixture poured into ice
water. The sticky residue was extracted with ethyl acetate (3 ꢀ 50 mL),
washed with water and dried over anhydrous sodium sulphate. Drying
and removal of the solvent gave thick dark colored liquid which was
subjected to column chromatography over silica gel and elution with
hexane:ethyl acetate (8.5:1.5) furnished a light yellow powder 1, m.p.
118–119ꢁC (11.8 g, 60%).
1H NMR (CDCl3) ꢀ: 1.36 (6H, s, 2 ꢀ CH3), 1.97 (3H, s, ¼C–CH3),
5.36 (1H, s, ¼CH), 6.43 (2H, m, 6 and 8-H), 7.06 (1H, d, J ¼ 8.5 Hz, 5-H).
13C NMR (CDCl3) ꢀ: 18.18 (CH3), 28.29 (2 ꢀ CH3), 76.50 (C-2),
103.77 (C-8), 107.49 (C-6), 116.2 (C-4), 124.0 and 124.80 (C-3 and 5),
126.68 (C-10), 154.42 and 156.15 (C-7 and 9).
MS: m/z at 191 (Mþþ1, 25), 176 (100), 161 (5), 147 (9), 92 (11), 78 (18).
IR (KBr) cmꢂ1: 3296, 2948, 1608, 1580, 1490, 1382, 1246, 1146, 1058,
1028, 984, 932, 903, 756, 662.
Preparation of 2,2-Dimethyl-4-formyl-7-methoxy-
(2H )-1-benzopyran 9
1 (5.2 g) was methylated with methyl iodide in presence of anhydrous
potassium bicarbonate (10 g) in acetone (50 mL) under reflux conditions.
The crude product 8 obtained after filtration and removal of solvent,
without purification is subjected to oxidation with selenium dioxide in
dioxane. In a three necked flask fitted with condenser and thermometer,
3 mL of dioxane, 0.55 gof selinium dioxide and 10 mL of water added
and the mixture is heated till all the solid dessolved. To this solution is
added 2.04 gof 2,2,4-trimethyl-7-methoxy-(2 H)-1-benzopyran and the
mixture is refluxed with stirringfor 5 h. The oxidation product was
obtained after filteringout the selenium and removal of dioxane–water
mixture through distillation. The crude product was subjected to column
chromatography over silica gel and elution with hexane:ethyl acetate
(9:1) to furnish a semi-solid 1.77 g(81%).
1H NMR (CDCl3) ꢀ: 1.53 (6H, s, 2 ꢀ CH3), 3.76 (3H, s, OCH3), 6.30
(1H, s, 3-H), 6.46 (1H, d, J ¼ 2.5 Hz, 8-H), 6.56 (1H, dd, J ¼ 2.5 and
8.5 Hz, 6-H), 8.20 (1H, d, J ¼ 8.5 Hz, 5-H), 9.66 (1H, s, CHO).
13C NMR (CDCl3) ꢀ: 26.85 (2 ꢀ CH3), 55.37 (OCH3), 76.15 (C-2),
109.2 (C-4), 102.42 and 107.25 (C-6 and 8), 126.85 (C-5), 131.93
(C-10), 147.34 (C-3), 154.17 (C-7), 161.57 (C-9), 191.57 (CHO).

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
584
Tripathi, Khan, and Taneja
MS: m/z at 218 (M,þ 21), 203 (100), 188 (25), 175 (31), 160 (7),
132 (6), 91 (5),77 (8).
IR (KBr) cmꢂ1: 2932, 1690, 1616, 1566, 1502, 1446, 1388, 1364, 1274,
1246, 1198, 1150, 1068, 1030, 976, 890, 798.
ACKNOWLEDGMENT
We are thankful to the Director RRL(J) for financial support and the
instrumentation section for spectral data.
REFERENCES
1. (a) Offe, H.A.; Barkow, W. Kondensation von resorcin und
resorcin-derivaten mit carbonsauren unter dem einfluß wasserfreier
flußsaure. Chem. Ber. 1947, 80, 458; (b) Talpatra, B.; Deb, T.;
Talpatra, S. Condensation of phenols & cinnamic acids in presence
of polyphosphoric Acid: A novel biogenetic-type oxidative self-
cyclisation of p-methoxycinnamic acid to 7-methoxycoumarin.
Indian J. Chem. 1986, 25B, 1122.
2. (a) Kondrat’eva, G.G.; Volkotrub, M.N.; Sin. Issled. Eff. Khim
Dobavok. Structure and conversion of the products of condensation
of mesityl oxide with o-cresol and resorcinol. Polim. Mater. 1969, 2,
373; Chem. Abstr. 1972, 76, 59369z; (b) Starkov, S.P.; Glushkova,
L.V. Structure and reactions of the condensation products of phe-
nols and unsaturated carbonyl compounds: condensation of 3,4-
xylenol with crotonaldehyde. Khim. Kreterotsiki. Soedin 1968, 1,
16; Chem. Abstr. 1968, 69, 77054c.
3. Kumiai Chemical Industries Co. Ltd. Mitsubishi Petrochemical
Co. Ltd Jpn Patent JP 82,109,779, 1982; Polyalkyl chromenols.
Chem. Abstr. 1982, 97, 198111f.
4. Liska, K.J. Preparation and antitumor properties of analogs of
acromycine. J. Med. Chem. 1972, 15, 1177.
5. Harada, H.; Usui, M. Jpn Patent JP 62,111,988, 1985; Preparation
of 7,70-dihydroxy-4,4,4040-tetramethyl-2,20-spirobi[chroman] as a
monomer and photographic film additive. Chem. Abstr. 1988,
109, 149374b.
6. Mitsui Petrochemical Ind. Co. Ltd. Jpn Patents (a) JP 82,16877,
1982; 2,4,4-Trimethyl-2-(2,4-dihydroxyphenyl)-7-hydroxy chroman,
Chem. Abstr. 1982, 97, 6153b and (b) JP 82,114,585, 1982; 2,4,4-

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Reaction of Resorcinol with Mesityl Oxide
585
Trimethyl-2-(2,4-dihydroxy phenyl)-7-hydroxy chroman. Chem.
Abstr. 1982, 97, 216003d.
7. (a) Livant, P.; Web, T.R.; Xu, W. Reaction of resorcinol with acet-
one. J. Org. Chem. 1997, 62, 737; (b) Livant, P.; Xu, W. Reaction of
resorcinol with a-b-unsaturated ketones. J. Org. Chem. 1998, 63,
636.
8. Reaction carried out at 35ꢀC in presence of diethyl ether.
9. Reaction at room temperature with constant stirring.
10. Reaction carried out at 60ꢀC with stirring.
Received in the UK October 8, 2001

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.