chapter 1 introduction -...

Chapter 1 Introduction

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2

Section A

Oxidative halogenations

In the present era, the prime goal for a synthetic organic chemist is to actively engage in

the development of efficient and environmentally benign synthetic protocols in response to the

increasing pressure to produce the large number of substances required by society in an

environmentally benign fashion. Various stringent regulations and stipulations that are placed on

the chemical industries, especially in the area of waste management, have inspired the scientists

to explore environmentally benign methods to carry out the reactions in an expeditious manner

with minimized waste generation.

1.1. Halogen compounds

It is difficult to imagine organic chemistry without organo-halogen compounds.

Halogenated organic compounds play a very important role in chemistry, they are essential in

organic synthesis as starting compounds and synthetic intermediates, as designer molecules for

material science, industrial chemicals and bioactive compounds [1–3].

The past 30 years have witnessed a period of significant expansion in the use of

halogenated compounds in the field of agrochemical research and development. There has been a

rise in the number of commercial products containing mixed halogens. A survey of new active

ingredients used as modern agrochemicals provisionally approved by ISO in the last 10 years

shows that around 78.5% of them are halogen substituted. However, the complex structure

activity relationships associated with biologically active molecules mean that the introduction of

halogens can lead to either an increase or decrease in the efficacy of a compound depending on

its change mode of action, physicochemical properties, target interaction or metabolic

susceptibility and transformation.


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Halogen-containing drugs have entered into usage only since 1820. The incorporation of

halogen atoms into a lead results in analogues that are more lipophilic and so less water soluble.

Consequently halogen atoms are used to improve the penetration of lipid membranes. However,

there is an undesirable tendency for halogenated drugs to accumulate in lipid tissue.

1.2. Naturally occurring organo-halogen compounds

The number of known naturally occurring organo halogen compounds has increased

tremendously during the last few decades. Fifty years ago there were less than 30 known

examples, whereas today there are more than 4500 documented examples of naturally occurring

organo-halogen compounds (ca. 120 iodinated, 2100 brominated, 2300 chlorinated and 30

fluorinated compounds) [4-6].

Among natural organo-halogen compounds, bromophenols are abundant in marine life.

These compounds are mostly isolated from red algae of the family Rhodomelaceae [7].

Bromophenols are important compounds in the field of functional food and pharmaceuticals.

They also exhibit a wide spectrum of useful biological activities [8] (Fig. 1.1-1.3).

OH

OH

Br

R

R = CO2CH3/CHO

Br

OH

OH

OH

O

OH

OH

Br

OH

OH

Br

BrO

Br

Br

OH

OH

O

Br

Br

OHOH

Br

OH

OH

Fig. 1.1. Bromophenols with anticancer activity

OH

OH

Br

R

Br

Br

R = CH2OH/CH2OCH3

/CH3/CHO

R

OH

Br CHO

R = OH/Br

S

OBr

OH

OH

Br

BrO

Br

OH

OH

Br

OH

OH O

OH

OH

R

OH

OH

OH

R

Fig. 1.2. Bromophenols with antioxidant activity


4

OH

OH

Br

R

Br

Br

R = CH2OCH3/CH2OH

OH

Br

NH2

Br

OH

OH

Br

Br OOBr

OH

OH

Br

Br

O

Br

Br

OH

OH

Br

Br

OH

OH

Fig. 1.3. Bromophenols with antimicrobial activity

1.3. Halogenation of organic compounds

Generally the halogenation of organic compounds performed by molecular halogens in

chlorinated solvents, either in the absence of catalyst or in presence of Lewis acid catalyst [9].

R H + X2

Chlorinated SolventsR X +

Lewis AcidH X

These methods have several environmental drawbacks like toxic molecular halogen,

catalysts and atom efficiency (only half of the halogen atoms react and the remainder are

converted into hydrohalic acid, thereby reducing the atom efficiency by 50%). In large scale

operations this is an environmental as well as an economic problem. As a result, many industrial

halogen compounds are no longer manufactured and are being banned. Therefore direct use of

molecular halogens in the reactions is no more recommendable and alternative strategy is

required for their use.

Hence, during present thesis work, efforts are being made for development of sustainable

halogenations using eco-friendly reagents such as NH4Br as a brominating agent and oxone as an

oxidant.

1.4. Oxidative halogenation

In-situ generation of halonium species via the oxidation of halides using suitable oxidants

under moderate reaction conditions.


5

HXOxidant

H2ORH

RX

X+

An increasing environmental concerns and advanced studies on oxidative halogenations,

it is desirable for synthetic chemists to study and understand in-depth the oxidative

halogenations. Oxidative halogenations is widely used in industry during the preparation of vinyl

chloride, where waste HCl generated during the production of isocyanate is regenerated by

passing it together with oxygen and ethylene in the gas phase over a Cu (II) catalyst at a

temperature of over 200oC [10].

1.4.1. Oxyhalogenations in nature

Nature has always served as a source of inspiration for those working in diverse areas

from creating intelligent systems to discovering new building blocks. In this respect, organic

chemistry is no exception, although chemists have yet to match the efficiency by which nature

synthesizes complex and chiral molecules. A good example is halogenation: Electrophilic

halogenation in nature mainly occurs by oxidative halogenation through the enzyme catalyzed

oxidation of the halide ion to form a halogenating reagent (An exception is fluorination, since it

is too difficult to oxidize fluoride) [11].

1.4.1.2. Enzymes

Halogenating enzymes are divided into five classes, which are shown in Table 1.1. The

first halogenating agent discovered in biological systems was the heme-dependent enzyme

chloroperoxidase (isolated from the fungus Caldariomyces fumago) which uses H2O2 and

chloride anions for “electrophilic” chlorination [12]. To date, chloroperoxidase from


6

Table 1.1. Classes of halogenating enzymes

Entry Enzyme Proposed

form of

activated

halogen

Substrate

requirements

Cofactor and

co substrate

requirements

1

2

3

4

5

Heme iron-dependent haloperoxidases

Vanadium-dependent haloperoxidases

Flavin-dependent halogenases

Non-heme iron-dependent halogenases

Nucleophilic halogenases

X+

X+

X+

X

X-

Aromatic and

electron-rich

Aromatic and

electron-rich

Aromatic and

electron-rich

Aliphatic, unactivated

Electrophilic, good

leaving group

Heme, H2O2

Vanadate,

H2O2

FADH2, O2

Fe(II), O2, R-

ketoglutarate

Caldariomyces fumago remains the most studied halogenating enzyme. The use of enzymes for

halogenation is still potentially the most effective and environmentally friendly route, but so far

large scale enzymatic halogenation has not been commercialized because of the low operational

stability of the haloperoxidase enzymes (resulting from either inactivation with H2O2 or the

organic solvent) [13]. Consequently, these reactions need to be performed in mixtures of dilute

aqueous buffer and organic solvents, thus rendering them economically unattractive.

Nevertheless, research on biological halogenation has boosted the interest in oxidative

halogenation and has resulted in the development of several environmentally friendly methods

with various catalysts, oxidants and reaction media.

1.4.2. Brominating reagents

Various brominating reagents are reported in the literature. The most classical primary

brominating reagent is liquid bromine. Other secondary reagents such as N-bromosuccinimide

(NBS), 2,4,4,6-tetrabromo-2,5-cyclohexadien-1-one (TBCD) etc. are also well reported. In the

recent years modified oxybrominating reagents are also developed.


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1.4.2.1. Liquid bromine

Liquid bromine is very good oxidizing as well as brominating reagent. It adds across

unsaturated hydrocarbons (carbon-carbon double and triple bond) to give addition product and

incorporated into aromatic nucleus to give nuclear brominated product through electrophilic

substitutions. Bromination reactions of organic substrates carried out with liquid bromine are

well reported [14]. Bromine combines with other supports such as Br2/NaY zeolite and

Br2/alumina are reported for bromination of aromatic substrates [15]. The bromine complex of

poly(styrene-co-4-vinylpyridine) [16a], hexamethylenetetramine-bromine/basic alumina [16b]

and dioxane–bromide/silica gel [16c] are effective for the conversion of ketones to

bromoketones.

1.4.2.2. N-Bromosuccinimide

N-Bromosuccinimide is used in radical bromination reactions and electrophilic addition

reactions in organic chemistry. NBS considered as a convenient source of cationic bromine and

used for selective oxidations and bromination reactions. The reaction of NBS catalyzed by

different catalysts such as Mg(ClO4)2 [17a], Amberlyst-15 [17b], trimethylsilyl

trifluoromethanesulfonate (TMSÆOTf) [17c], NaHSO4/Silica [17d], ammonium acetate [17e],

photons (light) [17f], Pd(II)/TfOH [17g], (+)-CSA/(DHQD)2PHAL [17h], [Rh(III)Cp*] [17i],

isoselenazolone [17j], Pd(OAc)2 [17k] and (S)TRIP/Ph3PS [17l] are effective systems for the

bromination of various organic compounds.

1.4.2.3. Other brominating reagents

Many metal centers such as iron, vanadium, molybdenum interact with oxidants having

suitable bromide source will react with organic substrate to provide oxybromination products.

Due to the better understanding of vanadium role in biological systems, the vanadium and


8

molybdenum complexes can act as functional mimics of enzyme vanadium peroxidase.

Oxybromination of various organic compounds can be achieved using aqueous solution of KBr-

H2O2 in presence of mineral acid with catalytic amount V2O5 [18]. Also the vanadium catalyzed

oxidative bromination of toluene [19a] alkenes and alkynes performed in the aqueous or in a

biphasic medium [19b]. A similar reaction has been reported using molybdenum catalyst [20a] as

well as in ionic liquids [20b]. Generally, the bromination of sp3 carbon is a challenging task. Reis

et al observed that salts of synthetic amavidine complex catalyze the bromination of cyclohexane

in acetonitrile/water medium in presence of KBr, HNO3 and H2O2 [21]. Schiff base binded and

polymer supported vanadium complexes are also effective for oxidative bromination [22]. The

reports for the preparation of β-bromoalkenes (Hunds Dicker reaction) from unsaturated

carboxylic acids using molybdenium catalyst (Na2MoO4.H2O) is available [23]. Similarly,

tungsten catalyst (LDH-WO42-

) has been used to brominate various alkenes in presence of

NH4Br and H2O2 [24]. Methyltrioxorhenium (MTO) used for rapid bromination of phenols and

phenyl acetylenes in quantitative yields [25]. The attempts were made to prepare asymmetric α-

bromination of aldehydes and ketones using C2-symmetric diphenylpyrrolidine [26a] and

[Pd(CH3CN)2(S)-Tol-BINAP](BF4)2 or [Pd(CH3CN)2(S)-METBOX](BF4)2 [26b] as catalysts.

Masuda et al [27] have employed NaBrO3-NaHSO3 reagent combinations for the preparation of

bromohydrins. The reaction of the N-methylpyrrolidin-2-one hydrotribromide complexes

(MPHT) with substituted-1-tetralones provided selective α,α-dibrominated tetralones [28]. The

reagents pyridiniumbromide perbromide [29a], quaternary ammonium tribromide [29b], and 2-

carboxyethyltriphenylphosphonium perbromide [29c] reagents are reported. The reagents

2,4,4,6-tetrabromo-2,5-cyclohexadien-1-one (TBCO) [30a] and 2,4,4,6-Tetrabromo-3-n-

pentadecyl-2,5-cyclohexadienone (TBPCO) [30b] are selective and useful brominating reagents.


9

NaBrO2 in acetic acid [31a] and Selectfluor/KBr [31b] are useful for oxybromination of alkenes

to α-bromoketones. NaBrO3/H2SO4 has shown to be a promising reagent for bromination of

aromatic rings having electron withdrawing substituents [32] NaBrO3/HBr in sulfuric acid or

acetic acid medium has been used for bromination of several amides and imides [33], while Ishii

et al. have shown that NaBrO3/NaHSO3 is a good reagent for the bromination of alkyl benzenes

and for the synthesis of bromohydrins from alkenes [27,34]. BrCl has been used for substitution

reactions and the reactions are reported to be faster than those involving bromine alone [35].

Recently, NaBr-H2O2 catalyzed by CeCl3 [36a], H2O/scCO2 [36b], HBr/O2 catalyzed by NaNO2

[36c], KBr-H2O2 catalyzed by polymer anchored Cu(II) [36d], NaBr/O2 catalyzed by palladium-

polyoxometalate [36e], LiBr/PhI(OAc)2 [36f], NaBr/NaIO4/H2SO4 [36g], NaBr/H2O2 over ionic

catalyst [36h], KBr/H2O2 catalyzed by V-MCM-41 [36i] and trifluoromethanesulphonic

anhydride with Grignard reagent or MgBr2 [37] were reported for oxybrominations.

In spite of large number of applications of liquid bromine in organic chemistry, it is not

recommendable because of its hazardous nature and extreme care for its production,

transportation and utilization particularly in graduate and undergraduate levels. Moreover, for

bromination reactions half of the bromine atoms end up in the effluent as hydrobromic acid

leading to low atom economy and generation of waste. NBS is safe and selective reagent but it

also generates succinimide as organic byproduct. Being organic in nature, succinimide creates

problems in isolation and purification of desired organic products in some cases. Also liquid

bromine is used for its preparation. Some of the handy reagents are prepared for example

pyridinium bromideperbromide which is easy to handle but its preparation also requires pyridine

as a starting substrate and pyridine is responsible for impotency. In some cases the halogen atom

efficiency is improved by using oxidants and transition metal catalysts. In order to minimize


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above indicated problems, alternatively safe and environmentally benign brominating reagents

and oxidants are utilized for the present research purpose which are described in the following

sections.

1.5. Applications of brominated organic compounds

1.5.1. Applications of brominated aromatic compounds

Brominated aromatic compounds are useful synthetic intermediates in the manufacture of

pharmaceuticals, fine chemicals, agrochemicals and other specialty chemicals like flame

retardants, pesticides, herbicides, etc [38]. They are also useful and important key intermediates

for cross coupling reactions [39] and as precursors to organometallic reagents [40]. In addition,

several aryl bromides are biologically active and used as potential antitumour, antibacterial,

antifungal, antineoplastic antipsycholic, antioxidizing and antiviral agents (Fig. 1-3) [41].

1.5.2. Applications of brominated carbonyl compounds

The α-bromination of ketones is an important transformation in synthetic organic

chemistry [42]. α-Bromoketones are among the most versatile intermediates in organic synthesis

and their high reactivity makes them prone to react with large number of nucleophiles to provide

a variety of biologically active compounds [43] (some of the biologically active compounds

which are synthesized from α-bromoketones are shown in Scheme 1.1). α-Bromoacetophenone

derivatives have been investigated for their active participation in the inhibition of protein

tyrosine phosphatase such as SHP-1 and PTP1B [44]. Bromination at the reactive position in a

1,3-keto compound enhances bioactivity, particularly cytotoxicity against breast cancer 1A9

cells, with respect to the unsubstituted compound [45].


11

Quinoxaline

R

O

Br

RINH2

R2CHO

O

R

N

R

CO2Et

O

OH

N

CO2Et

RINH2

PhNCS

Imidazole

2-Mercaptoimidazole

Benzofuran

Indolizine

Thiazol-2-imine

NH2

O

N

RR

4H-1,4-Oxazine

N

NH2

N

NR

Imidazo[1,2-a]pyridine

N

NR

R2

R1

N

NR

RI

R2

R2N N

R

S

O

O

R1

S N

R

NPh

R1

O

O

NH

NH

SR1

R2

NH2

NH2

R1

R2

Antibacterial, antitumor agents, pesticides,

glucagon receptors, antagonists, p38

mitogen-activated protein kinase inhibitors

and B-Raf kinase inhibitors [46].

Antithyroid drugs, anti-inflammatory,

inhibition of Tcell antigen receptors, potent

CCR2 antagonists as well as antioxidants

[47].

Anticancer, antioxidative and anti-

inflammatory properties [48].

Antibacterial, phosphatase and aromatase

inhibiting, antioxidant, antidepressant and

antitumor activities [49].

Antiinflammatory, analgesic and kinase

(CDK1, CDK5 and GSK3) inhibition,

antifungal, melanin-reducing activity (skin

whitening agent) and as platelet GPІІb/ІІІa

receptor antagonists [50].

Antibiotics (echinomycin, leromycin, and

actinomycin), wide application in dyes,

efficient electroluminescent material, organic

semiconductors, dehydroannulenes, and

chemically controllable switches [51].

Transthyretin amyloid fibril inhibitors [52].

Antiviral, antitumor, antimicrobial, herbicidal

and immunosuppressive agent [53].

Scheme 1.1. Biologically active compounds which are synthesized from α-bromoketones


12

1.5.3. Applications of bromohydrins, bromo ethers and dibromides

Vicinal bromohydrins, bromo ethers and dibromides are versatile intermediates for the

synthesis of pharmaceuticals, dyes, flame retardants, agrochemicals, additives, plasticizers and

specialty chemicals (Scheme 1.2) [54].

R

X

Br

NNH2

N

Cl

N

NH

X = OH

NNH2

N

Cl

N

N

OH

R

R O

Br

BrR

R

O

NNPh2

OR O

NHNPh2

NH

OH

N

OH

OH

R

X = OH

X = OH

X = OH

OH

OH

CO2Et

CO2Et

X = Br

O

O

CO2Et

CO2Et

R

NH

N

O

NH2

SH

X = Br

N

N

O

NH2

S

R

Scheme 1.2. Applications of bromohydrins, bromo ethers and dibromides


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1.6. Oxone

Oxone is a white crystalline solid, which contains component of a triple salt with the

formula 2KHSO5·KHSO4·K2SO4 [55]. The active component in the triple salt is KHSO5. Oxone

is also known as Potassium peroxymonosulfate, potassium monopersulfate and the trade name

Caroat. It is the potassium salt of peroxymonosulfuric acid.

Oxone is a cheap commercially available oxidant that easily oxidizes numerous

functional groups. It is an efficient single oxygen-atom donor since it contains a nonsymmetrical

O−O bond which is heterolytically cleaved during the oxidation cycle. It is an inexpensive

reagent ($0.02−0.04/g), which compares favorably with hydrogen peroxide and bleach. It is

about one-half as expensive as m-chloroperoxybenzoic acid (mCPBA). Its byproducts do not

pose an immediate threat to aquatic life upon disposal, and unlike chromium trioxide and bleach,

it does not emit pungent vapors or pose a serious inhalation risk. Its main advantage over

hydrogen peroxide is easier handling. HSO5- is proposed to be an intermediate in the atmospheric

oxidation of sulfur and it is hypothesized that 35% of the total sulfur species in clouds exist as

HSO5-.

As long as oxone is stored under dry and cool conditions, it loses about 1% activity per

month under release of oxygen and heat. Decomposition to SO2 and SO3 takes place under the

influence of heat (starting at 300oC). Acidic, aqueous solutions of the pure reagent in distilled

water are relatively stable. The stability reaches a minimum at pH 9, where the mono anion

(HSO5-) has the same concentration as the dianion (SO5

2-). Iron, cobalt, nickel, copper,

manganese and further transition metals can catalyze the decay of oxone in solution.

Oxone is also an environmentally friendly oxidant with no toxic by-products, and thus is

an attractive green reagent. These features make oxone attractive for large-scale applications.

http://en.wikipedia.org/w/index.php?title=Triple_salt&action=edit&redlink=1

http://en.wikipedia.org/wiki/Potassium

http://en.wikipedia.org/wiki/Salt_(chemistry)

http://en.wikipedia.org/wiki/Peroxymonosulfuric_acid


14

Uses of other oxidizing agents lack the desired ingredients to attract the interest of industry

because of tedious purification processes from their deoxygenated counterparts.

1.7. Applications of oxone

Owing to its high stability simple manipulation, non-toxic nature and efficiency, oxone

has found many applications in the oxidation of organic compounds, primary oxidant for water

oxidation catalyst and shock oxidizer.

1.7.1. Oxidation of organic compounds using oxone

Oxone has found many applications in the oxidation of functional groups such as alkanes,

alkenes, alkynes, alcohols, carbonyl compounds, carboxylic acids, amines, amides, nitro

compounds, boron, sulpher and phosphorus compounds (Scheme 1.3-1.9) [55].

R1R2

O

R1R2

OH

R1R2

Scheme 1.3. Oxidation of alkanes using oxone

R1COOH + R2COOHR1

R2

OH

OHR1

R2

O

R1

R2

N OPh

R1

X

R1

R2

O

OHR1

R2

NPhth

R1

R2

I

N3

R1

R2

Scheme 1.4. Oxidation of alkenes using oxone


15

R1COOH + R2COOH

R1

O

X X

R2

R1

R2

Scheme 1.5. Oxidation of alkynes using oxone

H

O

R1

OH

O

R1

X

O

R1

OTMSR1

R1

CO2Et

OH

R1R2

O

R1R2

Scheme 1.6. Oxidation of alcohols using oxone

R2 = H

R2 = HR2 = CH3O

R1R2

OH

O

R1

OR

O

R1

O

R1OR2R1

R2

O O

NO

R1

R

RCOOHRX

RCOODpm

Scheme 1.7. Oxidation of carbonyl compounds and carboxylic acids using oxone


16

R2 = H

NH

R1 R2

R1NO

R2 = NHR

R2 = CORN

OH

R1 R2

NN

RR1

N

O

R

Cl

R1

NH2

NH2

NH

NR

R1

OR

R2

R1

O

R2

R1

NO2

R2

Scheme 1.8. Oxidation of amines, amides and nitro compounds using oxone

(R)3B (RO)3B

RS

R RS

R

O

OR

SR

O

(or)

(R)3P (R)3P O

Scheme 1.9. Oxidation of boron, sulphur and phosphorus compounds using oxone

1.7.2. Oxone as a primary oxidant for water-oxidation catalyst

Increased global attention to the effects of releasing carbon dioxide into the atmosphere

by burning fossil fuels has led to investigation of alternative fuel sources. One of the most

promising of such methods is artificial photosynthesis. In an artificial photosynthetic cell, solar

energy is collected and passed to a water-oxidation catalyst (WOC) that splits water into

dioxygen, protons and electrons. The electrons produced can then reduce protons to form


17

dihydrogen or may be used to reduce other organic molecules or CO2 to products that can serve

as fuels.

Oxone, is a powerful two-electron oxidant that has seen success in characterizing WOCs

[56]. The reduction potential of oxone is 1.82 V vs. NHE, comparable to that of Ce(IV). Oxone

has seen extensive use in the study of the Mn terpyridine dimer, and has since been used with a

number of other first row transition metal complexes. In addition to being a two electron oxidant,

oxone also has the ability to behave as an oxo-transfer reagent, leading to the possibility that

oxygen produced by WOCs driven by oxone is unrelated to water oxidation.

As a two-electron oxidant, oxone can drive WOCs that form unstable complexes when

they undergo one-electron oxidation. This is the primary reason that oxone has been useful in

characterizing WOCs based on first row transition metals, which have a tendency to be more

labile than their second and third row counterparts. Oxone is also stable up to a pH of about 5.5,

allowing for characterization of WOCs at pH values close to neutral where an „artificial leaf‟

might function. Additionally, the reduction product of oxone is sulfate, a relatively benign by-

product.

1.7.3. Oxone as a shock oxidizer

Oxone can be used in swimming pools to keep the water clear, thus allowing chlorine in

pools to work to sanitize the water rather than clarify the water, resulting in less chlorine needed

to keep pools clean. The benefits of using oxone in pools are given below [57].

1) Keeps the water crystal clear

2) Reduces eye, nose and skin irritation

3) Eliminates the strong chlorine smell

4) Keeps pool surface and bathing suits looking newer

http://en.wikipedia.org/wiki/Swimming_pool


18

5) Very less time (15 minutes) is required to dissolve and spread through the water

1.8. Organic transformations using oxone in the present work

Oxidation of various organic compounds using oxone in the present thesis is shown in

Scheme 1.10 and which are deeply discussed in chapters 4 and 5.

Oxone

R D

D

R

R

R

R

RR

Br

OHRR

Br

Br

RR

Br

OR

R

OOH

I

O

OR

O

R

O

OH

O

O

O

OR

D D

R

R

R

R

R

R

O

R

O

O

R

O

Br

R

OR OR

Br

OH

R R

OO

Br

R R

OO

Br Br

R

R

Br

Br

OR

R

R

O

O

R

R

O

O

Scheme 1.10. Organic transformations in the present work using oxone


19

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12. (a) P. D. Shaw, L. P. Hager, J. Am. Chem. Soc., 81 (1959) 6527. (b) P. D. Shaw, L. P.

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14. B. M. Choudary, T. Someshwar, C. V. Reddy, M. L. Kantam, K. J. Ratnam, L.V. Sivaji,

Appl. Catal., A, 251 (2003) 397.

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25

Section B

Zeolites

1.10. Zeolite molecular sieves

Zeolites are defined as crystalline microporous aluminosilicates with pore structures

consisting of a three dimensional network of [SiO4] and [AlO4] tetrahedra linked by corner

sharing of oxygen ions. The term Zeolites (Greek, zeo,"to boil", lithos, "a stone") was originally

coined in the 18th

century by a Swedish mineralogist named Axel Fredrik Cronstedt who

observed, upon rapidly heating a natural mineral (Stilbite) that the stones began to dance about as

the water evaporated. Using the Greek words which mean "stone that boils", he called this

material as zeolite [1]. The first reported synthetic zeolite was Linde A. This was synthesized in

1949 by Milton, working at Union Carbide. Zeolites can be described with the following

empirical formula [2]:

M2/n. Al2O3. XSiO2. YH2O

Where M represents the exchangeable cations, n represents the cation valency and, X can

assume a value equal or greater than 2 as no two Al3+

can occupy the adjacent tetrahedral

position (Lowenstein rule) [3] and Y is the number of H2O molecules present in the channel or

cavities of the three dimensional network.

The porous materials may be divided into three types based on their pore dimensions,

namely, microporous (< 2 nm), mesoporous (2-50 nm) and macroporous (> 50 nm). The pores of

the zeolites are of molecular dimensions ranging between 0.5 and 1.0 nm in diameter. Hence,

zeolites are also known as molecular sieves because of their ability to discriminate the molecules


26

of different size and shape. The characteristics, which make molecular sieves useful as catalysts

are:

Generation of highly acidic sites when exchanged with protons.

Shape selective catalytic properties.

High surface area and thermal stability.

Ease of regeneration of the initial activity.

1.11. Nomenclature of zeolite molecular sieves

Milton, Breck and coworkers at Union Carbide employed Arabic alphabets, viz., zeolites

A, B, X, Y, L. Mobil and Union Carbide later used the Greek alphabets alpha, beta and omega.

Many of the synthetic zeolites have the structural topology of mineral, for example, synthetic

mordenite, chabazite, erionite and offretite.

The IUPAC nomenclature was evolved in 1979, with acronyms viz., ZSM-5, ZSM-11,

ZK-4 (Mobil); EU-1, FU-1, NU-1 (ICI); LZ-210, ALPO, SAPO, MeAPO, UOP (Union

Carbide), ECR-1 (Exxon) [4] etc. and is limited to the known zeolite type material. The IZA

Atlas of zeolite structure types published by the International Zeolite Association [5] assigns a

three-letter code to be used for a known framework topology irrespective of their chemical

composition. Table 1.2 provides the typical IZA Atlas nomenclature of various zeolites.

1.12. Classification

Several attempts have been made to classify the families of zeolites on the basis of their

morphological characteristics [6], crystal structure [7], chemical composition [8], effective pore

diameter [9] and natural occurrence.


27

Table 1.2. Pore dimensions and dimensionalities of zeotype structures

Pore size Structure

type

(IUPAC)

Trivial names Pore

diameter

(A°)

Dimen-

sionality

Adsorbed

molecules

Small

LTA

Zeolite A

4.1

3

n-hexane

Medium MFI

MEL

MTT

EUO

AEL

MTW

TON

ZSM-5, TS-1,

VS-1

ZSM-11,TS-2

VS-2

ZSM-23

EU-1

ALPO4-11

ZSM-48

MCM-22

ZSM-12

Theta-1,

ZSM-22

5.3X5.6

5.1X5.5

5.3X5.4

4.5X5.2

4.1X5.7

3.9X6.3

5.5

5.6

5.5X6.2

4.4X5.5

3

3

1

1

1

1

2; 1

1

1

Cyclohexane

-

-

-

-

-

-

-

-

Large MOR

BEA

AFI

EMT

FAU

Mordenite

NCL-1

Zeolite-β

ALPO4-5

Hexagonal

faujasite

Zeolite X or Y

6.5X7.0

2.6X5.7

6.5-7.0

7.6X6.4

5.5X5.5

7.3

7.1

7.4X6.5

7.4

1

1; 2

1

1; 2

3

Neopentane

Mesityline

-

-

-

Tributylamine

Extra

large

AET

CLO

VFI

ALPO4-8

Cloverite

VPI-5

7.9X8.7

13.2X4.0

12.1

1

3

1

-

Triisopropyl

benzene

Meso-

porous

MCM-41 15.0-100 1 -


28

1.12.1. Chemical composition

According to chemical composition zeolites can be classified on the basis of their silica to

alumina ratio [8] as low silica zeolites, medium silica zeolites, high silica zeolites and silicalites

(Table 1.3).

Table 1.3. Classification of zeolites on the basis of their Si/Al molar ratio

Type Si/Al ratio Examples

Low silica

Intermediate

High

All silica

1 to 1.5

~ 2 to 5

5 to 500

α

LTA, FAU (Y), LTL, etc

Natural zeolites: erionite, clinoptilolite, mordenite

Synthetic zeolites: Y, large pore mordenite, omega

MFI, BEA, NCL-1, etc

Si-MFI, Si-UTD-1, etc

1.12.2. Pore opening size

All zeolites have been classified by the number of T atoms, where T = Si or Al, that

define the pore opening. Zeolites containing these pore openings are also referred to as: small

pore (6 or 8 member ring), medium pore (10-member ring), large pore (12-member ring) and

ultra large pore (14-or more member ring). Some examples on the basis of pore size

classification are given below in Table 1.4.

On the basis of their morphology, zeolites are classified as fibrous, lamellar etc.

Structural classification of zeolites has been proposed depending on differences in secondary

building units. With the addition of new synthetic and natural zeolites, they are grouped into ten

classes: Analcime, Natrolite, Chabazite, Philipsite, Heulandite, Mordenite, Faujasite, Laumonite,

Pentasil and Clatharate.


29

Table 1.4. Classification of zeolites based on pore size (pore diameter <2 nm)

Zeolite type Pore opening Example

Small pore

Medium pore

Large pore

Extra large pore

8-membered ring

10- membered ring

12- membered ring

14- membered ring

MTN, NU-1, etc

MFI, MEL, etc

FAU, MTW, BEA, NCL-1, etc

UTD-1

1.13. Structural details of zeolite molecular sieves

Zeolites are crystalline aluminosilicates with an open lattice framework and contain silica

and alumina tetrahedra joined through oxygen bridges to form a three dimensional structure. The

primary building units of tetrahedra can arrange themselves in different ways to form different

rings of various dimensions. These rings are joined together to form complex secondary building

units [10].

The secondary building unit (SBU) consists of selected geometric groupings of primary

tetrahedra. There are nine such building units, which can be used to describe all of the known

zeolite structures. These secondary building units consist of 4, 6 and 8-membered single rings, 4-

4, 6-6 and 8-8 member double rings, and 4-1, 5-1 and 4-4-1 branched rings [11]. The topologies

of these units are shown in Fig. 1.4.


30

Fig. 1.4. Secondary building units and their symbols. Number in parenthesis indicates

frequency of occurrence

1.13.1. Zeolite β: structure and properties

Zeolite Beta is a high silica and large pore crystalline material. It is an old zeolite

discovered before Mobil began the "ZSM" naming sequence. As the name implies, it was the

second in an earlier sequence. Zeolite beta consists of an intergrowth of two distinct structures

termed Polymorphs A (tetragonal) and polymorph B (monoclinic). The polymorphs grow as two-

dimensional sheets and the sheets randomly alternate between the two. Both polymorphs have a

three dimensional network of 12-ring pores. The intergrowth of the polymorphs does not

significantly affect the pores in two of the dimensions, but in the direction of the faulting, the


31

pore becomes tortuous, but not blocked. The two hypothetical polymorphs are depicted in Fig.

1.5 & 1.6 and bond distances and bond angles in zeolite beta are shown in Table 1.5.

Fig. 1.5. Structure of zeolite Beta (poly type A)

Table 1.5. Bond distance and bond angles in zeolite Beta

Type Bond distance

Si – O (Å)

Bond angle

O – Si – O (deg)

Poly type A

Poly type B

1.616

1.616

109.47

109.47

Fig. 1.6. Structure of zeolite Beta (poly type B)

Zeolite Beta have several unique and interesting features. It is the only high silica zeolite

to have fully three dimensional 12-membered ring pore system and also the only large pore

zeolite to posses chiral pore intersections. It has high catalytic potential compared to the faujasite


32

type zeolite by virtue of its high silica content, acid site distribution and stacking faults [12]. In

addition, the comparatively smaller dimension of one of the two types of pores (5.5 A) offers a

certain level of the shape selectivity similar to that observed in medium pore zeolites.

1.13.2. ZSM-5 ( Zeolite Scony Mobile Number 5) structure and properties

ZSM-5 (Fig. 1.7) is the parent zeolite of the Mobile Five (MFI) group, patented by

Argauer and Landolt using Na-TPA system in 1972 [13]. The molar oxide composition of the

mixtures from which ZSM-5 is crystallized is as follows:

(R4N)2+O, M2/n, Al2O3, XSiO2, H2O

Where (R4N)+ is a quaternary ammonium ion and M is the alkali metal cation of valency

„n‟. A wide range of Silica-Alumina contents (Si/Al = 10-∞) in the reaction mixture yields ZSM-

5 phase.

Zeolite ZSM-5 is a member of shape-selective catalysts with unique medium pores

between large-pore faujasite and small pore zeolites such as Linde type A and erionite. The

framework structure is built up of pentasil blocks (Five membered SBUs) and so called pentasil

chains. These chains can similarly be connected to form sheets. The three dimensional network is

built up by cross linkage of the sheets. The framework contains two types of intersecting

channels. One type is straight and has elliptical opening of 10 membered rings of 5.2 X 5.8 Å

internal diameter and runs parallel to the b-axis of the orthorhombic unit cell. Nearly circular 10

membered rings of 5.4 X 5.6 Å internal diameter circumscribe another kind of channel. It is

sinusoidal (zig-zag) and directed along the a–axis. The maximum diameter at the intersections is

about 0.9 nm. The composition of the unit cell in Na form is Nan [Aln Si96-n O192]16 H2O. (n <27

and typically equal to 3) [14]. The number of atoms obtained from the unit cell is from relation

NAl = [96/(1+R)],


33

Where R = Nsi/Al, NSi and NAl are grams of atoms of Si and Al, respectively.

TO4 SBU (A) (B)

Fig. 1.7. Structure of MFI Zeolite (ZSM-5): (A) Mode of interconnection of pentasil

chains (B) with emphasized chain system.

1.14. Characteristic properties of zeolite molecular sieves

1.14.1. Shape selectivity of zeolites

The capability of molecular sieves to organize and to discriminate molecules with high

precision is responsible for their shape selective properties [15]. Shape selectivity has been

studied in reversible and acid catalyzed processes [16]. Csicsery [17] defined the three well-

known categories of shape selectivity (Fig. 1.8).

Reactant shape selectivity: Only molecules that are able to enter the zeolite channels

will react.

Product shape selectivity: Only molecules that are able to diffuse out of the zeolite

channels are found in the product mixture.

Restricted transition-state shape selectivity: Reactions occurs only when the required

transition state can be formed in the zeolite cavities.


34

Fig. 1.8. Mechanism of shape selective catalysis

1.14.2. Zeolite molecular sieves as acids and bases

Zeolite molecular sieves as acids: There are two types of acid catalytic activity

associated with zeolites namely, Bronsted acidity (H+) and Lewis acidity. In zeolites the centers

of the TO4 tetrahedra are occupied by silicon and aluminum atoms in a Si/Al ratio from 1 to ∞.

The difference in valencies of Si (tetravalent) and Al (trivalent) produce an overall negative

charge for each incorporated aluminum atom. These negative charges are balanced by alkali

and/or alkali earth cations. Bronsted acid site in catalyst arises when cations (often Na, K or Cs)

are replaced by proton (H+, from ammonium ion exchange, followed by the thermal

decomposition of the ammonium form to H+ form of the zeolites).


35

Lewis acid sites arise at the defect sites where triagonal Al is present either in the

framework or at charge compensating ions. The Lewis acidity can also be formed by high

temperature (>5000C) dehydroxylation of the Si (OH) AI (i.e. Bronsted) sites (Fig. 1.9).

Bronsted acid site (proton donor) Lewis acid site (e- acceptor)

Fig. 1.9. Schematic showing Lewis and Brønsted acid sites on an aluminosilicate surface.

The strength of these acid sites is found to vary with (i) zeolite structure (ii) Si/Al ratio

and (iii) isomorphously substituted metal ions in the zeolite framework [18]. The acid strength

increases with decreasing aluminum content and the number of acid sites decreases. The strength

of acidic sites is also influenced by the nature of the trivalent atom in the framework. Chu and

Chang [19] showed that substitution of Al by B, Fe or Ga in framework of MFI zeolite decreases

the strength of the Bronsted acid sites in the order Al-MFI > Ga-MFI > Fe-MFI > B-MFI.

The effects discussed above allow tailoring of basicity and acidity from weakly basic to

strongly acidic [20]. A metal cation or a proton that constitutes a Lewis- or a Brönsted- acid site,

respectively [21] balances the negative charge in the zeolite framework. In solid acid catalysts

the number of potential Bronsted acid sites is equal to the number of trivalent atoms present in

the silica framework. For zeolites it can be stated that the concentration of aluminum in the

lattice is directly proportional to the concentration of acid sites and the polarity of the lattice is

indirectly proportional to the strength of acid sites [22]. For a given chemical composition of the

zeolite, the polarity of the lattice increases with decreasing framework density [23]. Thus, by

changing the framework Si/Al ratio, either during synthesis or post-synthesis, it is possible to

change not only the total number but also the acid strength of the Bronsted acid sites.


36

Extra-framework aluminum also creates the acidity in zeolites. When zeolites are

dealuminated by steam-calcination part of the framework Al is extracted and generates extra-

framework species (EFAL) that can be cationic, anionic or neutral. Some of these EFAL species

can act as Lewis acid sites [24] or can influence the Bronsted acidity, by either neutralizing

Bronsted Acid sites by cation exchange or by increasing the acidity by a polarization effect

and/or by withdrawing electron density from lattice oxygens [25]. This opens the way to Lewis

acid catalysis by the Al [26].

Zeolite molecular sieves as bases: According to Barthomeuf and Kazansky, the extra

framework protons and cations in zeolites are the Bronsted and Lewis acid sites, respectively,

while the framework oxygens are their conjugated basic sites [27]. Except for non-oxide

catalysts among various heterogeneous basic catalysts the basic sites are believed to be surface

oxygen atoms. Oxygen atoms existing on any materials may act as basic sites because any

oxygen atom would be able to interact with a proton.

1.14.3. Hydrophobicity of zeolite molecular sieves

In zeolites, the hydrophilicity and hydrophobicity can be easily manipulated. Siliceous

and high SiO2/Al2O3 ratio zeolites are less hydrophilic and more organophilic, which are well

suited for chemical transformations. Hydrophobicity of the titanium silicate framework is held

responsible for the high activity of these materials in the heterogeneous catalytic oxidation of

organic compounds with aqueous hydrogen peroxide solutions compared to an amorphous

Titania-silica mixture [28].

1.14.4. The physico-chemical properties of zeolite related to its SiO2 /Al2O3 ratio

An important variable in the main group of zeolites is the Si/Al ratio, which has a bearing

on several properties as shown in Scheme 1.3 [29]. In the case of zeolites from type A to silicate


37

as Si/Al ratio increases, thermal stability and acidity increases. According to Olson [30], ion

exchange capacity and catalytic activity increases with increasing Al content, while

hydrophobicity increases with decreasing Al in the framework.

Scheme 1.11. Various properties depending on Si/Al ratio

1.15. Concepts of zeolite synthesis

1.15.1. Natural zeolites

Zeolites occur in nature in vugs and vesicles of basic lava, in specific kinds of rocks

subjected to moderate geological temperature and pressure. The formation of such zeolites with

volcanic glass and saline water as reactants must have occurred in temperature range 300-350 K

and pH > 13, requiring several years of crystallization [31]. Many of these natural zeolites have

been commercialized for purification of natural gas (chabazite), radioactive waste disposal

(clinoptilolites), ammonia recovery from sewage effluents (clinoptilolite) and various petroleum

and petrochemical catalyst applications (eronite, mordenite).

1.15.2. Concept of zeolitization

The hydrothermal synthesis of aluminosilicate zeolites, in a broad sense, corresponds to

the transformation of a mixture of silica and alumina compounds, inorganic bases like sodium

hydroxide, organic quaternary ammonium salts either in the form of hydroxides or halide and


38

water in the form of an alkaline super saturated solution into micro or mesoporous crystalline

aluminosilicates. The complex chemical processes involved in this transformation are

schematically presented in Fig 1.10.

Fig. 1.10. A schematic representation of zeolite formation process in an autoclave. (SDA =

Structure Directing Agent)

1.15.3. Zeolitization process sequence

The important steps involved in the zeolitization process are:

Rapid formation of an aluminosilicate hydro-gel.

Solid phase dissolution mediated by mineralizing agents to provide a solution of silicate

and aluminate monomer and oligomer.

Ageing of the hydrogel for specific period of time at predetermined temperature to

achieve desired crystalline characteristics [32].

Simultaneous dissolution or depolymerization of the silica sol particles, which is

catalyzed by alkaline conditions [33].

Copolymerization of the monomeric silicate anions in solution to yield negatively

charged oligomeric species.

Rapid intra and intermolecular exchange of silicate monomers [34].


39

Reaction of oligomeric silicate species with monomeric [Al(OH)4]¯ to produce

aluminosilicate structures [35]. They are more stable in the ring and cage like structures

than in the linear chains [36] and are called “secondary building units (SBU)”, which are

essential for both the nucleation and crystal growth processes.

Ageing and heating of hydrogel to crystallization temperature in the range of 60 to 200°C

[33].

1.16. Factors influencing zeolitization

The parameters such as molar composition, alkalinity, temperature, time of heating and

nature of template play a major role in the zeolitization process.

1.16.1. Molar composition of gel

The chemical composition of the hydrogel can be expressed in terms of: a SiO2 : b Al2O3

: c MxO : d NyO : e R : f H2O in which M and N stand for (alkali) metal ions, R for organic

template and „a‟-„f‟ are molar ratios. The relative amounts of Si, Al, M, N and R are key factors

in deciding the outcome of crystallization process. Their molar ratio can influence nucleation and

crystallization processes, nature of the crystalline material, lattice Al content and its distribution

and the crystal size and its morphology [37].

1.16.2. Alkalinity

The alkalinity of the synthesis solution (which is generally between 9.0 and 13.0) is a key

factor in zeolite formation. The OH¯ ions play a crucial role in the mineralization process for

bringing Si and Al oxides into solution at optimum rate. Increased pH can accelerate the crystal

growth, and shorten the induction period (the period before the formation of viable nuclei) by

enhancing the precursor concentration.


40

1.16.3. Temperature and time of heating

Temperature and time of heating have positive influence over zeolite formation. At

higher temperature, both the nucleation and the linear growth rates are increased. Zeolite

synthesis is governed by the occurrence of successive phase transformations with

thermodynamically least favorable phase crystallizing first. As time progresses, more stable

phases are formed. The precise effect of temperature and time parameters largely depends on the

type of the zeolite synthesis.

1.16.4. Nature of templates

Templates, which are also called as structure-directing agents, contribute both

thermodynamically and chemically to the formation of the zeolite lattices. Generally the

templates are cationic, anionic or neutral forms of organic / inorganic entities. The present

knowledge is not yet adequate to pre asses the type of template needed for obtaining a specific

zeolite with a required structure and composition. However, it is well established that the factors

like solubility, stability under synthesis conditions and steric compatibility are important for

template design [38]. The method of removing the template without destroying the zeolite

framework has also been standardized [39].

1.17. Applications of zeolite molecular sieves

Due to the diverse properties of zeolite molecular sieves, these materials are finding

applicability in a broad range of industrial processes that are environmentally sensitive. Zeolites

have been explored as catalysts in petrochemical [40] and to some extent in fine chemical

synthesis [41]. The industrial use of zeolites started at the beginning of 1960‟s with replacement

of cracking catalysts based on the amorphous alumino silicates [42]. Number of reviews have


41

documented the applications of zeolite molecular sieves [43]. Few important applications are

discussed here.

1.17.1: Zeolites in petrochemical processes

The use of silicon rich zeolites as highly acidic, extremely shape selective and thermally

stable catalysts led to new industrial petrochemical processes [44] selectoforming [45], olefin

oligomerizations [46], Dewaxing [47] and MTG (Methane to Gasoline) [48]. Zeolites are much

more active than silica-alumina in cracking of small molecules such as light alkanes. In the

petrochemistry, a major isomerization process based on zeolites is the xylene isomerization

process. The process essentially converts the less desired m-xylene into an equilibrium mixture

of xylenes. Both mordenite and ZSM-5 have been used as catalysts for this purpose.

1.17.2: Zeolites in fine chemical process improvements

The fine chemical industry is generally defined as the selective production of organic

compounds containing functional groups. Traditionally, many of these processes have been

homogeneous, liquid phase catalyzed systems that generate large quantities of waste during the

neutralization processes including contaminated water streams, salts and heavy metals. These

materials make the work up costly and can lead to corrosion problems and increased costs.

Zeolites are being extensively studied as heterogeneous catalysts that can be recovered and

recycled more easily and cheaply leading to less waste and fewer by-products [49]. The cost of

the materials is cheaper and the processes are more efficient, frequently combining all of the

reactants in one pot. Zeolites are also more selective in comparison to classic synthetic paths.

One such example is the use of microporous Titanium silicalite-1 [50] catalyst for selective

oxidation of a variety of organic substrates by aqueous H2O2 under milder conditions [51].

1.17.3: Zeolites in acid catalysis


42

Alkylation reactions are the major source of petrochemicals/bulk chemicals such as

ethylbenzene, cumene and xylenes. The earlier processes used mineral acids such as H2SO4, HF,

AlCl3 and BF3. The recent processes use zeolites (safe solid acids) as catalysts. An added benefit

of zeolites is their shape selective property, which results in the production of a specific isomer.

Examples of shape selective alkylations using zeolites practiced in the industry are the

production of p-diethyl benzene (modified ZSM-5), 2,6-dialkyl naphthalene and 4,4‟-dialkyl

biphenyls (dealuminated mordenite) [52]. Synthesis of 4-Methyl thiazole (4-MT) over Cesium

loaded zeolites is a first example of commercially useful basic zeolites [53].

1.17.4: Zeolites in rearrangement and cyclization reactions

Kulkarni et al. [54] have reported extensively in the cyclization and macro cyclization

reactions using zeolites or meso porous molecular sieves such as MCM-41 as catalysts. The

products of these reactions have resulted in very important organic intermediates, which are used

in the preparation of agro chemicals, drugs, and in host-guest chemistry.


43

1.18. Objectives and scope of the present work

To develop eco-friendly process for the oxybromination of aromatic compounds using

simple inorganic salt like NH4Br as bromine source and oxone as an oxidant.

To develop eco-friendly process for the α-bromination of ketones, 1,3-dicarbonyl

compounds and β-keto esters and α,α-dibromination of 1,3-dicarbonyl compounds and β-

keto esters using NH4Br/Oxone.

To develop eco-friendly process for the hydroxybromination, dibromination and

alkoxybromination of olefins using NH4Br/Oxone.

To develop eco-friendly process for the synthesis of cyclic acetals and esters from olefins

using I2 as a catalyst and oxone as a terminal oxidant.

To develop metal modified zeolites for the cyclization reactions in vapour phase for the

synthesis of annelated pyridines.

To develop metal modified zeolites for the tetrahydropyranylation of alcohols.

The scope of this thesis to develop a simple, economic and environmentally safe

processes for bromination of aromatic compounds, carbonyl compounds and olefins using

NH4Br as brominating agent and oxone as an oxidant. To develop eco-friendly process for the

synthesis of cyclic acetals and esters from olefins using I2 as a catalyst and oxone as a terminal

oxidant. To study the modification of zeolite Beta with Ni, Cu, Pb, La, Ce, Cr, Fe, W, Zn, Co,

Mo, Zr and Sn metal cations and characterize them by XRD, IR, and Elemental analysis. To use

above prepared metal modified zeolites as catalysts for the synthesis of various annelated

pyridines in vapour phase. To use metal modified zeolite Beta as catalysts for

tetrahydropyranylation of alcohols. The organic products were characterized by using GC, 1H

NMR, 13

C NMR, MASS, IR and CHNS elemental analyzer.


44

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