Water-mediated phosphorylative cyclodehydrogenation: An efficient preparation of flavones and flavanones

Article abstract of DOI:10.1080/00397911.2019.1643484

A new synthetic strategy utilizing POCl₃-water for the conversion of 2′-hydroxychalcones to flavanones and flavones has been developed. The reagent efficiently promoted one-pot conversion of 2′-hydroxychalcones to flavones through flavanones involving cyclization and oxidative dehydrogenation. By changing the stoichiometery of the reagents, the reaction can be tuned to generate either flavanone or flavone. The developed protocol was found to be applicable for a variety of 2′-hydroxychalcones.

Full text of DOI:10.1080/00397911.2019.1643484

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Water-mediated phosphorylative
cyclodehydrogenation: An efficient preparation of
flavones and flavanones
Manorama Vimal, Uma Pathak & Anand Kumar Halve
To cite this article: Manorama Vimal, Uma Pathak & Anand Kumar Halve (2019): Water-mediated
phosphorylative cyclodehydrogenation: An efficient preparation of flavones and flavanones,
Synthetic Communications, DOI: 10.1080/00397911.2019.1643484
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https://doi.org/10.1080/00397911.2019.1643484
Water-mediated phosphorylative cyclodehydrogenation: An
efficient preparation of flavones and flavanones
Manorama Vimala, Uma Pathaka, and Anand Kumar Halveb
aSynthetic Chemistry Division, Defence Research Development Establishment, Gwalior, MP, India;
bSchool of Studies in Chemistry, Jiwaji University, Gwalior, MP, India
ABSTRACT
ARTICLE HISTORY
Received 11 April 2019
A new synthetic strategy utilizing POCl3-water for the conversion of
20-hydroxychalcones to flavanones and flavones has been developed.
The reagent efficiently promoted one-pot conversion of 20-hydroxy-
chalcones to flavones through flavanones involving cyclization and
oxidative dehydrogenation. By changing the stoichiometery of the
reagents, the reaction can be tuned to generate either flavanone or
flavone. The developed protocol was found to be applicable for a
variety of 20-hydroxychalcones.
KEYWORDS
Flavanones; flavones;
20-hydroxychalcones;
oxidative cyclodehydroge-
nation; POCl3; single-
reagent-driven reactions;
water-mediated synthesis
GRAPHICAL ABSTRACT
O
O
11 examples
72-89 % yields
1 mmol POCl3-H2O
70-75°C
Flavanone
2 mmol POCl3-H2O
90-95°C
OH
O
2'-Hydroxychalcone
3 mmol POCl3-H2O
90-95°C
O
O
Flavone
19 examples
60-90 % yields
Introduction
Flavones and their derivatives are naturally occurring class of flavonoids.[1] These pro-
longed the attention of researchers due to their versatile biological activities.[2] The
CONTACT Manorama Vimal
manorama20@rediffmail.com
Synthetic Chemistry Division, Defence Research
Development Establishment, Tansen Road, Gwalior, 474002, MP, India.
Supplemental data for this article is available online at on the publisher’s website.
ß 2019 Taylor & Francis Group, LLC

2
M. VIMAL ET AL.
most common synthetic routes to the flavone[3] are through 20-hydroxychalcones[4] or
through the Baker–Venkataraman rearrangement.[5] Several other protocols to obtain
flavones have also been reported over recent years.[6] The Baker–Venkataraman
approach involves the rearrangement of o-benzoylated 20-hydroxyacetophenones to 1-
(2-hydroxyaryl)-3-arylpropan-1,3-diones by a base-promoted acyl transfer followed by
acid catalyzed cyclization to yield flavones. The 20-hydroxychalcone pathway implicates
the base-catalyzed Claisen–Schmidt condensation[7] of 20-hydroxyacetophenones with
aromatic or conjugated aldehydes followed by isomerization to flavanone that can be
affected by acid,[8] base,[9] thermal,[9] or photochemical conditions.[10] The resulting fla-
vanone is oxidized to flavone by an oxidizing agent.[11]
Most of them are two-step synthetic procedures requiring a different set of reagents,
reaction conditions, and cumbersome work-up procedures for isolation of the product.
Direct oxidative cyclization of 20-hydroxychalcone[12] with reagents such as I2/
DMSO,[12a] DDQ/Dioxane,[12b,c] SeO2,[12d] CuI/[bmim][NTf2],[13a] In(III)halides[13b]
and FeCl3–MeOH[13c] have also been reported. The classical I2-DMSO, DDQ/Dioxane,
and SeO2 mediated methods are limited by the high reaction temperature, use of diffi-
cult to remove solvents, cumbersome isolation, and poor yields. Metal-catalyzed reac-
tions are often not environmentally benign and suffer from the limitation of metal
contamination of the final product, which is often of pharmaceutical importance.
Additionally, metal catalyzed reactions require anhydrous reaction conditions which is
difficult to maintain, and long reaction times.
Hence, novel approaches for conversion of 20-hydroxychalcones to flavones by using
easily available, cost-effective and metal-free reagents are highly desirable. A single-
reagent-driven, one-pot preparation is advantageous in terms of reagent economy and
greener synthesis. Hence, we were interested in developing a single-reagent-driven one
pot method for the preparation of flavones from 20-hydroxychalcones. The reactivity of
POCl3 was explored with 20-hydroxychalcone and herein, we wish to report a
POCl3–H2O promoted oxidative cyclodehydrogenation of 20-hydroxychalcones
to flavones.
Results and discussion
The conversion of chalcones to flavone is a two-step method (Scheme 1). The first step
is isomerization of chalcone to flavanone and second step is dehydrogenation of flava-
none to flavone. Isomerization can be affected by acids, bases or UV light while
dehydrogenation of flavanone to flavones is achieved using different oxidants. Since we
were interested in developing a single-reagent-driven procedure for the preparation of
flavone from 20-hydroxychalcone, we were in search of a reagent that could serve as an
acid, as well as, dehydrogenating agent. Survey of the literature revealed that POCl3
may have the potential to carry out the above-mentioned transformation due to its
acidic and chlorinating nature.[14] To date, POCl3 has been reported for esterificatio-
n,[15a,16a] chlorination of enol[15b] and phenolic-OH14 and dehydration.[16b,c] Following
the reaction in Scheme 1, we anticipated it to yield flavones through flavanone.
As a model substrate 20-hydroxychalcone was chosen and phosphoryl chloride was
taken as a reagent. Efforts were directed to realize isomerization of 20-hydroxychalcone

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SYNTHETIC COMMUNICATIONSV
3
STEP-2
OH
O
O
O
O
O
H / OH
STEP-1
(i) X2
(ii) - HX
STEP-3
2
3
1
Scheme 1. Synthesis of flavanones and flavones from 2’-hydroxychalcones.
Table 1. Optimization of reaction conditionsa.
Entry
POCl3 (mmol)
H2O (mmol)
Temp. (ꢀC)
Time (h)
Productsb
2(80%)
4(80%), 2(20%)
2(90%), 3(10%)
2(85%), 3(15%)
2 (98%)
1
2
3
4
5
6
1
3
2
3
1
3
75
110
80
120
70–75
90–95
2.0
1.5
6
9
2.5
2
2
10
1
3
3 (95%)
aReaction was done with 1 mmol of 2’-hydroxychalcone. bConversions determined by GC-MS.
to flavanone which can be further subjected to dehydrogenation. Initially, 1 mmol
20-hydroxychalcone was reacted with 1 mmol POCl3 at 75 ꢀC. Within half an hour con-
version of 20-hydroxychalcone to flavanone (Table 1, entry 1) was observed. Since we
were interested in exploring its dehydrogenating potential, the reaction was further
investigated at different conditions. When the reaction was carried out with 3 mmol of
POCl3 under strictly anhydrous conditions (Scheme 3) formation of 2,3-dihydro-20-
hydroxychalcone 4 as the major product was observed (Table 1, entry 2). Interestingly,
when the reaction was conducted without maintaining the anhydrous condition forma-
tion of flavones was also observed (Table 1, entry 3). To achieve the complete formation
of flavone; concentration of POCl3 was increased but, either an increase in the concen-
tration of POCl3 or conducting the reaction for a prolonged period did not have the
desired effect. Increase in temperature led to degradation of the reaction and tar forma-
tion. Addition of bases such as pyridine or triethylamine made no difference in
the reaction.
This indicated that the presence of water has a positive impact on the formation of
flavones. Using excess of water with 3 mmol POCl3 led to the formation of a very small
quantity of flavone at 120 ꢀC (Table 1, entry 4) due to hydrolysis of reagent and reac-
tion remained incomplete even after 9 h. This suggested that the optimum quantity of
water plays a crucial role in conversion.
When 20-hydroxychalcone was reacted with 1 mmol POCl3 and 1 mmol water, max-
imum conversion to flavanone was observed (Table 1, entry 5). Further, incorporation
of an equimolar amount of water i.e. 3 mmol with POCl3 in reaction (Table 1, entry 6),
gave flavone neatly. Reaction pathway was then investigated. When 2,3-dihydro-20-
hydroxychalcone 4 was reacted with POCl3–H2O, no change occurred, thereby ruling
out the possibility of it being an intermediate. In order to probe the role of flavanone
in the reaction mechanism, 1 mmol flavanone was reacted with 2 mmol POCl3–H2O at
90–95 ꢀC (Scheme 2C). It gave flavone as the sole product indicating the formation of
flavones through flavanone. The optimized reaction follows as:
3 mmol POCl3 and 3 mmol water were added to 1 taken in toluene. The contents
were heated at 90–95 ꢀC till the conversion was complete. In the case of entry 5 and 8

4
M. VIMAL ET AL.
O
O
A
P
O
H 2
-
l 3
C
O
2
l
o
m
m
1
°
C
5
7
OH
O
-
0
2 mmol POCl3-H2O
7
C
90-95°C
3
m
m
o
l
P
O
C
l3
-
H
2 O
9
O
0
-
1
9
°
5
C
B
3
O
Scheme 2. Synthesis of flavanones and flavones by POCl3–H2O.
(Table 3), 1.5 mmol reagents were added further and the temperature was raised to
100 ꢀC to achieve complete conversion.
Further, we were interested to know whether a combination of acid and the oxidizing
agent is able to carry out this transformation. For this, acids such as H3PO4(85%), conc.
HCl, H2SO4, HNO3, acetic acid, mCPBA, oxalic acid, PSCl3, and PCl5 were explored.
Some oxidizing agents such as oxone, iodine, and H2O2 under various conditions were
tried. But, most of them yielded flavanone only.
Role of 20-hydroxy group for conversion was also investigated. When chalcone, with-
out the 20-hydroxy group, was subjected to optimized reaction condition, it did not gen-
erate any corresponding phosphoryl ester thereby suggesting that POCl3 binds to –OH
group at 20-position of phenyl ring initially.
To explore the general applicability of developed protocol various 20-hydroxychal-
cones were reacted. The reaction Scheme 2A was amenable to a variety of substrates
(Table 2).
In the case of Scheme 2B, the substituting groups have significant influence on the
conversion. The electron-donating groups at the para-position of phenyl ring (Table 3,
entries 2, 12, 15, 17) increased the conversion of the reactants while the electron-
withdrawing group (Table 3, entry 9) decreased the conversion. The presence of ortho
substituent (Table 3, entry 6 and 13) decreased the conversion and isolation of the
product. Halides (Table 3, entries 4, 6, 7, 13, 14) irrespective of their positions, showed
relatively slow conversions as compared to alkyl substituents. Substrates with bulkier
groups such as (Table 3, entries 3, 5, 8, 11, 16, 18 and 19) also reacted slowly in step-2
and appreciable conversion could be achieved only with additional reagent and
increased temperature. The developed protocol was found particularly advantageous for
the preparation of 4-hydroxy-flavanone (Table 2, entry 12) and 4-hydroxy-flavone
(Table 3, entry 20). 3-(4-Hydroxy-phenyl)-1-(2-hydroxy-phenyl)-propenone undergoes
very facile isomerization and oxidative cyclization without the need of protection/depro-
tection of p-hydroxyl group.
On the basis of all the results described above, the most plausible mechanism is
depicted in Scheme 4 for the transformation of substrate 20-hydroxychalcone to flava-
none and flavone.
Under the optimized reaction condition, 20-hydroxychalcone 1 initially forms an ester
1
with phosphoryl chloride. The H-NMR analysis of 20-hydroxychalcone (1 mmol)-POCl3

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5
OH
OH
O
3 mmol POCl3
110°C
+
O
4
O
1
O
2
Scheme 3. Reaction of 1 with 3 mmol POCl3.
Table 2. Conversion of 1 to 2.
OH
O
O
R
1 mmol POCl3-H2O
70-75°C
R
O
2
1
Entry
R
Time
Yielda (%)
1
2
3
4
5
6
7
8
Ph
1 h
45 min
30 min
1 h 20 min
1 h
2.5 h
1 h
1 h
1.5 h
1 h
2 h
2 h
88
87
88
85
86
86
86
85
88b
89
72b
75
p-OCH3-ph
p-Cl-Ph
2,4-(CH3)2-Ph
o-Br-Ph
3,4,5-(OCH3)3-Ph
p-CH(CH3)2-Ph
3,4-(OCH3)2-Ph
4-N(CH3)2-Ph
2-Naphthyl
2-Thienyl
9
10
11
12
4-Hydroxy-Ph
aIsolated yield. bConversion determined by GC-MS.
mixture after 5 minutes indicated that 20-OH signal at d 12.8 in the substrate disap-
peared thereby, confirms its involvement in the reaction (Figure 1). Except for phos-
phoester no other intermediate is isolable. Hence, it is assumed that a water molecule
then attacks the phosphorus atom of phosphoester followed by Michael addition of
phenolic oxygen on the double bond leads to the formation of flavanone. Another mol-
ecule of POCl3 is now attacked by the > C¼O group of intermediate flavanone. This
facilitates the addition of (H3O)Cl which is generated by autoionization of POCl3 in
presence of water.[14] It is followed by abstraction of oxygen atom from carbonyl group
by the oxophilic reagent to form 3-Chloro-flavanone. 3-Chloro-flavanone undergoes
dehydrochlorination to generate flavone.[11]
Conclusion
In conclusion, we have developed a new, water-mediated cyclodehydrogenation method
for synthesis of flavones from 20-hydroxychalcones by using POCl3. The conversion has
the advantage of mild reaction condition, less reaction time and equal relevance in the
synthesis of flavanones as well as flavones by simply changing the stoichiometry
of reagent. Under the optimized reaction conditions, POCl3–H2O served dual purposes
–
isomerization of chalcones to flavanones and their subsequent oxidative

6
M. VIMAL ET AL.
Table 3. Conversion of 1 to 3.
OH
O
O
O
R
3 mmol POCl3-H2
O
°
R
90-95 C
3
1
Entry
-R
Reaction time
Yielda %
1
2
3
4
5
6
7
8
Ph
2 h
2 h
4 h
6 h
90
85b
66b
62
75
63
65
76
60
60
75
85
69
70
85
75
63
75
70
72
p-OCH3-Ph
p-CH(CH3)2-Ph
p-Cl-Ph
3,4,5-(OCH3)3-Ph
o-F-Ph
m-Cl-Ph
3,4-(OCH3)2-Ph
p-NO2-Ph
2-Thienyl
2-Naphthyl
p-CH3-Ph
12 h, 4.5 mmol POCl3
4 h
6 h
7 h, 4.5 mmol POCl3
9
4.5 h
1.5 h
6 h
2 h
6 h
5.5 h
4 h
6.5 h
2 h
6.5 h
6 h
10
11
12
13
14
15
16
17
18
19
20
2,4-(Cl)2
p-F-Ph
p-CH2CH3-Ph
2,4-(OCH3)2-Ph
3-Methyl-thienyl
4-(C5H11)-Ph
4-(C6H13)-Ph
4-Hydroxy-Ph
5 h
aIsolated yield. bConversion determined by GC-MS.
O
P
Cl
Cl
O
Cl
Cl
P
O
P
Cl
O
OH
Cl
Cl
OH2
O
O
-HCl
O
O
1
O
O
O
H
O
P
O
Cl
Cl
Cl
-HCl
2
O
O
O
O
-HCl
Cl OH
O
P
Cl
O
3
O
Cl
Cl
Scheme 4. Plausible mechanism for preparation of flavanone and flavone.

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SYNTHETIC COMMUNICATIONSV
7
dehydrogenation to flavones. The protocol was applicable to a wide range of substituted
20-hydroxychalcones.
Experimental
General information
All chemicals were obtained commercially and were used directly without any purifica-
tion. Analytical thin-layer chromatography was performed using E. Merck silica gel 60 F
glass plates and E. Merck silica gel 60 (230–400 mesh) was used in flash chromatog-
raphy separations. MS analysis was performed by GC-MS Agilent 5975 turbo system.
1H NMR was recorded with Bruker Avance 400 MHz and 13C NMR spectra on Bruker
DRX 300 MHz (Bruker, Billerica, MA) with CDCl3 as a solvent. Chemical shifts were
reported in parts per million (d) using TMS as internal standard and coupling constants
were expressed in Hertz. IR spectra were recorded on a Thermo Electron FTIR-6700
spectrometer. Elemental analysis was performed with Vario Micro Cube CHNS analyzer.
Melting points were recorded using Optimelt MPA100, an automated melting point sys-
tem and uncorrected. Progress of the reactions was monitored by TLC and GC-MS.
The starting material 20-hydroxychalcones were prepared by the literature method.[7]
Synthesis of flavanones: General procedure
1 mmol POCl3 was added to 1 mmol chalcone and stirred till it is thoroughly mixed.
1 mmol water was added to the reaction mixture and then heated at about 70–75 ꢀC.
The reaction was continued until the conversion was achieved. Contents were neutral-
ized with 5 ml of 10% sodium bicarbonate solution. The crude product was isolated by
filtration and purified by recrystallization.
Synthesis of Flavones; General procedure
POCl3 (3 mmol) was added to chalcone (1 mmol) in toluene and mixed well. 3 mmol of
water was added to it. The reaction mixture was then refluxed at 90–95 ꢀC till conver-
sion to flavones was complete which takes approximately 2 h. Contents were loaded dir-
ectly on silica. The product was separated by column chromatography (95:5 Ethyl
acetate: hexane). Pure white crystals were obtained on solvent removal.
2-(3,4,5-Trimethoxy-phenyl)-chroman-4-one
White crystals (270 mg, 86%); mp 124–126 ꢀC; IR (KBR): 3358, 3077, 2970, 2947, 2826,
1689, 1602, 1510, 1467, 1424, 1371, 1226, 1124, 1071, 950, 849, 761, 691 cmꢁ1; 1H-
NMR(400 MHz, CDCl3): d 7.94 (d, 1H, J¼ 8Hz), 7.56–7.52(m, 1H), 7.10–7.08 (m, 2H), 6.72
(s, 2H), 5.44 (d, 1H, J¼ 13.2Hz), 3.99 (s, 6H), 3.88 (s, 3H), 3.16–3.12 (m, 1H), 2.90 (d, 1H,
J¼ 16.4); 13C NMR (100 MHz): d 178.5, 161.6, 153.7, 138.5, 136.4, 134.5, 133.9, 127.2, 121.9,
121.1, 118.3, 103.9, 79.9, 60.9, 56.5; MS(EI): m/z¼ 314[Mþ], 299, 283, 224, 207, 194, 179,
151, 121, 92, 77; Anal. Calcd. for C18H18O5: C, 68.78; H, 5.77; Found: C, 69.03; H, 5.23.

8
M. VIMAL ET AL.
Figure 1. 1H-NMR analysis of the reaction mechanism.
2-(4-Pentyl- phenyl)-4H-chromen-4-one
White crystals (219 mg, 75%); mp 80–82 ꢀC; IR (KBr): 3128, 2956, 2928, 2857, 1639,
1
1565, 1464, 1416, 1374, 756 cmꢁ1; H NMR (400 MHz, CDCl3): d 8.24 (dd, 1H, J ¼ 7.6,
1.2 Hz), 7.85 (d, 2H, J ¼ 8.4 Hz), 7.72–7.68 (m, 1H), 7.57 (d, 1H, J ¼ 8.4 Hz), 7.44–7.40
(m, 1H), 7.34 (d, 2H, J ¼ 8.4 Hz), 6.82 (s, 1H), 2.71–2.67 (m, 2H), 1.69–1.63 (m, 2H),
1.39–1.34 (m, 4H), 0.93–0.90 (m, 3H); 13C NMR (100 MHz): d 178.6, 163.8, 156.4,
147.4, 133.8, 129.3, 126.45, 125.86, 125.29, 124.18, 118.22, 107.18, 36.03, 31.01, 31.61,
22.68, 14.7; MS(EI): m/z ¼ 292 [Mþ], 235, 221, 120, 92; Anal. Calcd. for C20H20O2: C,
82.16; H, 6.89; Found: C, 82.01; H, 6.99.
1
Full experimental details, H and 13C NMR spectra can be found in the supplemen-
tary content section of this article’s webpage.
Acknowledgments
The authors thank Dr. D. K. Dubey, Director, DRDE for his keen interest and encouragement.
The authors also thank Dr. Avik Mazumdar and Mr. Ajeet Kumar for NMR support, Mrs. Tara
Yadav for Elemental Analysis DRDE internal review committee for valuable inputs (DRDE/SC/
013/2018).
Disclosure statement
We state that none of the authors have any conflict of interest in the context of this
communication.
References
[1] Bohm, B. A. Introduction to Flavonoids, Chemistry and Biochemistry of Natural
Products, Vol. 2. Harwood Academic Publishers: Reading, UK, 1988.
[2] Verma, A. K.; Pratap, R. Nat. Prod. Rep. 2010, 27, 1571. DOI: 10.1039/c004698c.

R
SYNTHETIC COMMUNICATIONSV
9
[3] Harborne, J. B.; Marby, H.; Marby, T. J. The Flavonoids. Springer-Science Business Media:
Dordrecht, Netherlands, 1975.
ꢀ
ꢀ
[4] Litkei, G.; Gulacsi, K.; Antus, S.; Blasko, G. Liebigs Ann. 2006, 1995, 1711–1715. DOI: 10.
1002/jlac.1995199509240.
[5] (a) Baker, W. J. Chem. Soc. 1933, 322, 1381–1389. DOI: 10.1039/jr9330001381. (b) Mahal,
H. S.; Venkataraman, K. J. Chem. Soc. 1934, 387, 1767–1769. DOI: 10.1039/jr9340001767.
(c) Mahal, H. S.; Venkataraman, K. J. Chem. Soc. 1933, 154, 616. DOI: 10.1039/
jr9330001381.
[6] (a) Hoshino, Y.; Takeno, N. BCSJ. 1987, 60, 1919. (b) Nishinaga, A.; Ando, H.;
Maruyama, K.; Mashino, T. Synthesis 1992, 1992(9), 839. DOI: 10.1055/s-1992-26241. (c)
Zubaidha, P. K.; Hashmi, A. M.; Bhosale, R. S. Heterocyclic Commun. 2005, 11, 97–100.
(d) Garg, S.; Ishar, M. P. S.; Sarin, R.; Gandhi, R. P. Indian J. Chem. Soc. 1994, 33B, 1123.
(e) Jung, J. C.; Min, J. P.; Park, O. S. Synth. Commun. 2001, 31, 1837. DOI: 10.1081/SCC-
100104333. (f) Varma, R. S.; Saini, R. K.; Kumar, D. J. Chem. Res.(S), 1998, 348. DOI: 10.
1039/a709146j. (g) Kumar, P. E.; Prashad, K. J. R. Indian J. Chem. 1999, 38B, 1277. (h)
Tsukayama, M.; Kawamura, Y.; Ishizuka, T.; Hayas, S.; Torii, F. Heterocycles 2003, 60,
2775. DOI: 10.3987/COM-03-9891. (i) Ghani, S. B. A.; Mugisha, P. J.; Wilcox, J. C.; Gado,
E. A. M.; Medu, E. O.; Lamb, A. J.; Brown, R. C. D. Synth. Commun. 2013, 43, 1549.
DOI: 10.1080/00397911.2011.647222.
[7] (a) Wheeler, T. S. Org. Synth. 1952, 32, 72. (b) Wheeler, T. S. Org. Synth. 1963, 4, 478.
ꢁ
(c) Claisen, L.; Claparede, A. Ber. Dtsch. Chem. Ges. 1881, 14, 2460–2468. DOI: 10.1002/
cber.188101402192. (d) Schmidt, J. G. Berichte Der Deutschen Chemischen Gesellschaft
1881, 14, 1459–1461.
[8] (a) Shi, L.; Feng, X. E.; Cui, J. R.; Fang, L. H.; Du, G. H.; Li, Q. S. Bioorg. Med. Chem.
Lett. 2010, 20, 5466–5468. DOI: 10.1016/j.bmcl.2010.07.090. (b) Lin, Y. -M.; Zhou, Y.;
Flavin, M. T.; Zhou, L. -M.; Nie, W.; Chen, F. -C. F. Bioorg. Med. Chem. 2002, 10, 2795.
(c) Maruyama, K.; Tamanaka, K.; Nishinaga, A.; Inada, A.; Nakanishi, T. Tetrahedron Lett.
ꢀ
1989, 30, 4145. DOI: 10.1016/S0040-4039(00)99344-4. (d) Sagrera, G.; Lopez, V.; Pandolfi,
ꢀ
ꢀ
E.; Seoane, G.; Eicher, T. Informacion Tecnologica 1998, 9, 11. (e) Aitmambetov, A.;
Kubzheterova, A. Russ. J. Biochem. 2001, 28, 165. (f) Sagrera, G. J.; Seoane, G. A. J. Braz.
Chem. Soc. 2005, 16, 851–856. DOI: 10.1590/S0103-50532005000500026. (g) Geissman, T.
A.; Clinton, R. O. J. Am. Chem. Soc. 1946, 68, 697.
[9] (a) Tanaka, K.; Sugino, T. Green Chem. 2001, 3, 133. DOI: 10.1039/b101826b. (b) D.;
Macquarrie, J.; Nazih, R.; Sebti, S. Green Chem. 2002, 4, 56. DOI: 10.1039/b109015c. (c)
Chandrasekhar, S.; Vijeender, K.; Reddy, K. V. Tetrahedron Lett. 2005, 46, 6991. DOI: 10.
1016/j.tetlet.2005.08.066. (d) Biddle, M. M.; Lin, M.; Scheidt, K. A. J. Am. Chem. Soc.
ꢀ
2007, 129, 3830. DOI: 10.1021/ja070394v. (e) Friden-Saxin, M.; Pemberton, N.;
Andersson, K. S.; Dyrager, C.; Friberg, A.; Grøtli, M.; Luthman, K. J. J. Org. Chem. 2009,
74, 2755. DOI: 10.1021/jo802783z. (f) Kabbe, H. J.; Widdig, A. Angew. Chem. Int. Ed.
Engl. 1982, 21, 247. DOI: 10.1002/anie.198202471.
[10] Iguchi, D.; Erra-Balsells, R.; Bonesi, S. M. Tetrahedron Lett. 2014, 55, 4653–4656. DOI:
10.1016/j.tetlet.2014.06.081.
[11] (a) Singh, O. V.; Muthukrishnan, M.; Raj, G. Synth. Commun. 2005, 35, 2723. DOI: 10.
1080/00397910500214490. (b) Lorette, N. B.; Gage, T. B.; Wender, S. H. J. Org. Chem. 1951,
16, 930. DOI: 10.1021/jo01146a016. (c) Bognar, R.; Rakosi, M. Chem. & Ind.(London), 1955,
773. (d) Zhou, Z.; Zhao, P.; Huang, W.; Yang, G. Adv. Synth. Catal. 2006, 348, 63. DOI: 10.
1002/adsc.200505223. (e) Lee, Y. J.; Wu, T. D. J. Chin. Chem. Soc. 2001, 48, 201. DOI: 10.
1002/jccs.200100033. (f) Looker, J. H.; Holm, M. J. Org. Chem. 1959, 24, 567. DOI: 10.1021/
jo01086a609.
[12] (a) Doshi, A. K.; Soni, P. A.; Ghiya, B. J. Indian J. Chem. 1986, 25B, 759. (b) Imafuka,
K.; Honda, M.; McOmie, J. F. W. Synthesis 1987, 1987(2), 199–201. DOI: 10.1055/s-
1987-27891. (c) Shankar, G.; Mallaiah, B. V.; Srimannargayanna, G. Synthesis 1983,
1983(4), 310–311. DOI: 10.1055/s-1983-30317. (d) Makrandi, J. K., Seema. Chem. & Ind.
(London), 1989, 607.

10
M. VIMAL ET AL.
[13] (a) Du, Z.; Ng, H.; Zhang, K.; Zeng, H.; Wang, J. Org. Biomol. Chem. 2011, 9, 6930–6933.
DOI: 10.1039/c1ob06209c. (b) Ahmed, N.; Ali, H.; van Lier, J. E. Tetrahedron Lett. 2005,
46, 253. DOI: 10.1016/j.tetlet.2004.11.062. (c) Kumar, K. H.; Perumal, P. T. Tetrahedron
2007, 63, 9531–9535.
[14] (a) Gutmann, V. Coordination Chemistry in Non-Aqueous Solution. Springer-Verlag: New
York, NY, 1968. (b) Huheey, J. E.; Kieter, E. A.; Kieter, R. L.; Madhi, O. K. Inorganic
Chemistry: Principles of Structure and Reactivity, IV edition. Pearson Education, New
Delhi, 2006; 256. (c) Belle-Oudry, D. A.; Satyapal, S.; Mussillon, T.; Houston, P. L. Chem.
Phys. Lett. 1995, 235, 235–241. (d) Toy, A. D. F. The Chemistry of Phosphorus.
Pergamon Press: Oxford, UK, 1975; 433. (d) Berkeley, C. C. C.; Evans, T. W.; Oakland,
C. U. S. Patent 2347151, Apr. 18, 1944.
[15] (a) Avakian, S.; Boiler, J. M.; Martin, G. J. U. S. Patent 2764596, 1956. (b) Arnott, E. A.;
Chan, L. C.; Cox, B. G.; Meyrick, B.; Phillips, A. J. J. Org. Chem. 2011, 76, 1653–1661.
DOI: 10.1021/jo102262k.
[16] (a) Bergel, F.; Cohen, A.; Haworth, J. W.; Hughes, E. G. U. S. Patent 2465320, Mar. 22,
1949. (b) Kumar, V.; Kalalbandi, A.; Seetharamappa, J. Syn. Commun. 2016, 46, 626–635.
DOI: 10.1080/00397911.2016.1160412. (c) Vyas, G. N.; Shah, N. M. Curr. Sci., 1948,
17(4) 134.