S u p e rv is o rs : P r o f e s s o r A lfre d F isch e r
P ro fe s s o r Frank P ric e Robinson
ABSTRACT
A s e r i e s o f twenty-two s u b s t i t u t e d fluorom cthylnaphthalenes
19 1
has been s y n th e s is e d and t h e i r F n .m .r . and H n .m .r . s u b s t i t u e n t chemical s h i f t s and coupling c o n sta n ts measured. An a n a ly s is o f th e s u b s t i t u e n t e f f e c t on th e s e n . m . r . param eters has been c a r r i e d out in terms o f a dual s u b s t i t u e n t p a ra m eter eq uation using a m u ltip le l i n e a r r e g r e s s io n tre a tm e n t:
H = OjPj 4.
The dual s u b s t i t u e n t p aram eter e q u atio n d e sc rib e s the e f f e c t o f a s u b s t i t u e n t in terms o f two independent p a ra m eters, and a _ , which
1 K
correspond to th e p o l a r in d u c tiv e and p o l a r resonance e f f e c t s
r e s p e c t i v e l y . Various s u b s t i t u e n t c o n sta n t s c a l e s are i n v e s t i g a t e d and t h e i r degree o f correspondence to th e dual s u b s t i t u e n t model f o r \ \ th e se d a ta a s s e s s e d .
Moderately good c o r r e l a t i o n s 'o f th e d ata with the dual s u b s t i t u e n t p aram eter model a re observed f o r coupling c o n sta n ts and n .m .r .
. s u b s t i t u t e d chemical s h i f t s ; good c o r r e l a t i o n s are shown w ith A<1> values f o r 4 - s u b s ti t u te d - l- f lu o r o m e th y ln a p h th a le n e s i n p a r t i c u l a r ;
' ■ ' .
c o r r e l a t i o n s f o r 3 - s u b s t i t u t e d d e r i v a t i v e s are f a r le s s good.
^ !.. ■'
The s ig n s and magnitudes o f th e r e a c t i o n c o n s ta n ts , p . and p , f o r
^ ' i K
19
F s u b s t i t u e n t chemical s h i f t s a re i n t e r p r e t e d i n terms o f c u r r e n t t h e o r i e s o f s c r e e n in g o f a f l u o r i n e nucleus i n arom atic molecules and
19
th e F n .m .r . response to s u b s t i t u e n t e f f e c t s i n arom atic system s.
# - '
TABLE OF CONTENTS
' y." " Page
CHAPTER 1. INTRODUCTION ... •... / , . . ... 1
■ ■
/
• L inear Free Energy R e la tio n s h ip s .../ ... 1~ ' ■ ■ /■ ■ (1) The Haiflmett Equation ... . 1
/
■ ( i i ) Extensions o f th e Hammett Equation to the C o r r e la tio n o f N.M.R. Chemical'^ S h i f t Data . . . 7; / ( i i i ) Dual S u b s t it u e n t Parameter R e la tio n s h ip . . . 15
(iv) Linear Free. Energy R e la tio n sh ip S tu d ies in the Naphthalene S e r ie s ...• 1 19 T h e o r e tic a l C o n sid e ratio n s o f Chemical S h i f t 7 S u b s titu e n t Parameter C o r r e la tio n s ... 24
( i ) Quantum Mechanical C a lc u la tio n o f S h ie ld in g Parameters ... ; . 24
( i i ) E le ctro n Density - S u b s titu e n t Parameter C o rr e la tio n s ■ • 26 Benzyl .Fluorides' and Fluorom cthylnaphthalenes ... 31
R e a c tiv ity o f Benzyl F lu o rid es ... 39
O bjectives o f th e P re se n t P ro je c t ... 44
CHAPTER 2 . EXPERIMENTAL ; 46
Introductxon . . . 4 6 P re p a ra tio n o f Compounds ...1, . . . 49
CHAPTER 3 . : ' RESULTS. : . i / . . . . . I T : . . . ... • ' 150
Recording o f Nuclear Magnetic Resonance S p e c tra . . . 150
Tables o f R esults ... ' . ... 153
y ?
-Page
Ci) Dual S u b s t it u e n t Parameter C o r r e l a ti o n s . . i . . . 168
- [ i i ) S in g le S u b s t it u e n t Parameter C o r r e l a ti o n s ... 190
[ i i i ) Comparison o f Fluorom ethylnaphthalene and Benzyl F lu o rid e D a t a ... 190 ■ . ■ V . . CHAPTER 4. DISCUSSION ... ... . , . ____ 193 S p e c tr a l . C h a r a c t e r i s t i c s o f S u b s t it u t e d Naphthalenes . . . , 193 ( i ) ^ I n f r a r e d S p e c t r a ... 194 ( i i ) Mass S p e c tra ... 195 ( i i i ) N uclear Magnetic R e s o n a n c e 'S p e c t r a ... 198
Fluorom ethylnaphthalene N.M.R. Parameters ... 214
C o r r e l a ti o n s o f N.M.R. Param eters o f S u b s t it u t e d Fluorom cthylnaphthalenes ...' . ... ... I n t e r p r e t a t i o n o f th e R e su lts ... 224
Conclusions ... 238
Table LIST OF.TABLES ■
1
. . ' 19 ■ ' 100 MHz F N . m . r . s u b s t i t u t e n t Chemical s h i f t s Pageand coupling c o n sta n ts f o r carbon t e t r a c h l o r i d e s o l u t io n s co n ta in in g 4% by weight 1-flu o ro m ethy l nap h th alen e and 8% by weight s u b s t i t u t e d -1- f l u o r o
m ethylnaphthalene ... 156 19
I I 60 MHz F Chemical s h i f t s , s u b s t i t u e n t chemical - s h i f t s and coupling c o n sta n ts f o r carbon t e t r a
c h lo r id e s o lu tio n s c o n ta in in g 4% by weight 1- f l u o r o m ethylnaphthalene and 8% by weight s u b s t i t u t e d -1-
fluorom ethylnaphthalene ... 157 19
I I I 60 MHz F Chemical s h i f t s , s u b s t i t u e n t chemical s h i f t s and coupling c o n sta n ts f o r carbon t e t r a c h lo r id e s o lu tio n s co n ta in in g 6% by weight 1-.
i ■
' fluorom ethylnaphthalene and 4% by weight s u b s t i t u t e d
1 rfluorom ethyInaphthalene ... . . . . 158 IV S u b s t it u e n t chemical s h i f t values o f s u b s t i t u t e d . ,
fluorom cthylnaphthalenes taken from Tables I , I I
and I I I ... ; ... 159 V ^ [F]^ H e tero n u clear decoupling freq u e n cie s and
coupling constants, o f s u b s t i t u t e d fluorom ethyl- ■■
naphthalenes ... ' ... 160
1
VI 100 MHz H N.m.r. chemical s h i f t s , s u b s t i t u e n t chemical s h i f t s and coupling c o n sta n ts f o r carbon t e t r a c h l o r i d e s o lu t io n s co n ta in in g 4% by weight
1-fluoxom ethylnaphthalene and 8% by weight s u b s t i t u t e d
T -flu o ro m eth y ln ap h th alen e , . ... 161
- ' . 1 ' - ' '
-VII 60 MHz H N.m.r. chemical s h i f t s , s u b s t i t u e n t chemical s h i f t s and coupling c o n sta n ts f o r carbon t e t r a c h l o r i d e s o l u t io n s co n ta in in g 4'â by weight
1-fluo ro m eth y ln ap h th alen e and 8% by weight ’
Table V I I I IX XI XII X III XIV XV XVI XVII XVIII v i i Pago 1 60 II N.m .r. chemical s h i f t s , s u b s t i t u e n t chemical s h i f t s and coupling c o n s ta n ts f o r carbon t e t r a c h l o r i d e s o l u t i o n s c o n ta in in g 6% by weight 1-
flu o ro m e th y ln a p h th a le n e and 4% by w eight s u b s t i t u t e d
1- flu o ro m e th y ln a p h th a le n e ... ... ..
S u b s t i t u e n t chemical s h i f t v a lu e s o f s u b s t i t u t e d j flu o ro m c th y ln a p h th a le n e s tak en from-Tables VI,
VII and VIII ... ... [H] H e te ro n u c le a r decoupling fr e q u e n c ie s and
r
coupling c o n s ta n ts o f s u b s t i t u t e d f lu o ro m e th y l- n a p h th a le n es ... ... L TT/v . . . . . . . Chemical s h i f t v alues measured under sta n d a rd c o n d itio n s - 5% i n CCl-^F o r CCl^ ... ... .... 60 MHz and S u b s t i t u e n t chemical s h i f t s
and coupling c o n s ta n ts f o r s u b s t i t u t e d benzyl f l u o r i d e s ... Values o f s u b s t i t u e n t p a ra m eters -... 19 M u ltip le l i n e a r r e g r e s s io n o f 100 MHz F S u b s t i t u e n t chemical shifts^orfv 4 s u b s t i t u t e d l -flu o ro m e th y in a p h th a le n e s . / . . . . ... ; ... \ 19 M u ltip le l i n e a r r e g r e s s io n ox. 100 MHz F s u b s t i t u e n t chemical s h i f t s o f 3 s u b s t i t u t e d l -flu o ro m e th y ln a p h th a le n e s ... ... 19 M u ltip le l i n e a r r e g r e s s io n o f 60 MHz F s u b s t i t u e n t chemical s h i f t s o f 4 - s u b s t i t u t e d - l - . flu o ro m e th y ln a p h th a le n e s ... 19 M u ltip le l i n e a r r e g r e s s io n o f 60 MHz F , - s u b s t i t u e n t chemical s h i f t s o f 3 - s u b s t i t u t e d - l i r ; flu o ro m e th y ln a p h th a le n e s ... ... ... 19 M u ltip le l i n e a r r e g r e s s io n o f 60 MHz F s u b s t i t u e n t chemical s h i f t s o f and m - s u b s t i tu t e d benzyl f l u o r i d e s / ... 163 164 .165 166 167 171 177 178 . t> 179 180 181
te-. XXI X IX M u ltip le l i n e a r r e g r e s s i o n c q r r c l a t i o n o f and 100,MHz ^11 s u b s t i t u e n t c h ^ i c a l s h i f t ! 4 - s u b s t i t u t c d - l - f l u o r o m e t h y l n a ] ^ t h a l é n e s ...' 182 i XX M u ltip le l i n e a r r e g r e s s io n o f 100 MHz Jj^P c o u p lin g c o n s ta n ts o f and 4 - s u b s t i t u t e d
flu o ro m e th y ln a p h th a le n e s and m- and ^ - s u b s t i t u t e d
^ ^ r f z y l f l u o r i d e s ... 183 XXI M u ltip le l i n e a r r e g r e s s io n o f 100 MHz s u b s t i t u e n t chemical s h i f t s o f 4 - s u b s t i t u t e d - l - flu o ro m e th y ln a p h th a le n e s. S u b s t i t u e n t s n o t s u b je c t t o S t e r i c t w i s t i n g by p e r i - h y d r o g e n s , Br, C l, F, CN, CH ... : ... 184 XXII M u ltip le l i n e a r r e g r e s s i o n o f 100 MHz and 60 MHz
19
-F s u b s t i t u e n t chemical s h i f t s o f 3 - s u b s t i t u t e d - 1 -flu o ro m e th y ln a p h th a le n e s o m ittin g -COOMe and
-COOEt p o i n t s ... ^ ___ 185___ XXIII L in e a r l e a s t sq u a re s c o r r e l a t i o n o f s u b s t i t u e n t
chemical s h i f t s and Brown o* v a lu e s f o r s u b s t l t u t e d -
1-flu o ro m e th y ln a p h th a le n e s and s u b s t i t u t e d benzyl
f l u o r i d e s , and c a l c u l a t e d z v a lu e s . ... ^... 187 Observed and c a l c u l a t e d s u b s t i t u e n t c h e m ic a l \ s h i f t
v a lu e s f o r - 4 - s u b s t i t u t e d - l - f l u o r o m e t h y l n a p h t h a l e n e s '
measured l'aï ] 100 MHz ... , . , . , 188 XXV Observed and c a l c u l a t e d s u b s t i t u e n t chemical s h i f t
v a lu e s f o r 3 - s u b s ti t u te d - l - f l u o r o m e t h y l n a p h t h a l e n e s
i x *
LIST OF PIGUULS
Fifluro Fago
1 The magnetic moment> y , r e s u l t i n g from th e r o t a t i o n .
o f th e p o s i t i v e charge d i s t r i b u t i o n o f a n u c le u s . . . 8
2 Diagram showing o r b i t a l o v e rla p in b e n z o t r i
-f l u o r i d c ... 38 3 A p l o t o f A({> mcasui'cd a t 94.08 MIlz a g a i n s t Brown o*
v a lu e s ^ f o r s u b s t i t u t e d 1 -f lu o ro m e th y ln n p h th a lc n c s .. 191 4 A graph o f 94.08 Mllz s u b s t i t u e n t cliemical s h i f t s f o r 3- and 4 - s u b s t i t u t e d flu o ro m e th y ln a p h th a le n e s 19 a g a in s t 56.45 MHz !• s u b s t i t u e n t chemical s h i f t s * f o r m- and g - s u b s t i t u t c d benzyl f l u o r i d e s ... 192 5 I n f r a r e d spectrum o f 1-flu o ro m e th y ln a p h th a le n e '^"^ctw ccn 4000-1200 cm ^ ... 196 6 ' I n f r a r e d spectrum o f 1-flu o ro m e th y ln a p h th a le n e —1 between 1350-400 cm -■... 197 7 Mass spectrum o f 1 - f l u o r o m e t h y l n a p h t h a l e n e ... 199 1 ■ 8 H N .m .r. spectrum o f 4-m ctliyl-1 -n a p h th y lc a r b in o l i n th e re g io n t 7-8 p .p .m ... 201 1
. 9 60 MHz H n . m . r . s p e c t r a o f 3-brom o-l-m
ethyl-n a p h th o a te w ith d i f f e r e ethyl-n t c o ethyl-n c e ethyl-n tr a tio ethyl-n s o f EuCfod)„
added ... 204 10 60 MHz ^H n . m . r . s p e c t r a o f i^ 3 - n i t r o - l - m e t h y l - n a p h th o a te , i i ) 3 - n i tr o - l - m e t h y ln a p h th o a t e w ith 0 .0 3 g E u (fo d )_ added t o t h e CCl^ s o l u t i o n ...205 1 11 220 MHz H n . m . r . spectrum o f 3-b'^omo-l-mcthyl-nap h th o a tc ... 206 1
12 220 MHz H n . m . r . spectrum o f 3-bromo- 1 -m eth y l-n a p h th o a te g e l-n e ra te d by i t e r a t i v e l-n . m . r . computer
13 N .m .r..c h e m ic a l s h i f t s and co u p lin g c o n s ta n ts f o r 3-bro m o -l-m eth y ln ap h th o ate (a) measured a t 220 MHz and (b) g e n e ra te d by i t e r a t i v e n .m .r .
computer program UEAVIC ... ... 209 14 N .m .r. spectrum o f (a) 1 ,4-dibrom om
cthyl-n a p h th a lc cthyl-n e , Cb) 1,4 - d in a p h th o ic a c i d , (c) 1 ,4 -
d i n it r o n a p h t h a lc n c ... 2 1 1
‘ 1
15 ^ (a) II N .m .r. spectrum o f n ap h th a le n e
C a l ^ l a t c d spectrum o f n a p h th a le n e with values
f o r chemical s h i f t s and co u p lin g c o n s ta n ts ... 2 1 2
19' *
1,6--- 60 MHz f n .m . r . spectrum o f 8% 1-flu o rom eth y
1-4-/ methojtynfethylnaphthalcne and 4% 1- f lu o ro m e th y l
n a p h th a le n e in carbon t e t r a c h l o r i d e ... 213
xi
ACKNOWLEDGEMENTS
The a u th o r wishes to ex p ress h e r a p p r e c i a ti o n to Dr. A. F is c h e r and Dr. F.P. Robinson f o r t h e i r c o n sta n t guidance and encouragement d u rin g th e course o f t h i s work.
F in a n c ia l s u p p o rt from th e U n iv e rs ity o f V i c t o r i a in th e form o f a Po st-G rad u ate Fellow ship (1969-1973) i s g r a t e f u l l y acknowledged.
N!y t h a n k s . a l s o gp to Miss P h y l l i s Watson o f th e U n iv e rs ity o f B r i t i s h Columbia, and Mrs. C h r i s t i n e Greenwood o f th e U n iv e rs ity o f V i c t o r i a f o r th e r e c o rd in g o f many o f th e n . m . r . s p e c t r a , and to Mrs. Diane Gray f o r th e ty p in g o f th e m a n u scrip t.
INTRODUCTION
L inear Frco Hncruy R e la tio n s h ip s (1) The Hammett nquatioii
S ev eral e m p iric a l r e l a t i o n s h i p s have been su g g e ste d i n a n ,a tte m p t t o c o r r e l a t e q u a n t i t a t i v e l y s u b s t i t u e n t e f f e c t s on r e a c t i o n r a t e s and . mechanisms. Tiie r a t e o r e q u ilib r iu m c o n s ta n t o f a r e a c t i o n o f a '
• '
molecule may be in flu e n c e d by s t r u c t u r a l m o d if i c a t io n s , through th e medium o f p o l a r , s t e r i c , o r reso n an ce e f f e c t s .
-I f one a c c e p ts t h a t most m o lecu lar p r o p e r t i e s a rc r e l a t e d t o th e e l e c t r o n i c n a tu r e o f th e s p e c i e s , in term s o f d i s t r i b u t i o n and
m agnitude, then i d e a l l y i t should be p o s s ib l e t o d e s c r i b e th e observed phenomena i n p r e c i s e quantum m echanical term s. Because th e p r e s e n t s t a t e o f u n d e rsta n d in g o f b o th th e phenomena and quantum mechanics docs n o t perm it such a complete and d e f i n i t i v e e x p la n a tio n , a tte m p ts to c o r r e l a t e observed phenomena have been in terms, o f e m p iric a l r e l a t i o n s h i p s , h o p e f u l l y o f a p r e d i c t i v e n a t u r e . Extension and refin e m e n t o f t h e d e t a i l e d form o f t h e s e e m p iric a l r e l a t i o n s h i p s have led t o a c l e a r e r u n d e rs ta n d in g o f t h e i m p lic a tio n s and i n t e r p r e t a t i o n o f th e p a ra m e te r s , in terms o f t h e p h y s ic a l p r o p e r t i e s o f th e system.
I ' ■ ' ■ ■
in v o lv in g th e lo g a rith m s o f r a t e s o r e q u il i b r i u m c o n s t a n t s . One o f 1
th e e a r l i e s t , p u t forward by Hammett ' i n 1937, d e s c rib e d th e
in f lu e n c e o f meta- and p a r a - s u b s t i t u e n t s on th e s i d e - c h a in r e a c t i o n s o f benzene d e r i v a t i v e s . As th e s ta n d a r d r e a c t i o n s e r i e s Hammett took
■■
th e i o n i s a t i o n o f th e meta- and p a r a - s u b s t i t u t e d benzoic a c id s in w a te r , as t h e r e wqre c o n s id e r a b le a c c u r a te d a ta a v a i l a b l e concerning t h i s s e r i e s . ; The e q u atio n i s o f th e fo rm
:-logCk/k ) = op f o r r a t e d a ta
log(K/K^) = op"- f o r e q u ilib riu m d a ta
In th e s e e q u a tio n s and r e f e r t o t h e p a r e n t compound, k and K t o th e s u b s t i t u t e d d e r i v a t i v e . For th e d e f i n i n g s u b s t i t u t e d b e n zo ic a c i d s e r i e s , p, th e r e a c t i o n c o n s ta n t i s equal t o u n i t y . (
The s u b s t i t u e n t c o n s ta n t o r 'sigm a-valueV , i n i t i a l l y d e fin e d as
o = logCK/K^)
\ • ■
f o r th e s ta n d a r d r e a c t i o n s e r i e s , measures th e p o l a r e f f e c t o f t h e ' s u b s t i t u e n t r e l a t i v e t o hydrogen, and so r e p r e s e n t s th e a b i l i t y o f a
s u b s t i t u e n t t o a t t r a c t o r r e p e l e l e c t r o n s by i n d u c tiv e and resonance - e f f e c t s . I f th e s u b s t i t u e n t has an e f f e c t o f o v e r a l l e l e c t r o n d o n atio n
then th e a -v a lu e i s n e g a t iv e ; i f th e o v e r a l l e f f e c t i s one o f e l e c t r o n - a t t r a c t i o n th e o -v a lu e i s p o s i t i v e . Any given s u b s t i t u e n t has d i f f e r e n t
o -v a lu e s f o r m eta- and p a r a - p o s i t i o n s , f o r example, th e Hammett o -v alu e f o r £-OCHj i s -0 .2 6 8 and f o r m-OCH^ i s +0.115. O r i g i n a l l y Hammett
d e v i a t i o n s from t h i s i d e a l s i t u a t i o n h as le d t o th e development b f more d e t a i l e d and more comprehensive l i n e a r c o r r e l a t i o n s , arTd-thrmigK t h e s e t o a c l e a r e r u n d e rs ta n d in g o f th e e f f e c t s o p e r a tin g . In th e Hammett e q u a tio n th e q u a n t i t y p i s th e r e a c t i o n ^ c o n s t a n t . . ' ^ - o r " r h o - v a lu e ” and t h i s r e p r e s e n t s th e s u s c e p t i b i l i t y o f a r e a c t i o n o ' * " ' . » s e r i e s to s u b s t i t u e n t e f f e c t s . R eactio n s aid e d by e le c t r o n
w ithdraw al from th e phenyl r i n g have p o s i t i v e p-rvalues; c o n v e rse ly , r e a c t i o n s aid ed by e l e c t r o n d o n a tio n have n e g a tiv e p - v a lu e s . The ■ p -v a lu e i s o b ta in e d from a p l o t o f log (k/k^) a g a i n s t a; knowledge o f o - v a lu e s f o r s u b s t i t u e n t s , and r a t e o r e q u ilib r iu m d a ta f o r r e a c t i o n s e r i e s w ith th e s u b s t i t u e n t s as members e n a b le s p - v a lu e s to be ~ c a l c u l a t e d f o r th e s e s e r i e s . C o rresp o n d in g ly , knowledge o f p - v a lu e s and r e a c t i v i t y d a ta e n ab les o -v a lu e s t o be c a l c u l a t e d . o-Values a re known f o r about a hundred s u b s t i t u e n t s , p -v a lu e s f o r about fo u r hundred r e a c t i o n s e r i e s . From t h e s e , r a t e or i o n i s a t i o n d a ta a re c a l c u l a b l e f o r . about f o r t y thousand d i f f e r e n t compounds. _
The dependence o f th e r e a c t i o n r a t e o r e q u ilib r iu m c o n s ta n t upon th e s o lv e n t system o r te m p e ra tu re , for. example, i s r e f l e c t e d in p.
L im ita tio n s and A p p lic a tio n s o f L in e ar Free Energy R e la tio n s h ip s A l i n e a r f r e e energy r e l a t i o n s h i p can be expected only under one o f t h r e e c irc u m s ta n c e s. Each r e a c t i o n s e r i e s ' m u s t - e x h i b i t one of th e fo llo w in g ty p es o f b e h a v io u r
:-(a) AH° i s c o n s ta n t throughout th e s e r i e s .
(b) AS" i s c o n s t a n t ^
■ . . 4
■ 2 '
B olton, Fleming and Hall r e p e a te d th e pK measurements o f th e benzoic a c id s e r i e s a t d i f f e r e n t te m p e ra tu re s and c a l c u l a t e d AG®, AH“ and AS® f o r th e s e compounds. R e la ti v e p l o t s ,of th e s e thermodynamic param eters gave l i n e a r r e l a t i o n s h i p s :
AH® vs AS®. r = 0.9992 ' - ■ AG® vs AH® . ,r = .0.9984
wherexr i s th e c o r r e l a t i o n c o e f f i c i e n t , and i s e s s e n t i a l l y a r a t i o which e x p re sse s th e e x te n t t o which changes in one v a r i a b l e a re accompanied by o r a re depen^nt.,^upon changes in a second v a r i a b l e . The more l i n e a r t h e r e l a t i o n s h i p th e c lo S e ^ ^ r\J ^ t o 1.00. From th e s e p r e c i s e measurements th e a u th o rs concluded t h a t th é 1 1-hear f r e e .e n e r g y r e l a t i o n s h i p observed
i n th e i o n i s a t i o n o f t h e .b e n z o ic a c id s e r i e s was a consequence o f AH b e in g l i n e a r l y r e l a t e d t o AS®. ■ - ^ ' ' . ■ . . . ' In g e n e ra l term s, th e - .e x p r e s s io n . lo g ( k /k ) i s p r o p o r t io n a l t b ' t h e ■ ' ~ ^ . ... d i f f e r e n c e i n th e f r e e e n e rg ie s o f r e a c t i o n o f th e s u b s t i t u t e d
d e r i v a t i v e and th e p a re n t compound i f th e K’s a re e q u ilib riu m c o n s t a n t s , o r t o th e d i f f é r e n c e in th e f r e e e n e rg ie s o f a c t i v a t i o n i f th e k ' s are r a t e c o n s t a n t s . . I t i s . n o t im m e d ia te ly ’a p p aren t t h a t .such a l i n e a r f r e e . energy r e l a t i o n s h i p should hold and t h a t one o f th e t h r e e c o n d itio n s be s a t i s f i e d , p a r t i c u l a r l y when i t i s r e a l i s e d t h a t en tro p y ,, k i n e t i c . , '
o ’ ■ ' ' ' - . \ ,
e n ergy, and p o t e n t i a l energy changes a l l c o n t r i b u t e t o t h e . f r ë e energy , change. I t .appears t h a t most o f th e r e a c t i o n s which c l o s e l y follow th e Hammett r e l a t i o n s h i p do not in v o lv e any a p p re c ia b le r e l a t i v e entropy
n o r t h e e n tro p y rem ains c o n s ta n t a r e n o t c o r r e l a t e d in term s o f th e Hammett e q u a tio n and t h a t th e e q u a tio n i t s e l f may t h e r e f o r e be
c o n sid e re d in t e r m s 'o f p o t e n t i a l energy d i f f e r e n c e s between a p p r o p r i a te energy s t a t e s , le a d s t o an e q u a tio n of- th e fo rm
:-log(K/K^y = A E (fin al) - A E ( i h i t i a l )
where AE term s a re themse-lves energy d i f f e r e n c e s between c o rre sp o n d in g p o t e n t i a l e n e r g ie s o f -the p a r e n t compound and th e s u b s t i t u t e d d e r i v a t i v e
AE - E - E o
I t w a s'b a se d on t h i s assumption t h a t Ehrenson c a r r i e d out a quantum m echanical p e r t u r b a t i o n f o r m u la tio n o f th e problem which he su b s e q u e n tly a p p li e d t o th e j u s t i f i c a t i o n o f th e s e p a r a t io n o f t h e in d u c tiv e and reso n an ce c o n t r i b u t i o n s t o th e a - c o n s t a n t . Assuming t h a t th e t o t a l H a m ilto n ia n 'c o u ld 'b e conceived as th e sura o f one e l e c t r o n o p e r a t o r s , he c o n sid e re d th e e f f e c t o f b o th th e s u b s t i t u e n t and th e r e a c t i o n .c e n tre on e a c h 'm o le c u la r o r b i t a l o f th e p a r e n t hydrocarbon, benzene. He o b ta in e d th e r e s u l t t h a t th e t o t a l change in. p o t e n t i a l .
energy was p a r t l y dependent on th e p e r t u r b a t i o n due t o t h e s u b s t i t u e n t , and t h i s was m u l t i p l i e d by. a term d e s c r i b i n g à p a r t dependence on th e p a r e n t r e a c t i o n s u b s t i t u e n t , o r , th e t o t a l p o t e n t i a l energy change between t h e two s t a t e s (ground s t a t e and t r a n s i t i o n s t a t e , say', f o r k i n e t i c d a ta ) was given by an e x p re s s io n i n which a s u b s t i t u e n t
6
th e form o f th e o r i g i n a l Hammett e q u a tio n . . /
■■ ■ ■ . I
£ This r e s u l t was o b ta in e d w ith o u t s p e c i f y i n g th e symmetry ty p e s
. . \ I
in v o lv e d . The o n ly assum ption made was t h a t th e t o t a l H am iltonian was th e sum o f one e l e c t r o n o p e r a t o r s . I f o r b i t a l ty p e s were t o be
' / ■ '
s p e c i f i e d , then t h i s would lea d t o a d i v i s i o n i n t o summations over
o-f
'
and iT-type o r b i t a l s . This p o s s i b i l i t y o f f f lis ./s e p a r a t i o n would be e xpected only i f p i and sigma e l e c t r o n p e r t u r b a t i o n s were d i s t i n c t l y
d i f f e r e n t and i f i n t e r a c t i o n s between th e two/were sm a ll. . T hroughout■l i n e a r f r e e energy s t u d i e s o r t h o - s u b s t i t u e n t s have
produced 'anom alous' r e s u l t s . The re a so n f o r lack o f c o r r e l a t i o n o f
^ ' . .. ^
o r t h o - s u b s t i t u t e d compounds i s j u s t i f i a b l e th e l i g h t o f th e p re v io u s
' / • ■ ■■
o b s e r v a tio n s and i n t e r p r e t a t i o n s . The r e s t r i c t i o n o f th e v a l i d i t y o f th e
.
.
I
e q u a tio n to meta- and p a r a - s u b s t i t u t e d b e n z e n e s, and th e e x c lu s io n o f
o r t h o - s u b s t i t u e n t s , le a d s t o th e c o n c lu sio n t h a t s t e f i c and o t h e r p ro x im ity phenomena p la y a l a r g e p a r t in th e e f f e c t s p e c u l i a r to- o r t h o - s u b s t i t u e n t s . .
. " . . . . . ■ . . ■
This,, o b s e r v a tio n has i m p l i c a ti o n s which have le d t o s e v e r a l im p o rta n t co n cep ts r e l a t i n g t o th e n a tu r e o f s u b s t i t u e n t e f f e c t s .. I t has le d to t h e p o s t u l a t i o n o f p rim ary s t e r i c e f f e c t s o f s e v e r a l k in d s , in c lu d in g s t e r i c h i n d r a n c e - t o s o l v a t i o n , or t o th e approach o f th e r e a g e n t , and, p ro x im ity e f f e c t s such as i n tr a m o l e c u l a r hydrogen bonding o r o t h e r
i n tr a m o l e c u l a r i n t e r a c t i o n s . Attempts h a v e.b e en made t o s e p a r a t e s t e r i c ' e f f e c t s from p o l a r and o t h e r e f f e c t s . - Many r e a c t i o n s have been s t u d i e d in t h i s c o n te x t, b u t v e ry l im i te d su ccess has a tte n d e d th e s e a tte m p ts t o o b ta in a g e n e ra l s e p a r a t i o n of. e f f e c t s o f o r t h o - s u b s t i t u e n t s . S h o r t e r has e x p re ss e d th e o p in io n t h a t " . . . t h e complexity, o f th e
t h i s view i s su b se q u e n tly r e i t e r a t e d by C harton. .
The U n s a t i s f a c t o r y n a tu r e o f th e c o r r e l a t i o n o f o r t h o - s u b s t i t u t e d systems does a ls o have b e a r in g on th e success o f that^shown in th é case o f th e meta and p a r a - s u b s t i t u t e d s e r i e s .
( i i ) Extension o f th e Hammett Equation t o th e C o r r e la tio n s of
N.M.R. Chemical S h i f t Data
-In a d d itio n t o e q u ilib riu m c o n sta n t and f a t e c o n s ta n t l i n e a r f r e e energy c o r r e l a t i o n s , t h e r e have been r e p o r t e d many c o r r e l a t i o n s w ith a v a r i e t y o f p h y s ic a l p r o p e r t i e s f o r v a r i o u s . s u b s t r a t e s ; n o ta b ly among t h e s e , chemical s h i f t s , in n u c le a r magnetic reso n an c e.
-The phenomenon o f n u c le a r magnetic resonance i s a consequence o f .
* r '
th e n u c le a r p r o p e r t i e s o f th e atomic s p e c ie s w ith in th e m olecule. Most n u c le i p o ssess a magnetic moment, and whep such a nucleus i s , . p lac ed in a magnetic f i e l d , i t ta k e s up one o f a number of q u a n tise d
o r i e n t a t i o n s w?th r e s p e c t t o t h a t f i e l d . Each o r i e n t a t i o n corresponds
■ ' '■ . . ' . '
t o an energy level^ th e lowest being t h a t i n which th e n u c le a r magnetic moment i s most c l o s e l y a lig n e d with th e f i e l d . N uclear magnetic resonance sp e ctro sc o p y ,co m p rise s t h e in d u c tio n o f t r a n s i t i o n s between such energy l e v e l s by means o f f l u c t u a t i n g magnetic f i e l d s o f th e a p p ro p r ia te
'freq u en cy . '
Although i t s volume i s sm a ll, a m a g n e tic n u c le u s ,g iv e s r i s e t o a f i n i t e . s p a t i a l d i s t r i b u t i o n o f p o s i t i v e ch arg e. I f , in a d d it i o n , th e
' . ' V ' . ■ ■ ■ ■
n u cleu s has sp in a n g u la r momentum, then t h i s phenomenon, which may be th o u g h t o f as th e sp in n in g o f th e n u c le u s , w i l l cause th e p o s i t i v e charge \ d i s t r i b u t i o n to r o t a t e and give r i s e t o th e ' ’ ‘
e q u i v a l e n t o f a c u r r e n t flow ing i n a c i r c u l a r p a th . This produces
a m agnetic f i e l d which i s n e a r l y p a r a l l e l , t o th e a x is o f s p i n , and thus th e n u c le u s p o s s e s s e s a m agnetic moment, p.
F ig . 1. The m agnetic moment, p, r e s u l t i n g . f r o m th e r o t a t i o n o f th e - p o s i t i v e charge d i s t r i b u t i o n o f a n u c le u s .
The quantum m echanical e x p re s s io n f o r th e a n g u la r momentum is giv en b y : - .
-r c i + i ) h /2Tî ;
where I i s th e sp in quantum number (o r sp in o p e r a t o r ) . I f I i s not eq u al t o z e r o , th en t h e , n u c l e u s has s p in a n g u la r momentum' and Under a p p r o p r i a t e c o n d it i o n s w i l l e x h i b i t n u c le a r m agnetic resonance
1 2 1 6 2 4 * 2 8 '
phenomena. Species w ith 1 = 0 in c lu d e C, 0, Mg, S i; s p e c ie s w ith I = 1/2 in c lu d e ^H, and Of a l l t h e s e , by f a r t h e most im p o rtan t from th e p o i n t o f view o f g e n e r a l a p p l i c a b i l i t y and
1 ' 19 31
w e ll r e s o lv e d s p e c t r a i s H, b u t F and P a re now c o n sid e re d r o u t i n e
In an a p p li e d magnetic f i e l d a p rô to n (I = 1/2) w i l l assume one o f two p o s s i b l e o r i e n t a t i o n s w ith r e s p e c t t o th e d i r e c t i o n o f th e a p p lie d m agnetic f i e l d , . (In g e n e r a l , th e number o f p o s s ib l e o r i e n t a t i o n s i s given by (21+ 1)). The o r i e n t a t i o n s co rresp o n d t o energy l e v e l s o f + yH , where y i s th e m agnetic moment o f th e s p e c ie s and H i s th e
■ - . ■ ■■ ■ ■ ° ■ ‘ ■
s t r e n g t h o f th e a p p l i e d ^ f i e l d . The t r a n s i t i o n o f a p ro to n from one o r i e n t a t i o n t o th e o t h e r and th u s from one energy l e v e l t o a n o th e r may be e f f e c t e d by th e a b s o r p tio n o r em ission o f a d i s c r e t e amount o f energy, such t h a t :
-E = hv = 2yH
where ,V i s th e freq u en cy o f th e e le c tr o m a g n e tic r a d i a t i o n absorbed or e m itte d , and i s t h e p r o c e s s io n a l freq u en cy (Larmor frequency) o f th e n u c le u s . Unless th e a x is o f th e n u c le a r magnet i s o r i e n t e d e x a c tl y p a r a l l e l o r a n t i p a r a l l e l with th e a p p lie d m agnetic f i e l d , s i n c e th e
n u c le u s i s s p in n in g , ‘i t s r o t a t i o n a l a x is draws o u t a c i r c l e p e r p e n d ic u la r ‘ t o t h e , a p p l i e d f i e l d , o r th e n u c le u s i s s a i d t o p r o c e s s . The n u c le a r
t r a n s i t i o n co rresp o n d s t o a change in t h e an g le t h a t th e a x is o f th e n u c le a r magnet makes with the a p p lie d m agnetic f i e l d . This change can. be b ro u g h t about by ap p ly in g e le c tr o m a g n e tic r a d i a t i o n whose m agnetic • ■ v e c t o r component r o t a t e s in à p la n e p e r p e n d ic u la r t o th e main m agnetic
f i e l d . IVhen th e frequency o f th e r a d i a t i o n i s equal t o t h a t o f th e p r e c e s s i n g n u c le u s then em ission o r a b s o r p tio n o f energy o ccu rs and th e ‘ c o n d itio n o f resonance i s a ch iev e d . For p ro to n s in a m agnetic f i e l d o
f-10 - - '''I
. 1.40 T esla th e frequency o f t h i s energy”*xs in th e r a d io -fre q u e n c y re g io n - about 60 MHz. For f l u o r i n e n u c le i in th e same m agnetic f i e l d th e .
frequency o f th e e le c tro m a g n e tic r a d i a t i o n re q u ir e d i s about 56.5 MHz., ■It i s p o s s i b l e t o induce a n u c le a r t r a n s i t i o n in one o f two ways; e i t h e r by m ain tain in g a c o n s ta n t v alu e b f th e a p p lie d magnetic f i e l d , and vary in g th e frequency o f th e r o t a t i n g magnetic f i e l d , o r by
m a in ta in in g th e frequency o f t h e r o t a t i n g f i e l d and vary in g th e s t r e n g th ■ o f th e a p p lie d f i e l d over a small range. This l a t t e r i s th e more common
procedure.' . r . ■
The f a c t t h a t n u c le a r magnetic resonance sp e ctro sc o p y * is such a
v a lu a b le tec h n iq u e i s due in la r g e p a r t t o th e f a c t t h a t n .m .r. fre q u e n c ie s ar,e t o a sm all degree dependent on th e m o lecu lar environment o f th e
n u c le u s . The su rro u n d in g e le c t r o n s s h i e ld th e nlscleus, and so th e
e f f e c t i v e magnetic f i e l d i s not th e same as t h a t appTded. I f any atom or m olecule i s p laced in a magnetic f i e l d i t a c q u ir e s a diam agnetic .moment ■by v i r t u e o f th e induced o r b i t a l motions o f i t s electronsV , These moving
e l e c t r o n s c o n s t i t u t e e f f e c t i v e c u rr e n ts w ith in th é molecule and th e re b y produce a secondary magnetic" f i e l d which a ls o a c t s on tJ jje ^ u c le i p re s e n t. The induced c u r r e n t s a re p r o p o r tio n a l to th e a p p lie d f i e l d f o r
diam agnetic m olecules. As a r e s u l t , th e l o c a l magnetic f i e l d a t th e p o s i t i o n o f th e n u cleu s i s given by
" l o c a l = " a p p l . C - " ) .. /
where a i s a non-dim ensional c o n s ta n t, independent a n d ' dependent upon th e e l e c t r o n i c environment. This -constant a i s known as th e s h i e ld i n g o r s c re e n in g c o n s t a n t , because th e l o c a l f i e l d i s u s u a lly
l e s s th a n th e a p p li e d . The e f f e c t o f t h e s c r e e n in g c o n s ta n t b r in g s th e e nergy l e v e l s c l o s e r t o g e t h e r , and so thQ energy o f th e t r a n s i t i o n i s s m a l l e r and resonance o ccurs a t lower fre q u e n cy . I f reso n an ce i s achieved a t a f ix e d freq u e n cy by v a ry in g t h e a p p lie d f i e l d , then a i a r g ^ ' f i e l d must be a p p lie d . ■ V
,
a p p i . 7V _ïk_J
Thus, exam ination-O f n . m. r . s p e c t r a o f a n u c l e a r s p e c i e s i n v a rio u s chemical environm ents, e i t h e r in th e same m olecule o r a d i f f e r e n t
m olecule, i n d i c a t e s t h a t th e s h i e l d i n g c o n s t a n t has d i f f e r e n t values', ^ A and so reso n an ce occurs i n a d i f f e r e n t p a r t o f th e spectrum f o r each
c h em ic ally d i s t i n c t p o s i t i o n . The d isp lacem en t o f a s i g n a l co rre sp o n d in g t o d i f f e r e n t chemical environm ents due to v a r i a t i o n s in s h i e ld i n g
c o n s t a n t s i s known as a chemical s h i f t and i s e x p re ssed as a disp lacem en t from th e resonance s i g n a l o f a s ta n d a rd re fe ren c e, compound. The chemical
' ■ ■ ' ' '
‘s h i f t f o r th e p ro to n i s d e f i n e d :
-H-H
6 =
H- X 10^
where H i s th e reso n an ce f i e l d o f th e sample
H i s - t h e reso n an ce f i e l d o f th e r e f e r e n c e s i g n a l,
r .
-_ 12
5 = O - G ■
r
The s h i e ld i n g t h a t a proton e x p erien c es i s a combination o f a t l e a s t t h r e e ty p es o f e l e c t r o n i c c i r c u l a t i o n s : l o c a l diam agnetic e f f e c t s , diam agnetic and param agnetic e f f e c t s from n eighbouring atoms, and e f f e c t s from in te r a to m ic c u r r e n t s .
A q u a n t i t a t i v e th e o r y o f th e atomic c o n tr i b u t i o n s to th e chemical s h i f t s observed in f l u o r i n e magnetic resonance was developed by Saika and S l i c h t e r . ^ Saika and S l i c h t e r suggested t h a t th e p r i n c ^ a l cause o f chemical s h i f t s observed in f l u o r i n e c o n ta in in g compounds, a s/p a.ra
-' , _ . - .
m agnetic i n o r i g i n . Using simple valen ce bond wave f u n c t i o n s , t h e y % c a l c u l a t e d th e param agnetic c o n tr i b u ti o n to s h i e l d i n g . This^ should
correspond to th e d i f f e r e n c e between a p u r e ly io n ic bond and a p u r e ly ' ' c o v a le n t bond. This i s s u b s t a n t i a t e d by th e o b se rv a tio n t h a t th e
f l u o r i n e - n u c l e i in F„ a re l e s s s h ie ld e d than in o t h e r f liid r in e compounds. The more i o n ic th e bond, th e more th e param agnetic c o n tr i b u ti o n i s
red u ced , and so t h i s ' would lead to an approxim ately l i n e a r dependence on th e e l e c t r o n e g a t i v i t y o f the neighbouring atom o r group. In a s e r i e s o f
19
b in a r y f l u o r i d e s XF th e F s h i e ld i n g in c r e a s e s in a l i n e a r fa sh io n . a s t h e e l e c t r o n e g a t i v i t y o f X d e c re a s e s . "
Many o f th e a tte m p ts a t e x p la in in g th e v a r i a t i o n s o f f l u o r i n e -• s h i e l d i n g c o n s ta n ts in molecules have c e n tre d on arom atic system s, and alm ost always on s u b s t i t u t e d benzenes. The f l u o r i n e chemical sc re e n in g c o n s ta n t i s a s e n s i t i v e means o f r e f l e c t i n g th e changes in th e
e l e c t r o n i c s t r u c t u r e o f a s u b s t i t u t e d aro m atic compound. The.changes a re l a r g e a t th e o rth o - and p a r a - p o s i t i o n s and l e s s so a t the,
meta-p o s i t i o n s . I f a flu o rin e , nucleus i s disposed p a r a - t o a s u b s t i t u e n t then _ th e observed chemical s h i f t depends t o a la r g e e x te n t on th e Tr-electron d i s t r i b u t i n g e f f e c t o f th e s u b s t i t u e n t . S u b s titu e n ts such as -NHg and -OH which r e s u l t in an in c r e a s e in ir-e le c tro n d e n s ity a t the p a r a - carbon atom give r i s e t o â h \in c r é a s e d s h i e ld i n g o f th e f l u o r in e atom;
co rresp o n d in g ly th e converse i s obseived with Tî-electron withdrawing s u b s t i t u e n t s . For f l u o r i n e , t h i s has been expressed
19
F = Ki9
J
where i s a c o n sta n t and Ap^ i s th e change in ir-e le c tro n d e n s ity 13 a t th e p a r a - carbon atom. S im ila r ly t h i s tr e n d i s observed in C and
1
H n u c le a r magnetic s h i e l d i n g . S u b s t it u e n t proton chemical s h i f t s in th e p a r a - p o s i t i o n a re b e lie v e d to a r i s e , t o a la rg e e x te n t, from changes in th e rr-elec tro n d e n s i ty a t th e p a r a - carbon, atom brought about by th e
% i n tr o d u c ti o n o f a s u b s t i t u e n t .
19
S tu d ie s concerning F n u c le a r magnetic s h i e ld i n g param eters have followed two main approaches. They have e i t h e r been concerned with d e s c r ib in g in d e t a i l th e connection between a n u c le a r magnetic resonance s h i e l d i n g c o n sta n t which i t i s thought r e f l e c t s e l e c t r o n d e n s i t y , and th e Hammett o-const^ant param eter d eriv ed from r a t e o r e q u ilib riu m c o n s ta n ts ; o r th e c a l c u l a t i o n o f s h i e ld i n g param eters from quantum mechanical o r e le c t r o n d e n s ity models and t h e i r subsequent comparison w ith e x p e rim e n ta lly observed v a lu e s.
■ - 19
The e f f e c t o f s u b s t i t u e n t s on F n u c le a r magnetic s h i e ld i n g in s u b s t i t u t e d fluorobenzenes i s very la rg e and can be a c c u r a t e l y measured.
14 19
A comparison o f th e F n u c l e a r m agnetic s h i e l d i n g in fluorobenzcne w ith t h a t in a s u b s t i t u t e d fluorobcnzeno i s 'u s c d t o d e fin e a ^ -p a ra m e te r. 6 *
19
i s th e F m agnetic s h i e l d i n g p ara m eter and i s d e fin e d :
H-Hf 6
X 10*
19
where H i s th e a p p lie d f i e l d f o r th e F reso n an ce in th e s u b s t i t u t e d 19
f lu o ro b e n z e n c , and i s t h e a p p lie d m agnetic f i e l d f o r th e F resonance *
in flu o ro b en zcn e i t s e l f .
---g
Gutowsky e t a l . in 1952 r e p o r t e d t h a t an e m p iric a l c o r r e l a t i o n o f chem ical s h i f t v a lu e s f o r meta- and p a r a - s u b s t i t u e n t s w ith th e
c o rre sp o n d in g Hammett s u b s t i t u e n t o - c o n s t a n t r e v e a le d sy s te m a tic
d i f f e r e n c e s which were a t t r i b u t e d t-o th e dependence o f th e o - v a lu e s on t h e n a t u r e o f th e e l e c t r o n i c i n t e r a c t i o n s o f th e s u b s t i t u e n t . These
/ C o n sid e rab le c o n fu sio n has a r i s e n in t h e measurement and r e c o rd in g o f I s u b s t i t u e n t chemical s h i f t s f o r s u b s t i t u t e d f lu o r o b enzones as a ^
r e s u l t o f v a rio u s co n v en tio n s used by d i f f e r e n t a u th o r s . - O r i g i n a l l y ~ s u b s t i t u e n t chemical s h i f t s in t h i s s e r i e s were d e fin e d acc o rd in g to vj
(H -H) 5
« = - f - x l O = r
where Hj. r e f e r r e d t o flu o ro b en zcn e i t s e l f and H t o th e s u b s t i t u t e d
d e r i v a t i v e . L atte rly ^^ * ^^ » th e convention has been w idely adopted where (H-H )
^ ^ - X 1 0°
r ^
The c o r r e l a t i o n r e p o r te d by T aft^ ^ shown on page 1 7 u ses t h e former
c o n v e n tio n . T his same c o r r e l a t i o n i s r e p o r t e d by Pople, S ch n eid er and B e r n s te in i4 1 as
= - ( 5 .8 3 ) o + (0 .0 ) o
m 1 K
6 = - ( 5 .8 3 ) o . - ( 1 8 .8 0 ) o_
P i K
Thus th e c o e f f i c i e n t s a re o p p o s ite in s ig n and d i f f e r by one o r d e r o f m agnitude. For r h i s reaso n c a re should be ta k e n t o v e r i f y th e c o n v en tio n ' u sed f o r th e 5 o r Aifi p a ra m e te rs .
w orkers r e p o r t e d a g e n e ra l c o r r e l a t i o n between and Hammett o-
p a r a m e te r s , but n o ted t h a t m eta-s u b s t i t u e n t s follow ed a t r e n d d i f f e r i n g from t h a t o f th e p a r a - s u b s t i t u c n t s . . I n t e r p r e t a t i o n o f th e d a ta by
s e p a r a t e s o l u t i o n s d em on strated a/fu n d am en tal d i f f e r e n c e in th e p a r t i c u l a r e f f e c t s o p e r a t i v e a t th e m eta- any, p a r a - p o s i t i o n s .
C i i i ) Dual S u b s t i t u e n t Param eter R e la ti o n s h ip
Throughout l i n e a r f r e e energy r e l a t i o n s h i p s t u d i e s workers i n v a r i a b l y n o t i c e d ' t h i s i n t r i n s i c d i f f e r e n c e in t h e n a tu r e o f th e
e l e c t r o n i c e f f e c t s t r a n s m i t t e d from meta- and p a r a - p o s i t i o n s . This was q u a l i t a t i v e l y e x p la in e d in term s o f th e i n d u c t i v e e f f e c t o n ly o p e r a t in g from th e m e t a - p o s it i o n ; th e i n d u c t i v e and reso n an ce e f f e c t s b o th o p e ra te
from th e p a r a - p o s i t i o n . - _
With d a ta o b ta in e d from a l i p h a t i c s e r i e s , T a ft^ d e fin e d a p a ra m e te r a , th e i n d u c t i v e p a ra m e te r , which en ab led him t o s e p a r a t e
A '
q u a n t i t a t i v e l y th e Hammett o -v a lu e i n t o independent i n d u c t i v e and . reso n an c e c o n t r i b u t i o n s a c c o rd in g t o t h e e q u a t i o n :
-/ ' '
a = Oi + Or
,
Oj i s t h e Reductive c o n t r i b u t i o n and may be re g a rd e d a s a measure o f th e e l e c t r o n i c e f f e c t o f th e s u b s t i t u e n t r e l a t i v e t o th e hydrogen atom
r e s u l t i n g from i t s power t o a t t r a c t o r r e p e l e l e c t r o n s through space and th ro u g h t h e sigma bonds o f th e benzene system . The reso n an ce c o n t r i b u t i o n , o „ , may b e re g a rd e d as a measure o f t h e e l e c t r o n i c e f f e c t r e s u l t i n g from reso n an c e i n t e r a c t i o n s o f th e s u b s t i t u e n t w ith th e n - o r b i t a l o f th e
16 13
R oberts and Moreland- o b ta in e d p u re in d u c t i v e v a lu e s o f from a s tu d y c a r r i e d out on an a l i p h a t i c s e r i e s . These workers d eterm ined th e
. . . .
r e a c t i v i t i e s o f a s e r i e s o f 4 s u b s t i t u t e d b i c y c l o [ 2 . 2 . 2 ] o c t a n e l -c a r b o x y li-c a -c i d s and t h e i r e s t e r s : - ^ '
T ran sm issio n o f e l e c t r i c a l e f f e c t s , thro u g h t h i s system i s n o t p o s s i b l e by reso n an ce i n v o lv in g co n ju g a te d u n s a t u r a t i o n and so o -v a lu e s o b ta in e d
from t h e s e s t u d i e s a r e p u re in d u c t i v e p a r a m e t e r s .
9 14 '' r . '
T a f t ’ s i m i l a r l y used a l i p h a t i c ’ r e a c t i v i t i e s i n t h e d e te r m in a tio n
■■ - ' : 15
- o f Oj. F o llo w in g -th e o b s e r v a tio n by In g o ld t h a t th e system would lend i t s e l f t o th e i s o l a t i o n o f t h i ^ e f f e c t , T a f t s t u d i e d th e a c id and base c a t a l y z e d h y d r o ly s e s o f a l i p h a t i c e s t e r s XClLCOOEt + H-0 ■ 2 2 ^0H“ ^ « XCH^'COOH + Eton The t r a n s i t i o n s t a t e s f o r th e s e c l o s e l y r e l a t e d r e a c t i o n s have s i m i l a r •= ; : - * s t e r i c r e q u ir e m e n ts , b u t c a r r y o p p o s ite c h a rg e s . Aromatic o - v a lu e s a r e o b ta in e d from th e e q u a t i o n : -.»* - [ l o g C l c / k g ) o H - - l o g ( l c / k ^ ) f , U / 2 - 4 8 ■
o
The r a t e c o n s ta n ts k r e f e r t o r e a c t i o n s o f RCOOR' and k t o r e a c t i o n s o f
• o
CHjCOOR’ as s ta n d a r d . The 0H~ and H r e f e r . t o b ase and a c id h y d r o l y s i s , c a r r i e d out f o r th e same e s t e r R ' , s o lv e n t and te m p e ra tu re . The p v alu e
■ * ' , .
■ o f 2.48 p u ts th e a v a lu e s on approxim ately th e same s c a l e as Hammett ^ ,
' ■ ■ . . ■ 13
o - v a l u e s . I t was found t h a t th e a ' v alu es, o f Roberts and Moreland . f o r s u b s ti t u e n ts - X .w e r e p r o p o r t io n a l t o a f o r -CH^X. The v a l u e ' f o r
-t h e r a -t i o o ' / u was +0.45 and so a new&g-t;sc a le o f i n d u c -tiv e s u b s -t i -t u e n -t
' ■ ■■ . ■■ ■ ■ +
c o n s ta n ts (Oj v a lu e s ) was t h e r e f o r e d e fin e d as Oj = 0.45 o . With a valu e f o r th e in d u c tiv e p a ra m e te r, i t was then p o s s i b l e to. c a l c u l a t e th e
resonance p ara m eter c o n t r i b u t i o n t o th e t o t a l Hammett o -v a lu e .
14 ' 19
T a ft r e - e v a l u a t e d th e F s h i e ld i n g p a ra m eters r e p o r te d ‘“by ■
S '
Gutowsky e t a l . f o r s u b s t i t u t e d flu o ro b en zen es in th e s e term s. T a ft found t h a t c o r r e l a t i o n o f n u c le a r m agnetic s h i e l d i n g e f f e c t s follow s an e q u a tio n o f th e g e n e ra l form
:-The e m p ir ic a l c o n s ta n ts ot and g may be reg ard ed as t l r e ^ u s c e p t i b i l i t i e s o f th e n u c le a r m agnetic s h i e ld i n g t o th e i n d u c tiv e and resonance i n t e r a c t i o n s o f t j ^ s u b s t i t u e n t s , r e s p e c t i v e l y . S p e c i f i c a l l y , f o r 'm e ta r ^ s u b s titu te d d e r i v a t i v e s : - \ 6^ = [ 0 .5 8 ) 0 , + [0 .0)On m i K f o r p a r a - s u b s t i t u t e d d e r i v a t i v e s 5^ = C0.58)a_ + [1 .8 8 )0 ^ . p . . i ■ K
18 (see Fo o tn o te page^ ' 4 ^ .
The Hammett sigm a^values f o w ^ q u a tio n s o f a s i m i l a r ' form:
p a ra
I f indeed 6 -v a lu e s and o -v a lu e s a re r e l a t e d t o o^ and
I o^ v h iiie s, then
one would re a so n a b ly expect t h a t i t would be by d i f f e r e n t fu n ctio n s^ .
• • ■
The form o f th e e q u a tio n s , however, lends c o n s id e r a b le su p p o rt t o th e t h e s i s t h a t both ô and o a re determ ined b y t h e same b a s i c p r o p e r t i e s o f th e s u b s t i t u e n t s , implying t h a t th e e l e c t r o n i c . e f f e c t o f a meta- and a p a r a - s u b s t i t u e n t on t h e f r e e energy o f a benzene d e r i v a t i v e f o l lo w s .t h e
above e q u a tio n . . . - ' ,
One o f th e most r e c e n t l i n e a r f r e e energy r e l a t i o n s h i p s t u d i e s r e p o r t e d i s a re fin e m e n t o f th e dual s u b s t i t u e n t p a ra m eter tre a tm e n t
(as t h i s s e p a r a t io n o f th e in d u c t i v e and. resonance c o n t r i b u t i o n s t o o- c o n s ta n ts has come to be c a l l e d ) and f u r t h e r improvement o f cr-values. The a r t i c l e e n t i t l e d "A G e n era liz ed Treatment o f S u b s t i t u e n t E f f e c ts in th e Benzene S e r i e s . A S t a t i s t i c a l A n aly sis o f th e Dual S u b s t i t u e n t P aram eter Equation" i s by Ehreason, Brownlee and T a f t . I t comprises a r ig o r o u s and e x te n s iv e s t a t i s t i c a l a n a l y s i s o f e x i s t i n g , d a t a , which len d s su p p o rt t o many o f th e e a r l i e r concepts concerning l i n e a r f r e e energy r e l a t i o n s h i p s , b u t a ls o extends th e i n t e r p r e t a t i o n o f th e d a ta . The a u th o rs s t a t e , " . . . ( 1 ) s t r u c t u r a l c o n s i d e r a ti o n s d i s c r i m i n a t e between a t l e a s t fo u r p r a c t i c a l c l a s s e s o f p i - d e l o c a l i z a t i o n behavior,, each - , o f which has " l i m i t e d g e n e r a l i t y " ; (2) th e b len d o f p o l a r and p i
-d e l o c a l i z a t i o n e f f e c t c o n t r i b u t i o n s t o th e observe-d e f f e c t o f a. s u b s t i t u e n t i s w id ely v a r i a b l e among d i f f e r e n t r e a c t i o n o r d a t a s e t s
fth e c o n t r i b u t i o n s may be o p p o s ite as w e ll as a l i k e in d i r e c t i o n ) , depending upon s t r u c t u r a l c o n s i d e r a t i o n s and th e n a tu r e o f th e
measurement; [3) s o l v e n t may p la y an im p o rta n t r o l e in d e te r m in a tio n o f th e o bserved b le n d o f e f f e c t s . . . " . The d i s c r i m i n a t i o n o f a t l e a s t f o u r p r a c t i c a l c l a s s e s o f p i - d e l o c a l i s â t ion e f f e c t s and a ls o fo u r c l a s s e s o f s u b s t i t u e n t c o n s ta n ts d e s c r ib e d above w i l l be d i s c u s s e d . a t len g th l a t e r .
Civ) L in e a r Free Energy R e la ti o n s h ip S tu d ie s in th e Naphthalene
S e r i e s ■
17
W ells, Ehrenson and T a f t extended t h e b a s i c dual s u b s t i t u e n t
p ara m eter e q u a t io n : - , , '
[th e in d ex i i n d i c a t e s th e p o s i t i o n o f th e s u b s t i t u e n t ) t o th e n ap h th a le n e system w ith two o b j e c t i v e s in mind. F i r s t l y , in o r d e r t o t e s t th e
v a l i d i t y o f a., and o_ ; i f th e s e p a ra m eters a re c h a r a c t e r i s t i c o f th e
i R ■ ' • ,
s u b s t i t u e n t th en th e y should be independent o f r e a c t i o n o r p o s i t i o n o f s u b s t i t u t i o n an d _should be a p p l i c a b l e t o a ro m atic systems o t h e r th an . benzene. Secondly, th e n ap h th a le n e system allow s t h e i n v e s t i g a t i o n o f t h e t r a n s m i s s io n o f e f f e c t s from more th a n two arom atic p o s i t i o n s , which i s a l i m i t a t i o n in \b e n ze n e s e r i e s . The dual s u b s t i t u e n t ’ p a r a m eter e q u a tio n was examined u sin g d a t a from th e stu d y o f th e a c i d i t y o f
18 19 ’ * 20 '
2 0' .
21 22
methyl n a p h th o a te s ; t h e a c i d i t y o f n a p h th y l anunoniura c a t i o n s ; the^
■ 23
a c i d i t y o f n a p h th o ls ; o f p y rid in iu m ^ o f q u in o lin iu m and is o q u in o lin iu m
24 19 ■
c a t i o n s . The a n a l y s i s was a ls o extended t o F n .m .r . s h i e l d i n g
25 •
e f f e c t s in v o lv in g a l l p o s i t i o n s o f n a p h th a le n e which are n o t s u b j e c t t o s e r i o u s s t e r i c e f f e c t s . The and p a ra m e te rs were f i t t e d
in d e p e n d e n tly t o th e n a p h th a le n e system, and th e r a t i o was d e fin e d as th e b le n d in g f a c t o r X. The b le n d in g f a c t o r would be c h a r a c t e r i s t i c o f th e d i f f e r e n t p o s i t i o n a l r e l a t i o n s and r e a c t i o n s .
In th e n a p h th a le n e s e r i e s th e cfjPj term has been a t t r i b u t e d t o th e 4 '
f i e l d and i n d u c t i v e e f f e c t s e s p e c i a l l y f o r s u b s t i t u e n t s in th e second r i n g . The w -in d u c tiv e e f f e c t where th e r e a c t i o n s i t e i s i n s u l a t e d from c o n ju g a tio n w ith t h e arom atic, system and a l s o where c o n ju g a tio n i s
p o s s i b l e has been e s t im a t e d , b u t shows l i t t l e correspondence t o th e o b served r e l a t i v e p a t t e r n o f i n th e n a p h th a le n e s e r i e s . A t h i r d e f f e c t may a ls o be expected to o p e ra te in s u b s t i t u t e d n a p h th a le n e s . I f s u b s t i t u t i o n i s i n th e 4, 5 or 8 - p o s i t i o n o f th e n a p h th a le n e system , t h e p e r i - hydrogen e x e r t s a t w i s t i n g e f f e c t on th o se systems f o r which a c o p la n a r conform ation w ith th e r i n g i s r e q u i r e d . This would tend to d e c r e a s e th e c o n ju g a tiv e e f f e c t o f s u b s t i t u e n t s in th e s e p o s i t i o n s .
A l a r g e p r o p o r t io n o f th e s t u d i e s which a tte m p t t o d e riv e and d e f i n e c o r r e l a t i o n s between n u c le a r m agnetic reso n an ce s h i e l d i n g
p a ra m e te rs and s u b s t i t u e n t c o n s ta n ts has been made on aro m atic systems ; a t f i r s t t h i s 'w a s mainly oh s u b s t i t u t e d b e n z e n e s . Of l a t e , a t t e n t i o n has been tu rn e d towards th e n a p h th alen e system i n o r d e r t o t e s t th e
g e n e ra l v a l i d i t y o f th e c o n c e p ts . The a r t i c l e by Wells e t a l . r evi ews
- ' ■ ■ ■ . .
in c lu d in g th e c o r r e l a t i o n . n . m . r . chemical s h i f t s . The n .m .r . s h i e l d i n g v alues showed a g o o d ^ f it w ith th e dual s u b s t i t u e n t , p aram eter equation^ a ls o showing two d i f f e r e n t p o l a r o r i n d u c t i v e p aram eter mechanisms. The r e a c t i o n t c o n s t a n t s a re s t r o n g l y r e a c t i o n and
p o s i t i o n dependent; in c o n t r a s t v alu es appear t o d is p la y e s s e n t i a l l y id e n tic a l p a t t e r n s in both n . m . r . and r e a c t i v i t y d a ta .
■ 17
The study confirmed t h a t th e a d d i t i v e b len d s o f p o l a r and p i -d e l o c a l i s a t i o n e f f e c t s as -d e s c rib e -d in the -dual s u b s t i t u e n t param eter
^ . . .
e q u a tio n with th e s u b s t i t u e n t param eters d e fin e d in p rev io u s s t u d i e s a re applicabl-e to th e n a p h th a le n e system, and a re in f a c t e s s e n t i a l f o r t h e r a t i o n a l i s a t i o n and c o r r e l a t i o n o f observed r e a c t i v i t i e s and chemical
s h i f t s . :
25
Dewar e t a l . , w h i l s t acknowledging th e s e p a r a t io n n e c e ssa ry f o r 19
t h e s u c c e s s f u l c o r r e l a t i o n o f s u b s t i t u e n t e f f e c t s with F n .m .r . chemical s h i f t s , have adopted a s l i g h t l y d i f f e r e n t approach.^^.^-.^^entially th ey combine th e d i r e c t f i e l d e f f e c t o f a s u b s t i t u e n t in i t s sim p le s t form
/-t h a /-t does n o /-t in c lu d e reso n an ce e f f e c /-t s , w i/-th a 'se c o n d /-term which makes allow ance f o r th e s e e f f e c t s . They su g g est th e e x p re ssio n
Mqi_
•
where F / r . . d e s c rib e s th e chan g e-in e le c t r o s t a t ^ jc energy c a l c u l a t e d f o r a p o i n t charge. The second term d e s c r ib e s t h e e f f e c t on a o f a change .
- :
in p i - e l e c t r o n d e n s i ty a t j by a s u b s t i t u e n t a t i c o n ju g a tin g with th e d e l o c a l i s e d arom atic system.
-22 flu o r o b ip h e n y ls 3’'- s u b s t i t u t e d - 4 - f l u o r o t e r p h e n y l s ; ^ ^ and to
' 17- . _
s u b s t i t u t e d 1- and 2 - f l u o r o n a p h t h a l e n e s . This s l i g h t l y i n t u i t i v e 27
approach has been c r i t i c i s e d in t h a t , by i t s n a t u r e , i t t a c i t l y 19
assumes t h a t F n .m .r . chemical s h i f t s a re determ ined by th e e l e c t r o
s t a t i c p o t e n t i a l energy a t th e f l u o r i n e atom caused by a p o l a r s u b s t i t u e n t ’ p lu s a term p r o p o r t io n a l t o th e p i - e l e c t r o n d e n s i t y . I f a s i m i l a r
e x p re s s io n i s d e riv e d from t h e o r e t i c a l c o n s i d e r a t i o n s , then th e
s h i e l d i n g c o n s ta n t i s p r o p o r t io n a l to both th e e l e c t r i c f i e l d component - alo n g th e bond to th e f l u o r i n e atom, and a ls o t o th e sq u are o f th e
e l e c t r i c f i e l d a t f l u o r i n e . 30
Tlie proponents o f t h i s tr e a tm e n t o f . s t r u c t u r e - r e a c t i v i t y
c o r r e l a t i o n s r e f u t e th e concepts o f T a f t ’s approach, and y e t in essence make s i m i l a r c o n s id e r a tio n s and r a t i o n a l i s e th e e x p erim en tal o b s e rv a tio n s ■ in s i m i l a r term s. Adcock and Dewai^^ have dem onstrated a good l i n e a r
c o r r e l a t i o n between th e s u b s t i t u e n t e f f e c t on th e chemical s h i f t (S .C .S .) o f th e s u b s t i t u t e d flu o ro n a p h th a le n e and th e pK^ o f th e c o rre sp o n d in g ly s u b s t i t u t e d n ap h th o ic a c i d (in which th e F o f th e flu o ro n a p h th a le n e i s r e p la c e d by COOH):
-S .C .-S. = a[pK ) + b ’■ i
^ - :
/ ‘ - „ ■ ■ ' .
However, th e r e l a t i v e s e n s i t i v ^ y o f th e F chemical s h i î ^ ^ t o the') e f f e c t o f th e s u b s t i t u e n t , compared w ith th e s e n s i t i v l t y / . p f ^ t h e ^pK^ v a lu e t o th e e f f e c t o f th e same s u b s t i t u e n t , i s very dependent on th e p o s i t i o n o f t h e s u b s t i t u e n t and th e f u n c tio n a l group. Thus when th e
/
6 -.p o sitio n (I) a in the above eq u atio n i s - 3 . 1 . . IVhen th e f u n c tio n a l group i s a t th e 2 - p o s i t io n and th e s u b s t i t u e n t ;is a t th e 6- p o s i t i o n
( I I ) , a i s - 1 2 .0 . X 4 5 Y = F.COOH X = s u b s t i t u e n t (I) Y = F, COOH X = s u b s t i t u e n t ( I I ) 25 '■ 19
Adcock and Dewar suggest t h a t th e F chemical s h i f t is dependent 'on the f i e l d along th e l in e o f th e C-F bond, i . e . , t h e r e i s an
a n i s o t r o p i c response o f f l u o r in e to an a p p lie d f i e l d . On th e o th e r hand, th e s t a b i l i s a t i o n o f the c a rb o x y la te ion (presumably th e im portant
f a c t o r in th e s u b s t i t u e n t e f f e c t on th e acid d i s s o c i a t i o n ) e x h i b i t s no such d i r e c t i o n a l dependence on th e f i e l d . I t i s to be noted t h a t in
( I I ) th e s u b s t i t u e n t d ip o le i s in l i n e w ith the C-F bond, and i s thus more fav o u rab ly p o s itio n e d than in (I) to e x e r t the maximum e f f e c t on
19 ■ •
^ .
^ ^ ' 2 4
T h e o r e tic a l C o n sid e ratio n s o f Chemical S h i f t - S u b s titu e n t Parameter C o r r e la tio n s
( i ) . Quantum Mechanical C a lc u la tio n o f S h ie ld in g Parameters Tliere have been m any,attempts to c a l c u l a t e the n u c le a r magnetic
?
s h i e ld i n g c o n s ta n ts o f f l u o r in c ^ n u c l c i P ^ h e s o c a l c u l a t i o n s have only ^ been a p p lie d to v e ry .s m a ll molecules i f a t th e same-time th e a u th o r
has made any claim to .m a th em atica l r ig o u r . Treatments ap p lied t o .la rg e r *
molecules are th c r e f o i'c based on p rin .c ip le s more e x h a u stiv e ly i n v e s t i g a t e d f o r small m olecules, e .g . P . , IIP and LiP.
-■ ■' ,4'- ■ 51
One o f th e e a r l i e s t attem p ts rep o rte d ,w as t h a t by Ramsey who
d e riv e d a s h i e ld i n g t e n s o r (o^ ) u sin g se co n d -o rd e r p e r t u r b a ti o n th e o r y , •zz
summed over a l l e l e c t r o n s (K) and a l l unoccupied unperturbed m olecular o r b i t a l s Tlio o p e r a to r i s the z component o f th e o r b i t a l
a n g u la r momentum o f e l e c t r o n K, and, r^j, i s th e d is ta n c e from the nucleus N t o the e l e c t r o n K. The f i r s t term summed over ground s t a t e wave .
fu n c tio n s i s known as th e diam agnetic term, and tlie second summed over th e unoccupied \-*ave fu n c tio n s i s known as th e paramagnetic, term.
K { I 4 ' K n^O '
, ' . . \
^ / '*'0K ^^zK ! '^nKV''^nK ^ ‘"zK /nK I '^OK I ^zK ^.NK t ’^nK^
For an atom in an s s t a t e th e second term o f t h i s equation i s zero; f o r example, th e s h i e ld i n g o f f l u o r in e in j:he f r e e f l u o r id e i s p u re ly a consequence o f th e diam agnetic behaviour o f th e e l e c t r o n s . One might t h e r e f o r e p r e d i c t a c o r r e l a t i o n between th e s h i e ld i n g co n stan t and th e i o n ic c h a r a c t e r o f th e b ond.in diatom ic f l u o r i d e s . As mentioned
■'7 ■ '
p r e v io u s ly , Gutowsky and Hoffman showed t h a t a very good c o r r e l a t i o n o f t h i s kind does e x i s t in t h i s s e r i e s , with one n o ta b le e x c e p ti o n ,' t h a t o f GIF. This exception has been r a t i o n a l i s e d in terms of the-param agnetic
.
term in Ramsey' s •equation being la r g e and p o s i t i v e due to a dominant term in th e -sum ovor unoccupied unperturbed m olecular o r b i t a l s which
* *
involves a tr -Hj t r a n s i t i o n between o r b i t a l s now c lo s e ly se p a ra te d in e n erg y .
To W k v e Ramsey's eq u atio n and hence c a l c u l a t e th e s h ie ld in g
k . ■
c o n sta n t r e q u ir e s a good s e t o f wave fu n c tio n s . Tlie f i r s t term, the summation over ground s t a t e wave fu n ctio n s may be e v a lu a te d , but,. ' th e second term ^involves a summation over unoccupied wavefunctions’ and. i s t h e r e f o r e very d i f f i c u l t f o r a l l but the sim p le st systems with few e l e c t r o n s . For th d se reasons s e v e ra l approaches have been adopted based in ^ th e f i r s t in sta n c e on Ramsey's tr e a tm e n t, but in c o rp o ra tin g
modifying assumptions which make s h ie ld in g co n stan ts amenable t o . c a l c u l a t i o n .
3 9 - .
Karplus and Pople “ assumed t h a t wave fu n c tio n s could be
ex p resse^ as l i n e a r combinations o f atomic o r b i t a l s ; a l l tw o-centre
/ ' ■ - C ’ ,
i n t e g r a l s were n e g le c te d . The modified eq uation fo r the s h ie ld in g • o f th e \ b c l e u s N w
