Approaches to bridged annulenes using both classical and reactive intermediates: the synthesis of the first diatropic bridged thiaannulene and several fused dihydropyrenes

APPROACHES TO BRIDGED ANNULENES USING BOTH CLASSICAL

AND REACTIVE INTERMEDIATES. THE SYNTHESIS OF THE FIRST

DIATROPIC BRIDGED THIAANNULENE AND SEVERAL FUSED

DIHYDROPYRENES

by

V IV E K A N A N TA N S. H E R

B.Sc., M adurai Kam araj University, IN D IA 1984 M.Sc., Indian In s titu te o f Technology, Bombay, IN D IA 1986

A Dissertation Submitted in P a rtia l F u lfilm e n t o f the Requirements for the Degree of

DOCTOR OF PHILOSOPHY

ill the Departm ent of Chemistry We accept this dissertation as conforming

to the required standard

Dr. R. H. M itchell Dr. A. Fischer

Dr. T. M. Fyles Dr. E. E. Ishiguro

Dr. R. V. W illiam s

© VIVEKANANTAN S. IYER,

1994 U niversity o f Victoria

A ll rights reserved. This disserta tio n may not he reproduced in whole or in part, by m im eograph or by any other m eans w ithout the perm ission o f the author.

Supervisor: Professor Dr. R. H. Mitchell

ABSTRACT

The successful synthesis of the first bri~ged thia[13]annulene, trans-9b,9c-dimethyl-9b,9c-dihydrophenyleno[l,9-bc)thiophene, 120, was achieved in 11 steps, starting from 3-methylthiophene,

111.

Using the external and internal proton chemical shifts of 120, it was shown unambiguously to be the first diatropic bridged thia annulene. From the proton chemical shifts of 120, its diatropicity was estimated to be about 35-40% that of dimethyldihydropyrene 12. Synthesis of the potential intermediate 2,4-bis(bromomethyl)-3-methylthiophene, 110, is expected to lead to syn these;, of a variety of new bridged annulenes.

Synthesis of the quasi-biphenyiene, 155, was attempted. The precursor to 155,

1,3-bis(methoxymethyl}-2-methylbiphenylene, 170, was synthesised from 1,2-dibromobenzene, 82, in 4 steps. Attempts to convert 170 into the corresponding dibromide were unsuccessful.

The synthesis of

trans-14b,14c-dimethyl-14b,14c-dihydro-benzo[l",2":3,4]cycloLata[l,2-b]naphtho[2,1,8-fgh:,mthracene, 192, was achieved from the oxa[l 7]annulene 63. A detailed nmr analysis of 192. was made using lD and 2D nmr techniques together with a bond order-chemical shift correlation for 192. From the 1

Hnmr data of 1S2, using Mitchell's method, the diatropicity of biphenylene was estimated to be 50-55% that of benzene.

The adduct 209, from cycloheptatriene and oxa[l 7)annulene 63, was obtained in in 60% yield, but attempted dehydration/deoxygenation reactions were unsuccessful. The cyclopropene adduct 224, was obtained in 41% yield from the oxa[l 7iannulene

63. Attempted synthesis of the benzocyclopropene fused dihydropyrene 218 gave partial success. The proton nmr data obtained frora the reaction mixture seem to indicate the lack of Mills-Nixon effect in benzocyclopropene, 181.

Some attempted reactions of the dihydropyryne 62, did not yield any of the expected products.

A new synthesis of symmetrical 1,2-diketones from Grignard reagents was developed. 1,2-Bis(2'-methyl-3'-methoxymethylphenyl)ethanedione, 241, was synthesised using this method. anti-9,25-Dimethylquinoxalino[l0,ll-b]-2-thia[2.3]metacyclophane-l0-ene, 287, was synthesi·md from the c'iketone 241.

An

X-Ill

ray crystal dete1mination showed its anti geometry. The unstable trnns-14c,14d-dimethyl-14c,14d-dihydrotribenzo[abc]phenazine, 279, was synthesised from the thiacyclophane 287. The proton nmr spectrum of 279, revealed its similarity to the naphtho[e]dihydropyrene 58.

From the proton chemical shifts of 279, the diatropicity of quinoxaline was estimated to be the same as that of naphthalene.

The teraryl 281 and the thiophene dioxide 296 were symhesis12d Exploratory moJel reactions of 296, resulted in various teraryls. Complexation of the thiophene dioxide 296 resulted in the complex 297. An X-ray crystal determination of 297

showed it have a syn geometry. Barrier to rotation in the teraryls obtained in this work was studied by variable temperature nmr. The results are rationalised in terms of varying ring size of arenes.

Examiners:

Dr. R. H. Mitchell, Supervisor (Department of Chemistry)

DZ.

Fi~cher,

Department member (Department of Chemistry) Dr. T. M. Fyles, Department member (Department of Chemistry)

Dr.

E.

E. Ishiguro, Out3ide member (Department of Biochemistry and Microbiology)

;;;/

TABLE OF CONTENTS

A b s tra c t ii Table o f co ntents iv L is t o f T ables ix L is t o f F ig u re s x L is t o f a b b re v ia tio n s xii A ckn o w le d ge m e n ts xiv D e d ica tio n xv

CHAPTER ONE

INTRODUCTION

1.1 P rologue 1

1.2 D e te c tio n o f a ro m a tic ity 5

1.2.1 R in g c u rre n t th e o ry and a ro m a tic ity 9

1.2.2 Resonance and a ro m a tic ity 16

1.3 E s tim a tio n o f a ro m a tic ity 18

1.3.1 M itc h e ll’s m ethod o f e s tim a tio n o f a ro m a tic ity 21

1.3.1.1 B e n z a n n e la tio n stu d ies on D M D H P 23

1.4 S y n th e tic ro u te s to D M D H P and its d e riv a tiv e s 33

1.4.1 The d ith ia c y c lo p h a n e ro u te 33

1.4.2 T he d ih y d ro p y re n e /o x a [ 171 a n n u le n e ro u te 35

V

CHAPTER TWO

SY N TH ESES U SIN G THE DITHIACYCLOPHANE STRATEGY

2.1 In tro d u c tio n 39

2.2 B ro m o m e th y la tio n o f arenes 40

2.3 Search fo r a 1 ,2 ,3 -su b stitu te d sy n th o n 43

2.4 S yn th e sis o f 2,4 -b is(b ro m o m e th y l)-3 -m e th y lth io p h e n e , 110 46 2.5 S yn th e sis o f th e f ir s t d ia tro p ic b rid g e d th ia a n n u le n e 50

2.5.1 S yn th e sis o f th e d ith ia cyclop h a n es,

123

53

2.5.2 a n £ i-9 ,1 7 -D im e th y l-2 ,ll-d ith ia [3 ]m e ta c y c lo [3 ](2 ,4

)-th io p h e n o p h a n e 54

2.5.3 S yn th e sis o f £rans9b 9 c D im e th yl9 b ,9 cd ih yd ro p h e n yle n o

-[l,9 -b c ]th io p h a n e ,

120

57

2.5.4 T he f ir s t d ia tro p ic b rid g e d th ia a n n u le n e 60

2.5.4.1 In tro d u c tio n 60

2.5.4.2 U V -V is s p e c tru m o f

120

63

2.5.4.3 N M R spectra o f th e th ia a n n u le n e ,

120

65

2.5.4.4 A lo o k a t v ic in a l c o u p lin g constants, geom etries and com parison

w it h o th e r b rid g e d h e teroannulenes 70

2.5.4.5 E s tim a tio n o f d ia tro p ic ity in th e th ia [ 13]a n n u le n e

120

75 2.5.

4.6

C o m p a riso n o f th e d ia tro p ic ity o f

120

w it h o th e r

h e te ro -D M D H P s 81

110

83 2.7 A tte m p te d syn th e sis o f the q u a s i-b ip h e n yle n e

157

86

2.7.1 In tro d u c tio n 86

2.7.2 R e tro s y n th e tic analyses fo r

157

86

2.7.3 S yn th e sis o f l,3 -b is (m e th o x y m e th y l)-2 -m e th y lb ip h e n y le n e 89 2.7.4 A tte m p te d syn th e sis o f th e b is-brom ides

159

91

2.8 T hio ph e n e-1 ,1-d io xid e s in syntheses 93

2.9 S u m m a ry 95

CHAPTER THREE

SY N TH ESES U SIN G REACTIVE INTERM EDIATES

3.1 In tro d u c tio n 96

3.2 S yntheses u s in g o xa [1 7 ]a nn u len e 98

3.2.1 S yn th e sis o f th e b ip h e n yle n e fused D M D H P ,

192

98

3.2.1.1 S tru c tu re o f th e a d d u c t

191

99

3.2.1.2 A tte m p te d d e h y d ra tio n re a ction s on

191

103 3.2.1.3 S yn th e sis o f tra ils - 14b, 14c-dim e th yl- 14b,

14c-dihydrobenzo-[ 1" ,2": 3,4] cyclobuta14c-dihydrobenzo-[ 1,2-b] n a ph tho 14c-dihydrobenzo-[2,1,8-fgh] anth race n e

,1 9 2

104 3.2.1.4 P ro p e rtie s o f th e b ip h e n y le n o D M D H P

192

106

3.2.1.5 l3C n m r s p e c tru m o f

192

108

vii

3.2.1.7 C o u p lin g constant-bond o rd er c o rre la tio n s in

192

114 3.2.1.8 E s tim a tio n o f d ia tro p ic ity o f b ip h e n yle n e fro m

192

120 3.2.2 A tte m p te d synth e sis o f th e m e th a n o l 10]a n n u le n o

-D M -D H P

208

125

3.2.2.1 A tte m p te d synth e sis o f th e c y d o p ro p a b e n z o [a ]D M D H P 129

3.3 S yntheses u s in g arynes 137

3.4 S u m m a ry 140

CHAPTER FOUR

SY NTH ESES U SIN G CLASSICAL INTERM EDIATES - APPRO ACH ES

TO [e]-ANNELATED D M D H Ps

4.1 In tro d u c tio n 141

4.2 M o d el stu d ies u s in g 2 ,6 -dichlorotoluene 143

4.3 S earch fo r a d ire c t syn th e sis o f 1,2-diketones 147

4.4 A ne w syn th e sis o f s y m m e tric a l 1,2-diketones 149 4.4.1 S yn th e sis o f l,2 -b is (3 ’-m e th o x y m e th y l-2 ’-m e th y lp h e n y

l)-e th anl)-edionl)-e,

241

152

4.5 S ig n ifica n ce o f th e d ike to n e s y n th o n

241

154 4.5.1 1,2-D iketones in th e synthesis o f v a rio u s a ro m a tic rin g s 154 4.5.2 Some m odel r in g syntheses u s in g th e dione

249

156 4.6 U t i li t y o f th e 1,2-diketone-synthesis

4.6.1 S tru c tu re o f th e th ia cyclo p h a n e 287 162

4.6.2 S yn th e sis o f th e d ih y d ro p y re n e

279

109

4.6.3 'H m n r sp e ctru m o f th e d ih y d ro p y re n e

279

and com parison w ith

th e n a ph tho [e ] d ih y d ro p y re n e 58 171

4.7 Syntheses u s in g th io ph e n e -1 ,1-d io xid e - F o rm a tio n

and some re a ctio n s o f th e th io p h e n e d io xid e

296

176

4.8 B a r r ie r to r o ta tio n in o -te ra ry ls 181

4.8.1 In tro d u c tio n 181

4.8.2 R o ta tio n a l is o m e rs im and e x p e rim e n ta l e s tim a tio n 182

4.9 S u m m a ry 188

5

CO NCLUSIONS

180

6

EXPERIM ENTAL

208

R E FE R E N C E S

254

ix

LIST OF TABLES

Table page

1 'H n m r chem ical s h ifts o f selected annulenes. 11

2 R E P E (in (3 u n its ) o f some selected conjugated com punds 19

3 C a lc u la tio n s o f th e RE o f benzene (kca l/m ol) 20

4 RE o f some heterocycles fro m th e rm o ch e m ica l d a ta in k c a l/m o l 23 5 C he m ica l s h ifts o f in te r n a l CH., p rotons fo r s u b titu te d D M D H P . 25 7 P re d icted and observed in te r n a l m e th y l p ro to n chem ical s h ifts

o f some fused D M D H P s. 28

8 C o m p a rison o f th e longest Xm.ix o f

120

and re la te d annulenes 65 9 C h e m ica l s h ifts o f H a and CH., o f seme th ia a n n u le n e s . 69 10 C o m p a riso n o f J A/ J B ra tio s o f

141

and re la te d system s 72 11 C o m p a rison o f some M M re s u lts and J A/J B r a tio o f

120, 63

and

12

74 12 C o u p lin g c o n s ta n t and bond order d a ta fo r com pound

120

78 13 C o m p a rison o f d ia tro p ic itie s o f

12, 1L0, 63

and

33,

fro m

th e chem ical s h ifts o f th e ir e x te rn a l and in te r n a l p ro to n s 82 14 C o m p a rison o f 13C chem ical s h ifts o f

47, 12, 192

and

49

111 15 C o m p a riso n o f tc-S C F bond orders and bond orders

d e rive d fro m ,3J ’s 116

16 C o u p lin g co n sta n t, bond o rd e r and chem ical s h ift d a ta fo r com pound

18 C o m p a riso n o f d e v ia tio n s in angles in cyclophanes 287, 288, 289

and

290

166

19 C o m p a riso n o f to rs io n a l angles in

287, 291,292

and

288

168 20 C o m p a riso n o f p re d icte d and observed chem ical s h ifts of 58 and

279

174 21 C o u p lin g constants, Bond orders and calculated C he m ica l s h ifts

fo r

279.

175

22 T h e rm o d y n a m ic d a ta fo r th e b a rrie r to ro ta tio n in

3’,3 "-d ich lo ro -2 ,,2 "-d im e th y l-o -te ra ry ls 185

LIST OF FIG U R ES

F ig u re page

1 In d u ce d r in g c u rre n t and p ro to n m ag ne tic

d e s h ie ld in g in benzene. 10

2 Selected bond le n g th s and bond angles in D M D H P , 12. 22

3 Space f illin g m odel o f D M D H P ,

12.

22

4

250 M H z 'H n m r s p e c tru m o f

123a.

55

5 O R T E P d ia g ra m o f an X -ra y s tru c tu re o f

123a.

55

6 U V -V is s p e c tru m o f

120

in cyclohexane. 64

8a 8b 9

10

11 12 13 14 15 16 17 18 18a 19

20

21 22 23 24 25 26 27

xi

P ro to n co u p lin g constants in th e b rid g e re g io n o f 191. 100 D e fin itio n o f d ih e d ra l angle betw een H a and H b in 191. 100

S tru c tu re o f exo-191. 101 S tru c tu re o f endo-191. 101 U V -V is s p e c tru m o f 192 in cyclohexane. 107 "!C -'H H e tC o rr s p e c tru m o f 192 (a ry l region). 109 360 M H z ’H n m r sp e ctru m o f 192 (a ry l region). 113 C O S Y -H s p e ctru m o f 192 (a ry l region). 114 ’H n m r sp e ctru m o f th e adducts 209-211. 127

'IJ iu n r sp e ctru m o f th e adducts 224. 134

’H n m r s p e ctru m o f th e pro du cts fro m re a c tio n o f 224 w it h T i(0 ). 135

'H n m r sp e ctru m o f 241. 154

’ ’C n m r sp e ctru m o f 241. 154

250 M H z 'H n m r s p e ctru m o f 287. 163

O R T E P d ia g ra m o f an X -ra y s tru c tu re o f 287. 164

D e s c rip tio n o f a, (3, d, and d2. 166

P la n e p ro je c tio n o f th e in te r n a l m e th y l onto th e opposite rin g . 167

250 M H z 'H n m r s p e ctru m o f 279. 172

'H n m r d a ta o f 279 and 58. 173

O R T E P d ia g ra m o f a n X -ra y s tru c tu re o f 297. 178

F lip p in g processes in o -te ra ry ls . 184

A r, Aroxn a ro m a tic rin g bp b o ilin g p o in t n -B u L i /z -b u ty llith iu m £-Bu £-butyl CDC1;! ch lo ro fo rm -d C D 2C12 d ic h lo ro m e th a n e -d 2 l,!C n m r ca rb o n -13 n u c le a r m agnetic resonance m -C P B A m -chloroperoxybenzoic acid

decomp. decom position

D IB A H d iis o b u ty la lu m in iu m h y d rid e D M F d im e th y lfo rm a m id e D M S O d im e th y ls u lfo x id e E tO H e th a n o l ‘H n m r p ro to n m a g n e tic resonance IR in fra re d sp e ctru m

L iT M P lit h iu m 2 ,2 ,6 ,6 -te tra m e th y lp ip e rid e L D A lit h iu m d iis o p ro p y la m id e

M e m e th y l

M e O H m e th a n o l

M S mass sp e ctru m

C l chem ical io n is a tio n

E l e le ctron im p a c t N M P l-m e th y l-2 -p y rro lid in o n e N M R n u c le a r m a g n e tic resonance s s in g le t d d o u b le t t tr ip le t dd d o u b le t o f doublets m m u ltip le t p p m p a rts pe r m illio n P h p h e n y l RE resonance energy

REPE resonance energy per electron

T H E te tra h y d ro fu ra n

T M E D A N ,N ,N ,N -te tra m e th y le th y le n e d ia m in e U V u ltr a v io le t sp e ctru m

ACKNOWLEDGEMENTS

I w o u ld lik e to express m y sincere th a n k s to P rofessor R. H . M itc h e ll f ir s t fo r in tro d u c in g me to th e c h e m is try o f annulenes and cyclophanes and secondly th e fre e d om to explore v a rio u s aspects o f th is c h e m is try d u rin g m y s ta y here. I am also v e ry g ra te fu l to P rofessor M itc h e ll fo r h is encouragem ent, patience and s u p p o rt d u rin g th e course o f th is w o rk .

I w is h to th a n k P rofessor W . J. B a lfo u r fo r re a d in g and co rre c tin g p a r t o f th is th e sis and h is k in d h e lp d u rin g the fin a l year.

I a m g ra te fu l to m a n y fa c u lty m em bers o f th is d e p a rtm e n t fo r th e ir encouragem ent and h e lp , in p a rtic u la r: Professor T . E. G ough fo r h is tim e ly rescues. D r T. W . D in g le fo r c a lc u la tin g th e rc-SCF bond orders re p o rte d in th is th e s is and P rofessor A. F isch e r fo r some v a lu a b le discussions d u rin g th e

e a rly p a r t o f th is w o rk . I w o u ld lik e to th a n k M rs. C. G reenw ood fo r h e r h e lp in re c o rd in g th e n m r spectra, D r. D. M c G illiv ra y fo r re c o rd in g th e m ass spectra and K . A . B eve rid g e fo r th e X -ra y d e te rm in a tio n s .

I a m g ra te fu l to th e U n iv e rs ity o f V ic to ria and th e d e p a rtm e n t o f

c h e m is try fo r th e fin a n c ia l s u p p o rt w h ic h fin a n ce d m y s tu d y a t th is U n iv e rs ity . I a m v e ry th a n k fu l to a ll m y frie n d s and colleagues fo r t h e ir h e lp and su p po rt.

I w o u ld also lik e to express m y g ra titu d e to a ll m y fa m ily fo r th e ir

XV

To m y m o th e r

CHAPTER ONE

INTRODUCTION

1.1 P r o lo g u e

A ro m a tic compounds c o n s titu te a broad class o f chem icals and are connected to a w id e range o f topics, s ta rtin g fro m th e che m ica l e vo lu tio n o f lif e 1 to c a rc in o g e n ic ity .2 Yet, a ro m a tic ity is one o f th e m o s t d if f ic u lt and h ard to d efine concepts am ong bonding theories. A fte r th e disco ve ry o f benzene by F a ra d a y in 1825,3 and the subsequent g ro w th o f the c h e m is try o f benzene d e riv a tiv e s , the d e fin itio n o f a ro m a tic ity has undergone several changes.'*"’’ K e k u le ’s in t u it iv e idea o f the s tru c tu re o f benzene and its d e riv a tiv e s ,6 gave some u n d e rs ta n d in g o f the c o n s titu tio n o f these com pounds, a n d g re a tly aided th e in v e n tio n o f new dyes w hich helped th e e s ta b lis h m e n t o f several chemical in d u s trie s based on coal-tar.

A ro m a tic compounds, though th e y fa ll u n d e r th e broad category o f u n s a tu ra te d com pounds, have several d is tin c t c h a ra c te ris tic s such as h ig h e r th e rm a l s ta b ility and low e r chem ical re a c tiv ity . H tic k e l’s m o le c u la r o rb ita l (H M O ) th e o ry m ade the fir s t successful a tte m p t to a cco un t fo r such s ta b ility based on th e ir 7t-electron c o n fig u ra tio n .7 A cco rd in g to H iic k e l th e o ry , p la n a r, m onocyclic, conjugated molecules h a v in g (4n+2) 7r-electrons (w here n is an

2

stable th a n a conjugated acyclic polyene. I t follow s fro m th is p re d ic tio n th a t the m olecules w hich do not sa tisfy a ll three c rite ria , n a m e ly p la n a rity , fu lly conjugated rc-electrons and monocyclic, w ill be o f in te rm e d ia te s ta b ility . L a te r, the p la n a r, m onocyclic, conjugated m olecules w ith (4n+2) ^-electrons were term ed as a ro m a tic, those w ith (4n) ^-electrons as a n tia ro m a tic and the rest n o narom atic.

T he p o p u la rity o f H M O th e o ry am ong s y n th e tic chem ists led to the syntheses o f several n o n -n a tu ra l cyclic system s such as tro p y liu m c a tio n ,s cycloo ctate tra en yl d ia n io n 9 and several n e u tra l system s. Such m olecules, e.g., 2-6, a lo n g w ith know n compounds, lik e benzene i , w ere fou n d to behave in accordance w ith H M O theory. The 4rc-system, cyclob u ta d ien e ,

7,

was shown to be h ig h ly reactive and could no t be stu d ied u n d e r n o rm a l c o n d itio n s .10 O n ly re ce ntly, u n d e r special su rro u n d in g s, could a 'H n m r s p e c tru m o f

7

be obtained a t room te m p e ra tu re .11

\z J

1

₂

3

6

C o n fo rm a tio n a l m o b ility in the case o f la rg e r cyclic com pounds, called the a nnulenes, such as the [10 ]a n n ule n e 8 (th e n u m b e r 10 refers to the n u m b e r o f p e rip h e ra l atom s in th e rin g ) and the [1 4 ]a n n u le n e 9, renders them n o n -p la n a r a t n o rm a l te m p e ra tu re and hence n o n -a ro m a tic .12 T h is problem was overcom e in tw o d iffe re n t ways. One approach was due to S ondheim er and N aka g a w a , who in tro d u ce d large s u b s titu e n ts and tr ip le bonds to m ake the la rg e a n n u le n e rin g s rig id and p la n a r.13 F o r exam ple, th e annulenes 10 and 11 are a ro m a tic.

f

I

r ^ H H S

II

10

11

The o th e r approach was th ro u g h th e e ffo rts o f B oekelheide and Vogel and em ploys th e s tra te g y o f u sin g sa tu ra te d in te r n a l b rid g e s to in tro d u ce

r ig id it y a n d to a rre s t th e co n fo rm atio n a l m o b ility . The [1 4 ]a n n u le n e , tra n s - 10b,10c-d im eth yl-1 0 b ,1 0c-d ih ydro p yre ne (D M D H P ), 12, synthesised by

B o e k e lh e id e 14 and the [10 ]a n n ule n e, l,6 -m e th a n o [1 0 ]a n n u le n e , IP m ade by V o g e l15 a re r ig id conjugated systems.

W h ile H M O th e o ry could e xp la in and p re d ic t th e s ta b ilitie s o f m onocyclic conjugated hydrocarbons, i t fa ils to account fo r the b e h a v io u r o f several cross conjugated systems and n o n a lte m a n t system s. M o d ific a tio n s o f the H M O th e o ry can e x p la in th e p ro p e rtie s o f conju g a te d heterocyclic com pounds.Ih

Polyacenes such as perylene, 14, n o n -H iic k e l system s such as 15, and n o n -p la n a r system s such as 16, can now be considered as a ro m a tic , according

to R a n d ic’s conjugated c irc u it th e o ry .17 I t states th a t regardless o f th e to ta l 71- electron count, system s th a t possess o n ly (4n+2) conjugated c irc u its are a ro m a tic and those w ith o n ly (4n) conjugated c irc u its are a n tia ro m a tic .

can also be m ade on th e basis o f a graph th e o re tica l a p p ro a c h .17

1.2 D e te c tio n o f a r o m a tic ity

T he in te rp la y o f th e o ry and practice in a ro m a tic c h e m is try has led to syntheses and discoveries o f a ric h v a rie ty o f com pounds. One o f the recent discoveries, guided by th e o re tic a l p re d ic tio n , b e in g th e fu lle re n e (Cfin) 17.111 T h is is a stable, spherical a ro m a tic com pound fo r w h ic h new theories had to be developed to account fo r its chem ical and p h y s ic a l b e h a v io u r.19,20

17

W ith such new and com plex m olecules b e in g added to th e class o f a ro m a tic com pounds fro m tim e to tim e , the m eans o f d e te c tin g the a ro m a tic

c h a ra c te r th ro u g h a single p ro p e rty becomes d iffic u lt. We s h a ll now b rie fly consider some o f th e m eans o f d e te ctin g a ro m a tic ch a ra c te r.

C h e m ica l and th e rm a l s ta b ilitie s , a lth o u g h in d ic a to rs o f a ro m a tic c h a ra cte r, c a n n o t be a p p lie d as u n iv e rs a l c rite ria . F o r exam ple, le t us consider the [1 4 ]a n n u le n e s

18

and

12.

T he d ih y d ro p y re n e

18

is oxidised e a sily in to

6

pyrene 19 by a ir 21 and D M D H P 12, though re s is ta n t to a ir o xid a tio n , undergoes th e rm a l re a rra n g e m e n t to 2 0 .22 Y e t b o th are now considered a ro m a tic by o th e r c rite ria .

12

20

D ata can be o b ta :ned fro m X -ra y m easurem ents, fo r exam ple, the equal bond le n g th s observed in benzene d e riv a tiv e s and th e o n ly sm all d e v ia tio n s fro m p la n a r ity led to consideration o f la ck o f bond a lte m a n c e and p la n a r ity as c r ite r ia fo r a ro m a tic ity . Benzene is p la n a r and has equal C-C bond le n g th s o f 1.398

A.

The tendency to w a rds c o p la n a rity o f th e rc-system atom s is due to th e fa c t th a t th e c o lin e a rity o f th e axes o f th e p o rb ita ls fo r th e ir m a x im u m o ve rla p is achieved th u s le a d in g to th e lo w e s t energy o f the m olecule. In tro d u c tio n o f s tra in g e n e ra lly leads to d e v ia tio n fro m p la n a rity .

rin g is d is to rte d in to a boat fo rm w ith a d e v ia tio n o f 15-17° fro m p la n a rity w hen n = 7, a n d 20-21° w hen n = 6.

D esp ite the s tra in , the bond len g th s in th e benzene rin g o f 21 and 22 re m a in a lm o s t equal and suggest along w ith o th e r c rite ria th a t the a ro m a tic ity in th e benzene r in g is n o t lost. The necessity to grow single c ry s ta ls o f X -ra y q u a lity and th e som etim es m is le a d in g in fo rm a tio n th a t can be o b ta in e d due to ste ric factors m akes th is m e th o d d iffic u lt to a p p ly as a g eneral c rite rio n o f a ro m a tic ity . A lso carbon-carbon bond le n g th s cannot be com pared to bond le n g th s in v o lv in g heteroatom s. I t sh o u ld be noted th a t fused system s such as n a pth ale n e, show bond a lte rn a tio n , and th u s in te rp re ta tio n o f th is as a d ire c t m e asurem ent o f a ro m a tic ity needs care. We sh a ll consider th is la te r.

T he concept o f bond o rd e r (p), is a th e o re tic a l one th a t depends on the vale n cy m u ltip lic itie s betw een atom s in m olecules, and is re la te d to bond le n g th .25 T he q u a n tity p has a p h ysica l sign ifica nce th a t is associated w ith the b in d in g p o w e r o f a bond since th e p ro d u c t o f th e coeffcients o f a d ja ce n tly

bonded atom s m a y be considered as a bond electron d e n sity.

8

Pr s = ^ n. cJr (1)

where

n = n u m b e r o f electrons in the j th m o le c u la r o rb ita l c,r = c o e fficie n t o f atom r in the j th m o le c u la r o rb ita l_{j r J}

Benzene has a bond order o f 0.667, w h ile in a p e rfe c tly delocalised [ 14)annulene, th e value is 0.642 and th u s the valu e depends on th e r in g size. The bond orders o f the 1-2 and 2-3 bonds in n a p h th a le n e have va lu e s o f 0.725

and 0.603, respectively, in d ic a tin g bond a lte rn a tio n . A lth o u g h , i t is d iffic u lt to d e te rm in e a range o f bond orders by w h ic h a system m a y be classified ar a ro m a tic ,28 bond orders can be used (as are bond le n g th s ) as in d ic a to rs o f bond fix a tio n , w h ic h is re la te d to a ro m a tic ity . The m ore u n e q u a l o r a lte rn a tin g are the bonds in a system , the less a ro m a tic is it.

W h ils t a ll a ro m a tic compounds give u ltr a - v io le t spectra, w h ic h are

co n ven ie nt c la s s ific a tio n tools, the spectra o b tained r e s u lt fro m th e energy differences betw een the ground and th e excited states o f th e m olecules, and th u s do n o t d is tin g u is h the presence or absence o f a ro m a tic ity .

A ro m a tic hydrocarbons have ve ry d is tin c t m a g n e tic p ro pe rtie s. E x p e rim e n ta l w o rk done in the la te 1920s, revealed th e h ig h e r m a g n e tic e x a lta tio n and pronounced a n iso tro p ic b e h a v io u r o f a ro m a tic com pounds.27

T h is led R am an and K ris h n a n to re su rre ct an e a rlie r hypothesis o f E h re nfe st to ra tio n a lis e th e anom alous d iam agnetic b e h a v io u r.'8 Based on th is w o rk, P a u lin g , u s in g the th e n ava ila ble q u a n tu m m echanical theo ry, gave a th e o re tic a l e x p la n a tio n .29 P a u lin g ’s model, lik e th e E h re n fe s t hypothesis, assumes L a rm o r precession o f the electrons in benzene to account fo r its pronounced d ia m a g n e tic b e h a vio u r and i t form ed th e basis fo r the p o p u la r "rin g c u rre n t" th e o ry, discussed below.

1.2.1 R in g c u r r e n t th eo ry a n d a ro m a ticity

W ith th e a d ve n t o f n u cle a r m agnetic resonance (n m r) spectroscopy, P a u lin g s m odel fo r benzene u n d e r the influence o f an ap plied m a g n e tic fie ld , ,nned a tte n tio n and was f ir s t used by Pople,30 in a classical sense, to e x p la in p ro to n ch e m ica l s h ifts . L a te r, im pro ve m e nts by o th e r W’o rke rs, gave rise to the "rin g c u rre n t" th e o ry o f w h ic h a com prehensive re v ie w has appeared.81

In th e r in g c u rre n t model, a p la n a r a ro m a tic m olecule assumes a p e rp e n d ic u la r o rie n ta tio n to the applied m ag ne tic fie ld . T he a p p lie d fie ld is assum ed to "in d u ce" a "rin g c u rre n t" in the rc-electrons o f th e m olecule. T h is w ill produce a secondary m agnetic fie ld w hich is a g a in s t th e a p p lie d m a g n e tic fie ld a t th e ce n tre o f th e m olecule, and w ith che a p p lie d fie ld on the outside o f th e m olecule. As a re s u lt o f th is, the e x te rn a l p ro to n s o f th e m olecule experience a s tro n g d e s h ie ld in g and w ould appear in th e low fie ld region o f the n m r sp e ctru m . A n y protons present inside th e r in g experience a s tro n g

10

s h ie ld in g and v j u i " ^ i < the h ig h fie ld region o f th e spectrum . The rin g

c u rre n t model \ benzene - c illu s tra te d in F ig u re 1.

A p p lie d M a g n e tic F ie ld In d u c e d m a g n e tic fie ld P ro to n m a g n e tic D e s h ie ld in g c — Indu ce d r in g c u rre n t

F ig u r e I Indu ce d r in g c u rre n t and p ro to n m a g n e tic d e s h ie ld in g in benzene. ■dthough th e re is no proot th a t rin g c u rre n ts e xist, th e r in g c u rre n t th e o ry does a d eq u a te ly e x p la in th e chem ical s h ifts o f a nnulenes, and i t has

become a w id e ly accepted concept. In (4n+2) annulenes, th e e x te rn a l p rotons are deshielded due th e r in g c u rre n t and are te rm e d d ia tro p ic . I n (4n) annulenes, th e e x te rn a l p ro to ns are shielded due to w h a t is ca lle d "a p a ra m a g n e tic r in g c u rre n t” and such (4n) annulenes are called p a ra tro p ic . Those a n nu le ne s w h ic h do n o t show d e lo ca lisa tio n o f th e jt-e le ctro n s are called atropic.

11

Table 1 lis ts some exam ples o f n e u tra l, charged and hetero versions o f (4n+2) and (4 n ) a nnulenes w ith th e chem ical s h ifts o f th e ir in n e r and o u te r protons.

T able 1 'H ru n r chem ical s h ifts (8) o f selected a nnulenes in ppm. 12 C om pound n e 8 O u te r protons 8 In n e r p ro to n s R ef 1 6 7.27 — 32

23

8 5.70 — 33

13

10 7.27-6.05 -0.52 34

24

12 5.5-5.2 6.06 35 9 14 7.88 -0.61 36

25

14 8.77-8.04 -4.53 37

12

14 8.67-7.98 -4.25 38

26

14 8.74-7.50 -2.06 39

27

2 11.1 — 40

2

10 5.70 — 41

28

10 6.8-5.4 -0.7,-1.2 42

29

16 -3.19- -3.96 21 43 3 0 6 8.5-7.46 — 44

31

6 7.7-6.05 — 45 32 10 8.23-6.5 0.65- -0.4 46 33 14 9.5-8.7 -3.75,-3.80 47

F ro m T a b le 1, i t is e vid e n t th a t the (4n+2) a n n u le n e s are d ia tro p ic . We s h a ll now b r ie fly discuss some aspects w h ic h a ffe c t th e s h ie ld in g and d e s h ie ld in g o f protons.

A m o n g th e n e u tra l annulenes, the p rotons o f benzene, 1, w h ic h is considered b y some schools as ‘the real a ro m a tic m o le cu le ’, resonate a t 7.27 ppm , a b o u t 1.5 p p m d o w n fie ld fro m a n o rm a l o le fin . T h is a d d itio n a l d e s h ie ld in g in d ic a te s th e presence o f a rin g c u rre n t. In th e [1 4 ]a n n u le n e 9, the in n e r p ro to n s are shielded due to the rin g c u rre n t and a p pe a r a t -0.61 ppm . W hereas, in th e isoe le ctro n ic b rid g e d annulenes 25 and 12, th e s h ie ld in g o f the in n e r p ro to n s is stro n g e r. T h is difference is a ttrib u te d to th e r ig id it y and n e ar p la n a r p e r ip h e iy o f th e b rid g e d annulenes. A n y d e v ia tio n fro m p la n a r ity leads to a re d u c tio n o f r in g c u rre n t. The bridge protons o f th e m e th a n o a n n u le n e 13, appe a r a t -0.52 p p m and are th u s n o t so s tro n g ly shielded. T h is m olecule has a b e n t p e rip h e ry . T h e cis-dm dhp 26, has its in te r n a l m e th y l p ro to ns a t -2.06 ppm , a m a rk e d re d u c tio n in s h ie ld in g com pared to 12. T h e in te r n a l m e th y ls in 13 p o in t a w a y fro m th e x -n e tw o rk and th e o ve ra ll g e o m e try o f th e m olecule is lik e t h a t o f a saucer. W hen an annulene suffers a to ta l la c k o f p la n a rity , th e d e lo c a lis a tio n o f th e x-electrons is d isru p te d . As a re s u lt, th e re is no rin g c u rre n t and hence i t is a tro p ic. F o r exam ple, cycloo ctate tra en e 23, is tu b shaped. Its p ro to n s are n o t shielded (as w o u ld be expected fo r a 4n a n nulene),

in d ic a tin g an absence o f a r in g c u rre n t. O n th e o th e r h a n d , in th e n e a r-p la n a r [1 2 ]a n n u le n e 24 , th e in n e r p rotons are m ore s tro n g ly sh ie ld e d th a n th e o u te r

14

protons. T h is p a ra tro p ic behaviour is q u ite d ra m a tic in case o f the p a ra tro p ic d ia n io n 29, whose in te rn a l m e th y l protons appear some 25 ppm d o w n fie ld fro m those o f the d ia tro p ic 12.

The p rotons o f the [2]annulene, cyclop ro p e niu m cation, resonate d o w n fie ld a t 11.1 ppm . In th is case the p o sitive charge also deshields the protons. A n u p h e ld s h ift is experienced by p ro to n s in a n e g a tiv e ly charged system . The chem ical s h ift o f the a ro m a tic cyclo o ctate ra e n yl d ia n io n is the same as th a t o f th e n o n a ro m a tic cyclooctatetrene.

In heterocycles, the chem ical s h ift differences depend on th e dipole m om ents. The isoelectronic p y rid in e 30, and p y rro le 31, have a difference o f about 1 ppm in th e chem ical s h ift o f th e ir protons. T h is is due to th e d ire c tio n o f the dipoles in these systems. The d ire c tio n o f th e d ip o le is to w a rd s n itro g e n in p y rid in e and aw ay fro m n itro g e n in p yrro le .

These chem ical s h ift differences, re s u ltin g fro m charge a n d/o r dipole m om ents, do n o t re fle c t th e tru e s h ie ld in g o r d e s h ie ld in g o f p ro to n s due to rin g c u rre n t. V o g le r has d erived an equation re la tin g th e observed s h ie ld in g (a) to

the s h ie ld in g due to rin g c u rre n t and o th e r factors.48 T h is is given in equation

2.

a = o1*0 + a 1^ + a p° + a vq (2)

W here a1*0 = S h ie ld in g due to rin g c u rre n t

a1^ = S h ie ld in g due to th e local a n is o tro p y op° = The zero o f th e chem ical s h ift scale avq = S h ie ld in g due to excess Ji-electron d e n s ity

So, in te rp re ta tio n o f th e chem ical s h ifts in annu le ne s has to be ca rrie d o u t w ith e xtrem e caution, especially in th e case o f charged system s and heterocycles w here th e s h ie ld in g a ris in g due to loca l a n is o tro p ic c o n trib u tio n s and excess x -e le ctro n d e n sity are o f equal im p o rta n c e .49 N evertheless, the d ia tr o p ic ity o f an annulene can be considered as a c rite rio n fo r a ro m a tic ity , p ro vid e d th a t th e above m en tion e d factors (w h ic h can be calculated th e o re tic a lly ) are ta k e n in to consideration.

A n o th e r m ag ne tic p ro p e rty o f conjugated system s, d ia m a g n e tic s u s c e p tib ility , has been re la te d to a ro m a tic ity th ro u g h th e e m p iric a l q u a n tity , d ia m a g n e tic s u s c e p tib ility e x a lta tio n (D S E ).50

16

1.2.2 R e so n a n c e a n d a ro m a ticity

A lth o u g h re ce ntly new in s ig h ts have been offered about the o rig in o f the s ta b ilis a tio n in aro m a tic c o m p o u n d s / i t is believed th a t the d e lo ca lisa tio n o f jr-electrons low ers the to ta l energ y o f th e a ro m a tic m olecule re la tiv e to th e h y p o th e tic a l bond localised s tru c tu re . A th e o re tic a l p a ram e te r, called resonance energy (RE), has been a ttrib u te d to th e lo w e rin g o f energy due to d e lo ca lisa tio n and i t has beer suggested as a s u ita b le c rite rio n for d e te rm in in g th e a ro m a tic ity o f a com pound. T a k in g benzene, 1, as an exam ple, i f the calculated energy o f th e s tru c tu re 34 was th e same as the

e x p e rim e n ta l v a lu e w it h in e xp e rim e n ta l d e v ia tio n , tli^ n s tru c tu re 34 w ould ve ry w e ll re p re se n t benzene. I f the e x p e rim e n ta l v a i ie o f th e energy o f benzene is g re a tly d iffe re n t from the calculated e n erg y o f th e s tru c tu re 34, the s tru c tu re 34 w o u ld th e n be a poor re p re s e n ta tio n o l m e re a l m olecule. T h is energy d iffe re n ce m ay be a ttrib u te d to th e resonance s tru c tu re 1.

T h e o re tic a l ca lcu la tion s can be p e rfo rm e d to e s tim a te th e resonance energ y o f a g iven m olecule. H ow ever, th e choice o f a m odel is v e ry c ritic a l. E a r lie r p ro ble m s encountered in H M O th e o ry , u s in g ethene o r cyclohexene as

m o o d s, have been overcome by D ew ar, who u sin g th e P o p le -P a ris e r-P a rr a p p ro x im a tio n (PPP), derived more reasonable values te rm e d D ew a r Resonance E nergies (D R E )/’4 O th e r m o d ifica tio n s by Hess and S ch a a d ,’5 Herndon,™ A ih a ra ,r’7 and T rin a js tic '"s are also ava ila ble .

T able 2: R E P E (in (3 u n its ) o f selected conjugated com pounds

N u m b e r C om pound Hess-Schaad™ D R E T R E M 7 C yclobutadiene -0.268 -0.136 -0.307 1 Benzene 0.065 0.120 0.046 30 P y rid in e 0.058 0.110 0.038 31 P y rro le 0.039 — 0.040 35 T hio ph e n e 0.032 -- 0.033

4 C yclo p e nta die n yl — 0.094

Hess a n d Schaad suggested the use o f the te rm resonance energ y p e r (k) e le ctron (R E P E ) as a m ore su ita ble p a ra m e te r th a n th e to ta l resonance energy. R E P E is a co n ven ie nt p a ra m e te r to com pare system s w it h d iffe re n t n u m be rs o f rc-electrons. H ow ever, i t m u s t be p o in te d o u t th a t the R E P E does n o t re fle c t th e o v e ra ll s ta b ility o f a m olecule and s tr ic tly re fe rs to th e e x te n t o f s ta b ilis a tio n o r d e s ta b ilis a tio n due to co njugation. T a b le 2 co n ta in s the

R E P E ’s fo r a few systems as calculated by Hess and Schaad u s in g the H M O m ethod and by T rin a js tic by the graph th e o re tic a l m ethod (topological resonance energy or TR E).

A ro m a tic compounds have a positive R E P E , a n tia ro m a tic compounds have a negative REPE and no na ro m a tic compounds possess an R E P E close to zero.

A m ong the c rite ria we allu d ed to in the p re ced in g pages, none can be e xclu sive ly re la te d to a ro m a tic ity , and none w hen v io la te d are good enough to d isco u n t the p ro p e rty . Based on the present consensus am ong chem ists,59 and th a t o f G a r r a tt’s "d e fin itio n ",60 one m ig h t say: a n a ro m a tic com pound is a cyclic d ia tro p ic system w it h a p ositive D e w a r resonance energy (>3 k c a l/ m o l) in w h ic h a ll the c o n tr ib u tin g atoms are involved in a single conjugated system.

1.3 E stim a tio n o f a r o m a tic ity

Because o f th e d iffic u ltie s one encounters in d e fin in g and d e te ctin g a ro m a tic ity , a n y e x p e rim e n ta l "m easurem ent" o f i t is fu tile . One could o n ly hope to get an e s tim a te o f a ro m a tic ity , re la tiv e to a w e ll s tu d ie d m olecule such as benzene.

T h e rm o ch e m ica l estim ates o f resonance e n erg y s u ffe r fro m th e same d ra w back as th e th e o re tic a l e stim a te o f resonance energ y its e lf. B o th need a su ita b le , h y p o th e tic a l m odel to a rriv e a t th e resonance energy. Tw o m ethods are used to e s tim a te th e resonance energy o f a m olecule u s in g th e rm o che m ica l

data. One m e th o d is to use the heat o f a to m is a tio n o f a com pound. For exam ple, a sim p le c a lc u la tio n o f the h e at o f a to m is a tio n fo r cycloh e xa trie ne 34 w ould be to sum the bond energies o f six C-H, th re e C-C and th re e C=C bonds. Then one can d e rive th e resonance energy o f benzene e ith e r as (i) 46.7 kca l/m o l by ta k in g th e bond energy o f ethylene as th e double bond in the

c a lc u la tio n or as (ii) 35.3 kcal/m ol by ta k in g th e bond energy o f a cis- d is u b s titu te d e th yle n e double bond (i.e. cyclohexene) in th e c a lc u la tio n (Table 3).

T able 3 C a lc u la tio n s o f the RE o f benzene (kca l/m ol)

C -H C-C C —C A H U °(34) A H a “(1) RE

C A L C .(i) 6(98.5) 3(83.1) 3(143.7) 1271.4 1318.1 46.7

C A L C .(ii) 6(98.5) 3(83.1) 3(147.5) 1282.8 1318.1 35.3

A n o th e r m ethod is to use h yd rog e n atio n d a ta . F o r exam ple, th e he at o f h y d ro g e n a tio n fo r cyclohexatriene 34 can be ca lc u la te d as 85.8 k c a l/m o l by m u ltip ly in g th a t o f cyclohexene by 3, i.e., 3 x 28.6 = 85.8 k ca l/m o l. C om parison o f th is v a lu e w it h th e e x p e rim e n ta l valu e o f h e a t o f h y d ro g e n a tio n o f benzene (49.8 kc a l/m o l) gives th e resonance energy o f benzene as 36 k ca l/m o l.

R ecently, u s in g th e same p rin c ip le described above, an a tte m p t has been made to e s tim a te th e D R E o f heterocycles fro m th e rm o c h e m ic a l d a ta (T able 4 ).61

20

Table 4 D R E o f some heterocycles fro m the rm o che m ica l d a ta in k c a l/m o lhl

C om pound N um b e r RE P y rid in e

30

35.2 P y rid a z in e

36

30.1 P y rro le

31

26.5 F u ra n

37

20.8

36

3 7

V e ry re c e n tly , K a tr itz k y and cow orkers have m ade an a tte m p t to q u a n tify a ro m a tic ity in heterocycles, u s in g p rin c ip a l com ponent an alysis o f several p ro p e rtie s .62 Since, each p ro p e rty used it s e lf is a re s u lt o f m a n y a p p ro x im a tio n s , and th e m ethod used to a rriv e a t th e re s u lts was p u re ly a n a ly tic a l, i t is d if fic u lt to com m ent on th e r e lia b ility o f th is approach. T h is

1.3.1 M itc h e ll’s m eth o d o f e stim a tio n o f a r o m a tic ity

T w e n ty years ago, M itc h e ll’s group s ta rte d th e ir w o rk on annelated dm dhps. tra n s - i0 b ,1 0 c -D im e th y l- 1 0b,lO c-dihydropyrenc (D M D H P ), 12, is a re la tiv e ly sta b le com pound w h ich is s tro n g ly d ia tro p ic . I t has a n e ar p la n a r, rig id skeleton, h e ld by th e ethano bridge, and is lit t le s tra in e d . W ith n e a rly equal p e rip h e ra l bond len g th s i t acts as a stereochenucally fixe d , ’p e rfe c t’ H iic k e l, [1 4 ]a n n u le n e . D M D H P bears its m e th y l s u b s titu e n ts w ith in the 14 71-

electron cloud, p la c in g th e m in the centre o f the d ia m a g n e tic c u rre n t. The in te rn a l hyd rog e n s are w e ll in s u la te d fro m the Tt-network (by 3 o bonds) and th e ir chem ical s h ift is n o t affected appreciably upon s u b s titu tio n w ith a v a rie ty o f groups in a n u m b e r o f po sitio n s (Table 5).

F ig u re 2 shows selected bond len g th s and angles fro m an X -ra y c ry s ta l d e te rm in a tio n 6'5 o f D M D H P ,

12.

The space f illin g m odel o f D M D H P is depicted in F ig u re 3, and Table 5 lis ts the in te rn a l m e th y l chem ical s h ifts o f a n u m b e r o f d e riv a tiv e s o f 12.

I t can be seen fro m Table 5 in com pounds

38-47

th a t th e in te rn a l m e th y l p ro to n ch e m ica l s h ift o f 12 is n o t affected v e ry m uch by e x te rn a l s u b s titu e n ts . T h e p ro to ns o f

12

its e lf appear a t 5 -4.25 ppm , some 5.2 ppm shielded fro m those o f th e a tro p ic model

48.

22

1.39A 1 38 A

1 2 0 1

1.38 A

123 2

F ig u re 2 Selected bond lengths and angles o f

12.

I V \ :

J

F ig u re 3 Space fillin g model o f

12.

5 -4.25 ppm

12

48

in p p m .

Com pound S u b stitu e nt(s) Position § (ppm) Ref

38

Br 2 -4.07,-4.08 64

39

C O C H , 2 -4.03 65

40

C(Ph);t 2 -3.92,-4.03 65

41

N O , 2 -4.03 65

42

2 -D M D H P 2 -3.68,-3.77 66

43

C H , 2,7 -4.09 67

44

B r 2,7 -4.02 68

45

C O O C H , 2.7 -3.92 67

46

/-B u 2,7 -4.06 69

47

O C O C H , 2,4,7 -3.83 70

The above m entioned features m ake D M D H P a good probe to detect changes in d e lo c a lis a tio n caused by anne la tion .

1.3.1.1 B e n z a n n e la tio n stu d ie s on DM DHP

B e n z a n n e la tio n o f an annulene was p r im a r ily used by S o n d h e im e r,'' S ta a b '2 and Nakagawa™ to b rin g about s ta b ility and increase the r ig id it y o f

24

m acrocyclic annulenes. Studies done by S taab,72 B o e kelh e id e 74 and M itc h e ll7'' on a n n e la te d b rid g e d annulenes provided a d d itio n a l in fo rm a tio n on the changes th a t occur due to a n ne la tion , as discerned fro m th e 'H n m r d ata. A n e xce lle n t re v ie w on benzannelated annulenes is a v a ila b le .76

Some o f the changes w h ich occur on fu s io n o f benzene to D M D H P , w h ic h are s im ila r to the changes in a n y a n n u le n o a n n u le n e , are th e fo llo w in g : 1. B e n z a n n e la tio n leads to bond a lte rn a tio n in b o th th e benzene and the D M D H P rin g s.

2. As a re s u lt, th e bond orders, p, change fro m a f u lly delocalised value, and th u s so do th e v ic in a l co upling constants o f th e p ro to n s on th e m olecule. 3. The s h ie ld in g caused by the rin g c u rre n t, experienced b y th e in te r n a l m e th y l protons in D M D H P is reduced, and is reflected by a lo w e r fie ld chem ical s h ift o f th e in te r n a l m e th y l protons. F o r exam ple, in th e b e n z o -D M D H P 4 9 ,77 the in te rn a ' m e th y l protons resonate a t -1.60 ppm , s h o w in g a d o w n fie ld s h ift o f 2.65 p p m fro m th a t o f th e p a re n t D M D H P . A lso th e v ic in a l c o u p lin g constants in the m olecule v a ry between 6.52-8.93 Hz.

1.60

V

J

25

These changes in chem ical s h ift o f th e in te r n a l p ro to n s and the co u p lin g con sta n ts o f th e e x te rn a l protons are b ro u g h t ab ou t o n ly by the fusion o f a r in g w ith a cyclic a rra y o f K-electrons. In com pounds 50, 51, and 52, w here th e fused r in g is a tro p ic, th e in te rn a l m e th y l chem ical s h ifts are n o t ve ry d iffe re n t fro m those o f th e p a re n t D M D H P , 12 (Table 6).

Table 6 In te r n a l m e th y l chem ical s h ifts o f some fused d e riv a tiv e s o f D M D H P , in ppm . N u m b e r § (ppm ) R e f 12 -4.25 14 50 -4.23 78 51 -3.72, -3.73 79 52 -4 .1 5 ,-4 .1 6 80

50

51

52

26

E x a m in a tio n o f the chem ical s h ift values give n in Tables 5 and 6, c le a rly show t h a t any change in the in te rn a l m e th y l chem ical s h ifts b ro u g h t

about by s u b s titu tio n or by the fusion o f an a tro p ic r in g on th e D M D H P rin g is n o t v e ry s ig n ific a n t. M itc h e ll and coworkers have show n th a t th e average d e v ia tio n o f th e bond orders in the D M D H P fra g m e n t o f benzannelated D M D H P s correlates lin e a rly w ith the change in th e in te r n a l m e th y l chem ical s h ifts .82 The bond orders can be calculated e ith e r u s in g th e rc-SCF m e th o d or fro m th e v ic in a l co u pling constants 3J, u s in g e q u a tio n 3.83 T h is e q uation o rig in a lly d e rive d b y G u n th e r b y p lo ttin g 3J values o f benzenoid. hydrocarbons a g a in st the corresponding calculated ti-SC F va lu e s,83 w as used b y M itc h e ll and coworkers in th e ir e a rlie r w o rk. B e tte r c o rre la tio n s r e la tin g 3J and calculated 7t-SCF bond orders fo r th e D M D H P d e riv a tiv e s w ere o b ta in e d , re c e n tly by Zhou, and we w ill use these co rre la tio n s in o u r w o rk and also show the advantage o f these im p ro ve d co rre la tio n s over th a t o f G u n th e r’s

in d e ta il in c h a p te r 3.

pmn = 0.104 3J mn - 0.120 (3)

A p lo t o f A r, th e average d e v ia tio n in th e bond o rd e r fro m the expected H iic k e l va lu e o f 0.642, fo r a p e rfe c tly delocalised [1 4 ]a n n u le n e fo r each m acrocyclic r in g o f

49, 53, 54, 55,

a g a in s t th e ch e m ica l s h ift s h ie ld in g A8, gave a s tra ig h t lin e , fro m w h ic h e q ua tio n 4 was o b ta in e d :84

58

AS = 5.533 - 27.52 A r

28

(4)

T h is c o rre la tio n is va lu a b le in tw o respects. F ir s t, i f bond orders can be ca lc u la te d e ith e r b y u sing equation 3 or tu-S C F c a lc u la tio n s , th e n the chem ical s h ift s h ie ld in g can be predicted. Secondly, a m ea sure d chem ical s h ift can be used to com m ent on the average bond o rd e r d e v ia tio n s and hence on the s h ie ld in g changes due to anne la tion . The chem ical s h ifts o f a ll th e p ro to n s can also be ca lcu la te d according the m ethod o f V o g le r.85 T a b le 7 in c lu d e s some o f the p re d ic te d a n d observed chem ical s h ift values fo r th e in te r n a l m e th y l group protons fo r a n u m be r o f benzannelated D M D H P s.

Table 7: P re d ic te d and observed in te rn a l m e th y l p ro to n ch e m ica l s h ifts fo r some fused D M D H P s , in ppm.

C om pound 5CH 3(predicted) 5CH 3(observed) R e f

56

-2.75 -2.78 86

57

-3.97 -4.19,-4.28 87

58

-1.25 -0.74 88

59

-3.84 -3.32 89

F ro m th e ta b le, i t can be seen th a t th e re is a good agreem ent

D M D H P and th e a n n e la tin g rin g s are n o t deform ed v e ry m u ch due to a n n e la tio n . D ue to th e la ck o f a v a ila b ility o f a n y X -ra y s tru c tu re in fo rm a tio n , fo rce -fie ld c a lc u la tio n s have been used to ca lcu la te th e g e om e try o f the m olecules and these calculations in d ica te th a t th e g e om e try indeed is not a lte re d v e ry m u ch .75 V o g le r calculates th a t even in th e case o f e xtre m e ly crow ded m olecules such as 60, th e chem ical s h ift change due to d e fo rm a tio n is n e g lig ib le .85

Aro

60

Zhou, u s in g th e H a ig h -M a llio n equa tio n , has show n th a t th e th ro u g h space a n is o tro p y effect o f th e a n n e la tin g benzene rin g s , is v e ry s m a ll.90 In the m olecule 61, p ro to n E is th e fa rth e s t fro m th e a n n e la tin g r in g a n d is th u s lea st affected by a n is o tro p y and geom etry changes. R e ce n tly,91 a q u a n tita tiv e c o rre la tio n has been de rive d th a t re la tes th e in te r n a l m e th y l r in g c u rre n t che m ica l s h ift, 5rCM, to th a t o f th e rin g c u rre n t chem ical s h ift o f p ro to n E, 5RCH, fo r a n u m b e r o f a n n e la te d D M D H P d e riva tive s. T h e fo llo w in g e q u a tio n , w h ic h re p re se n ts a s tr a ig h t lin e p lo t, was obtained:

30

SrCM = -2.60 8rch - 0.029 (5)

w here

5rcm = 0.97 - 5CH.j, and ^rch = 6.13 - 5e

8e = Observed chem ical s h ift o f p ro to n E

T he va lu e o f 0.97 is th e chem ical s h ift fo r th e m odel 48 and 6.13 is th a t o f a conjugated polyene in th e absence o f a n y r in g c u rre n t effect.92,93

T he values o f chem ical s h ift s h ie ld in g s th u s o b ta in e d have been re la ted to D e w a r resonance energies (DRE.) o f th e a n n e la tin g fra g m e n ts .94 F o r the 14rc-system to fu lly delocalise in 49, the d e lo c a lis a tio n o f benzene m u s t be in te rru p te d , le a v in g o n ly a cts-butadiene re s id u a l. T he loss o f RE th e n is a p p ro x im a te ly th a t o f benzene. B y analogy, fo r th e d ib e n z a n n e la te d analogue

54,

the loss o f R E is tw ice th a t o f 49. F o r th e n a p h th -fu s e d D M D H P ,

56,

a styrene is le ft w hen th e 147t-system delocalises. H ere , th e loss o f RE a p p ro xim a te s to th e difference betw een th a t o f n a p h th a le n e and styrene. B y p lo ttin g th e ca lcu la te d REs o f v a rio u s re s id u a ls and th e co rresponding s h ie ld in g changes (A) in the in te r n a l m e th y l chem ical s h ifts (5), V e n ug o p a la n o b ta in e d th e fo llo w in g equation (e q ua tio n 6).

A = 2.5366 R E ’ + 0.2141 (6)

(Correlation coefficient = 0.9905) where A = |-4.25 - 8| and

32

E q u a tio n 6 dem onstrated th e lin e a r re la tio n s h ip betw een change in the chem ical s h ift s h ie ld in g and the resonance energy a n d th u s fu r th e r s u b s ta n tia te d th e v a lid ity o f u sin g the in te rn a l m e th y l chem ical s h ifts to e stim a te th e a ro m a tic ity o f va rio u s a ro m a tic rin g s .

A n o th e r, sim ple and d ire c t approach was developed by M itc h e ll who used th e chem ical s h ift changes o f the in te rn a l a n d e x te rn a l p ro to ns o f an an ne la te d D M D H P w ith respect to those o f th e b e n z o [a ]D M D H P , 49.

"A ro m a tic ity " = [5(CH3)R ing - 5(C H 3)12 / 5(C H 3)49 - 5 (C H ;j)12] (7)

E q u a tio n 7 gives a re la tiv e m easure o f th e a ro m a tic ity o f an a n n e la tin g r in g w ith respect to th a t o f benzene based on its bond fix in g a b ility in th e a n n e la te d D M D H P . Due to its s im p lic ity , i t is v e ry easy to get an e stim a te o f th e re la tiv e a ro m a tic ity o f a m olecule w it h respect to th a t o f benzene b y s im p ly m e a su rin g the chem ical s h ift o f th e in te r n a l m e th y l protons.

T h u s, th e D M D H P m olecule is a good n m r probe fo r a ro m a tic rin g s and one could com m ent on the e x te n t o f a ro m a tic c h a ra c te r o f a n y a ro m a tic com pound by fu s in g i t to th e D M D H P rin g .

1.4 S y n th e tic r o u te s to DMDHP and its d e r iv a tiv e s

B oekelheide and coworkers developed several s y n th e tic m ethods to D M D H P .95 A m o n g those know n routes, the d ith ia c y c lo p h a n e route, inve n te d by M itc h e ll and B oekelheide is the m ost co n ven ie nt and p ra c tic a l one.95 M itc h e ll and Zhou have shown th a t the d ih y d ro p y ry n e

62

(page 36), could be generated and tra p p e d w ith va rio u s furans, le a d in g to several benzo-fused D M D H P s .97 M itc h e ll and Zhou have also synthesised th e o xa [1 7 ]a nn u len e

63

(page 36), w h ic h could be used as a synthon fo r v a rio u s fused D M D H P s .98 M itc h e ll and cow orkers have used the th ia cyclo p h a n e ro u te to synthesise [e ]a n n e la te d D M D H P s , s ta rtin g from the a p p ro p ria te ly s u b s titu te d o -te ra ry ls ." Since th is th e sis is m a in ly concerned w ith th e u tilis a tio n o f the e x is tin g s y n th e tic p a th w a y s to m ake a nnelated D M D H P s and th e possible e x p lo ra tio n o f c o m p le m e n ta ry new syn th e tic strategies, i t is a p p ro p ria te here to discuss b rie fly th e k n o w n m ethodologies in th e fo llo w in g pages.

1.4.1 T h e d ith ia c y c lo p h a n e rou te

We s h a ll illu s tr a te the d ith ia cyclop h a n e s tra te g y by u s in g the synthesis o f b e n z o [a ]D M D H P 49 as th e exam ple. The syn th e sis is show n in Scheme 1.

T h is s tra te g y in vo lve d th e c o n stru ctio n o f a m a cro cyclic r in g by co u p lin g

the d ith io l 69, w ith th e d ib ro m ide 73, u n d e r h ig h d ilu tio n co n ditio n s. The re s u ltin g s y n /a n ti m ix tu re o f the thiacyclophanes 74, w ere th e n rin g contracted by m eans o f a W it t ig re a rra n g e m e n t and the th io la te s fo rm e d w ere m e th y la te d

3 4 Scheme 1 64 65 CN 66 CHO 67 c h2o h 68 CH2Br Thiourea X *1 KOH Br H30 HS SH 69 68 7 0 N B S

>

71 Br Br2 / F e - > 5 S T E P S

>

HBr - (CH20 ) 3 < ---71 AcOH - P.T.C 69 73 SH HS KOH / EtOH 74 nBuLi Me 75 (MeO)2CHBF4 t-BuOK tr S Me

w ith M e l to y ie ld the an^i-cyclophanes 75. The S -m e th y la te d [2,2]cyclophanes 75, were fu r th e r m e th y la te d w ith B orsch rea ge n t and the re s u lta n t s u lp h o n iu m salts, upon tre a tm e n t w ith base, e lim in a te d M e2S to y ie ld the cyclophanediene 76. The cyclophanediene form ed, re a rra n g e d , in situ, to the b e n z o [a ]D M D H P 49. The key synthons, the d ib ro m id e 73, and th e d ith io l 69, were synth e sise d fro m the com m ercial 2 ,3 -d im e th y ln a p h th a le n e 70, and 2,6- d ic h lo ro to lu e n e 64, usin g s ta n d a rd tra n s fo rm a tio n s , as shown in Scheme 1.

F ro m th e exam ple given, i t is clea r th a t th e essential in te rm e d ia te s in th is m e th o d o lo g y are a 1 ,2 ,3 -s u b s titu te d arene and 2,6- b is(m e rca p to m e th yl)to lu e n e , 69. Though the b is (b ro m o m e th y l)n a p h th a le n e 73, is now accessible in tw o steps fro m 2 ,3 -d im e th y ln a p h th a le n e , v ia o u r phase tra n s fe r catalysed b ro m o m e th y la tio n p ro ced u re ,100 th e synth e sis o f such in te rm e d ia te s is n o t tr iv ia l and is often tim e consum ing. Even th e synthesis o f th e d ib ro m id e 68, involves fo u r steps. So, i t was o u r in te n tio n to fin d a s h o rte r ro u te to 2,6 -b is(b ro m om e thyl)to lu en e and an a p p ro p ria te ly s u b s titu te d diene sy n th o n w h ic h could lead to va rio u s fused 1 ,2 ,3 -su b stitu te d benzenes via D ie ls -A ld e r reactions.

1.4.2 T h e d ih y d ro p y ry n e/o x a [1 7 ]a n n u len e r o u te

T he d ih y d ro p y ry n e , 62, could be generated by th e action o f sodam ide and a c a ta ly tic a m o u n t o f f-B u O K on the b ro m o D M D H P 77, in th e presence o f a tra p p in g agent. F o r exam ple, th e a d d u ct 78, can be o b ta in e d in 75% y ie ld

36

by tra p p in g o f the aryne 62, w ith fu ra n .

A lth o u g h Zhou has u tilis e d th is m e th o d to synthesise several bon/.annelated D M D H P s, the p o te n tia l o f th is v e ry u s e fu l in te rm e d ia te has not boon fu lly explored. Hence, we w ere in te re s te d in fin d in g o th e r possible uses of th is aryne in te rm e d ia te .

The oxa[17]annulene 63, obtained by th e re a c tio n o f th e te tra z in e 79, w ith the fu ra n adduct, is a re la tiv e ly stable com pound to handle. T h is has boon shown to cyclo-add to arynes to give adducts w h ic h on deoxygenation lead to benzannelated D M D H P s. F o r exam ple th e m ix tu re o f [a ja n n e la te d D M D H P s 80 and 81 were synthesised fro m th e oxa[ 17]a n n u le n e in tw o steps.98

77 NaNH t-BuOK Furan 62 78 75% 79

80

81

1.4.3 S y n th e s e s o f [e]fu sed DM DHPs

M itc h e ll and coworkers had developed a m ethodology based on the a ry l-a ry l c o u p lin g re a ction between a G rig n a rd re a g e n t and a brom oarene m edia te d b y tr a n s itio n m e ta l c a ta ly s ts ." F o r exam ple, th e b e n zo [e ]D M D H P was synthesised as shown in Scheme 2. The s a lie n t fe a tu re s o f th is s tra te g y are: (i) The N i(0 ) m edia te d coupling o f the m o n o -G rig n a rd d e rive d fro m 2,6-d ic h lo ro to lu e n e an2,6-d 1,2-2,6-dibromobenzene to y ie l2,6-d th e o -te ra ry l 84.

(ii) H ig h d ilu tio n co u p lin g o f the dib ro m ide 89, w ith N a aS w h ic h re su lte d in th e a n /i-c y c lo p h a n e 90.

( iii) W it t ig re a rra n g e m e n t, stepwise m e th y la tio n o f th e rin g contracted cyclophane, fo llo w e d b y the H o fm a n n e lim in a tio n o f th e re s u lta n t s u lp h o n iu m s a lt p ro v id e d th e b e nzo [e]D M D H P 53.

T h is m ethodology, a lth o u g h re lia b le , needs a 1,2-dibrom oarene. The syn th e sis o f w h ic h is often d iffic u lt, as th e re are no general, co n ve n ie n t m ethods a v a ila b le to synthesise l,2*dibrom oarenes. F o r exam ple, th e synthesis o f a n th ra c e n o [e ]D M D H P 94, w ou ld re q u ire 2,3 -d ib ro m o an th ra ce n e, 93, and the o -te ra ry l o b ta in e d w o u ld be subjected to fo u r fu n c tio n a l group tra n s fo rm a tio n s (fro m chloro to b ro m o m e th yl), m a k in g th e synthesis lo n g a n d tedious.

Hence, we decided to explore p o s s ib ilitie s to fin d and synthesise a com m on in te rm e d ia te w hich w ould lead to v a rio u s, p ro p e rly s u b s titu te d , o -te ra ry ls .

3 8 Schem e 2 Br Br 89 90 92 heat vis light nBuLi Me 53 *S Me 91 94 9 3

CHAPTER TWO

SY NTH ESES USING THE DITHIACYCLOPHANE STRATEGY

2.1 In tr o d u c tio n

In th is chapter, we w ill describe ou r e ffo rts to devise a s tra te g y to synthesise a p ro p e rly s u b s titu te d diene as a com m on p re c u rs o r to v a rio u s [a] fused D M D H P s . The synthesis o f th e f ir s t d ia tro p ic b rid g e d th ia [1 3 ]a n n u le n e w ill be described next, to g e th e r w ith estim ates o f its d ia tr o p ic ity based on the chem ical s h ifts o f its in te rn a l and e x te rn a l p ro to ns and on c o u p lin g constant- chem ical s h ift co rrela tio ns. S ynthesis o f l,3 -b is (m e th o x y m e th y l)-2 - m e th y lb ip h e n y ie n e fro m 1,2-dibrom obenzene, in fo u r steps, w ill be described next. A n account o f th e a tte m p te d conversion o f th is b is -e th e r in to 1,3- b is (b ro m o m e th y l)-2 -m e th y lb ip h e n y le n e , en route to th e syn th e sis o f a quasi- b ip h e n y le n e -D M D H P w ill be given. A s u m m a ry o f possible fu tu r e syntheses o f [a] fused D M D H P s and h e te ro D M D H P s based on th e in te rm e d ia te s d erived in th is p ro je c t w ill be presented. B u t fir s t, we w ill o u tlin e o u r re s u lts on the

b is -b ro m o m e th y la tio n o f 4-£-butyltoluene and th e c o n d itio n s fo r th is e ffic ie n t b ro m o m e th y la tio n procedure.

40

2.2 B r o m o m e th y la tio n o f a ren es

As seen fro m Scheme 1, one o f th e key s yn th o n s fo r th e c o n s tru c tio n o f the D M D H P nucleus, 2 ,6-bis(brom om ethyl)toluene, 68, can be synthesised from com m ercial 2,6-dichlorotoluene,

64,

in fo u r steps. A ll a tte m p ts to sh o rte n th is syn t ds th ro u g h the b is -G rig n a rd re a g e n t

96

o r th e d ilith io d e riv a tiv e 97 have so fa r been unsuccessful.101

(C H 20 )

T a s h iro et al. have used th e £-butyl g ro up as a b lo c k fo r e le c tro p h ilic s u b s titu tio n re a ctio n s on arenes.102 A fte r th e s u b s titu tio n , th e i- b u ty l group is rem oved, le a v in g the sp e cifica lly s u b s titu te d arene. F o r exam ple, 4-t- b u ty lto lu e n e ,

98,

on n itr a tio n yield s th e d in itro to lu e n e

99

w h ic h on de-t- b u ty la tio n w ith an A lC lg/C H aN O ^toluene system p ro vid e s 2 ,6 -d in itro to lu e n e ,

1 0 0 .103 H o S O . U N O -N O A IC I3 /C H 3 N O 3 > T o lu e n e NO, _{N O N O ,} 98 99 100

T a s h iro ’s group has also shown th a t 4 -i-b u ty lto lu e n e can be bis- c h lo ro m e th y la te d , a lb e it in low yields, to give th e b is -c h lo ro m e th y l com pound

101.104

x Cl CHoOCH 101 40% 98

T h is procedure re q u ire s a larg e excess o f th e expensive a n d h ig h ly toxic, c h lo ro m e th y lm e th y le th e r as th e c h lo ro m e th y la tin g ag en t. T h e h a rs h co n d itio n s necessary to b rin g ab ou t th is re a ctio n also lea d to u n d e s ira b le F rie d e l-C ra fts (F-C ) a lk y la tio n products, th u s lo w e rin g th e y ie ld o f the expected 101.