Chapter-3 SOCl2 β-Cyclodextrin: A New and Efficient...

Chapter 3

52

Chapter-3

SOCl2/β-Cyclodextrin: A New and Efficient

Catalytic System for Beckmann Rearrangement

and Dehydration of Aldoximes Under Aqueous

Condition

3.1 Introduction

3.2 Review of Literature

3.3 Present Work

3.4 Conclusion

3.5 Experimental Section

3.6 Spectral Data

3.7 References

Synthetic Communication 2013, 43 (1), 118-128.

Chapter 3

53

3.1 Introduction

The rearrangement of ketoximes to corresponding amides, known as

“Beckmann reaction or rearrangement”, is a common method in organic chemistry1

and is a topic of current interest. The Beckmann rearrangement, named after the

German chemist Ernst Otto Beckmann (1853–1923).1c

The Beckmann rearrangement

has been tremendous interest to all practicing organic chemist, as the reaction affects a

nitrogen insertion into a carbon framework. It generally proceeds through anti

migration. Beckmann rearrangement is industrially important for the manufacture of

Nylon-6 precursor, ε-caprolactum. The amide functionality is an important motif in

polymers, natural products, and pharmaceuticals.2 The amide bond is a key functional

group in organic and biological chemistry.3 Beyond conventional methods toward the

synthesis of amides,4 many alternative strategies have been reported.

5 In fact, the

development of new amide forming reactions till in demand with improvements by

the pharmaceutical industry.6

Amide has an immensely important due to its role as a privileged

pharmacophore and building block in a myriad of biomolecules as well as

pharmaceutically interesting compounds.7 The benzazepines having amide

functionality have been reported, which may be used in the treatment of certain

diabetic conditions.8 Amide derivative of Ibuprofen resulted in improved analgesic,

gastroprotective as well as anti-inflammatory activity.9 Ibuprofen heterocyclic amides

are also investigated for their analgesic and toxicological properties.10

A series of

5,5-diarylpenta-2,4-dienoicacids and their amides have been synthesized and

evaluated as antimalarial agents.11

The amides also act as precursors for the synthesis

of heterocycles like pyrimidine derivatives,12

δ-lactums,13

for the synthesis of

sulphenylated oxazolines, oxazines or tetrahydropyrroles,14

etc. Bioactive amides

moieties are shown in Figure 3.1.

Chapter 3

54

NH

NN

O

H2N

Antifungal20

HN

O

CH2OH

Amide derivative of Ibuprofen10

(Analgesic)

Cl CH CHCH CHCONH-iPr

Antimalerial11

Figure 3.1: Bioactive amide derivatives.

The nitrile functionality is a key constituent of numerous natural products and

also serves as an important synthetic intermediate for pharmaceuticals,15

agricultural

chemicals, dyes, material sciences16

and as intermediates in microbial metabolism.17

Nitriles are also products of the petrochemical industry and are widely used as

chemical solvents, recrystallizing agents. Nitriles are of important synthon in

preparative organic chemistry due to their conversion into carboxylic acids,

aldehydes, amides, amines and ketones15,18

. Nitrile compounds are viable precursors

for preparation of a variety of nitrogen-containing functional compounds,18

amino

acids by Strecker reaction,19

synthesis of bioactive heterocycles like

5-aminopyrazoles,20

aryl 2-oxazolines,21

tetrahydropyridinethione, pyridopyrimidines,

pyridotriazines dihydropyridines22

and oxazolines,23

etc.

3.2 Review of Literature

The most common methods for the preparation of amides are the reaction

between carboxylic acid derivatives particularly acid halides, acid anhydrides, and

esters with the amines. Despite their wide scope, limitations are associated with the

use of acid halides, anhydrides, and esters. Limitations are mostly due to the limited

stability of many acid chlorides, reactions with esters require strongly basic or acidic

catalysts.24

Conventional Beckmann rearrangement usually requires relatively high

temperature, large amount of strongly acidic and dehydrating media such as

concentrated H2SO4 (forms ammonium sulfate as byproduct),25a

polyphosphoric

acid,25b

P2O5-methanesulfonic acid,25c

that leads to the large waste products

(formation of inorganic salts caused by neutralization) and not applicative to sensitive

Chapter 3

55

substrate. Consequently research is being pursued to make the process mild and

catalytic. To avoid these requisite harsh conditions several methodologies in liquid

phase,26-28

supercritical water,29

ionic liquid,30

vapour phase31

have been developed.

Many catalytic systems such as boria hydroxyapatite, metal ilerite, supported oxide

and zeolite have been reported.31

However these processes require high reaction

temperature (300 0C), low selectivity and can suffer from rapid decay in the activity

of catalyst. Various inorganic catalyst such as terpyridine ruthenium,5e

AlCl3.6H2O/KI/H2O/CH3CN,28c

metal lewis acid- Ga(OTf)3,28d

[RhCl(cod)]2, Au/Ag

co-catalytic system,32

triphosphazene in HIIP or acetonitrile26a

also reported. The

other reagent includes cyanuric chloride/DMF,28a

anhydrous oxalic acid,31d

chlorosulfonic acid in toluene.26b

However some of these processes require hazardous

high cost solvents like DCM, DMF, acetonitrile, toluene, etc with high reaction time.

Therefore, the development of simple, highly efficient and selective Beckmann

rearrangement process is still highly demandable.

Furuya Y. et al. (2005)33

Furuya Y. et al. have reported the commercially available cyanuric chloride as

an effective organocatalyst for the Beckmann rearrangement of ketoximes into amides

in acetonitrile under refluxing condition (Scheme 3.1).

R1 R2

NOH

CH3CN, reflux

CNC (2 or 5 mol%), ZnCl2 (2 mol%)NH

O R2

R1

Scheme 3.1

Ramalingan C. et al. (2007)34

Ramalingan C. et al. has found an acetonitrile solution of mercury(II) chloride

as an efficient catalytic system for rearrangement of diverse range of ketoximes to

their corresponding amides/lactums (Scheme 3.2).

R' R

NOH

CH3CN, 80 0C, 8 h

NH

O R

R'HgCl2 (12-30%)

Scheme 3.2

Chapter 3

56

Li Z. et al. (2008)35

Li Z. et al. developed an efficient and rapid method for Beckmann

rearrangement of ketoximes by using recyclable and reusable silica-supported

phosphorus chloride as catalyst under microwave irradiation in anhydrous

tetrahydrofuran (Scheme 3.3).

R1

R2

NOH SiO2-OPCl2

THF, MW, 3-8 Min.

R1, R2 = alkyl, aryl

NH

O

R1R2

Scheme 3.3

Liu X. et al. (2009)36

Liu X. et al. reported a mild, efficient and eco-friendly procedure for

Beckmann rearrangement catalyzed by a series of novel Bronsted acidic ionic liquids

(ILs) consisting double SO3H cations mediated zinc chloride (ILs–ZnCl2) catalytic

system (Scheme 3.4). High yields of amides were achieved by using 5 mol % of

ILs–ZnCl2 catalysts. In addition, the catalyst system could be recycled and reused for

three times.

R1 R2

NOH

solvent

NH

O R2

R1Acidic ionic liquid- ZnCl2

Scheme 3.4

Yadav L. D. S. et al. (2010)37

Yadav L. D. S et al. have performed Bromodimethylsulfonium bromide

(BDMS)-catalyzed Beckmann rearrangement of a variety of ketoximes in the

imidazolium-based ionic liquid [bmim]PF6 under mild conditions without using any

additional co-catalyst or solvent to afford excellent conversion and selectivity

(Scheme 3.5). The ionic liquid is recovered and reused for up to three runs without

any loss of efficiency.

R1 R2

NOH

[bmim]PF6, 80 0C

NH

O R2

R1

S +Br

_Br

BDMS

R1, R2 = phenyl, alkyl, cycloalkyl

Scheme 3.5

Chapter 3

57

Yadav L. D. S. et al. (2010)38

Yadav L. D. S et al. has been shown Bromodimethylsulfonium bromide, in

combination with zinc chloride, an excellent catalytic system for liquid-phase

Beckmann rearrangement of various ketoximes into the corresponding amides/lactams

in acetonitrile at reflux temperature (Scheme 3.6) with good to excellent yields.

R1 R2

NOH

ZnCl2, MeCN, reflux

NH

O R2

R1

S +Br

_Br

BDMS

Scheme 3.6

Liu L. F. et al. (2011)39

Liu L. F. et al. invented aluminum chloride, an inexpensive and commercially

available lewis acid catalyst for Beckmann rearrangement. The stoichiometric

amounts of catalyst smoothly promote the Beckmann rearrangement of various

ketoximes to the corresponding amides in anhydrous acetonitrile under reflux

temperature (Scheme 3.7).

R1

R2

NOH AlCl3 (10 mole %)

CH3CN, reflux, 2 h NH

O

R1R2

R1, R2 = alkyl, aryl

Scheme 3.7

At the same time, dehydration of aldoximes to nitriles is also an important

transformation in organic synthesis and a number of methods have been developed.40

There are many methods using SOCl2 for dehydration of aldoximes to nitriles has

been reported like silica gel/SOCl2,41a

SOCl2-benztriazole,41b

Na2CO3/SOCl2.41c

Although the methods developed so far have their own limitations for example, the

use of extremely anhydrous reaction condition, toxic and hazardous chemicals and the

need of cumbersome work-up procedures.42

One of the most general methods for

synthesis of alkyl nitriles is direct nucleophilic substitution of alkyl halides with

inorganic cyanides, although the reaction is frequently accompanied by elimination of

hydrogen halides, especially with bulky alkyl halides.43

They were also usually

prepared by regenerating CN group via oxidation,44

rearrangement45

or elimination.

The direct preparation of nitriles from aldehydes was generally achieved by the

dehydration of the corresponding aldoximes using classical reagents46

or other new

Chapter 3

58

reagents like trichloroisocyanuric acid,47

trichloroacetyl chloride/triethylamine,

dicyclohexyl carbodiimide, phosphonitrilic chloride,40b

CuCl2,48

chlorosulfonyl

isocyanate, triphenylphosphine, Burgess reagent49

and also include the use of

expensive (2,4-dinitrophenyl hydroxylamine)50

, (hydroxylamine-o-sulfonic acid),51

hazardous (selenium dioxide)52

or corrosive (formic acid)53

reagents. Some other

method for synthesis of nitriles includes use of hypervalent iodine (III) reagent in

aqueous ammonium acetate,54

microwave reaction with catalytic amount of

pyridine,55

microwave mediated solvent free reaction in presence of TiO2,56

CuCl2 in

acetonitrile under ultrasound irradiation,57

etc.

Yang S. H. et al. (2001)58

Yang S. H. et al. performed catalytic dehydration of aldoximes with catalytic

system [RuCl2(p-cymene)]2/molecular sieves under essentially neutral and mild

conditions resulting into various types of cyano compounds with good to excellent

yields (Scheme 3.8).

N

H

ROH + [RuCl2(p-cymene)]2

(2 mol %)

MS 4 A0

CH3CN, 80 0C

10-60 min

R CN

Scheme 3.8

Lee K. et al. (2004)59

Lee K. et al. reported the various aliphatic, aromatic and heterocyclic aromatic

type of aldoximes conversion to corresponding nitriles in good to excellent yields

using 2-chloro-1-methylpyridiniun iodide (CMPI) as a dehydrating agent using

triethylamine in dichloromethane under Argon atmosphere (Scheme 3.9).

R

HN

OH CMPI, Et3N, CH2Cl2

rt, 1-2 h, ArR CN

R = aliphatic, aromatic, heterocyclic aromatic

Scheme 3.9

Saini A. et al. (2005)60

Saini A. et al. developed an efficient method for the transformation of

aldoximes to nitriles induced by zinc-iodine system in good to excellent yields in

acetonitrile at room temperature (Scheme 3.10).

Chapter 3

59

R

HN

OH Zn / I2

CH3CN, rtR CN

Scheme 3.10

Gucma M. et al. (2008)61

Gucma M. et al. have mentioned the transformation of benzaldehyde

aldoximes with electron donating group to corresponding nitriles with the help of

N-chlorosuccinimide and pyridine in acetonitrile (Scheme 3.11). In this method for

the simple benzaldehyde oxime and alkanal aldehyde oximes get deprotected into

corresponding benzaldehyde.

ArCH NOH + NCl

O

O

pyridine

MeCNArCN + NH

O

O

+ py.HCl

Scheme 3.11

Singh M. K. et al. (2009)62

Singh M. K. et al. have converted an easily synthesized aldoximes to the

corresponding nitriles by a reaction with 1H-benzotriazol-1-

yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) and DBU in

CH2Cl2, THF, or DMF (Scheme 3.12). As an alternative reagent that eliminates the

formation of hexamethylphosphoramide as a byproduct, use of 1H-benzotriazol-1-yl-

4-methylbenzenesulfonate (Bt-OTs) and DBU was also investigated.

R

HN R CN

Ar orAr or

NN

N

x

DBU, CH2Cl2

BPO: x = OP+(NMe2)3PF6-

Bt-OTs: x = OTs

OH

Scheme 3.12

Saha D. et al. (2009)63

Saha D. et al. described a simple and convenient procedure for the synthesis of

nitriles by dehydration of aldoximes using an ionic liquid, 1-pentyl-3-

methylimidazolium tetrafluoroborate, [pmim]BF4 under organic solvent-free

condition (Scheme 3.13). A variety of aromatic, heteroaromatic and aliphatic

Chapter 3

60

aldoximes were converted to the corresponding nitriles. The ionic liquid was

recovered and reused for subsequent reactions.

RCH NOH RCN[pmim]BF4

90 0C

R = aryl, heteroaryl, alkyl

Scheme 3.13

Rad M. N. S. et al. (2010)64

Rad M. N. S. et al. reported a facile and efficient method for dehydration of

aldoximes into nitriles using N-(p-toluenesulfonyl) imidazole (TsIm) (Scheme 3.14).

In this method, aldoximes were refluxed with TsIm in the presence of

1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU) in dimethylformamide (DMF) to afford

the corresponding nitriles in good yields. This methodology is highly efficient for

various structurally diverse aldoximes including aromatic, heteroaromatic and

aliphatic oximes.

R

HN

OH Tslm/DBU

DMF, reflux 15-90 min.

R CN

H3C S

O

O

NN

Tslm =

Scheme 3.14

Li Y. T. et al. (2011)65

Li Y. T. et al. invented catalytic dehydration of aldoximes efficiently with

NiCl2 in acetonitrile under neutral condition and in N2 atmosphere. Under these

conditions, various functionalized aldoximes produce the corresponding nitriles in

good to excellent yields (Scheme 3.15).

N

H

ROH

NiCl2 (0.025 mmol)

MS 4 A0

CH3CN, reflux,

3 h

R CN

Scheme 3.15

Rad M. N. S. et al. (2012)66

Rad M. N. S. et al. developed a rapid and highly convenient synthesis of

nitriles from the corresponding aldoximes using 8-bromocaffeine (8-BC) (Scheme

3.16). In this protocol, aldoximes react with 8-BC in the presence of

1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and N,N-dimethylformamide (DMF) to

Chapter 3

61

furnish the corresponding nitriles under both microwave-assisted and/or conventional

heating (reflux) conditions in short times and in good to excellent yields.

R

HN

OH 8-BC, DBU, DMF

Conventional heatingor Microwave

R CN

N

N

O

O N

NBr8-BC = DBU = N

N

Scheme 3.16

3.3 Present Work

In comparison with some inflammable and toxic organic solvents, water may

serve as superior solvent that is safe to use in organic reactions.67

The low cost of

water renders the chemical processes more economical. In many cases, water can be

recycled to improve the problem of solvent disposal. Furthermore, using water as a

solvent may also have advantages of simple operation and high efficiency in many

organic reactions. Synthetic chemists continue to explore new methods to carry out

chemical transformations. Herein we present our results on highly selective

SOCl2/β-cyclodextrin catalyzed Beckmann rearrangement and dehydration of

aldoximes to corresponding nitriles (Scheme 3.17). As the Beckmann rearrangement

usually requires electrophilic activation of oxime hydroxy group, we hypothesized

that β-CD facilate the transformation of ketoximes to amide or dehydration of

aldoximes by hydrogen bonding with β-CD hydroxyl groups by supramolecular

interaction. The hydrogen bonding with oxygen may also force up for departing of

leaving group and accelerate the rate of migration or rate of dehydration.

R

R'N

OHi. SOCl2 , Acetone

ii. -CD , H2OR

HN

O

R' ORR

C N

If R' = H80 0C5

6 a-g

7 a-m Scheme 3.17

In order to explore the best reaction condition the 4-bromoacetophenone

oxime was selected as a model molecule under various reaction conditions (Table

3.1).

Chapter 3

62

Table 3.1: Screen of reaction conditions.a

Br

NOH

Mei) SOCl2, Acetone

ii) Beta-CD (0.5 mmol),

H2O Br

NH

Br

O

Me+

Me

O

A B

Entry Temp. (0C) Time (h) Yield (%)

b

A B

1

2

3

4

Room temp.

40

60

80

12

2.45

0.5

0.41

30 68

38 53

47 50

85 -

a Reaction condition : To a solution of 4-bromoacetophenone oxime in acetone, SOCl2

added dropwise at 0-10 0C. Then clear solution of β-CD dissolved in distilled water

(10 mL) was added at room temperature and stir at given temperature. A mole ratio of

oxime: SOCl2: β-CD = 5: 6: 0.5 b Isolated yield.

Table 3.2: Transformation of ketoximes to amide using different amount of catalyst

at 80 0C.

a

i) SOCl2, Acetone

ii) Beta-CD, H2O, 80 0C

Br

NOH

Me

Br

NH Me

O

Entry Catalyst (mmol) Time (min.) Yield (%)

1 0.5 25 85

2 1 25 84

3 2 28 84

4 4 30 80

5 5 40 80

6 - 35 41

a A mole ratio of oxime: SOCl2 = 5: 6 was used.

The effect of temperature for above reaction has been studied and it was found

that at lower temperature (entry 1, Table 3.1), the rate of migration was very slow,

require high reaction time and leading to the side product identified as 4-bromo

acetophenone (by TLC comparison and Mp with authentic sample). Increase in

Chapter 3

63

temperature fevers the rate of migration and best result was found at 80 0C (entry 4,

85%, Table 3.1). The reactions were also carried out by varying amount of catalyst

(Table 3.2) at 80 0C. When we have increased the amount of catalyst from 0.5 to 5

mmol, no yield improvements were observed. When same reaction was carried out at

80 0C without β-CD catalyst, formation amide and starting carbonyl compound takes

place. The efficiency of catalyst have been studied for the structurally divers ketoxime

(Table 3.3). The reactions were found to be complete within 5 – 25 min. As per usual

migratory aptitude of Beckmann rearrangement, here only migration of aryl group

was observed. The naphthalene and diphenyl compounds also show good results

(entry 6d – 6g, Table 3.3). In our results the electronic effect of substituents on

aromatic ring was not more pronouns.

Table 3.3: Catalytic conversions of various ketoximes to amide using SOCl2/β-CD as

catalysta.

R

R'N

OHi. SOCl2 , Acetone

ii. -CD (0.5 mmol),

H2O, 80 0C

R

HN

O

R'

56 a-g

Entry Amide Time

(min.)

Yield b

(%)

Melting point (0C)

Measured Reported

6a HN

O

5 86 113 11470

6b HN

O

8 88 150 149-15169

6c HN

OBr

25 85 165-167 16770

6d

HN O

20 90 159-166 16070

6e HN

O

15 91 129-132 -

Chapter 3

64

6f HN

O

20 93 162 16270

6g HN

Cl

O

18 94 197-200 19470

a A molar ratio of ketoximes: SOCl2: β-CD = 5: 6: 0.5,

b Isolated yield after column

chromatography.

The starting oximes used in present study are mostly mixture of syn and

anti isomer, but we obtained majority of single amide isomer as the product which is

favored based on migratory aptitude (except entry 6g). The equilibrium among

involved isomer is faster than rearrangement so that the product composition is

determined by the relative rates of migration of involved groups. On prolonged

heating at 80 0C there was no further dehydration of amide to nitrile or hydrolysis of

amide to acid and amine occurs. The reaction was also carried out in absence of

SOCl2 for prolonged time but the starting oximes get isolated. The catalyst is

quantitatively recovered and reused up to three cycles (Table 3.4).

Table 3.4: Reuse of β-CD for 6c.

No. of use Yield (%) Recovery of β-CD (%)

1 85 96

2 85 90

3 83 85

Table 3.5: Catalytic dehydration of aldoximes to corresponding nitriles using SOCl2/

β-CD as a catalyst.a

RN

OH

H RC N

i. SOCl2 , Acetone

ii. -CD (0.5 mmol),

H2O, 80 0C7 a-m

Entry Nitrile Time

(min.)

Yield b

(%)

Melting point (0C)

Measured Reported

7a CN

15 90 190 (Bp) 19170

Chapter 3

65

7b CN

NO2

8 98 116-118 11870

7c CN

O2N

10 91 148 14970

7d CN

Cl

10 96 96 9670

7e CN

Br

15 91 112 11370

7f

NH

CN

20 94 180-182 179-18269

7g CN

HO

12 91 112 11369

7h CN

MeO

12 91 58 57-5970

7i CN

MeO

OMe

MeO

15 92 92-94 -

7j CN

Cl

15 94 44 43-4669

7k CN

Me

20 92 216-218 21870

(Bp)

7l CN

HO

OMe

25 93 84 85-8769

7m Me CN 10 89 96-98 9770

(Bp)

a A molar ratio of aldoximes: SOCl2: β-CD = 5: 6: 0.5.

b Isolated yield after column

chromatography.

Chapter 3

66

With promising results in hand for the formation of amide from ketoximes, we

next tested for the aldoximes to examine generality of this reaction under identical

condition. Aldoximes

were found to be undergoing dehydration furnishes the

corresponding nitriles in good to excellent yields and within short reaction time

(8 - 25 min, Table 3.5). On comparison of the overall reactivity of aldoximes and

ketoximes in our results with respect to time and yields, aldoximes were found to be

more reactive. The effect of substituent on aromatic ring like nitro, halide, hydroxyl,

methoxy, and methyl was found to be less on reaction efficiency and selectivity. The

same reaction proceeds much slowly when reaction carried out in acetonitrile at

similar condition affording side product (monitor by TLC). Not only aromatic

aldoximes were efficiently converted to aromatic cyano compounds but heterocyclic

(entry 7f) as well as aliphatic aldoxime (entry 7m) could also be employed as a good

substrate with similar selectivity to affords the corresponding nitriles. Compounds

entry 7a, 7d, 7h, 7k were isolated in 90, 96, 91 and 92% yields in shorter reaction time

while using a literature procedure60,68

these compounds were isolated in 82, 87, 82

and 85% yields in 1 h reaction time. Furthermore catalytic activity of recovered

catalyst (β-CD) was examined. As shown in Table 3.6, the yield of

3-nitrobenzonitrile in second and third use of catalyst not found to be decreasing

much more. In each case almost > 86% of β-CD was easily recovered by cooling of

aqueous layer. However when these reactions were carried out in presence of simple

oligosaccharides such as glucose or dextrose, the reaction was completed in 30 min.

and 20 min. with yields only 45% and 55% for 4-bromoacetophenone oxime and

4-nitrobenzaldehyde oxime respectively. It confirms that cyclodextrin may form

complex with oxime, thus yields of reaction increased to 85% and 91% respectively.

Glucose or dextrose also not recovered from aqueous layer quantitatively.

Table 3.6: Reuse of β-CD for 7b.

Number of use Yield (%) Recovery of β-CD

(%)

1 98 94

2 94 90

3 90 86

Chapter 3

67

3.4 Conclusion

In conclusion, we have described a highly efficient protocol for conversion of

ketoximes to amide and dehydration of aldoximes to nitrile using nontoxic and

inexpensive β-CD catalyst in water. The advantages of this protocol includes a simple

reaction set-up not requiring specialized equipment, mild reaction condition, high

product yields, very short reaction time, reusable catalyst and eliminating the use of

hazardous solvents.

3.5 Experimental Section

Chemicals required for the synthesis were obtained from Aldrich,

Spectrochem. Melting points were taken in open capillary tubes and are uncorrected.

IR spectra were recorded on Shimadzu FT-IR IRAffinity-1 using KBr. 1H NMR

spectra were recorded with a Varian Mercury at 300 MHz in CDCl3 with TMS as an

internal standard. Mass spectra were under ESI mode, on Thermo Finnigan (Model-

LCQ Advantage MAX) mass spectrometer.

Typical procedure for transformation of oximes into amide and nitriles

To a solution of oxime (5 mmol) in acetone (2 mL), SOCl2 (6 mmol) was

added dropwise with stirring at 0-10 0C. Then clear solution of β-CD (0.5 mmol) in

distilled water (10 mL) was added at room temperature and stir at 80 0C for

appropriate time (monitored by TLC, Hexane: Ethyl acetate 9:1). The organic

material was extracted in ethyl acetate (3 x 20 mL). The aqueous layer was cooled to

0 0C; in which β-CD reappeared as a white solid. The obtained white solid mass was

filtered, dried to recover β-CD and reused. The organic phase dried over anhydrous

Na2SO4, solvent was evaporated under reduced pressure, the crude product purified

by column chromatography using hexane-ethyl acetate (9:1) as eluent to afford pure

product.

The selected products were characterized by FTIR, NMR, Mass spectroscopy,

whereas the remaining products characterized by their physical constants,

comparative TLC and are found to be in good agreement with the authentic samples.

Chapter 3

68

3.6 Spectral Data

N-p-Tolyacetamide: H

N

O

Molecular formula: C9H11NO

Molecular weight : 149

Mp : 150 0C

IR (KBr, cm-1

) ν : 3300, 2922, 1664, 1602, 817 1H NMR (CDCl3, 300 MHz, ppm) δ : 7.36 (d, 2H, J = 8 Hz, Aromatic), 7.20

(brs, 1H, NH), 7.11 (d, 2H, J = 8Hz,

Aromatic), 2.30 (s, 3H, COCH3), 2.15

(s, 3H, CH3)

MS (m/e) : 150 [M+1]

N-(Naphthalene-6-yl) acetamide: HN

O



Mp : 129-132 0C

IR (KBr, cm-1

) ν : 3284, 2983, 1668, 1589 1H NMR (CDCl3, 300 MHz, ppm) δ : 8.17 (s, 1H, NH), 7.79 – 7.76 (m, 3H,

Aromatic), 7.45 – 7.39 (m, 4H,

Aromatic), 2.23 (s, 3H, COCH3)

MS (m/e) : 186 [M+1]

N-Phenylbenzamide: HN

O



Mp : 162 0C

IR (KBr, cm-1

) ν : 3344, 3053, 1654, 1598, 750 1H NMR (DMSO-d6,

300 MHz, ppm) δ :

10.2 (brs, 1H, NH), 7.96 – 7.07 (m, 10H,

Aromatic)

MS (m/e) : 198 [M+1]

4-Chloro-N-phenylbenzamide:

HN

O

Cl

Molecular formula: C13H10ClNO


Mp : 197-200 0C

IR (KBr, cm-1

) ν : 3350, 3057, 1653, 1598, 848 1H NMR (CDCl3, 300 MHz, ppm) δ : 7.85 – 7.16 (m, 9H, Aromatic), 7.74

(s, 1H, NH)

Chapter 3

69

MS (m/e) : 232 [M+1]

4-Nitrobenzonitrile: CN

O2N

Molecular formula: C7H4N2O2


Mp : 148 0C

IR (KBr, cm-1

) ν : 2223, 1600, 1348, 860 1H NMR (CDCl3, 300 MHz, ppm) δ : 8.36 (d, 2H, Aromatic), 7.90 (d, 2H,

Aromatic)

1H-Indole-3-carbonitrile:

NH

CN

Molecular formula: C9H6N2


Mp : 180-182 0C

IR (KBr, cm-1

) ν : 3230, 3122, 2227 1H NMR (CDCl3, 300 MHz, ppm) δ : 8.68 (brs, 1H, NH), 7.80 – 7.26 (m, 5H,

Aromatic)

MS (m/e) : 143 [M+1]

4-Hydroxybenzonitrile: CN

HO



Mp : 112 0C

IR (KBr, cm-1

) ν : 3275, 3169, 2233, 1610, 1166, 839 1H NMR (CDCl3, 300 MHz, ppm) δ : 7.56 (d, 2H, Aromatic), 6.93 (d, 2H,

Aromatic), 6.09 (s, 1H, OH)

MS (m/e) : 120 [M+1]

4-Methoxybenzonitrile: CN

MeO



Mp : 58 0C

IR (KBr, cm-1

) ν : 3024, 2843, 2218, 1604, 1024, 829 1H NMR (CDCl3, 300 MHz, ppm) δ : 7.60 (d, 2H, Aromatic), 6.98 (d, 2H,

Aromatic), 3.88 (s, 3H, OCH3)

MS (m/e) : 134 [M+1]

Chapter 3

70

2-Chlorobenzonitrile: CN

Cl

Molecular formula: C7H4ClN


Mp : 44 0C

IR (KBr, cm-1

) ν : 3093, 2229, 1591, 759 1H NMR (CDCl3, 300 MHz, ppm) δ : 7.69 – 7.34 (m, 4H, Aromatic)

4-Hydroxy-3-methoxybenzonitrile: CN

HO

OMe

Molecular formula: C8H7NO2


Mp : 84 0C

IR (KBr, cm-1

) ν : 3226, 3028, 2225, 1028 1H NMR (CDCl3, 300 MHz, ppm) δ : 7.26 – 6.95 (m, 3H, Aromatic), 6.06 (s,

1H, OH), 3.93 (s, 3H, OCH3)

MS (m/e) : 150 [M+1]

3.6.1 Spectra

Table 3.7: FTIR, 1H NMR and Mass spectra of selected compounds.

Sr.

No.

Spectra

1 FTIR of N-p-Tolyacetamide

2 1H NMR of N-p-Tolyacetamide

3 Mass of N-p-Tolyacetamide

4 FTIR of N-(Naphthalene-6-yl) acetamide

5 1H NMR of N-(Naphthalene-6-yl) acetamide

6 Mass of N-(Naphthalene-6-yl) acetamide

7 FTIR of 4-Hydroxy-3-methoxybenzonitrile

8 1H NMR of 4-Hydroxy-3-methoxybenzonitrile

9 Mass of 4-Hydroxy-3-methoxybenzonitrile

Chapter 3

71

Chapter 3

72

Chapter 3

73

Chapter 3

74

Chapter 3

75

Chapter 3

76

Chapter 3

77

Chapter 3

78

Chapter 3

79

Chapter 3

80

3.7 References

1. (a) Gawly, R. E. Org. React. 1988, 35, 1. (b) Smith, M. B.; March, J. Advanced

Organic Chemistry, 5th

Ed.; John Wiley and Sons, New York, 2001, 1415 and

references therein. (c) Beckmann, E. Chem. Ber. 1886, 89, 988.

2. Humphrey, J. M.; Chamberlin, A. R. Chem. Rev. 1997, 97, 2243.

3. (a) Cupido, T.; Tulla-Puche, J.; Spengler, J.; Albericio, F. Curr. Opin. Drug

Discovery Dev. 2007, 10, 768. (b) Bode, J. W. Curr. Opin. Drug Discovery Dev.

2006, 9, 765.

4. (a) Han, S.-Y.; Kim, Y.-A. Tetrahedron 2004, 60, 2447. (b) Montalbetti, C. A.

G. N.; Falque, V. Tetrahedron 2005, 61, 10827. (c) Valeur, E.; Bradley, M.

Chem. Soc. Rev. 2009, 38, 606.

5. (a) Martinelli, J. R.; Clark, T. P.; Watson, D. A.; Munday, R. H.; Buchwald, S.

L. Angew. Chem., Int. Ed. 2007, 46, 8460. (b) Park, J. H.; Kim, S. Y.; Kim, S.

M.; Chung,Y. K. Org. Lett. 2007, 9, 2465. (c) Cho, S. H.; Yoo, E. J.; Bae, L.;

Chang, S. J. Am. Chem. Soc. 2005, 127, 16046. (d) Cao, L.; Ding, J.; Gao, M.;

Wang, Z.; Li, J.; Wu, A. Org. Lett. 2009, 11, 3810. (e) Gnanamgari, D.;

Crabtree, R. H. Organometallics 2009, 28, 922.

6. Constable, D. J. C.; Dunn, P. J.; Hayler, J. D.; Humphrey, G. R.; Leazer, J. L.;

Linderman, R. J.; Lorenz, K.; Manley, J.; Pearlman, B. A.; Wells, A.; Zaksh, A.;

Zhang, T. Y. Green Chem. 2007, 9, 411.

7. (a) Hili, R.; Yudin, A. K. Nat. Chem. Biol. 2006, 2, 284. (b) Kleeman, A.;

Angel, J. Pharmaceutical Substances: Syntheses, Patents, Applications, 4th

ed.;

Georg Thieme: Stuttgart, 2001. (c) Barton, D. H. R., Nakanishi, K., Meth-Cohn,

O., Eds; Comprehensive Natural Products Chemistry Vol. 4; Elsevier: Oxford,

1999. (d) Craig, P. N. Comprehensive Medicinal Chemistry; Drayton, C. J., Ed.;

Pergamon Press: New York, 1991.

8. (a) Kondo, K.; Kan, K.; Tanada, Y.; Bando, M.; Shinohara, T.; Kurimura, M.;

Ogawa, H.; Nakamura, S.; Hirano, T.; Yamamura, Y.; Kido, M.; Mori, T.;

Tominaga, M. J. Med. Chem. 2002, 45, 3805. (b) Kondo, K.; Ogawa, H.;

Yamashita, H.; Miyamoto, H.; Tanaka, M.; Nakaya, K.; Kitano, K.; Yamamura,

Y.; Nakamura, S.; Onogawa, T.; Mori, T.; Tominaga, M. Bioorg. Med. Chem.

1999, 7, 1743.

9. Mehta, N.; Aggarwal, S.; Thareja, S.; Malla, P.; Misra, M.; Bharadwaj, T. R.;

Chapter 3

81

Kumar, M. Int. J. Chem Tech Res. 2010, 2 (1), 233.

10. Cocco, M. T.; Congiu, C.; Onnis, V.; Morell, M.; Cauli, O. Eur. J. Med. Chem.

2003, 38, 513.

11. Colwell, W. T.; Lange, J. H.; Henry, D. W. J. Med. Chem. 1968, 11, 749.

12. Movassaghi, M.; Hill, M. D. J. Am. Chem. Soc. 2006, 128, 14254.

13. Nicolaou, K. C.; Baran, P. S.; Zhong, Y. L.; Barluenga, S.; Hunt, K. W.; R.

Kranich, Vega, J. A. J. Am. Chem. Soc. 2002, 124, 2233.

14. Samii, Z. K. A. E.; Ashmawy, M. I. A.; Mellor, J. M. Tetrahedron Lett. 1987,

28, 1949.

15. Friedrich, K.; Wallensfels, K. ‘The Chemistry of Cyano Group’ Rappoport Z,

Ed., Wiley-Interscience, New York, 1970.

16. Fatiadi, A. J.; Patai, S.; Rappaport, Z. ‘Preparation and Synthetic Applications

of Cyano Compounds’, Wiley-Interscience, New York, 1983.

17. Graham, D.; Pereira, R.; Barfield, D.; Cowan, D. Enzyme Microb. Technol.

2000, 26, 368.

18. Mowry, D. T. Chem. Rev. 1948, 42, 189.

19. Bandyopadhyay, D.; Velazquez, J. M.; Banik, B. K. Org. and Med. Chem. Lett.

2011, 1:11.

20. Aggarwal, R.; Kumar, V.; Kumar, R.; Singh, S. P. Beilstein J. Org. Chem. 2011,

7, 179.

21. Prasad, A. S.; Satyanarayana, B. Der Pharma Chemica 2012, 4(1), 93.

22. Hafiz, I. A.; Ramiz, M. M. M.; Mahmoud, F. F.; Darwish, E. S. J. Chem. Sci.

2008, 120, 339.

23. Moghadam, M.; Mirkhani, V.; Tangestaninejad, S.; Mohammadpoor-Baltork, I.;

Kargar, H. J. Iran. Chem. Soc. 2009, 6, 251.

24. (a) Yazawa, H.; Tanaka, K.; Kariyone, K. Tetrahedron Lett. 1974, 15(46), 3995.

(b) Wang, W.-B.; Restituyo, J. A.; Roskamp, E. J. Tetrahedron Lett. 1993,

34(45), 7217.

25. (a) Gregory, B. J.; Modooie, R. B.; Schofield, K. J. Chem. Soc. B 1970, 2, 338.

(b) Guy, A.; Gutte, J. P.; Long, G. Synthesis 1980, 3, 222. (c) Eaton, P. E.;

Carison, G. R.; Lee, J. T. J. Org. Chem. 1973, 38, 4071.

26. (a) Hashimoto, M.; Obora, Y.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2008, 73,

2894. (b) Li, D.; Shi, F.; Guo, S.; Deng, Y. Tetrahedron Lett. 2005, 46, 671. (b)

Chapter 3

82

Ronchin, L.; Vavasori, A. J. Mol. Catal. A: Chem. 2009, 313, 22.

27. (a) Iranpoor, N.; Firouzabadi, H.; Aghapour, G. Synth. Commun. 2002, 32,

2535. (b) Antikumar, S.; Chandrasekhar, S. Tetrahedron Lett. 2000, 41, 5427.

(c) Ren, R. X.; Zueva, L. D.; Ou, W. Tetrahedron Lett. 2001, 42, 8441.

28. (a) De Luca,L.; Giacomelli, G.; Porcheddu, A. J. Org. Chem. 2002, 67, 6272.

(b) Arisawa, M.; Yamaguchi, M. Org. Lett. 2001, 3, 311. (c) Boruah, M.;

Konwar, D. J. Org. Chem. 2002, 67, 7138. (d) Yan P.; Batamack P.; Prakash G.

K.; Olah G. A. Catalysis Letter 2005, 103(3-4), 165.

29. (a) Boero, M.; Ikeshoji, T.; Liew, C. C.; Terakura, K.; Parrinello, M. J. Am.

Chem. Soc. 2004, 126, 6280. (b) Ikushima, Y.; Hatakeda, K.; Sato, M.; Sato, O.;

Arai, M. Chem. Commun. 2002, 19, 2208. (c) Ikushima, Y.; Hatakeda, K.; Sato,

O.; Yokoyama, T.; Arai, M. Angew. Chem. Int. Ed. 1999, 38, 2910.

30. (a) Guo, S.; Du, Z.; Zhang, S.; Li, D.; Li, Z.; Deng, Y. Green Chem. 2006, 8,

296. (d) Betti, C.; Landini, D.; Maia, A.; Pasi, M. Synlett 2008, 908.

31. (a) Forni, L.; Fornasari, G.; Giordano, G.; Lucarelli, C.; Katovic, A.; Trifiro, F.;

Perri, C.; Nagy, J. B. Phys. Chem. Chem. Phys. 2004, 6, 1842. (b) Mao, D.; Lu,

G.; Chen, Q. Appl. Catal. A 2005, 279, 145. (c) Dongare, M. K.; Bhagwat, V.

V.; Ramana, C. V.; Gurjar, M. K. Tetrahedron Lett. 2004, 45, 4759. (d) Kim, S.

J.; Jung, K. D.; Joo, O. S.; Kim, E. J.; Kang, T. B. Appl. Catal. A 2004, 266,

173.

32. Ruben, S. R.; Johann, B.; Silvia, D. G.; Nicolas, M.; Steven, P. N. J. Org.

Chem. 2010, 75, 1197.

33. Furuya, Y.; Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc. 2005, 127, 11240.

34. Ramalingan, C.; Park, Y.-T. J. Org. Chem. 2007, 72, 4536.

35. Li, Z.; Lu, Z.; Zhu, A.; Feng, X.; Liu, J.; Tian, G. Catal. Lett. 2008, 120, 100.

36. Liu, X.; Xiao, L.; Wu, H.; Li, Z.; Chen, J.; Xia, C. Catal. Commun. 2009, 10,

424.

37. Yadav, L. D. S.; Garima, ; Srivastava, V. P. Tetrahedron Lett. 2010, 51, 739.

38. Yadav, L. D. S.; Rajesh, P.; Vishnu, P. S. Synthesis 2010, 11, 1771.

39. Liu, L. F.; Liu, H.; Pi, H. J.; Yang, S.; Yao, M.; Du, W.; Deng, W. P. Synth.

Commun. 2011, 41, 553.

40. (a) Mona, H. S. Synthesis 2005, 5, 787. (b) Goffredo, R.; Graziano, B.;

Sandro, C. J. Org. Chem. 1973, 38, 1060. (c) Kokare, N. D.; Shinde, D. B.

Chapter 3

83

Monatsh Chem. 2009, 140, 185. (d) Kiasat, A. R.; Kazemi, F. Phosphorus,

Sulfur and Silicon, 2003, 178, 1377. (e) Kusurkar, R. S.; Naik, N. H.; Naik, P.

N. Synth. Commun. 2008, 38, 1952. (f) Tomami, B.; Kiasat, A. R. J. Chem. Res.

(S), 1999, 444.

41. (a) Kazemi, F.; Kisat, A. R.; Fadavipoor, E. Phosphorus, Sulfur and Silicon,

2004, 179, 433. (b) Chaudhari, S. S.; Akamanchi, K. G. Synth. Commun. 1999,

29, 1741. (c) Kazemi, F.; Kiasat, A. R.; Javeherian, M. Ind. J. Chem. 2005, 44B,

1954.

42. (a) Sosnovsky, G.; Krough, J. A. Synthesis 1978, 703. (b) Ho, T. L.; Wong, C.

M. Synth. Commun. 1975, 5, 423. (c) Dulcere, J. P. Tetrahedron Lett. 1981, 22,

1599.

43. Fatiadi, A. J. „The Chemistry of Triple-Bonded Functional Group, Part 2‟, Ed

by Patai, S. and Rappoport, Z. John Wiley and sons, New York, 1983.

44. Stevens, T. E. J. Org. Chem. 1961, 26, 2531.

45. Pakusch, J.; Ruchardt, C. Chem. Ber. 1991, 124, 971.

46. Harrison, I. T.; Harrison, S. „Compendium of Organic Synthetic Methods‟,

Interscience Publishers, New York, 1971, Vol. I, 457 and 1972, Vol. II, 185.

47. Olah, G. A.; Narang, S. C.; Garcia-Luna, A. Synthesis 1980, 659.

48. Vowinkel, E.; Bartel, J. Chem. Ber. 1974, 107, 1221.

49. Binoy, J.; Sulatha, M. S.; Madhavan, P. P.; Prathapan, S. Synth. Commun. 2000,

30, 1509.

50. Miller, M.; Loudon, G. A. J. Org. Chem. 1975, 40, 126.

51. Fizet, C.; Streith, J. Tetrahedron Lett. 1974, 15, 3187.

52. Sosnovsky, G.; Krogh, J. A.; Umhoefer, S. G. Synthesis, 1979, 722.

53. Olah, G. A.; Keumi, T. Synthesis, 1979, 112.

54. Zhu, C.; Ji, L.; Wei, Y. Synthesis 2010, 3121.

55. Pasha, M. A.; Nizam, A. Indian J. Chem. 2010, 49B, 1127.

56. Hoelz, L. W.; Goncalves, B. T.; Barros, J. C.; Silva, J. F. M. Molecule 2010, 15,

94.

57. Jiang, N.; Ragauskas, J. Tetrahedron Lett. 2010, 51, 4479.

58. Yang, S. H.; Chang, S. Org. Lett. 2001, 3, 4209.

59. Lee, K.; Han, S-B.; Yoo, E-M.; Chung, S-R.; Oh, H.; Hong, S. Synth. Commun.

2004, 34, 1775.

Chapter 3

84

60. Saini, A.; Kumar, S.; Sandhu, J. S. Indian J. Chem. 2005, 44B, 1427.

61. Gucma, M.; Golebiewski, M. Synthesis 2008, 13, 1997.

62. Singh, M. K.; Lakshman, M. K. J. Org. Chem. 2009, 74, 3079.

63. Saha, D.; Saha, A.; Ranu, B. C. Tetrahedron Lett. 2009, 50, 6088.

64. Rad, M. N. S.; Nezhad, A. K.; Behrouz, S.; Amini, Z.; Behrouz, M. Synth.

Commun. 2010, 40, 2429.

65. Li, Y. T.; Liao, B. S.; Chen, H. P.; Liu, S. T. Synthesis 2011, 16, 2639.

66. Rad, M. N. S.; Behrouz, S.; Nekoei, A. R. Synlett 2012, 23, 1191.

67. (a) Reichardt, C. Solvents and Solvent Effects in Organic Chemistry, VCH,

Weinheim, Germony, 1988. (b) Li, C. J. Chem. Rev. 1993, 93, 2023. (c) Li, C. J.

Organic Reactions in Aqueous Media, Wiley, New York, 1997. (d) Lindstrom,

U. M. Chem. Rev. 2002, 102, 2751.

68. (a) Kazuya, Y.; Hiroshi, F; Yoshiyuki, O; Miyuki, K.; Noritaka, M. Angew.

chem. Int. Ed. 2007, 46, 3922. (b) Sarvari, MH. Synthesis 2005, 787. (c) Yan,

P.; Butamack, P.; Prakash, G.; Olah, G. Catal. Lett. 2005, 101, 141.

69. Handbook of fine chemicals, Aldrich Advancing Science 2011.

70. (a) Vogels Textbook of Practical Organic Chemistry; Fifth Edition; Pearson

Education. (b) Thakur, A. J.; Boruah, A.; Prajapati, D.; Sandhu, J. S. Synth.

Commun. 2000, 30, 2105.

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