shodhganga.inflibnet.ac.inshodhganga.inflibnet.ac.in/bitstream/10603/67018/12/12_chapter 4.pdf ·...

REGENERATION OF CARBONYL COMPOUNDS FROM THEIR OXIMES,PHENYLHYDRAZONES AND

SEMICARBAZONES DERIVATIVES BY OXIDATIVEMETHODS

Part A Chapters

REGENERATION OF CARBONYL COMPOUNDS FROM THEIR OXIMES,

PHENYL HYDRAZONES AND SEMICARBAZONES DERIVATIVES BY

OXIDATIVE METHODS

A. DEOXIMATION REACTION - A REVIEW

Introduction:

Oximes are nitrogen derivatives of Aldehydes and Ketones and are

crystalline compounds. Oximes are prepared by the reaction of carbonyl

compounds in the form of their hydrochloride or other Bronsted acid salts.

The mechanism of oxime formation is shown in Scheme A.ill.1.

Scheme A.III.1

R) = 0 + NH2OH

R2

1R- ----NH2OH

R2

O -H

R1 j f

2

NHOH

1R)= NO H

R2

Oximes are extensively used for purification and characterization of

carbonyl compounds and they play an important role as protecting and

selectively a-activating groups in multistep synthesis, in synthetic organic

chemistry1'3. Furthermore their synthesis from non-carbonyl compounds

provides an alternative pathway to carbonyl compounds4.

There has been increasing interest in the development of mild, fast

and environmentally benign methods for the conversion of oximes into their

corresponding carbonyl compounds. Regeneration of carbonyl compound

from the oxime is popularly known as de-oximation.

x

72

Part A Chapter 3

Hydrolytic Methods:

Hydrolysis of oximes to produce the parent carbonyl can be achieved

under acidic, basic or neutral conditions. An alternative to the acid hydrolysis

which limits the scope of the reaction as it excludes acid-sensitive or

asymmetric ketones or aldehydes is basic hydrolysis, which is a little less

efficient and excludes base-sensitive carbonyl compounds. Neutral

hydrolysis also does not allow achievement of good results because the

equilibrium do not moved completely towards the carbonyl compound.

The oldest method for the generation of carbonyl compound for the

corresponding oximes is hydrolysis under acidic conditions, which removes

the hydroxylamine from the equilibrium (Scheme A.III.2). An equilibrium

reaction of hydroxylamine with the carbonyl compound is involved which

may take several hours to completion when hydrolysis is done under neutral

conditions.5

Scheme A.III.2

1 1R h 2o /h + r + .

V = N -O H --------------► /= 0 + NH3OHR 2 R 2

R1 = alkyl, aryl

R2 = H, alkyl, aryl

Acid hydrolysis has been carried out with various acids such as oxalic

acid6, acetic acid7, p-toluene sulfonic acid8, phthalic anhydride-water9,

hydrobromic acid10, sulfuric acid11, which have been used in aqueous

solution or another cosoivent in relation to the solubility of the oxime.

73

Part A Chapter 3

Hydrolysis has also been employed in neutral or alkaline medium, but

the results were unfavourable in comparison to those for acidic conditions.

Some catalytic salts also have been added to the acid medium to achieve

complete conversion. Some of the ionic catalysts used are cupric sulfate

pentahydrate13, cupric nitrate supported on silica gel14, iron (ill) ammonium

sulfate to dif H2SO415 , Clayan16, Dowex-5017.

Hydrolysis can also be afforded with sodium hydrogensulfite, a simple

inexpensive and mild reagent, which interacts with the oximic compounds in

acidic medium, to give a sulfine, which produces the carbonyl compound on

exposition to cold acid. The most used acids were hydrochloric and sulfuric

acid whose treatment continues until the disappearance of sulfur dioxide

(Scheme A.III.3)

Surfactant promoted l2 catalyzed cleavage of the >C=N bond of

oximes in water under neutral condition has been exploited very recently

(Scheme B.I1I.4)18.

Scheme A.III.3

Scheme A.III.4

sulfate (SDS) X=OH, Ph 25-40°C

74

Part A Chapter 3

It is proposed that the surfactant promotes micelle formation from

iodine and the oxime in water, in which the electrophilic iodine activates

hydration o f the carbon-nitrogen double bond, possibly via an iodonium ion,

that suffers attack by water to form carbonyl compounds and iodine in the

reaction mixture (Scheme A.III.5).

Scheme A.III.5

Exchange reaction with other carbonyl compounds:

The exchange reaction with other carbonyl compounds has been an

extensively applied method, formaldehyde being the most used carbonyl

compounds as it is economic and gives the best yields with aldoximes

(Scheme A.III.6)

75

PartA Chapters

Scheme A.III.6

R CH20/H

Conversion of various oximes into the corresponding carbonyl

compounds has also been achieved mostly in quantitative yields by simply

allowing them to react with an excess of acetone at temperatures ranging

between 20°C and 80°C (Scheme A.1II.7).

This method offers some advantages over the conventional exchange

procedures as it involves a non-acidic reaction medium, simple work-up and

inexpensive reagents. However, this method is not good for aldehydes, as it

gives low yields because of the thermal stability of the carbonyl compound.

offers additional advantages of hydrolyzing selectively non-conjugated

ketoximes in the presence of conjugated ketoximes.

Photohydrolysis:

Both aromatic aldoximes and ketoximes were found to readily

undergo photohydrolysis via their lowest singlet state with <j> (quantum yields)

generally in the 0.01-0.15 range. Both neutral oxime and oximate anion

Scheme A.1II.7

Pyruvic acid19 and levulinic acid20 has also been used. The latter

76

Part A Chapter 3

undergo phofohydrolysis with the former reaction being acid catalyzed. For

the neutral form, there is also a less efficient hydrolysis mechanism, which is

important at pH 8-10 and involves the non-catalyzed addition of water to the

C=N bond.21

Enzymatic Methods:

An exceptionally mild, convenient and facile method was reported for

the deoximation reaction of a variety of aldoximes and ketoximes employing

baker’s yeast.22 The ultrasonic pre-treatment of baker’s yeast not only

enhanced the yields by a 35%, but accelerated these transformations also.

Reductive Methods:

The conversion of oximes into the corresponding carbonyl

compounds by many of the hydrolytic reagents are quite non-selective.

Reductive reagents have been developed, but these, even if convenient and

efficient, are less numerous. Many types of reductive reagents such as

hydrogen and heterogenous catalysts, metal carbonyls, metals and acids,

hydrides, sulfurated reagents were used. But transition metal ions such as

titanium (II), titanium (III), chromium (II), vanadium (II) and molybdenum (III)

were more extensively used because of their convenient redox potential.23The selection of these reductive reagents are on the premise that the

reduction would cause the fission of the oxime N-0 linkage to give an imine,

which then would suffer rapid hydrolysis to the carbonyl compounds

(Scheme A.iil.8).

77

Part A Chapters

Scheme A.IIL8

A smooth reductive transformation of ketoximes afforded good yields

of ketones by using Raney nickel in the presence of boric acid and acetone24

which entirely eliminates the side-products present in the reaction mixture.

Oximes were also found to be cleaved by addition of zinc dust to a solution

of molybdenyl chloride in tetrahydrofuran.25 Hexamethylphosphoramide

(HMPA) is reported to be able to divert the lithium aluminium hydride (LAH)26

reduction of oximes from its normal amine products. The conversion of

ketoximes to ketones is independent of whether homogeneous solutions of

LAH or HMPA or whether a slurry of commercial LAH in HMPA is used and it

can be done with only 10% HMPA in THF27 if a high molar ratio of HMPA to

LAH is maintained. In LAH/HMPA, this dehydration proceeds at lower

temperature due to the basicity of the LAH (Scheme A.III.9).

Scheme A.III.9

78

Part A Chapter 3

Finally, the LAH/HMPA reduction system has been employed for the

selective 1, 4-reduction o f conjugated enones to ketones via ene-oximes.

Among the metal carbonyls, those o f iron have been mostly used, but

also cobalt and molybdenum carbonyls have demonstrated efficiency. The

reaction o f diiron nonacarbonyl or iron pentacarbonyl with ketoximes under

photoirradiation or thermal conditions afforded the corresponding ketones in

modest to good yields.28 A proposed mechanism involves an initial

complexation o f the free or solvated tetracarbonyl irons species to the

nitrogen atom o f the oxime group and subsequent bond cleavage to give an

imido complex. Then the imido complex could collapse to the corresponding

ketone via an imine intermediate in protic media (Scheme A.III.10).

Scheme A.III.10

R

RN -O H

Fe(CO)s R OH

N

R ^ Fe(CO).

R

R

R

R

R

R

N -F e (C O ).

N = F e(C O )4

H20

H20 rn

= N - H

R

The use o f molybdenum hexacarbonyl in the presence o f water

induced the conversion o f oximes into the ir corresponding aldehydes and

79

ketones. Dicobaltoctacarbony! [C 0 2(C 0 )8] was found to serve as an

alternative tool fo r the easy generation o f carbonyl functionalities from their

oxime derivatives.29 However, when the oxime was exposed to acetyl

chloride, an improved chemical yield was obtained.

The cleavage o f oximes was achieved in excellent yield at room

temperature using one molar equivalent o f titanium chloride.30 The titanium

tetrachloride / sodium iodide31 (TiCI4/Nal) system generating low-valent

titanium (LVT) is a mild, efficient and selective reagent, which operates the

reductive cleavage o f oximes to afford the corresponding carbonyl

compounds. The reaction is very rapid using acetonitrile as solvent and a

1:2:2 ratio o f oxim e/ sodium iodide/titanium tetrachloride. The following

mechanism was proposed (Scheme A .III.11).

Schem e A.III.11

Part A Chapter 3

TiCI4 + Nal

CH3CN----------- »».

r.t[LVT] + 12

) = N — O H + [LVT] R 2

CH3CN

r.t

H20

OHO

Reductive deoximation o f oximes can also be accomplished in good

yields by treatm ent o f a tetrahydrofuran solution o f oxime with aqueous

vanadium chloride at room temperature under a nitrogen atmosphere with

the advantage o f an easy work-up, which is practically free o f side products.

The reaction proceeds by the following mechanism22 (Scheme A.III.12).

80

Part A Chapter 3

Scheme A.III.12

------------- V = N—H — ^ y=0-V O C I2 r 2 H20 R 2

R

Sulfurated reagents such as sodium dithionate and sodium

hydrogensulfite have also been used for deoximation. The treatment of

oximes with aqueous sodium dithionite (Na2S204)33 at room temperature

either alone or in the presence of sodium hydrogen carbonate or sodium

acetate, afford the parent carbonyl compound after acid addition. The

dithionate cleavage of oximes completes favourably with known procedures

for generation of carbonyl compounds from oximes. The reaction offers the

following advantages -

a) Sodium dithionite is inexpensive and readily available

b) The reaction conditions are mild (room temperature at neutral pH).

c) The generation is rapid

d) Both aldehydes and ketones are generated successfully.

Tributylphosphine34 in the presence of diphenyl disulfide34 was found to be a

mild reagent to reduce ketoximes under essentially neutral conditions.

Regeneration under Microwave irradiation:

Microwave activation as a non-conventional energy source, a means

of rapid heating has gained popularity in recent years. Due to the relatively

short duration of irradiation-generated heat pulses and shortening of reaction

81

PartA Chapters

times, microwave irradiation usually gives better yields and lower amounts of

by-products.

By means o f the preparation and utilization o f a silica supported

chromium trioxide oxidant35, the selective deoximation o f oximes under

microwave irradiation was accomplished in high yields while microwave

irradiation with pyridinium chlorochromate36 and bismuth trichloride in

tetrahydrofuran solution37 resulted in a dramatic reduction o f reaction time.

The inexpensive reagent and solvent free conditions make the

procedure using clay-supported ammonium nitrate “clayan”,38 ammonium

chlorochromate adsorbed on Montmorillonite39 and bis(trimethylsilyl)

chromate40 simple and economic . The reaction with sodium bismutate41

proceeds efficiently under irradiation giving high yields at room temperature

within a few minutes.

Microwave irradiation o f a solution o f oximes in aqueous acetone in

the presence o f N,N/-Dibromo-N,N/-1,3-proylene-bis[(4-methylphenyI)

sulfonamide] give the carbonyl compounds in good yield. This procedure is

useful fo r chemoselective oxidative deoximation and fo r deoximation of

oximes tha t contain an OH functional group.42

Recently, it has been observed that bismuth nitrate supported onto

montmorillonite K-10, can efficiently and rapidly deprotect oximes under

microwave irradiation (Scheme A ,lll.13)43a. However, this method suffers

from one limitation that is, it is not successful fo r the deoximation o f aliphatic

aldoximes and ketoximes.

82

Part A Chapters

Scheme A.1II.13

NOH OMont morillonite K-10

ArX RAr R MW

Another facile and convenient microwave assisted regeneration of

aldehydes in fair to excellent yields and in short time from aldoximes using

an environment-friendly and inexpensive reagent phosphoric acid42b in

solvent-free conditions at ambient pressure in open vessels, has been

reported (Scheme A.III.14). A noteworthy advantage of this method is that

aldoximes are selectively deprotected to form the corresponding aldehydes.

Oxidative Methods:

Many methods have been developed so far for the generation of

carbonyl compound from oximes with numerous and different oxidizing

agents. But with the exception of few methods, other methods are not

efficient because of the very low solubility of the oxidative reagents in most

organic solvents. Furthermore, when these methods are extended to

complex molecules having multiple functional groups, they are prone to

oxidation under reaction conditions and therefore have limited applicability.

These oxidation procedures were carried out with varying degrees of

success depending on the nature of the oxime and the oxidizing agents.

Scheme A.III.14

83

Part A Chapter 3

Among the chromium based oxidizing agents, chromium (VI) ion,

such as dichromate or chromate, is known to be optimum oxidizing agent

which have given good results in the mild oxidative deoximation o f

ketoximes, but not in deoximation o f aldoximes, as these reactions afford

over oxidized products. The best results were obtained when the counter-ion

was a pyridinium ion as in pyridine dichromate (PDC)44 or tetrakis

(pyridine)silver ion or poly(vinylpyridine N-oxide)-supported d ichrom ate45

Halochromates such as pyridinium46 or quinolinium47 fluorochromate and

pyridinium chloroehromate48 have found extensive use as an oxidizing

agents. O ther halochromates are dimethylammonium49 and

methylammonium50 chloroehromate adsorbed on alumina, which are easily

accessible and stable reagents. Another useful addition to the array of

deoximating reagent is 2,6-dicarboxypyridinium chloroehromate

(2,6-DCPCC).51 A noteworthy advantage o f the reagent is the exclusive

oxidation o f oximes irrespective o f the presence o f semicarbazones and

phenylhydrazones.

A combination o f pyridinium dichromate and f-butyl hydroperoxide52

have been found to provide excellent reagents for the new, highly selective

deblocking procedure o f ketoximes. Recently, it has been reported that

quinolinium chloroehromate53 give excellent results in deoximation. It was

observed that electron withdrawing substituent on aromatic ring also gave

good yields and no over oxidation was observed. Some methods of

deoximation using chromium based oxidizing agents are summarized below

(Scheme A .III.15).

84

I

Part A________________ _____ Chapter 3

Scheme A.III.15

NHCrd3

Et3NHCICr03/ CICH2CH2Cl

CrO,

R

R^=NOH

3-carboxypyridiniumchlorochromate

pyridinium dichromatepyridinium fluorochromate quinolinium fiurochromate

R

> = 0R 2

Many interesting results of deoximation have been observed with

Mn7+, Mn4+ and Mn3+ for a wide variety of oximes. The oxidizing ability and

selectivity of the permanganate ion is dependent upon the nature of counter

ion (Scheme A.III.16).

Scheme A.III.16

1R

N -O HR ‘

YM n04

CH 3CN/H20

Y+= K , Ba! CT/V BPS, B(2,2'-BP)Cu2+

Due to the disadvantages of metallic permanganates, high oxidizing

power and consequent low selectivity, organic ligands have been employed,

for example bis(pyridine)silver permanganate54 operates in dichloromethane,

benzene or acetone at room temperature.

85

Part A Chapter 3

In a variant which gives excellent yields of carbonyl compounds from

a variety of aldoximes and ketoximes, potassium permanganate was

supported on Zeolites.55 Commercially available activated Mn0256 in aprotic

solvents such as hexane or dichloromethane at room temperature has been

used recently showing the following advantages.

a) Simple reaction procedure

b) High yields from aldoximes and ketoximes

c) Wide applicability to highly functionalised oximes including acyclic

galactose pentaacetate oxime.

Recently, manganese dioxide has been used for the regeneration of

^-aminofl.l-biphenyl]-2~carbaldehyde (Scheme A.III.17)57.

Scheme A.III.17

Finally an elegant method for oxidative deoximation is reported by Demir et

al. wherein it is reported that manganese (III) acetate58 is a further possible

reagent to employ under mild reaction conditions (Scheme A.III.18).

Scheme AJII. 18

R

R-

RN— O H + Mn(OAc)3 - ^ = 0 +N2 + Mn(OAc)2 + AcOH

R 2

Application of bismuth (III) nitrate pentahydrate as a relatively non

toxic, air-sensitive and inexpensive reagent which, coupled with a relatively.................. ................ - Y ' ' ................ .... ............ ....

86

Part A Chapter 3

non-toxic solvent system (acetone-water, 9:1) constitutes of an attractive

alternative to the existing routes for deprotection of oximes.59

Because of their low price and versatility, halogens and halogenated

compounds have been used successfully in reactions of deoximation and

have delivered good results. In particular, the deoximation using the Dess-

Martin periodinane (DMP)60 and O-iodoxybenzoic acid (IBX) has been

particularly interesting because it overcomes many of the disadvantages

associated with other methods. The salient features of Dess-Martin

periodinane (DMP)61 and 1 -hydroxy-1,2-benziodoxol-3(1 H)-one 1-oxide

(IBX)62 methods are

a) mild nature of DMP and IBX

b) the reaction occurs in water-saturated ether (DMP method) or in

DMSO-THF (IBX method)

c) at room temperature with rapid rate and easy work-up procedure.

d) obtaining high yields.

The rate of deoxidation was neither affected by electron donating or

withdrawing substituents in the para-position nor by steric effects. Moreover,

acid-sensitive as well as base sensitive protecting groups and ester and

ether linkages can survive under the reaction conditions. In addition to that,

stereochemical integrity at the aldehyde bearing carbon was retained. The

proposed mechanism for DMP deoximation is shown below (Scheme

A.III.19).

87

Part A Chapter3

Scheme A.III.19AcO

Recently, a convenient variation was described63 when oximes were

converted into the corresponding carbonyl compounds upon treatment with

Dess-Martin periodinane / sodium acetate in dichloromethane.

Iodine in acetonitrile was used under heating64 as a new deoximating

agent giving good results. N-bromo succinimide65 and N-bromoacetamide66a

were also found to be an efficient and selective reagents for the mild

oxidative cleavage of oximes to yield their corresponding carbonyl

compounds in good to excellent yields.

Recently, deoximation of oximes using a mild and environmentally

friendly oxidizing agent, 2-iodylbenzoic acid, catalyzed by cyclodextrins with

water as a solvent has been reported (Scheme A.lll.20).66b Cyclodextrins

exert a micro environmental effect and catalyze reactions by supramolecular

catalysis through non-covalent bonding.

88

Part A Chapter3

Scheme A.III.20

The yields obtained were impressive. This methodology is compatible

with functionalities such as halo, nitro, hydroxy, methoxy, isopropoxy and

conjugated double bonds.

Little attention has been paid to the oxidation cleavage of oximes by

persulfates and only a few reports are available. Peroxomonosulfuric acid

(H2S2O5), Caro’s acid, supported on silica gel in acetic acid at room

temperature has been shown to be a powerful oxidant for regeneration of

various oximes to give the corresponding carbonyl compounds in high

yields.67 Amberlyst supported peroxodisulfates68, (tetrabutylammonium69,

n-butyltriphenylphosphonium70 and benzyltriphenylphosphonium71),

[(PhCH2PPh3)2S208], of which the latter is an easily prepared and stable

reagent, have proved to be efficient and highly chemoselective reagents for

the cobnversion of oximes into their corresponding carbonyl compounds

under mild conditions. It is noteworthy that the reaction medium of (n-

BuPPh3)2 S2Os is almost neutral so that some sensitive functionalities such

as C=C double bond remains intact.

Another deoximation was carried out by nitric oxide72 in the presence

of oxygen and gave good results with a variety of oximes.

89

Part A____________________ _____________________________ Chapter 3

Deoximation is also carried out by nitrosyl chloride, generated in situ

through a system consisting of sodium nitrate and acetyl chloride at room

temperature (Scheme A.III.21)73.

Scheme A.III.21

H Cl— N—OH

)= N -O H + NOCI— »- / r C \

P h - i VO 0

H iCI

Ph':O ^N ==^-r*0-— H

0-HCi -n2o

HV_o

Ph—^OPhotosensitized deprotection of oximes by platinum (II) terpyridyl

acetylide complex74 has been reported recently. Platinum (II) terpyridyl

acetylide complex photosensitizes the oxidation of aldoximes, aliphatic

acyclic and cyclic ketoximes and aromatic ketoximes into their corresponding

carbonyl compounds with good to excellent yields in acetonitrile solution.

The deprotection of oximes proceeds via singlet oxygen (1C>2)

mechanism (Scheme A.III.22). Singlet oxygen, generated by

photosensitization, reacts with aldoximes and ketoximes to produce their

corresponding carbonyl compounds. This deprotection of oximes employs

molecular oxygen as the oxidant and the process is environmentally benign.

After completion of the reaction, the sensitizer can be easily separated from

the products and unreacted starting material and can be reused many times

without loss o f102-generation capacity.

90

Part A Chapter3

S ch e m e A .ill.2 2

,0 HN '

R - C - R/ 10 „

o-oI l

R - C - N - O H

O11 /

R - C - R + H N 0 2

R /

B . C L E A V A G E O F > C = N B O N D O F H Y D R A Z O N E S A N D S U B S T IT U T E D

H Y D R A Z O N E S - A R E V IE W

T h e formation of hydrazone derivatives is a common method for

isolation and purification of carbonyl com pounds. H ydrazones derivatives of

carbonyl com pounds are highly crystalline. Purification of these derivatives

followed by regeneration of the parent ketone is a good procedure for

isolation o f desired ketone from a com plex m ixture.2

H yd razone can be prepared by the condensation reaction of a

hydrazine and an a ldehyde or ketone. H ydrazine itself gives hydrazones only

with aryl ketones but with other a ldehydes or ketones, either no useful

product can be isolated o r the remaining - N H 2 group condenses with a

second m olecule o f carbonyl com pound to give an azine so that a mixture of

two products is usually obtained (Schem e A .lil.2 3 ).

91

Part A Chapters

Scheme A.III.23

R) = o + h 2n — n h 2— *•

R

n h n h 2

R OH

-H20 R/

LR^^NNH,a hydrazone

-H20

RR

/, k v ^ISL ^R

R N ^

R

an azme

In order to obtain derivatives for the characterization of carbonyl

compounds, usually mono and disubstituted arylhydrazines, especially

phenyl and 2,4-dinitrophenyl are used much more often. The substituted

hydrazines give the corresponding hydrazones with most aldehydes or

ketones.75 Being solids, they make excellent derivatives.

2,4-dinitrophenyihydrazine is usually preferred to phenylhydrazine because it

gives products which have higher melting point and are more easily isolated.

A convenient small scale method is to add hydrochloric acid dropwise to a

mixture of carbonyl compound and 2,4-dinitrophenylhydrazine in

diethyleneglycol dimethyl ether, when it precipitates out.

The main advantage of this method is that no azines are formed

under these conditions. The hydrazones derivatives play an important role in

protecting a carbonyl group in a multistep synthesis. They are also found to

92

Part A Chapter 3

be of considerable synthetic significance.76 They are the starting material for

preparation of nitriles77, thioketones78 and others.

The development of mild and efficient methods for the selective

cleavage of these nitrogen containing derivatives to afford carbonyl

compounds continue to be a significant aspect of organic chemical

transformation. Efforts have been made for the development of new

reagents and methods for the regeneration of carbonyl compounds from

these derivatives. As a result, many new cleavage reagents have been

developed over the past few decades which are compatible with a wide

range of other functionalities. In general, cleavage procedures can be

classified into (a) hydrolytic (b) reductive and (c) oxidative methods. Some of

the important methods for the regeneration of carbonyl compounds from

their hydrazones derivatives are reviewed below:

Hydrolytic Cleavage Procedures:

Hydrazones can be hydrolyzed to the corresponding aldehydes or

ketones. Hydrolysis or arylhydrazones is much easy and often a reactive

aldehyde is added to combine with the liberated amine, formaldehyde being

the most commonly used aldehydes but levulinic acid excellent for

hydrolyzing arylhydrazones.79 (Scheme A.III.24).

Scheme A.III.24

7iN -W

H20

+OH,i 2

-C—

N -W

OHl

-C—INHW

OHI

-C—+

oII

-c-

93

PartA Chapters

Silica gel80 is also used for the cleavage of substituted hydrazones

giving the corresponding ketones containing other acid-sensitive

functionalities such as THP groups, benzyl ether moieties and acetal groups,

which remain intact. Generally, the cleavage of hydrazones using acidic

reagents suffer from the lack of selectivity in the presence of acid-sensitive

groups. However, this method seems to be less versatile for the cleavage of

a-branched ketones.

BF3, OEt2, a suitable Lewis acid is also found to promote hydrolysis of

hydrazones regenerating the corresponding carbonyl compound in good

yields.81 (Scheme A.III.25). Compared to ozonolytic cleavage, BF3.OEt2 gave

higher yields but with longer reaction time.82.

Ketones and aromatic aldehydes have been regenerated

biocatalytically from their corresponding phenyl- and

N,N-dimethylhydrazones in quantitative yield on incubating with baker’s

yeast.83

O xidative C leavage Procedures:

In the recent years, attention has been paid to developing efficient

and mild reagents and methods for the oxidative cleavage of

phenylhydrazones and 2,4-dinitrophenyl hydrazones, since direct hydrolysis

Scheme A.III.25

94

Part A Chapters

and/or exchange methods for the conversion of hydrazones to carbonyl

compounds leads to condensation byproducts or hydrolysis of sensitive

protecting groups. So, the main efforts of synthetic organic chemist is in the

development of mild, fast and environmentally benign methods for the

conversion of substituted hydrazones into their corresponding carbonyl

compounds.

An efficient and convenient conversion of phenylhydrazones and

tosylhydrazones into their corresponding carbonyl compounds was

accomplished by potassium peroxymonosulfate (2 KHSO 5, KHSO4, K2S 0 4),

commercially known as Oxone in glacial acetic acid84 under mild conditions.

The reagent is convenient, inexpensive and the regeneration of carbonyl

compound is found to be quantitative (Scheme A.III.26).

The treatment of hydrazones with Dioxiranes to generate the parent

carbonyl compound has been reported by Edwards e t ai.65 The reagent has

the advantages of high selectivity, mild reaction conditions and ease of

product isolation. The most commonly used dioxiranes are dimethyldioxirane

(I) and methyl (trifluoromethyl) dioxirane (II)87 These two have been applied

to perform a variety of synthetic transformations, including generation of the

Scheme A.III.26

R

X=NHPh or NHTs

95

Part A Chapter 3

carbonyl moiety from acetals, ketals, orthoesters as well as from Fischer

carbene complexes.88

The oxidation proceeds very rapidly. It has been observed that the oxidation

of more electron rich hydrazones require a considerably shorter reaction

time. Under the reaction conditions, C=C double bonds were not attacked

and acetoxy groups not hydrolyzed. The procedure is also chemoselective

leaving C=C double bond intact. The method is very promising as chiral

hydrazones regenerate their carbonyl moiety without loss of optical activity.

Kim et a/ .89 reported a convenient procedure to transform dialkyl or

diaryl hydrazones with dinitrogen tetroxide (N20 4), a very good nitrosation

reagent, yielding the parent carbonyl compound, in moderate to good yields

(Scheme A. 11.27). The reaction can be carried out in aprotic solvents such as

THF, CHCI3, CCI4, CH3CN under mild conditions and at a wide range of

temperature from 0°C to -40°C. The reaction time is shorter and the product

yields are higher than those from the known methods. This method appears

to have broad applicability for the substrates which are soluble in aprotic

organic solvents.

Scheme A.III.27

NNH?11 2

R7 C _ R 23eq N20

CH3CN

O11

— R— c r 2

96

M e c h a n is t ic s tu d y re v e a ls th a t d in itro g e n te tro x id e is in e q u ilib riu m

Part A Chapter 3

w ith N O + a n d N 0 3 ion . T h e re a c tio n a p p e a rs to b e in itia te d b y n itro s a tio n on

n itro g e n a to m to fo rm a n a z o fo u r m e m b e re d ring in te rm e d ia te b y fo llo w in g

s u b s ta n tia l ring c le a v a g e (S c h e m e A . I I I .2 8 ) .

S c h e m e A . I I I .2 8

R

V/ C = H N H 2 +

R2

n = n n h 2 +

T h e r e a r e s e v e ra l tra n s itio n m e ta l b a s e d o x id iz in g a g e n t w h ic h a re

u s e d fo r th e c le a v a g e a t > C = N - b o n d to re g e n e r a te th e p a re n t c a rb o n y l

m o ie ty . T h e c o v a le n t n a tu re o f tra n s itio n m e ta l f lu o r id e s a n d c h lo r id e s in h igh

o x id a tio n s ta te s s u c h a s M o F 690, M o O C I, C o F 391, W F 6 92 a n d U F 693 a llo w s th e

u s e o f n o n -a q u e o u s s o lv e n ts su c h a s C H C I3 , C H 2 C I2 a n d F re o n d u rin g th e

h y d ra z o n e c le a v a g e . A lth o u g h , it is k n o w n th a t s o m e o f th e s e c o m p o u n d s

a r e f lu o rin a tin g a g e n ts fo r c a rb o n y l g ro u p s , n o f lu o r in a te d p ro d u c ts w e r e

o b s e rv e d . T h e re a g e n ts a r e e a s y to h a n d le a n d g la s s is n o t a t ta c k e d . T h e

d e s ire d c a rb o n y l c o m p o u n d s m a y b e o b ta in e d in m o d e ra te to e x c e lle n t

y ie ld s . In th e U F 6 c a s e , it w a s d e m o n s tra te d th a t k e to n e , e s te r , a m id e , n itrile

a n d n itro m o ie tie s w e r e to le ra te d u n d e r th e re a c tio n c o n d itio n s . T h e

97

Part A Chapter 3

proposed m echanism of M oF6 cleavage is depicted in Schem e A .lli.2 9 and

w as show n to work similarly for the other cases.

M o F 6 attacks in an electrophilic m anner at the alkylated or arylated

nitrogen o f hydrazone. T h e treatment of the activated hydrazonium salt with

w ater furnishes the carbonyl com pound and d iazene as byproduct.

Scheme A.IIL29

N^NR2

MoFc

R R

R

, n ;,R

N T " " M o F fi

R R

H20

N

R O.1 iVN — R + R ' ^ R

-M o F 4, -H F

diazene carbonyl com pound

O f the num erous method available for the regeneration of carbonyl

com pounds from hydrazones, the cobalt (III) trifluoride offers distinct

advantages. T h e reagent is e a sy to handle and show s significant selectivity,

giving generally the highest yields with N, N -dim ethyl hydrazones. How ever,

the basis fo r selectivity is not yet fully understood. T h e reaction is believed to

proceed b y the following pathways (Schem e A .III.30 ).

98

Part A Chapter3

Scheme A.1H.30

R

2•=rN~N

/+ Co(lll) F3 —

XF

R RCoF.2

h2o

2HF + Co(H) O + O

A solid phase method of oxidative cleavage was reported by Laszlo et

al.9A wherein the authors have used extremely inexpensive Clayfen. Clayfen

(ferric nitrate impregnated on K-10 bentonite clay) is a nitrosonium ion

source comparable to NOBF4 and is capable of effecting cleavage of

phenylhydrazones, 2,4-dinitrophenylhydrazones, tosylhydrazones and

dimethylhydrazone. The reaction is fast and exothermic, giving the

corresponding carbonyl compounds in very good yields (Scheme A.1II.31).

Scheme A.III.31

99

Part A Chapter 3

However, it suffers from the limitation that hydrazones derivatives of

a, p-unsaturated ketones does not result in satisfactory regeneration of the

parent carbonyl compounds, instead undefined product mixtures were

obtained.

Barton et a !95 has reported that the carbonyl groups of various

hydrazone derivatives of a-keto esters can be readily regenerated in high

yields through oxidative hydrolysis using hypervaient organoiodine (III)

reagent [hydroxy(tosyioxy)iodo] benzene (HUB or Koser’s reagent). The

oxidative cleavage is also effected in good yields with the very cheap bulk

chemical sodium perborate96 (NaB03) in buffer solution and tert-butanol as

cosolvent. The procedure is also chemoselective, leaving a C=C double

bond intact.

It has been reported by Ruoho et al.97 that wet silica-supported

potassium permanganate affords carbonyl compounds from their phenyl

hydrazone derivatives in a shorter reaction period under solvent-free

condition (Scheme A.III.32). The oxidative cleavage of these derivatives

takes place at room temperature in the absence of solvent.

Scheme A.III.32

R 1 R 1\ KMn04/W etSi02 \C = N — NHPh ----------------------------- - C = 0

/0 solvent free - AR 2 R

Solid state cleavage of phenylhydrazones with clay supported ammonium

persulfate98 has also been explored. The reaction is completed in less than a

minute under the influence of microwaves. The transformation probably

100

Part A C h a p te r 3

in v o lv e s th e d e c o m p o s itio n o f a m m o n iu m p e rs u lfa te c la y (w h ic h is a c id ic a n d

c o n ta in s w a te r ) u n d e r th e in flu e n c e o f m ic ro w a v e s th u s g e n e ra tin g O 2 a n d

NH4HSO4. T h e im in o n itro g e n o f p h e n y lh y d ra z o n e is p ro to n a te d a n d

n u c le o p h ilic a t ta c k o f s u lfa te ion o n th e im in o c a rb o n lib e ra te s th e c a rb o n y l

c o m p o u n d (S c h e m e A . 111.33)

S c h e m e A .I1 I.3 3

2 ( N H 4)2S 20 8 + 2 H 20 4 N H 4 H S 0 4 + 0 2

C la y o r H S 0 4 2‘

R

RN — N H — P h

- H 2N N H P h

- S 0 3"

(N H 4)2S 20 8 i c la y

M W

M ic ro w a v e irra d ia tio n o f p h e n y lh y d ra z o n e s a n d to s y h y d ra z o n e s w ith

p h o s p h o ric a c i d " a ls o re g e n e ra te th e c a rb o n y l c o m p o u n d in e x c e lle n t y ie ld s

(S c h e m e A . I I I .3 4 ) .

S c h e m e A . I I I .3 4

R 1\

C = N — RH3PO4

R 1\

* . C = 0M W , 1 0 -2 0 s e c s A

R

101

Part A Chapter 3

The cleavage of hydrazones and substituted hydrazones was also

achieved in excellent yield with some quaternary “onium" reagents. Among

the chromium based oxidizing agent benzyltriphenylphosphonium

chlorochromate (BTPPCC)100 have been used extensively. The reagent is

effective for deprotection of phenylhydrazones and

2,4-dinitrophenylhydrazones (Scheme A.III.35). Lewis acid in the form of

AlCI3 is necessary as a co-reagent. Another additional advantage of this

reagent is that it can be stored for long without decomposition.

Scheme A.IH.35

R.2R = N — X

BnPPh3.CrO3.HCI/AICI3

MeCN, reflux

X=NHPh

Cetyltrimethylammonium permanganate (CTAP)101, obtained by

mixing cetyltrimethylammonium bromide or chloride with an aqueous

solution of KMn04, is reported to have afforded maximum yield of the

product carbonyl compounds. The reagent is mild and selective and is

capable of effecting the oxidative cleavage of carbon-nitrogen double bond

in the presence of other functional groups.

Tetrabutylammonium peroxydisuifate [(TBA^SaOs] has been shown

to be a good source of sulfate anion radical, which has the potential to be

widely applicable in organic reactions.102 This radical anion is considered to

oxidize the C=N double bond giving the parent ketones in excellent yields.

Because the reaction medium is at pH close to neutral, cleavage reactions

102

Part A Chapter3

have been found to proceed for hydrazones which contain sensitive

functional groups such as acetal and olefin moieties. A lthough the reaction

m echanism is not clear, the cleavage appears to be initiated via the addition

of sulfate radical to the carbon of C = N bond, and the oxygen of the carbonyl

product probably originates from the peroxysulfate.

It m ay be mentioned here that m any reagents have been developed

to regenerate the carbonyl com pounds from the corresponding hydrazones,

which are com patible with a wide range of functionalities. T h is has allowed

the use o f hydrazones in the synthesis o f com plex natural products.

How ever, ow ing to the importance o f hydrazone m ethodology, there is still

an interest in designing new and mild reagents fo r hyd razone cleavage.

C. CARBONYL REGENERATION FROM SEMICARBAZONES

- A REVIEW

Nucleophilic addition reaction between the sem icarbazide and

carbonyl com pound gives the corresponding sem icarbazone (Schem e

A .III.36).

Scheme A.III.36

Sem icarbazones are preferred over oxim es and hydrazones for

characterization and purification o f carbonyl com pounds103,104 as reaction of

the carbonyl com pounds gives almost quantitative yield o f sem icarbazone.

103

Part A Chapter 3

M oreover, sem icarbazones are highly crystalline com pounds with sharp

melting points and other physical properties. T h e se com pounds are also

useful as efficient protecting groups for a ldehydes and ketones.105 Therefore

regeneration o f the parent carbonyl com pounds from sem icarbazones is an

important step in a multistep organic synthesis w here carbonyl group needs

to be protected. A lthough there are severa l m ethods available for the

regeneration of carbonyl com pounds from oxim es and h yd ra zon e s,106 not

m any m ethods are available to regenerate carbonyl com pounds from

sem icarbazones under mild conditions.107

Ram e t a il08 reported a metal ion catalysis of sem icarbazone w here a

suspension o f sem icarbazones and hydrated copper (II) chloride in

acetonitrile w as refluxed affording the carbonyl com pounds in high yield

(Schem e A .III.37 ).

Scheme A.III.37

104

Part A Chapter 3

It was proposed that copper (II) ion, due to chelation, exert a

favourable effect on the hydrolysis of semicarbazones at the imino bond by

making it more electrophilic as well as stabilizing the leaving group in the

transition state. However, other salts such as copper (II) nitrate, acetate and

sulphate and nickel (II) and cobalt (II) chlorides are not effective. The

reaction is fast, cost effective, and extremely simple to work-up. The reaction

shows interesting chemoselectivities also.

The oxidative cleavage of semicarbazones has been explored with

clay supported ammonium persulfate also.109 In the absence of mineral

supports, the attempted cleavage of semicarbazones failed under both,

microwave as well as ultrasonic irradiation. It has been found that out of a

variety of mineral support mont morillonite K10 clay provides a clean

regeneration of the corresponding ketones. In some examples cited in the

report, conversion was completed in less than a minute on exposure of the

reaction mixture to microwave irradiation. However, the reaction becomes

sluggish, when all the reactants are mixed simultaneously.

Another method of using inexpensive clay supported ferric nitrate for

oxidative cleavage was reported by Laszo et a/.110 (Scheme A.III.38). The

method is simple and results in high yield of the carbonyl compounds.

Scheme A.III.38

105

Part A Chapter 3

Kirk et a /.111 used lead tetra-acetate (LTA ) in acetic acid to cleave a

3-sem icarbazone in a novel preparation of 18-hydroxycorticosterone. The

m ethod is rapid and it cleaves the sem icarbazone efficiently at room

tem perature.

D ow ex-50, a cation exchange resin, has also been used for

regeneration o f carbonyl com pound from sem icarbazone.112 This m ethod is

especially good for recovery o f p-keto esters and vinylogous p-keto ester,

which are, in general, susceptible to decarboxylation in acidic m edia.

Moreover, this procedure show considerable selectivity for the regeneration

of ketones over that o f aldehydes. This m ethodology is m anipulatively

simple, mild, highly selective and economical.

A convenient, inexpensive and powerful oxidant used for this

transform ation is potassium peroxym onosulfate (2 K S O 5, K H S O 4, K2S O 4)

com m ercially known as "Oxone”.113 T h e oxidative c leavage o f > C = N - bond

simply entailed addition o f aliquots o f oxone solution to the sem icarbazone

substrate. This m ethod is efficient as it regenerates carbonyl compounds

quantitatively from their sem icarbazones. H ow ever, derivatives o f a , p-

unsaturated carbonyl compounds does not result in satisfactory regeneration

of the parent carbonyl com pounds, but leads to a m ixture of products.

A nother oxidizing agent benzyltriphenyl phosphonium chlorochromate

(B T P P C C )114 has been used successfully for deprotection o f sem icarbazone

to afford th e corresponding carbonyl com pounds. T h e yield is m oderate to

high.

106

Part A Chapter 3

In the recent years, the use o f solid supports has becom e popular due

to their characteristic properties such as enhanced selectivity and reactivity,

straight forward work up procedure, m ilder reaction conditions and

associated ease o f manipulation .115 Th e re has also been increasing interest

in reaction that proceed in the absence of so lvent116 as it provides

ecofriendly system .

A sim ple and ea sy method under solid -state conditions that offers

carbonyl com pounds from their derivatives in a shorter reaction period is by

w et silica-supported potassium perm anganate .117 M oreover, the oxidative

cleavage o f these derivatives takes place at room tem perature in the

absence of solvent. A lso , this oxidation system is able to convert

com plicated sem icarbazones in the presence o f other oxid izable functional

group to the parent carbonyl com pounds.

Phosphoric acid, an environm ent friendly reagent, has also been used

for generation of carbonyl com pounds from sem icarbazones under solvent

free conditions .118 T h e yield is fair to excellent.

It m ay be mentioned here that although som e reactions are carried

out under m ilder conditions and satisfactory for sim ple m olecules, they are

less useful fo r com plex m olecules because o f (a) oxidation o r reduction of

other easily oxid izable o r reducible groups present in the m olecule and (b)

overoxidation o r overreduction o f the liberated a ldehydes o r ketones. Often,

these reagents are toxic and inexpensive. Th us , there is still dem and for a

reagent that w ould be mild, selective, nonhazardous and inexpensive.

107

PartA Experimental Chapter 3

D. R EG EN ER A TIO N O F C A R B O N YL C O M P O UN D S FROM O XIM ES B Y

O X ID A TIVE C L E A V A G E USING TETR A -n -A LK YLA M M O N IU M B R O M A TES

In this chapter, the experim ental details of the use of

tetra -n -a lkylam m onium brom ates as a convenient deoxim ation reagent is

reported. It has a lready been mentioned in earlier chapters that, quaternary

ammonium salts are not only being used as versatile phase transfer catalyst

for accelerating a variety o f transform ations including oxidation reactions, a

m odern da y synthetic organic chem ist is constantly exploring possibilities of

preparing new quaternary ammonium salts w hich m ay act as the reagent

itself. T h e usual and cheaply available quaternary ammonium salts can be

easily converted to another form and the best advantage of these salts is

that they are freely soluble in both organic solvents as well as in w ater and

hence capable o f carrying out reactions in a varie ty o f solvents including

water depending upon the dem and of the substrate.

In this study, two quaternary ammoniumbromates namely the

tetra-n-propylammoniumbromate and tetra-n-butylammoniumbromates

were prepared. The preparation procedure of these two bromates and their

physical and chemical characteristics are mentioned in the previous

Chapter 1. The fact that these bromates are efficient and clean oxidizing

agents have also been demonstrated and reported earlier. In this study, the

bromates have been used as reagents for the oxidative deoximation of a

variety of oximes derived from a wide variety of carbonyl compounds. A

review of literature on deoximation reagents and methods, indicate that

108

Part A Experimental Chapter 3

brom ates have never been used earlier. A s such the

tetra -n -a lkylam m onium brom ates m entioned here are new reagents

developed for the deoxim ation. It has a lready been m entioned in the review

that m ost reagents used for deoxim ation suffer from the disadvantage of

being insoluble in organic solvents, they are also incapable of restricting the

reaction to the carbonyl function. In case of a ldehydes, overoxidation is the

general rule rather than the exception. The tetra -n -a lkylam m onium m rom atesused

here overcom es first o f the two disadvantages being soluble in all organic

solvents as well as in water.

Experim ental results have show n that deoxim ation of aldoxim es

leaves the a ldehyde without further oxidation to the carboxylic acids. Th e

conditions under which deoxim ation done is mild, recovery and workup

procedures are simple and the yields o f the product carbonyl is high. All

these results indicates that the tetra -n -a lkylam m onium brom ates are

excellent reagents for oxidative deoxim ation o f oxim es. T h e transform ation

is show n in the Scheme A .I 1.39.

S ch e m e A . II. 39

R ,

RN O H

+ — R4N B rQ 3

Solvent / reflux RO

T h e general procedure of oxidation involved dissolving the oxim e

and the quaternary amm oniumbromate in a suitable solvent and refluxing

the solution for different period o f time. T h e progress of the reaction w as

monitored by T L C on prepared silica gel plates using ethylacetate:hexane

1 0 9


(1:9) as the eluent. The reaction mixture was run in the chromatogram along

with authentic samples o f the substrate oxime and the target carbonyl

compound and the end point o f the reactions were indicated by a complete

disappearance o f the substrate oxime in the chromatogram. Several oximes

were deoximated and the results are summarized in the Table A.III.2. From

the results, it can be concluded that a comparision o f the efficiency o f both

the quaternary ammonium bromates used can be made. Results indicated

that te tra-n-propylam m onium bromate is a better reagent than

tetra-n-butyiam m onium brom ate in terms o f yield and reaction time. More

than 70% yield o f the parent carbonyls were observed.

Experimental:

All starting compounds were purified before use by methods reported

in literature67. The preparation o f tetra-n-alkylam m onium brom ates and their

spectral, physical and chemical characteristics have already been mentioned

in C hapterl. The starting oximes were prepared from their carbonyl

compounds by standard methods reported in literature. Some o f the carbonyl

compounds from which the oximes were prepared namely benzaldehyde,

4-chlorobenzaIdehyde, 4-nitrobenzaldehyde, 2-nitrobenzaldehyde,

2,6-dichlorobenzaIdehyde , 4,4-dim ethylam inobenzaIdehyde, anisaldehyde

4-hydroxybenzaidehyde, cyclohexanone , napthylmethylketone, benzil,

cam phor were prepared and recrystallized or distilled under reduced

pressure (for liquids) before use. Other carbonyl compounds such as

chalcone, benzalacetone, were prepared from appropriate reagents. M.p./

110


b.p. were recorded in an apparatus from Scientific Devices, India, TypeMP-D

in open capillaries; UV was recorded in Hitachi 3210 spectrophotometer, IR

recorded in KBr pellets in a Perkin Elmer 1600 FT-IR spectrometer; 1H-NMR

in Bruker AVANCE 300(300 MHz) spectrometer in CDCI3 with TMS as

internal standard.

Preparation o f chalcone ( mp 58°C)119:

2-2g of NaOH is placed in a mixture of 20 mL of water and 12 mL of

EtOH. The flask is immersed in an ice bath and to it 5.2g (5.5 mL) of

acetophenone is added and the mixture stirred vigorously. To this mixture

4.4 mL of pure benzaldehyde is added carefully so that the temperature of

the mixture does not exceed 25°C. The reaction mixture is stirred for 30

minutes and kept overnight and the solid product is recover by filtration. The

crude chalcone is purified by recrystallization from rectified spirit. Pure

chalcone, i.e. benzylidene acetophenone, m.p. 58 °C.

Preparation of benzylidene acetone ( m.p. 42°C)119:

4 mL of pure benzaldehyde and 6.3 mL of pure acetone was taken in

a 100 mL flask equipped with a mechanical stirrer. The reaction flask was

immersed in an ice bath and 5 mL of a 10% aqueous solution of NaOH was

added dropwise so that the reaction temperature does not exceed 25°C. The

mixture was stirred at room temperature for 2 hours. The mixture was then

made slightly acidic by careful addition of HCI. The product benzylidene

acetone was extracted with toluene. Toluene was then removed by

distillation under reduced pressure. The residue on standing gave

benzyiideneacetone. m.p. 429C. ____

111


P r e p a r a t io n o f o x im e s 120:

1g o f h y d ro x y la m in e h y d ro c h lo r id e a n d 2 g o f s o d iu m a c e ta te is

d is s o lv e d in 5 - 1 0 m L o f w a te r . T o th is s o lu tio n 0 .5 g o f a ld e h y d e s o r k e to n e is

a d d e d a n d s h a k e n . T o o b ta in a c le a r so lu tio n it w a s n e c e s s a ry , s o m e tim e s ,

to a d d a s m a ll a m o u n t o f a lc o h o l o r w a te r . F o r w a te r in s o lu b le a ld e h y d e o r

k e to n e , 0 .5 m L o f p y r id in e is a d d e d . T h e m ix tu re is re f lu x e d o n a w a te r b a th

fo r 1 5 - 6 0 m in u te s . E th a n o l is re m o v e d e ith e r b y d is tilla tio n (w a te r b a th ) o r

b y e v a p o ra t io n o f th e h o t s o lu tio n in a s tre a m o f a ir (w a te r p u m p ). T h e n 5m !

o f co ld w a te r is a d d e d to th e re s id u e a n d s tirre d in a n ic e b a th till th e o x im e

re c ry s ta llize d . T h e so lid is f ilte re d o ff, w a s h e d w ith a little w a te r a n d d ried .

F in a lly , it is re c ry s ta lliz e d fro m E tO H , b e n z e n e o r b e n z e n e - l ig h t p e tro le u m

(b .p . 6 0 ° - 8 0 ° C ) .

112


T A B L E A.IIL1

Physical characteristics of oxim es prepared

M.P. (°C)SI. No. Carbonyl Compound Oxime -------------------' obs. lit.

Ph Ph

( continued)

113


114

Part A Experimental C h a p te rs

Deoximation of oximes to carbonyl compounds:

General procedure:

0.001 mol of the oxime and 0.001 mol of the tetra-n-propylammonium bromate were dissolved in 25 mL toluene and refluxed. The progress of the reaction was monitored by T IC in prepared

silica gel plates using ethylacetate:hexane (1:9) as the eluent. The test

solution was run along with authentic samples of the starting oxime and the

expected target carbonyl compound. Disappearance of the oxime indicated

completion of the reaction. The progress of the reaction was also followed by colour change of the reaction mixture. The initial yellow to orange colour of the solution changed to an almost colourless solution. After the completion of

the reaction, toluene was removed by reduced pressure distillation in a

rotavapour and water was added to the semisolid obtained. The solid was

washed several times with distilled water. The solid product was then

dissolved in minimum volume of ethanol and the solution filtered on to a

beaker containing large volume of water. This process of dissolution,

filtration and reprecipitation was repeated several times till pure product of

the carbonyl compound was obtained.In case where liquid carbonyl compounds were the end product, the

reaction mixture was distilled under reduced pressure to separate out the

solvent and the product from the spent quaternary ammoniumbromate.

Careful fractional distillation of the mixture of solvent and product gave the product carbonyl compounds in the pure form. The final identification of the

liquid arbonyl compounds were done by measuring their boiling points and

also by converting them to the 2,4-dinitrophenylhydrazones using Brady s

reagent. The physical characteristics of the product carbonyl compounds,

reaction time and percentage yield is given in Table A.III.2.

115

PartA Experimental C h a p te r 3

Table A.111.2

( Ref. Scheme A.IH.39 )

SI. No. OximeCarbonyl Reflux time Yield (%) M.P. (°C)

Compounds ^hrs^( j ,| obs lit.

2.

C!

3 3 85 82 47 48

O 2.5 3 89 85 47 47

3. XX̂ N0H( CH3 )2 (C H 3)2t> 2.5 3 79 82 72 73

4.NO.

NOH

NO.O 2.5 3 84 80 104 106

CCNOH

NO,

6 .

Cl

ciCN°Ha^O 1-5 2 92 78 42 44

NO,

Cl

"0 2.5 2.5 78 76 71 71Cl

7. I ^ j^ N O H ft "J x'o 2.5 3 92 81 115 116

H O ^ ^ HO'

< continued}

116


I indicates reaction with tetra-n-propylammoniumbromate and II indicate reaction with

tetra-n-butylammoniumbromate.

1 1 7


E. REGENERATION OF CARBONYL COMPOUNDS FROM

HYDRAZONES AND SUBSTITUTED HYDRAZONES USING

TETR A-n- ALKYLAMMONIUMBROMATES

In the present study, the tetra-n-alkyiammoniumbromates were used for

the oxidative cleavage of the >C=N- bond of phenylhydrazones for the

regeneration of the parent carbonyl compound. Two different quaternary

“Onium” bromates were used for this regeneration of the carbonyl group.

One of the reagent namely the tetra-n-propylammoniumbromate and the

other is tetraethylammoniumbromate. The preparation of these two bromates

is already mentioned in Chapter 1. Several hydrazones, phenylhydrazone

and 2,4-dinitrophenylhydrazones were synthesized by established

procedure from the corresponding carbonyl compounds.

These hydrazones were refluxed with equimolar proportion of the

appropriate quaternary ammoniumbromate in an organic solvent for a

varying period of time. It was observed that ordinarily the yield of parent

carbonyl compounds was not found satisfactory. However, in the presence

of trace amounts of mineral acid or acetic acid, the oxidative cleavage

proceeded smoothly and the yield of the parent carbonyl was excellent and

almost quantitative. It is probable that the presence of mineral acid or acetic

acid accelerated the decomposition of the bromate with concomitant release

of oxygen which is responsible for the oxidative cleavage. In a typical

reaction procedure, equimolar quantities of the hydrazone and the “onium

1 1 8


bromate" was dissolved in an appropriate organic solvent and to this mixture

trace of dil.HCI or acetic acid was added and refluxed. The progress of the

reaction could be easily followed by observing the colour change of the

reaction solution. The progress of the reaction was also monitored by

drawing aliquots of the reaction mixture and performing cochromatography

of the reaction mixture with authentic samples of the substrate hydrazone

and the target carbonyl compound. Disappearence of the coloured

hydrazone from the reaction mixture indicated the end of the reaction. TLC

was performed in prepared silicagel G plates using ethanohethylacetate

(9:1) mixture as the eluent.

At the end of the reaction, the reaction mixture was added to a large

volume of distilled water, the product carbonyl compound separated out as

a solid whereas the byproducts, if any, and the spent bromates remained

dissolved in the aqueous solution. Recovery was done by filtration and

decolourized using activated charcoal. The products were identified by

comparing the melting points, IR and 1H-NMR spectra with authentic

samples. Yield of the product carbonyl compound was obtained to the

extent of about 95% in some cases. The details are given in the table and

the reaction carried out is summarized in Scheme A.fU.40.

119


Scheme AJII.40

Oxidative cleavage of>C=N-bond using

tetra-n-alkylammoniumbromates

R2-3 drops of H+

QNBrOa

organic solvent/ reflux

Where QN+B r(V = Tetra-n-propylammoniumbromate

= TetraethylammoniumbromateExperimental:

All starting materials were purified by establish procedures

available in text 24. Melting points and boiling points were recorded in an

apparatus from Scientific Devices, India, Type MP-D in open capillaries; IR

spectra were recorded in KBr pellets in a Perkin Elmer 1600 FT-IR

spectrophotometer; UV was recorded in Hitachi U 3210 spectrophotometer;

1H-NMR in Bruker AVANCE 300(300 MHz) spectrometer in CDCI3 with TMS

as internal standard. C,H,N, analysis of the product was recorded in Hitachi

026 CHN analyzer. Chromatography was done on prepared silica gel G

plates.

The quaternary ammoniumbromates namely tetraethylammoniumbromates

and tetra-n-propylammoniumbromates were prepared by procedures

mentioned in Chapter1.

Preparation of hydrazones from carbonyl compounds:

1) Preparation of hydrazone :

A solution of 0.8 g of NaOAc in 5 mL of water were prepared and

0.5 g of hydrazine hydrochloride were dissolved in it. To this solution 0.4 g of

120

PartA Experimental Chapter 3

aldehyde or ketone dissolved in a little ethanol were added. The resulting

mixture was shaken and a little more ethanol was added to remove the

resulting turbidity. The solution was warmed on a water bath for 10-15

minutes and cooled. The crystalline derivative obtained was filtered off and

dried. The products were recrystallized from dil.ethanol.

2) Preparation of phenythydrazone:

A solution of 0.8 g of NaOAc in 5 mL of water were prepared and

0.5 g of the colourless phenylhydrazinehydrochloride was dissolved in it. To

this solution 0.4 g of aldehyde or ketone dissolved in a little ethanol were

added. The resulting mixture was shaken and a little more ethanol was

added to remove turbidity that appeared. The solution was warmed on a

water bath for 10-15 minutes and cooled. The crystalline derivative obtained

was filtered off and dried. The products were recrystallized from dil. ethanol.

3) Preparation of 2 ,4 -dinitrophenylhydrazones :

0.25 g of 2,4-dinitrophenylhydrazine was suspended in 8 mL of

CH3OH and 0.5 mL of conc.H2S04 was cautiously added to it. The warm

solution was filtered and 0.2 g of carbonyl compound dissolved in a small

volume of methanol was added to it and the resulting mixture was warmed

in a water bath for about 5 minutes. The mixture was allowed to cool to

room temperature. The crystalline solid which separated out within few

minutes was filtered by suction and was washed with a little amount of

methanol. The product was recrystallized methanol. The physical

characteristics of the product obtained was reported in Table A.III.3.

121


Table A.III.3

Physical characteristics of hydrazones prepared

122


b ) M elting po ints a re re c o rd e d in a n a p p a ra tu s fro m Sc ien tific D e v ic e s , India,

T y p e M P -D in o p e n c a p illa r ie s .

123


Oxidative cleavage of hydrazones using tetra-n- alkylammonium

bromates:

General procedure:

A mixture of 0.001 moi of the hydrazone and 0.001 mol of the

tetra-n-aikylammoniumbromates were dissolved in 25 mL of ethanol or

acetic acid and the mixture was refluxed for varying amount of time. The

progress of the reaction was periodically monitored by TLC in prepared silica

gel G plates using authentic samples of the starting and the target

compounds as references. The end of the conversion was indicated by the

disappearance of the starting compound. After the completion of the

reaction, the solution was poured in a large excess of water. The solid was

filtered and washed several times with water. The solid products obtained

were recrystallized from the appropriate solvent. With different products,

minor variations were made in the work up procedure. The results of the

experiments carried out are summarized as shown in Table A.III.4. The

product carbonyl compounds were identified by recording their m.p./ b.p. and

comparing the IR.UV and 1H-NMR spectra with authentic samples.

1 2 4


Table A.III.4

( Ref. Scheme A.III.40 )Physical characteristics of the regenerated carbonyl compounds

Reflux Time Yield M. P / B . P .S i. N o. Substrate Product Reagent /Solvent (h r s ) ( % ) of products ( ° C )

Obs Ut

2 hrs (1 *) 80 48 48 (m .p.)

^ z ,2.

HO' HO'

EtOH 3 hrs 15 mins 71 108 109 (m .p.)

d * )

3. TTW o o Oioxan 9 hrs ( II*) 95 95 95 ( m.p.)

ho TOMe

EtOH

Dioxan

EtOH

Toluene

2 hrs (1*) 83 80 81 (m .p.)

2 hrs 45 mins 75 51 53 ( m.p.)

( H )

1 hrs 45 mms 78 243 247 (b.p.)

(1 *)

3 hrs 50 mins 66 n o 112 -114 ( b.p.)

d * )

a. y s^2 j

Ny / \ / \ EtOH

O

6 hrs45mins 69 125 12 7 (b.p.)

(1 *)

( continued)

125


a ) l indicates yield with tetraethylammoniumbromate and II with tetra-n-propylammoniumbromateNO,

b ) Z, = N-NHj, Z j= N-NH-Ph , Z,= N02

c ) • indicates 3 -4 drops cone HCI ** indicates 2 -3 drops cone H2S04

d ) 2-3 drops of cone. HCI was added to the reaction mixture in all cases except SI. 10.11, and 12.e ) In case of liquid products % yield was obtained by conversion to the corresponding oximes.f ) M.p. / B. p. recorded in open capillaries.

126


F. REGENERATION OF CARBONYL COMPOUND FROM SEMICARBAZONES

USING TETRA-n-ALKYLAMMONIUMBROMATES

In this study, semicarbazones of several aldehydes and ketones were

prepared by established procedures and characterized by comparing their

melting points, IR and 1H-NMR spectra with those found in literature. These

semicarbazones were then reacted with the tetra-n-alkylammoniumbromate

and under reflux conditions, the parent carbonyl compound could be

generated.In other words, the tetraethylammoniumbromate obtained from

the easily available and cheap tetraethylammoniumbromide could be

conveniently used in a simple oxidative method for the cleavage of the

>C=N- bonds of semicarbazones to give the carbonyl compounds. The

conversion involved, mere heating the semicarbazone with the bromate in an

appropriate solvent in the presence of trace amount of mineral acid. The

parent carbonyl was regenerated in high yield. The workup procedure for

isolation and separation of the carbonyl compounds was also simple and

required filtration and washing with water only. The target products were

obtained in more than 70% average yield. The results obtained are given in

a tabular form in Table A.III.5 and the reaction is shown in Scheme A.III.41.

Scheme A, III, 41

R

Solvent , reflux

127


T h e re g e n e ra te d c a rb o n y l w a s id e n tif ie d b y re c o rd in g th e ir m .p /b .p .

a n d a ls o b y c o n v e rs io n to th e ir 2 , 4 - D N P d e r iv a tiv e s w h ic h a re re p o rte d in

l ite ra tu re . T h e ta rg e t p ro d u c ts w e r e a ls o id e n tif ie d b y re c o rd in g th e ir IR a n d

1H -N M R s p e c tra a n d c o m p a rin g th e re s u lts w ith th o s e o b ta in e d fro m

a u th e n tic s a m p Ie .A g e n e ra l p ro c e d u re fo r o x id a tiv e re g e n e ra tio n o f th e

c a rb o n y l fro m th e ir s e m ic a rb a z o n e s is g iv e n in th e e x p e r im e n ta l s e c tio n .

E x p e r im e n ta l :

AH s ta rtin g c o m p o u n d s w e r e o b ta in e d f ro m E . M e rc k In c . a n d u s e d

w ith o u t fu r th e r p u rific a tio n . M e ltin g p o in ts a n d b o ilin g p o in ts w e r e re c o rd e d in

a n a p p a ra tu s fro m S c ie n tific D e v ic e s , In d ia , T y p e M P - D in o p e n c a p illa rie s ;

IR s p e c tra w e r e re c o rd e d in K B r p e lle ts in a P e rk in E lm e r 1 6 0 0 F T - IR

s p e c tro p h o to m e te r; U V w a s re c o rd e d in H ita c h i U 3 2 1 0 s p e c tro p h o to m e te r;

1H -N M R in B ru k e r 3 0 0 M H z s p e c tro m e te r in C D C I3 w ith T M S a s in te rn a l

s ta n d a rd . C h ro m a to g ra p h y w a s d o n e on p re p a re d s ilic a g e l G p la te s .

P r e p a r a t io n o f s e m i c a r b a z o n e s 120

G e n e r a l p r o c e d u r e :

A s o lu tio n o f 0 .8 g o f N a O A c in 5 m L o f w a te r w e r e p re p a re d a n d

0 .5 g o f s e m ic a rb a z id e h y d ro c h lo r id e w e r e d is s o lv e d in it. T o th is c le a r

s o lu tio n 0 .5 g o f a ld e h y d e o r k e to n e d is s o lv e d in a little e th a n o l w e r e a d d e d .

T h e re s u ltin g m ix tu re w a s th e n h e a te d g e n tly o n a w a te r b a th fo r u p to 1 0

m in u te s a n d c o o le d in ic e -w a te r . T h e p ro d u c t o b ta in e d w a s filte re d o f f a n d

w a s h e d w ith a little c o ld w a te r a n d re c ry s ta lliz e d fro m a q u e o u s e th a n o l. T h e

p h y s ic a l c h a ra c te r is tic s o f th e p ro d u c ts a re g iv e n in Table A.III.5.

128


Table A.III.5

Physical properties of semicarbazones prepared

SI. No. Substrate semicarbazoneM.P. (

Obs.

°C ) .

u .

1.

0cno NZ

Q^O 165 165

2. cc° r t ^ V ^ NZ^ N 0 2

254 256

3.OjN o2n

220 221

4.no2 no2

246 245

5. xr°Cl Cl

231 232

6. j O ^ °HO

£T*NZHO

225 224

7. OCT"" OCT- 244 245

8. XT"MeO )

OCOPh

£T*nzMeO |

OCOPh

234

( continued)

129


nz=nhconh2Ph=Phenyl

130


General procedure for oxidative cleavage o f >C=N-bond of

sem icarbazones: Regeneration o f the carbonyl com pounds

0.01 mol of the substrate semiearbazone and 0.01 mol of the tetra-n-

alkylammoniumbromate were dissolved in an appropriate solvent, 2-3 drops

of dil. HCI was added and the solution refluxed for varying amount of time.

The progress of the reaction was followed by drawing aliquots from the

reaction mixture at time intervals of 10 minutes and chromatography

performed on prepared TLC plates using silica gel as absorbent and ethanol

as eluent. Chromatography was performed along with the authentic samples

of semiearbazone and the carbonyl compounds. The disappearance of the

semiearbazone was taken as time of completion of the conversion. The

reaction mixture was cooled and added to large excess of distilled water and

kept overnight to obtain the white solid carbonyl compound. In some cases,

precipitation did not occur, in which case the aqueous solution was

extracted with ether and the solid obtained on room temperature removal of

ether. The products were finally purified by column chromatography in silica

gel using toluene as the eluent. For benzoin and benzyl two equivalents of

the oxidants were used. The results are summarized in Table A.III.G.

131


Table A.III.6

(Ref. Scheme A.III.41)

Physical characteristics of oxidized products of semicarbazone

(continued)

132


(1) Where oxidant I = tetraethylammoniumbromate, II = tetra-n-propylammoniumbromate.

(2) 2 = — N H — C — NH,iiO

{3} % yield of liquid carbonyl compounds were obtained by conversion to their 2,4-DNP derivatives.

(4) 'a' and 'b' indicates the time of reflux was 13 hrs and 18 hrs respectively.

133

Part A Experimental Chapters

Recovery procedures for individual products :

1. For 4-hydroxyacetophenone: Reaction mixture was added to a large

volume of water. Precipitate obtained on standing. The product was

purified by column chromatography using silica gel as absorbent and

toluene as eluent,

Using this procedure the other carbonyl compounds recovered were benzoin, benzyl, benzophenone, 4-nitrobenzaidehyde, vanillin, 2~nitrobenzaldehyde, 4-hydroxybenzaldehyde, and 4~chtorobenzaidehyde.

2. For methyl-2-naphthyi ketone: The reaction mixture was added to

large excess of water. The aqueous solution extracted with ether and

ether removed by evaporation at room temperature. Using the same

procedure camphor was also recovered.

In case of liquid carbonyl compounds, the reaction mixture was

subjected to column chromatography with toluene as the eluent and the

extracted product separated by fractional distillation in a rotary evaporator.

The yields were calculated on the basis of the amount of 2,4-DNP

derivatives obtained.

134

Part A Spectral Data Chapter 3

Some spectral characteristics o f the regenerated

carbonyl com pounds from oxime

> Product 1: Benzophenone

UV: Xmax (95% EtOH) 282.6 nm ;

IR(KBr): cm ~11710.5(>C=O);

1H NMR (300 MHz, CDCI3); 8 7.2(s, 10H).

> Product 2 :4-ChIorobenzaldehyde

UV: Xmax (95% EtOH) 285.7nm ;

IR(KBr): cm ~11740.4(>C=O);

1H NMR (300 MHz, CDCI3): 8 9.2(s, 1H),

7.3-7.7(d, 4H).

> Product 3 :4-N,N-dimethylaminobenzaldehyde


IR(KBr): cm ~11726.5(>C=0);

1H NMR (300 MHz, CDCI3): 8 9.9(s, 1H), 7.8(m, 4H),

3.1(8, 6H).

> Product 4 :4-Nitrobenzaldehyde


IR(KBr): cm "11745.7(>C=0), 1529.4,1290.6(-NO2) ;

1H NMR (300 MHz, CDCI3): 8 9.1(s, 1H),

7.7-7.9(broad, 4H).

135


> Product 5: 2-Nitrobenzaldehyde

UV: Xmax {95% EtOH) 277.8 nm ;

IR(KBr): cm "11730.7(>C=O), 1552.3, 1332.2{-N02) ;

1H NMR {300 MHz, CDCI3): 5 9.1 {s , 1H),

8.1 {broad, 4H).

> Product 6:2,6-DichlorobenzaIdehyde


IR(KBr): cm ~11680.4(>C=Q);

1H NMR (300 MHz, CDCI3): 8 9.5{s, 1H), 7.9{m, 3H).

> Product 7:4-HydroxybenzaIdehyde


IR(KBr): cm ~11675.8(>C=0), 3168.6{-OH);

1H NMR (300 MHz, CDCI3): 8 9.8(s, 1H), 6.9(s, 1H),

7.4-7.8(m, 4H).

> Product 8:4-Methoxybenzaldehyde


IR(KBr): cm "11665.4(>C=0);

1H NMR (300 MHz, CDCI3): 8 7.6(m, 4H), 3.8{s, 3H),

3.2(s, 3H).

136

Pari A Spectral Data Chapters

> Product 9 : Anisylideneacetophenone

UV: Xmax(Dioxan) 356.6 nm ;

IR(KBr): cm ~11656.2 ( > C = 0 ) ;

1H NMR (300 MHz, CDC!3): 5 7.9(m, 4H), 7.7{d, 1H),

6.5(d, 1H), 3.7(s, 3H).

> Product 10: Benzylideneacetone

UV: X max (95% EtOH) 343.7nm ;

IR(KBr): cm ~11650.8(>C=O);

1H NMR (300 MHz, CDCI3): 8 7.3-7.6(m, 5H), 7.4(d, 1H),

6.6(d, 1H), 2.0(s, 3H).

> Product 11: Methyl-2-naphthyiketone

UV: W (95% EtOH) 312.8nm ;

IR(KBr): cm ~11685.6(>C=0);

1H NMR (300 MHz, CDCI3): 5 7.5(m, 7H), 2.2(s, 3H).

> Product 12: Cyclohexanone


IR(KBr): cm ~11702.1 (> C = 0 );

1H NMR (300 MHz, CDCI3): 6 2.3-3.1(s, 10H).

> Product 13 : Benzil


IR(KBr): cm _11692.4( > C = 0 ) ;

1H NMR (300 MHz, CDC!3): 8 7.3-7.9(s, 10H).

137

Part A Spectral Data Chapters

> Product 14: Acetophenone

UV: Xmax (95% EtOH) 244,3 nm ;

IR(KBr): cm “11695.5(>C=0);

1H NMR (300 MHz, CDCI3): 5 7.8(m, 5H), 2.2(s, 3H).

> Product 15: Camphor


IR(KBr): cm ' 11742.3 ( > C = 0 ) ;

1H NMR (300 MHz, CDCI3): 5 3.1-3.6(m, 6H),

2.1-2.5(m, 9H).

138

PartA Spectral Data Chapter 3

Som e spectral characteristics o f the regenerated

carbonyl com pounds from hydrazones


Spectral characteristics are given in page no. 135

> Product 2 :4-Hydroxyacetophenone

UV: X max (95% EtOH) 275.6 nm ;

IR(KBr): cm ~11690.8(>C=O), 3493.5(-OH );

1H NMR (300 MHz, CDCI3): 5 7.7-8.0(m, 4H),

6.1(s, 1H), 2.1(s, 3H).

> Product 3 : Benzil


> Product 4: Vanillin


IR(KBr): cm "11665.3(>C=0), 3190.6 (-OH );

1H NMR (300 MHz, CDCI3): 5 9.8(s, 1H), 7.2(m, 3H),

6.6(s, 1H), 3.9(s, 3H).> Product 5 : 2-Naphthaldehyde


IR(KBr): cm ~11710.8(>C=O);

1H NMR (300 MHz, CDCI3): 5 9.3(s, 1H),

7.3 -7.6(broad, 7H).

1 3 9


> Product 6: 4-MethoxybenzaIdehyde


IR(KBr): cm "11665.2(>C=0);

1H NMR (300 MHz, CDCI3): 5 7.6(m, 4H), 3.8(s, 3H),

3.2(s, 3H).

> Product 7 : 4-HydroxybenzaIdehyde


> Product 8: Hexan-2-one

UV: W (95% EtOH) 275.6 nm ;

IR(KBr): cm ~1 1750.8(>C=O);

1H NMR (300 MHz, CDCIS): 6 2.4(s, 3H),

1.2-1.6(m, broad, 9H).

> Product 9 : Cyclohexanone


> Product 10: Cinnamaldehyde


IR(KBr): cm -1 1695.6(>C=0 ap - unsaturated) ;

1H NMR (300 MHz, CDCI3): 5 9.9(s, 1H), 7.8(d, 1H),

7.3(m, 5H), 6.4(d,1H).

> Product 11: 4-Methoxybenzaldehyde


140


> Product 12: Acetophenone


> Product 13: 4 - Nitrobenzaldehyde


IR(KBr): cm ~11745.4(>C=0), 1529.5, 1290.3(-NOZ);

1H NMR (300 MHz, CDCI3): 8 9.1 (s, 1H),

7.7~7.9(m, 4H).

> Product 14 :4,4/- Bis(dimethylamino)benzophenone

UV: A,max (95% EtOH) 290.7 nm ;

IR(KBr): cm 1591.1 ( 0 = 0 ) ;

1H NMR (300 MHz, CDCI3): 8 6.6-7.7(sym,m,8H),

3.0(s,10H).

141


Some spectral characteristics of the regenerated

carbonyl compounds from semicarbazone


UV: X m ax (95% EtOH) 282.6 nm ;

IR(KBr): cm “11710.5(>C=O);

1H NMR (300 MHz, CDCI3): 8 7.2(s, 10H).






UV: Xmax (95% EtOH) 295.6 nm.

IR(KBr): cm "11713.5(>C=0), 1515.4, 1320.3(-NO2) ;

1H NMR (300 MHz, CDCI3): 5 8.7 (s, 1H ),

7.3-7.8(d, 4H).> Product 5: 4-Chlorobenzaldehyde


> Product 6 :4-Hydroxybenzaldehyde


> Product 7 : 2-Naphthaldehyde


142

Part A Spectra! Data Chapter 3

> Product 8: Benzoyl vanillin


IR(KBr): cm "1 1725.5(>C=0), 1765.6(>C=0);

1H NMR (300 MHz, CDCI3): S 7 .6 -8 .1(m, 8H),

4.2(s, 3H).

> Product 9: Dibenzylideneacetone

UV: k max (95% EtOH) 314.7 nm ;

IR(KBr): cm "11690.4(>C=O);

1H NMR (300 MHz, CDCI3): 8 8.1(m, 10H),

7.6(d, 2H), 6.6(d, 2H).

> Product 10: Benzil


> Product 11: Camphor


> Product 12: Hexan-2-one


> Product 13: Benzaldehyde


> Product 1 4 : Cyclohexanone


> Product 15 : 4-Methoxybenzaldehyde


143


> Product 16: Pentan-2-one


IR(KBr): cm ~11695.7(>C=0);

1H NMR (300 MHz, CDCI3): S 2.2(s, 3H),

1.4-1.8(broad, 7H).

144

PartA Conclusion Chapter 3

Conclusion:

In conclusion, it m ay be mentioned that this m ethodology involving

quaternary ammonium bromates, is the first o f its kind developed for

deoxim ation. M oreover, it is also found to be suitable fo r cleavage of

sem icarbazone and hydrazone to carbonyl com pounds. O n e m ajor

advantage o f this m ethodology is the w ater solubility o f the brom ates as well

as by-products which m akes it ea sy to separate out the product carbonyl

com pounds in the pure state. T h is w as found to be particularly e a sy with

tetra-n-propylam m onium bromate as its solubility in w ater w as higher

com pared to the tetra -n -butyi analog. Consequently, recovery and w ork-up

procedures w ere found to be simple and yield obtained are high. A nother

noteworthy feature is that quaternary ammonium brom ates donot oxid ize

other oxid izable groups present in the m olecule such as olefmic bond,

ph eno lic -O H etc. Even sterically hindered cam phor oxim es have been

successfu lly deoxim ated with ease and in high yield.

T h e present procedures for the regeneration of carbonyl com pounds

from oxim es, sem icarbazones and hydrazones have m any advantages over

the existing m ethods and it is hoped that it will make an important and useful

addition to the present m ethodology.

145

Part A References Chapter 3

1. Sandler, S.R.; Karo, W. in Organic Functional Group Preparations; Academic

Press: London, 1989; p 430.

2. Greene, T.W.; Wuts, P.G.M. in Protective Groups in Organic Synthesis, W iley:

New York, 1991; p 214.

3. Kim, Y. H.; Jung, J.C.; Kim, K.S. Chem. Ind. 1992, 31.

4. Barry, R.H.; Hartune, W.M. J. Org. Chem. 1957, 12, 460.

5. Clarke, H.T. Handbook of Organic Chemistry, 4th ed,; Arnold : London, 1956; p

229.

6. Royals, E.E.; Chemerda, J.M. J. Am. Chem. Soc. 1955, 77,1221.

7. Taub, D.; Hoffsommer, R.D.; Slates, H.L.; Kuo. C.H.; Wender, N.L. J. Am.

Chem. Soc. 1960, 82, 4012.

8. Ponnusamy, S.; Pitchumani, K. Indian J. Chem., Sect. B 1999, 38, 861.

9. Gillam, A.E.; West, T.F. J. Chem. Soc. 1945, 95.

10. Sachs, H.; Kempf, H. Chem. Ber. 1903, 36, 3300.

11. Issac, Y.A.Z. Naturforsch, TeiiB. 1999, 54, 1048.

12. Muller, E.; Bottcher, E. Tetrahedron Lett. 1970, 35, 3086.

13. Attanasi, O.; Gasperoni, S.; Carletti, C. J. Prakt. Chem. 1980, 322,1063.

14. Lee, J.G.; Hwang, J. P. Chem. Lett. 1995, 7, 507.

15. Vander Lee, J. Reel. Trav. Chim. Pays-Bas 1926, 45, 682.

16. Meshram, H.M.; Reddy, G.S.; Srinivas, D.; Yadav, J.S. Synth. Commun. 1998,

28, 2593.

17. Ranu, B.C.; Sarkar, D.C. J. Org. Chem. 1988, 53, 878.

18. Gogoi, P.; Hazarika, P.; Konwar, D. J. Org. Chem. 2005, 70,1934-1936.

146

Part A R eferences Chapter 3

19. Hershberg, E. B. J. Org. Chem. 1948, 13, 542.

20. De Puy, C.H.; Ponder, B.W. J. Am. Chem. Soc. 1959, 81, 4629.

21. Haley, M.F.; Yates, K. J. Org. Chem. 1987, 52, 1818.

22. Kamal, A.; Rao, M.V.; Meshram, H.M. J. Chem. Soc. Perkin Prans. 1 1991,

2056.

23. Ho, T.L. Synthesis 1979, 1.

24. Curran, D.P.; Brill, J.F.; Rakiewicz, D.M. J. Org. Chem. 1984, 49, 1654.

25. Olah, G.A.; Welch, J.; Parakash, G.K.S.; Ho, T.L Synthesis 1976, 808.

26. Balachander, N.; Wang, S.S.; Sukenik, C.N. Tetrahedron Lett. 1986, 27, 4849.

27. Rerick, M.N.; Trottier, C.H.; Daignault, R.A.; De Foe, J.D. Tetrahedron Lett.

1993, 629.

28. Nitta, M.; Sasaki, I.; Miyano, M.; Kobayashi, Y. Bull. Chem. Soc. Jpn. 1984, 57,

3357.

29. Mukai, C.; Nomura, I.; Kataoka, O.; Hanaoka, M. Synthesis 1999,1872.

30. Vakatar, V.V.; Tatake, J.G.; Sunthankar, S.V. Chem. Ind. (London) 1977, 742.

31. Balicki, R.; Kaczmarek, L. Synth. Commun. 1991, 21, 1777.

32. Olah, G.A.; Arvanaghi, M.; Prakash, G.K.S. Synthesis 1980, 220.

33. Pojer, P.M. Aust. J. Chem. 1979, 32, 201.

34. Barton, D.H.R.; Motherwell, W.B.; Simon, E.S.; Zard, S.Z. J. Chem. Soc.,

Chem. Commun. 1984, 337.

35. Bendale, P.M.; Khadilkar, B.M. Tetrahedron Lett. 1998, 39, 5867.

36. Chakraborty, V.; Bordoloi, M. J. Chem. Res., Synop. 1999,120.

1 4 7

PartA References Chapter 3

37. Boruah, A.; Boruah, B.; Prajapati, D.; Sandhu, J.S. Tetrahedron Lett. 1997, 38,

4267.

38. Meshram, H.M.; Srinivas, D.; Reddy, G.S.; Yadav, J.S. Synth. Commun. 1998,

28, 4401.

39. Heravi, M.M.; Beheshtiha, Y.S.; Ghassemzadeh, M.; Hekmatshoar, R.; Sarmad,

N. Monatsch. Chem. 2000, 131,187.

40. Heravi, M.M.; Ajami, D.; Tajbakhsh, M,; Ghassemzadeh, M. Monatsch. Chem.

2000, 131,1109.

41. Mitra, A.K.; De, A.; Karchaudhuri, N. Synlett. 1998,1345.

42. Khazaei, A.; Manesh, A.A.; Ghasemi, A.H. Synthesis 2004, 17, 2784-2786.

43a. Mojtahedi, M.M.; Heravi, M.M. Indian J. Chem. 2005, 44B, 831-833.

43b. Banerjee, K.; Mitra, A.K. Indian J. Chem. Sect.B 2005, 44B, 1876-

1879.

44. Satish, S.; Kalyanam, N. Chem. Ind. (London) 1981, 809.

45. Tamami, B.; Goudarizian, N. Eur. Polim. J. 1992, 28 ,1035.

46. Bhattacharjee, M.N.; Choudhuri, M.K.; Dasgupta, H.S.; Roy, N. Synthesis 1984,

588.

47. Bose, D.S.; Narsaiah, A.V. Synth. Commun. 2000, 30 ,1153.

48. Ager, D.J. Tetrahedron Lett. 1983, 24, 5441.

49. Zhang, G. -S.; Yang, D. -H.; Chen, M. -F. Synth. Commun. 1998, 28, 3721.

50. Zhang, G. -S.; Yang, D. -H.; Chen, M. -F.; Cai, K. Synth. Commun. 1998, 28,

2221.

148


51. Hosseinzadeh, R.; Tajbakhsh, M.; Niaki, Y.M. Tetrahedron Lett. 2002, 43,

9413-9416.

52. Chidambaram, N.; Satyanarayana, K.; Chandrasekharan, S. Synth. Commttn.

1989, 19, 1727.

53. Singh, J.; Bhandari, M.; Kaur, J.; Kad, LG . Indian J. Chem. 2003, 428,405-407.

54. Firouzabadi, H.; Sardarian, A.R. Synth. Commun. 1983, 13, 863.

55. Jadhav, V.K.; Wadgaonkar, P.P.; Joshi, P.L.; Salonkhe, M.M. Synth.

Commun. 1999, 29 ,1989.

56. Shinada, T.; Yoshihara, K. Tetrahedron Lett. 1995, 36, 6701.

57. Coutts, I.G.C.; Pavlidis, V.H.; Reza, K.; Southcott, M.R.; Wiley, G. Tetrahedron

Lett. 1997, 38, 5563.

58. Demir, A.S.; Tanyeli, C.; Altinel, E. Tetrahedron Lett. 1997, 38, 7267.

59. Nattier, B.A.; Eash, K.J.; Mohan, R.S. Synthesis 2001, 1010.

60. Dess, D.S.; Martin, J.C. J. Am. Chem. Soc. 1991, 113, 7227.

61. Chaudhuri, S.S.; Akamanchi, K.G. Synthesis 1999, 760.

62. Bose, D.S.; Srinivas, P. Syntett. 1998, 9, 977.

63. Bose, D.S.; Narsaiah, A.V. Synth. Commun. 1999, 29, 937.

64. Yadav, J.S.; Sasmai, P.K.; Chand, P.K. Synth. Commun. 1999, 29, 3667.

65. Bandgar, B.P.; Kale, R.R.; Kunde, L.B. Monatsch 1998,129,1057.

66a. Bandgar, B.P.; Kunde, L.B.; Thote, J.C. Synth. Commun. 1997, 27,1149.

66b. Krishnaveni, N.S.; Surendra, K.; Nageswar, Y.V.D.; Rama Rao, K. Synthesis

2003, 13,1968-1970.

67. Movassagh, B.; Lakouraj, M.M.; Ghodrati, K. Synth. Commun. 2000, 30,4501.

149

PartA References Chapter 3

68. Lakouraj M.M.; Bahrami, K.J. J. Chem. Res., Synop. 2000, 222.

69. Chen, F.; Liu, A.; Yan, Q.; Liu, M.; Zhang, D.; Shao, L. Synth. Common, 1999,

29,1049.

70. Mohammadpoor-Baltork, I.; Hajipour, A.R.; Haddadi, R. J. Chem. Res., Synop.

1999, 102.

71. Mohammadpoor-Baltork, l.; Hajipour, A.R.; Mohammadi, N. Bull, Chem. Soc.

Jpn. 1998, 71, 1649.

72. Mao, Y.Z.; Liu, Z. L.; Wu, L.M. Chin. J. Chem. 2000, 18, 789.

73. Goswami, P.; Choudhury, P.K. Indian J. Chem., Sect. B. 2001, 40,157.

74. Yang, Y.; Zhang, D.; Wu, L. -Z.; Chen. B.; Zhang, L. -P.; Tung C. -H. J. Org.

Chem. 2004, 69,4788-4791.

75. Buckingham, J. Quart. Rev. 1969, 23, 27.

76. Reese, C.B. Protective Groups in Organic Chemistry, Plenum Press : New

York, 1973.

77. de Mayo, P.; Grazina, L.R.; Weedon, A.C. Tetrahedron Lett. 1978,4621.

78. Jirincy, J.; Orere, D.M.; Reese, C.B. J. Am. Chem. Soc. 1980,1487.

79. Depuy, C.H.; Ponder, B.W. J. Am. Chem. Soc. 1959, 81,4629.

80. Mitra, R.B.; Bhaskar. Reddy, G. Synthesis 1989, 694-698.

81. Gawley, R.E.; Termine, E.J. Synth. Commun. 1982, 12,15-18.

82. Enders, D.; Dyker, H.; Raabe, G. Angew. Chem., Int. Ed. Engl. 1992, 31, 618-

620.

83. Kama!, A.; Rao, M.V.; Meshram, H.M. Tetrahedron Lett. 1991, 32, 2657-2658.

150


84. Bose, S.D.; Vanajatha, G.; Srinivas, P. Indian J. Chem. 1999, 35B, 835-836.

85. Altamura, A.; Curci, R,; Edwards, J. J. Org. Chem. 1993, 58, 7289-7293.

86. Adam, W.; Chen, Y. Y.; Cremer, D.; Gauss, J.; Schindler, M. J. Org. Chem.

1987, 52, 2800.

87. Mello, R.; Fiorentino, M.; Fusco, C.; Curchi, R. J. Am. Chem. Soc. 1989, 111,

6749.

88. Lluch, A.M.; Sanehez-Baeza, F.; Camps, F.; Messeguer, A. Tetrahedron Lett.

1991, 32, 5629.

89. Shim, B.S.; Kim, K.; Kim, Y.H. Tetrahedron Lett. 1987, 28, 645-648.

90. Olah, G.A.; Welch, J.; Prakash, G.K.S.; Ho, T.L. Synthesis 1976, 808-809.

91. Olah, G.A.; Welch, J.; Henninger, M. Synthesis 1977, 308-309.

92. Olah, G.A.; Prakash, G.K.S.; Ho, T.L. Synthesis 1976, 809-810.

93. Olah, G.A.; Welch, J.; Ho, T.L. J. Am. Chem. Soc. 1976, 98, 6717-6718.

94. Laszlo, P.; Polla, E. Synthesis 1984, 439-440.

95. Barton, D.H.R.; Jaszberenyi, J.C.; Liu, W.; Shinada, T. Tetrahedron 1996, 52,

14673-14688.

96. Me Killop, A.; Tarbin, J.A. Tetrahedron 1987, 4 3 ,1753-1758.

97. Clark, J.H.; Ross, J.C.; Macquarrie, D.J.; Barlow, S.J.; Bastock, T.W.

Chem. Commun. 1997,1203.

98. Varma, R.S.; Meshram, H.M. Tetrahedron Lett. 1997, 38, 7973-7976.

99. Baerjee, K.; Mitra, A.K.; Patra, A. Indian J. Chem. 2006, 45B, 537-539.

151


100. Hajipour, A.R.; Mallakpour, S.E.; Baltork, I.M.; Backnejad, H. Indian J.

Chem. 2002, 41B, 1740-1743.

101. Vankar, P.; Rafhore, R.; Chandrasekharan, S. J. Org. Chem. 1986, 51,

3063-3065.

102. Choi, H.C.; Kim, Y.A. Synth. Commun. 1994, 24, 2307-2311.

103. Eisenbraun, E.J.; Wesley, R.P.; Budhram, R.S.; Dewprasad, B. Chem.

Ind. (London) 1989, 459-460.

104. Kabalka, G.W.; Summers, S.T. J. Org. Chem. 1981, 46.

105. Kirk, D.N.; Slade, C.J. Tetrahedron Lett. 1980. 21, 651-654.

106. Vankar, P.; Rathore, R.; Chandrasekaran, S. J. Org. Chem. 1986, 51,

3063-3065.

107. Narayanan, S.; Srinivasan, V.S. J. Chem. Soc., Perkin Trans.2 1986,

1557-1559.

108. Ram, N.R.; Varsha, K. Tetrahedron Lett. 1991, 32, 5829-5832.

109. Varma, R.S.; Meshram, H.M. Tetrahedron Lett. 1997, 38, 7973-7976.

110. Laszlo, P.; Polla, E. Synthesis 1985, 439-440.

111. Kirk, D.N.; Slade, C.J. Tetrahedron Lett. 1980, 21, 651-654.

112. Ranu, B.C.; Sarkar, D.C. J. Org. Chem. 1988, 53, 878-879.

113. Bose, D.S.; Vanajatha, G.; Srinivas, P. Indian J. Chem. 1999, 35B, 835-

836.

114. Hajipour, A.R.; Mallakpour, S.E.; Baltork, I.; Backnejad, Hossein, Indian

J. Chem. 2002, 41B, 1740-1743.

152


115. Smith, K. Solid Supports and Catalysis in Organic Synthesis; Prentice

Hall: New York, 1992.

116. Hajipour, A.R.; Mallakpour, S.E.; Adibi, H. Chem. Lett. 2001, 64.

117. Hajipour, A.R.; Adibi, H.; Ruoho, A.R. J. Org. Chem. 2003, 68, 4553-

4555.

118. Banerjee, K.; Mitra, A.K.; Patra, A. Indian J. Chem. 2006, 45B, 537-539.

119. Vogel, A. I. “A Texbook of Practical Organic Chemistry'’, 5th Ed.,

English : Pearson Education Re Ltd : Singapore, 2004; p 1034-1259.

120. Clarke, H.T.; Haynes, B. “A Handbook of Organic Analysis", 5th ed.;

Edward Arnold (Publishers) Limited : London, 1975.

153

shodhganga.inflibnet.ac.inshodhganga.inflibnet.ac.in/bitstream/10603/67018/12/12_chapter 4.pdf ·...

Documents

Transcript of shodhganga.inflibnet.ac.inshodhganga.inflibnet.ac.in/bitstream/10603/67018/12/12_chapter 4.pdf ·...