A Project Report On

“Hydroxybenziodoxolone: Synthesis Strategies and Versatile application in organic

synthesis”’’
Submitted to

Sant Gadge Baba Amravati University, Amravati

Project report submitted for the Partial Fulfillment of Requirement for the Award of Degree of Master
of Science
In Chemistry
(Session: 2023-2024)

Submitted By:

Ms. Anuradha Shivpalsing Jadhav

(M.Sc.-II SEM-IV)
(Enrolment Number :.)
Under the Guidance of

Prof. H S Kumar Chandak sir

(NET, SET, GATE, POST DOC)
Department of Chemistry,
G.S. Science, Arts and Commerce College, Khamgaon, Dist-Buldana-444303

Center Code: 301

City Code: 061

May-2024

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 Certificate
This is to certify that the work presented in this project entitled
““Hydroxybenziodoxolone: Synthesis Strategies and Versatile application in organic
synthesis”

has been completed and submitted as bonafide work carried out by MS.
Anuradha Shivpalsing Jadhav, for the partial fulfillment of degree of Master of
Science in Chemistry. The project work is satisfactorily carried out under my
supervision in the P.G Department of Chemistry, G.S. Science, Arts and
Commerce College, Khamgaon District. Buldhana. During the academic session
2023-2024 and to the best of my knowledge the matter embodied in this project
report has not been submitted elsewhere for any diploma or degree

Date: …/…/2024 Prof. H S Kumar Chandak ….

Place: Khamgaon (Project Guide)

Prof. Dr. Hemantkumar S. Chandak

Professor and HOD
Department of Chemistry
G. S Science, Arts and Commerce College Khamgaon

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 Declaration

The work presented in this project entitled “Hydroxybenziodoxolone: Synthesis

Strategies and Versatile application in organic synthesis”

. Under the guidance of Prof. H S Kumar Chandak. During the academic year
2023-2024 as a partial fulfillment of project of MSc-II Semester-IV at P.G
Department of Chemistry G.S. Science, Arts and Commerce College, Khamgaon.
I further declare that this project work or any of this work has not been previously
submitted for any degree in this university or any other university.

Date: …/…/2024 Ms. Anuradha Shivpalsing Jadhav

Place: Khamgaon (M.Sc.-II Semester-IV)

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 Title: “Hydroxybenziodoxolone: Synthesis Strategies and Versatile application in
organic synthesis”

Table of Contents
1. Title of project report ....................................................................................................... 1
2. Abstract ............................................................................................................................. 1
3. Key word ........................................................................................................................... 1
4. Introduction ...................................................................................................................... 1
5. Research problem ............................................................................................................. 2
6. Research gap ..................................................................................................................... 2
7. Originality of project work .............................................................................................. 2
8. Literature review .............................................................................................................. 3
9. Aims and objectives .......................................................................................................... 5
9.1 Aim: ............................................................................................................................ 5
9.2 Objectives ................................................................................................................... 5
10. Scope and implications .................................................................................................... 5
11. Methodology (Experimental) .......................................................................................... 5
12. Result and Discussion ...................................................................................................... 9
13. Conclusion ...................................................................................................................... 12
14. Reference ........................................................................................................................ 13

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 Acknowledgement

It is my pleasure to place on record my sincere gratitude towards my guide

Pro. H S Kumar Chandak.P.G Department of Chemistry, G.S. Science, Arts and
Commerce, College Khamgaon whose guidance I received. It was his direction
and encouragement at every moment and step that motivated me to steer the
research (project) work complete confidently and successfully
I deem it great pleasure privilege to offer my sincere and cordial thanks to
Prof. Nilkesh k Dhruve (Research Scholar) who spend their precious time
providing continuous idea and exert guidance and constant encouragement
throughout the course of this research (Project) work.
We also extend our thanks to college management and Principle, G.S.
Science, Arts and Commerce, College Khamgaon for providing all the necessary
facilities and valuable support.
Also we would like to thank to all PG Chemistry teaching and non-teaching
staff of the department for their valuable guidance, encouragement, co-operation
and helps.
Our great thank to all who wished us success especially parents, friends
whose support and care makes us stay on earth.

Ms. Anuradha Shivpalsing Jadhav

[M.Sc-II SEM-IV]

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1. Title of project report
“Hydroxybenziodoxolone: Synthesis Strategies and Versatile application in
organic synthesis”
2. Abstract:
Hydroxybenziodoxolone is a key compound with significant importance in organic
synthesis. This project delves into two primary aspects: the synthesis strategies
employed to obtain Hydroxybenziodoxolone and its diverse synthetic applications. The
synthesis methods encompass various approaches, such as reactions involving
iodobenzene derivatives, phenols, and iodosylbenzene, each offering unique
advantages and selectivity. On the other hand, the synthetic applications of
Hydroxybenziodoxolone showcase its versatility as a reagent in oxidative
transformations, C-H functionalization, C-C bond formation, cyclization reactions,
halogenation reactions, cross-coupling reactions, and as a valuable reagent in organic
synthesis methodologies. This comprehensive study sheds light on the synthesis and
utility of Hydroxybenziodoxolone, highlighting its crucial role in modern organic
chemistry.
3. Key word
Hydroxybenziodoxolone, 2-Iodo benzoic acid (IBA), hypervalent iodine reagent, C-O
bond formation.

4. Introduction
Hypervalent iodine compounds are generally defined as “ions or molecules of iodine
bearing more electrons than the octet within a valence shell”. Compounds were first
described as “hypervalent” by Jeremy I. Musher who laid foundation of their chemistry
in a 1969 paper though their characteristic bonding had been described by Pimentel in
a 1951 report on bonding in trihalide anions and by Rundle in a report on pentaiodide
anion. Hypervalent bonds are weaker and longer than covalent linkages. Hypervalent
bonds are the result of a highly polarized linear three-centre- four-electron (3c-4e)
electronic distribution (hypervalent model), in which the central atom bears a positive
charge and two monovalent ligands share the corresponding negative charge.
Hypervalent iodine compounds have always fascinated chemists, due to their non-
classical bond character and exceptional reactivity.1 nevertheless, the research in this
area has been mostly curiosity-driven for several decades, and it is 20 only more
recently that general synthetic applications have emerged. For example, the Dess-
Martin periodinane (DMP) as a mild and non-toxic reagent is now one of the most often
used oxidant in organic synthesis. Structurally, it belongs to the benziodoxole-derived
iodine compounds, which are 25 characterized by the inclusion of the iodine atom
inside a ring.3 This cyclic structure confers to the benziodoxole-derived reagents an
exceptional stability when compared to other Hypervalent iodine, and their use for
oxidation reactions is now well-established.
Besides simple electron-transfer, the use of Hypervalent iodine for oxidative atom
transfer reactions is also emerging as a promising area, both for hetero- and carbon-
atom transfer reactions. In contrast to oxidation reactions, non-cyclic reagents have
been used in the vast majority of cases. In fact, one may argue that the lower reactivity
of benziodoxol-based reagents is an obstacle for their use as oxidative functionalization
reagents. In the case of highly unstable structures or for the development of catalytic
methods, less reactive reagents are desirable, however. Despite promising preliminary

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 results mostly for heteroatom transfer, the number of benziodoxol -based reagents used
in functionalization reactions other than simple oxidations constitutes only a fraction of
the reported structures and most of them are based on the iodine benziodoxolone
structure Whereas the formation of C-C bond using non-cyclic iodonium reagents has
been very successful in the last decades for acetylene transfer reactions (1).
Hypervalent iodine compounds are powerful reagents for numerous organic
transformations, such as oxidations, rearrangements, and single-electron-transfer and
radical reactions, leading to the formation of carbon–carbon, carbon–heteroatom and
heteroatom–heteroatom bonds International Edition 1.
hypervalent iodine reagents[1] has gained importance as a safe alternative to heavy-
metal reagents for performing a variety of organic transformations. In view of recent
demands for ecologically friendly chemical processes in the agrochemical and
pharmaceutical industries, polymer-supported hypervalent iodine reagents should be a
new and useful tool as a result of their versatility, low toxicity, high yields, simple work-
up procedures, and recyclability. 2

5. Research problem
After the extensive literature revived, we were convinced to focus on the green
synthesis of hydroxybenziodoxolone. Because it shows several potential bioactivities
as well as unique physical and chemical properties.
Under this project we intend to develop the green synthesis of hydroxy derivatives and
its application. This compound is often use in organic synthesis as a Hypervalent iodine
regent. Some potential research problem related to hydroxybenziodoxolone could
include exploring its synthetic applications, investigating its reactivity with various
substrate, optimizing its synthesis for improve efficiency, or studying its mechanistic
pathway in different reaction.

6. Research gap
From the review of literature it is observed that derivatives of Hydroxy benziodoxolone
has been received much more attention in the field of organic synthesis due to their mild
condition, easy to handling, and environmentally safe, commercially available, ease of
discovery, and easy for recyclability.
Through the extensive literature review in this particular domain, we came to know that
synthetic application of Hydroxy-benziodoxolone derivative is rare and their synthetic
application are not fully explore.

7. Originality of project work

This project report is in its original form and has not been conducted by any other
researchers in any university jurisdiction, in any Indian university .our finding may
contribute a new method, knowledge and new approach in the synthesis of Hydroxy-
benziodoxolone reaction so far, and the originality is concerned.

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 8. Literature review

Synthesis of Hydroxy benziodoxolone

The synthesis of derivative from Hydroxy benziodoxolone directly from iodine is
presented. The methodology provides hydroxyl benziodoxolone with the 2-
iodobenzoic acid (IBs) moiety as dummy group. The protocol avoids the customary use
of iodine, which can be both expensive and toxic. Excess reagents are not required, and
the reactions are performed under different condition.

S.N Author Journal/DOI Title Source

1) Hideyasu China et https://doi.org/10.3390/ Practical Synthesis of 2- Google

al3. molecules26071897 Iodosobenzoic Acid Scholar
(IBA) without
Contamination by
Hazardous 2-
Iodoxybenzoic Acid
(IBX)
under Mild Conditions

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2) Benziodoxole-Based Google
Jonathan P. Brand, DOI: Hypervalent Iodine Scholar
etal4. 10.1039/b000000x Reagents for Atom-
Transfer Reactions

3) Victor V DOI.org/10.1002/0470 1-Hydroxy-1,2- Google

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Zhdankin(4).etal . 84289X.rn00605.pub2 benziodoxol-3(1H)-one1 Scholar

4) Ahmad A. DOI: 1-Phenyl-1,2- Google

Almasalma[a] and 10.1002/ejoc.20170094 benziodoxol-3-(1H)-one Scholar
Esteban Mejía*[a] 0 as Synthon for Phthalide
Eur. Synthesis through Pd-
(5)etal6.
Free, Base-Free,
Sonogashira-Type
Coupling Cyclization
Reaction

5) First synthesis and First synthesis and Google

Marcel Mülbaier oxidative properties of oxidative properties of Scholar
and Athanassios polymer-supported IBX polymer-supported IBX
Giannis (6)etal7.

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6) Sachin S. 2-Iodoxybenzoic Acid 2-Iodoxybenzoic Acid Google
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Chaudhari(7)etal . (IBX) and Dess- (IBX) and Dess- Scholar
Martin Periodinane Martin Periodinane
(DMP) (DMP)

9. Aims and objectives

9.1 Aim
“Hydroxybenziodoxolone: Synthesis Strategies and Versatile application in
organic synthesis”

9.2 Objectives
1) Synthesis of Hydroxybenziodoxolone.
2) Synthetic application of Hydroxybenziodoxolone.

10. Scope and implications

• The present study work is limited to the synthesis of Hydroxybenziodoxolone
reagent.
• Scope of the present project work covers
• Synthesis of the HIR that is
• Hydroxy benziodoxolone reagent.
• The synthetic methodology so developed will be very useful
o To access active pharmaceutical ingredient
o To access natural products
o

11. Methodology (Experimental)

11.1 MATERIALS
All solvents and chemicals are purchase from commercially sources and use after
purification. Melting point were determined in open capillary and are collected. The
compound were washed and separated with the help of cinterd funnels. Evaporation of
the solvents done with the help of rotary evaporator.

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11.2 GENERAL SCHEME

Experimental Procedure:

Experiment No: 1

Procedure:
To a solution of 2-IBs(1.24g,5.0mg) in acetonitrile (10ml0 was added Oxone
(3.070g,10mmol) and water (10ml), after the mixture was stirred at room temp for the
appropriate time , the product was filtered under reduced pressure. The residue was
washed with water and acetone to obtain the corresponding IBA as a white powder.

Experiment No: 2

Observed melting point:

Procedure:
To a solution of 2-IBs (260.00mg), molecular Swiss(1g) then add 10 ml of methanol
.after the mixture was stirred at 60° temp for the appropriate time, then molecular Swiss
was filtered by using DCM(CH2Cl2) and the solvent is removed by evaporation
process. Then the residue is washed with hexane and filtered to remove the
corresponding alcohol completely. Then the residue was dissolved with DCM and

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extract was filtered through the filter paper to remove unreacted substrate. Removal of
solvent by evaporation and get the corresponding product as a white powder.

Experiment No: 3

Observed melting point: 252◦C

Procedure:
To a solution of 2-IBs (260.00mg), molecular Swiss (1g) then add 10 ml of Ethanol
.after the mixture was stirred at 60° temp for the appropriate time, then molecular Swiss
was filtered by using DCM (CH2Cl2) and the solvent is removed by evaporation
process. Then the residue is washed with hexane and filtered to remove the
corresponding alcohol completely. Then the residue was dissolved with DCM and
extract was filtered through the filter paper to remove unreacted substrate. Removal of
solvent by evaporation and get the corresponding product as a white powder. We
developed reaction between iodobenzoic acid and alcohol using molecular Swiss this
is the new method.
Experiment No: 4

Observed melting point:

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12. Result and Discussion
An atom-efficient and simple one-pot synthesis of hydroxy benziodoxolone derivative
would involve treatment of Hydroxy with a commercially available oxidant in the
presence of an MS A0 and alcohol as suitable solvent the anion of which would end up
in the iodonium salt. A screening of possible oxidants, acids and solvents that could be
employed in the selected model reaction between iodobenzoic acid and alcohol to get
a good yield hydroxy beziodoxolone.
S.N Solvent Time Temperature Product % Yield
1 Acetonitrile + water 2h RT R = OH 98%
2 Methanol 2h 60◦ R = Me 89%
3 Ethanol 1h 80◦ R = Et 95%
4 Acetic acid 1h RT R = Ac 80%
A mixture of (1.0 mmol) of iodobenzoic acid (1 equivalent), molecular swiss (1g)
solvent 10ml. The best result in term of yield was obtained using iodobenzoic acid in
alcohol at 60-800c for 2h. Some reaction was proceed at room temperature. Alcohol was
found to be the best solvent other than for this reaction.

95% Yield was obtained using 1 mmol % of iodobenzoic acid in alcohol at 60-800C for
2h. This reaction was did not proceed at room temperature

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12.6 Characterization data (1H NMR data)

1. 1
H NMR (400 MHz, DMSO-d6) δ 8.44 (dd, J = 7.7, 0.7 Hz, 1H), 8.26 – 8.18
(m, 2H), 7.99 (ddd, J = 8.1, 6.3, 1.9 Hz, 1H), 2.53 (s, 3H).

13. Conclusion
In summary, the green synthesis of hydroxy benziodoxolone by using iodobenzoic acid
and alcohol is successfully synthesized. Iodobenzoic acid (IBA) are easily available,
cheap and nontoxic, inexpensive and ecofriendly. This is an economic strategies
represent a new methodology for highly selective synthesis of hydroxy
benziodoxolone. They are use in pharmaceutical.

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 14. References

(1) Kaschel, J.; Werz, D. B. Ethynyl Benziodoxolone ( EBX ): Installing Alkynes the Reversed Way
**. 2015, 8876–8878. https://doi.org/10.1002/anie.201503405.
(2) Tohma, H.; Maruyama, A.; Maeda, A.; Maegawa, T.; Dohi, T.; Shiro, M.; Morita, T.; Kita, Y.
Hirofumi Tohma,* Akinobu Maruyama, Akihisa Maeda, Tomohiro Maegawa, Toshifumi Dohi,
Motoo Shiro, Tetsuichiro Morita, and Yasuyuki Kita*. 2004, 3595–3598.
https://doi.org/10.1002/anie.200454234.
(3) China, H.; Kageyama, N.; Yatabe, H.; Takenaga, N.; Dohi, T. Practical Synthesis of 2-
Iodosobenzoic Acid (IBA) without Contamination by Hazardous 2-Iodoxybenzoic Acid (IBX)
under Mild Conditions. Molecules 2021, 26 (7). https://doi.org/10.3390/molecules26071897.
(4) Brand, J. P.; González, D. F.; Nicolai, S.; Waser, J. Benziodoxole-Based Hypervalent Iodine
Reagents for Atom-Transfer Reactions. 2011. https://doi.org/10.1039/b000000x.
(5) Yusubov, M. S.; Soldatova, N. S.; Postnikov, P. S.; Valiev, R. R.; Yoshimura, A.; Wirth, T.;
Nemykin, V. N.; Zhdankin, V. V. 2-Iodoxybenzoic Acid Ditriflate: The Most Powerful
Hypervalent Iodine(v) Oxidant. 2019, 7760–7763. https://doi.org/10.1039/c9cc04203b.
(6) Almasalma, A. A.; Mejía, E. 1-Phenyl-1 , 2-Benziodoxol-3- ( 1 H ) -One as Synthon for Phthalide
Coupling Cyclization Reaction. https://doi.org/10.1002/ejoc.201700940.
(7) Mülbaier, M.; Giannis, A. First Synthesis and Oxidative Properties of Polymer-Supported IBX.
2003, 2003 (vi), 228–236.
(8) Zhdankin, V. Benziodoxole-Based Hypervalent Iodine Reagents in Organic Synthesis. Curr. Org.
Synth. 2005, 2 (1), 121–145. https://doi.org/10.2174/1570179052996982.

(9) Zhdankin, V. V. Hypervalent Iodine Compounds: Reagents of the Future. Arkivoc2020.

https://doi.org/10.24820/ARK.5550190.P011.145.

(10)Greenwood, N. N.; Earnshaw, A. Chemistry of the Elements; Elsevier, 2012.

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