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65 Ozonation of Polycyclic Aromatics
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X V . Carcinogenicity and K - and/or L-Region Additivity towards Ozone EMIL
J.
MORICONI
and
LUDWIG
SALCE
Fordham University, Bronx, N. Y.
Ozonation of benzo[r,s,t]pentaphene (7) followed by oxidative workup led to benzo[r,s,t]pentaphene-5,8-dione (12) (14%), phthalic acid (13) (4%), p-terphenyl-2,2',3',2"-tetracarboxylic acid-2',3'-anhydride (14) (10%), and 2-(o-carboxyphenyl)-1,10-phenanthrenedicarboxylic acid anhydride (15) (3%), with a 56% recovery of unreacted 7. Ozonation of pentaphene (11) led to a peroxidic mixture which on oxidative workup led to 2,2'-binaphthyl-3,3'-dicarboxaldehyde (16) (16%), 2,2'-binaphthyl-3,3'-dicarboxylic acid (17) (16%), and 13 (2%), with a 28% recovery of unreacted 11. A comparison of the reactivity to ozone of carcinogenic polycyclic aromatics benzo[c]phenanthrene (1), 7,12-dimethylbenz[a]anthracene (2), 3-methylcholanthrene (3), dibenz[a,j]- (4), and dibenz[a,h]anthracene (5), benzo[a]pyrene (6) and 7, and the noncarcinogen 11, all determined in our laboratory, leads us to conclude that there is no simple, consistent correlation between carcinogenicity, K -and L-region additivity towards ozone and the Pullmans' electronic theory of carcinogenesis.
/^\ne of the most s t i m u l a t i n g theories
a d v a n c e d to relate
structure
w i t h c a r c i n o g e n i c a c t i v i t y of p o l y c y c l i c aromatics has b e e n
the
" e l e c t r o n i c theory of carcinogenesis" p r o p o s e d b y the F r e n c h s c h o o l of t h e o r e t i c a l chemists l e d b y A . P u l l m a n a n d B . P u l l m a n (30, 32) D a u d e l a n d R . D a u d e l (13).
and P.
T h i s q u a n t u m m e c h a n i c a l s t u d y of t h e
electronic structure of p o l y c y c l i c aromatics has d i s c l o s e d t w o regions of h i g h e l e c t r o n d e n s i t y w h i c h are of p a r t i c u l a r significance i n t h e i r 65 Mayo; Oxidation of Organic Compounds Advances in Chemistry; American Chemical Society: Washington, DC, 1968.
66
OXIDATION
chemical behavior.
OF
ORGANIC
COMPOUNDS
III
T h e s e sites c o r r e s p o n d to the 9,10-bond i n p h e n a n -
threne ( K - r e g i o n ) a n d the 9,10-positions
i n anthracene
(L-region).
A
t h i r d site ( M - r e g i o n ) i n v o l v e s the positions reactive i n m e t a b o l i c p e r hydroxylation. L-region M-region
T h e t w o most r e c e n t l y expressed f u n d a m e n t a l , q u a n t i t a t i v e p r o p o sitions of the theory are
(30):
( 1 ) T h e a p p e a r a n c e of c a r c i n o g e n i c a c t i v i t y i n a r o m a t i c h y d r o c a r bons is d e t e r m i n e d b y the existence of a K - r e g i o n , w h o s e c o m p l e x i n d e x is e q u a l to or smaller t h a n 3.31/2. ( T h e s e c o m p l e x i n d i c e s are d e f i n e d b y P u l l m a n a n d P u l l m a n ( 3 0 ) ; /? is expressed i n terms of resonance i n t e g r a l ( ^ 2 0 k c a l . / m o l e ) ; the n u m e r i c a l l i m i t s l i s t e d ( 3 . 3 l £ a n d 5.66)8) are those c a l c u l a t e d f o r the K - a n d L - r e g i o n s of d i b e n z [ a , / ] a n t h r a c e n e (4), c o n s i d e r e d as the weakest p o l y c y c l i c c a r c i n o g e n . ( 2 ) If, h o w e v e r , the m o l e c u l e contains also a n L - r e g i o n , its c o m p l e x i n d e x s h o u l d b e e q u a l to or greater t h a n 5.66/2 (see above). S i m p l y stated, one of the essential steps i n carcinogenesis
is
the
" r e a c t i o n " b e t w e e n the c a r c i n o g e n i c p o l y c y c l i c a r o m a t i c a n d the " c e l l u l a r r e c e i v e r , " at or t h r o u g h the K - r e g i o n of the c a r c i n o g e n . A necessary b u t not sufficient c o n d i t i o n for " r e a c t i v i t y " is a n a c t i v e K - r e g i o n complex index: = complex index:
<
(calcd.
/ > 3.31)8). A too-reactive L - r e g i o n , h o w e v e r , ( c a l c d . 5.66/3) m a y d i v e r t the p o l y c y c l i c c a r c i n o g e n to
a
noncarcinogenic reaction. V e r i f i c a t i o n of these p r o p o s i t i o n s has taken t w o different p a t h w a y s : ( 1 ) T h e o r e t i c a l : q u a n t i t a t i v e calculations w h i c h , f o r e x a m p l e , pre d i c t e d (30) the c a r c i n o g e n i c i t y of b e n z o [ r , s , t ] p e n t a p h e n e (7) whose m e a s u r e d p o t e n c y (H—|—1-+) ranks it b e t w e e n 3 - m e t h y l c h o l a n t h r e n e (3 ) a n d b e n z o [a] p y r e n e (6) (18,35). ( 2 ) C h e m i c a l : c o m p a r i s o n of c y c l o a d d i t i o n reactions o c c u r r i n g either at t h e K - r e g i o n ( o s m i u m t e t r o x i d e ) (1, 2) or L - r e g i o n ( m a l e i c a n h y d r i d e a n d p h o t o - o x i d a t i o n ) (29, 31). T h e i n a d e q u a c i e s of this c h e m i c a l p r o o f seemed to us t w o f o l d : the c y c l o a d d i t i o n reactions w e r e u n r e l a t e d c h e m i c a l l y , each o c c u r r i n g at either the K - / L - r e g i o n s , whereas the t h e o r y c o n s i d e r e d b o t h regions s i m u l taneously; f u r t h e r , these reactions d i d not occur, or at least h a d not b e e n t r i e d w i t h a sufficient n u m b e r of c a r c i n o g e n i c a n d n o n c a r c i n o g e n i c p o l y c y c l i c aromatics.
Mayo; Oxidation of Organic Compounds Advances in Chemistry; American Chemical Society: Washington, DC, 1968.
65.
MORICONI
Polycyclic
A N D SALCE
67
Aromatics
F o r a c h e m i c a l r e a c t i o n to h a v e relevance, i t seemed necessary that the r e a c t i o n o c c u r s i m u l t a n e o u s l y at b o t h K - a n d L - r e g i o n s a n d w i t h a l l c a r c i n o g e n i c a n d n o n c a r c i n o g e n i c p o l y c y c l i c aromatics.
I n our view,
this c o m p e t i t i v e response to the c h e m i c a l reactant at the t w o sites w i t h i n the substrate m o l e c u l e c o u l d l e a d , i n t r a m o l e c u l a r l y , to a c o n c l u s i o n o n the r e l a t i v e r e a c t i v i t y of t h e K - a n d L - r e g i o n s . F u r t h e r , since t h e c h e m i cal reaction could be studied under identical reaction conditions, the results c o u l d also l e a d , i n t e r m o l e c u l a r l y , to v a l i d c o m p a r i s o n s of r e l a t i v e reactivity. W h e n this research b e g a n , t h e o z o n a t i o n r e a c t i o n seemed i d e a l l y suited. O z o n e w a s k n o w n to react at b o t h the K - r e g i o n [ i n p h e n a n t h r e n e (8)]
(4,5,34,37)
a n d L - r e g i o n ( i n a n t h r a c e n e ) (6,7,33).
D u r i n g the
d e c a d e since, w e h a v e i n v e s t i g a t e d the r e a c t i o n b e t w e e n ozone a n d some 11
p o l y c y c l i c aromatics
(1—11).
Other
laboratories
have
CARCINOGENS
CH Benzo[c]phenanthrene (19) 1
2
3-Methylcholanthrene (21)
Dibenz[a,/]anthracene (20)
Benzo [a] pyrene (25)
5
Benzo [r,s,f] pentaphene (26)
6
8
Dibenz [a,h] anthracene (24)
4
3
Phenanthrene (34)
:<
7, 12-Dimethylbenz[fl]anthracene (20)
7
Benz [a] anthracene (27) 9
Napthacene (28) 10
Pentaphene (26) 11
Mayo; Oxidation of Organic Compounds Advances in Chemistry; American Chemical Society: Washington, DC, 1968.
reported
68
OXIDATION
OF
ORGANIC
COMPOUNDS
HI
o n eight m o r e ( n a p h t h a l e n e (8), t r i p h e n y l e n e (11), p y r e n e (36), c h r y sene (11), b e n z o [g] chrysene (11), p i c e n e (11), d i b e n z [c,g] p h e n a n threne (11), a n d p e r y l e n e (12). A l l react w i t h ozone, a n d r e a c t i o n occurs u n i q u e l y at one or m o r e of the three relevant sites, the K - , L - , and M-regions. H e r e , w e r e p o r t o n the o z o n a t i o n of t w o s y m m e t r i c a l l y s t r u c t u r e d p o l y c y c l i c aromatics at opposite ends of the c a r c i n o g e n i c s p e c t r u m — t h e h i g h l y c a r c i n o g e n i c (18, 35) benzo[r,s,t~\pentaphene ( 7 ) a n d the i n a c t i v e (10) p e n t a p h e n e ( 1 1 ) — a n d s u m m a r i z e the results of o u r s t u d y of 1 - 7 a n d 11. T h e p r e p a r a t i o n of 7 a n d 11 a n d the i s o l a t i o n a n d i d e n t i f i c a t i o n of o z o n a t i o n p r o d u c t s 1 2 - 1 8 h a v e b e e n r e p o r t e d p r e v i o u s l y (26). Ozonation of Benzo[ r,s,t']pentaphene (7) m
and Pentaphene (11)
O z o n a t i o n of 7 i n m e t h y l e n e c h l o r i d e at — 78 ° C . w i t h 3.5 m o l e equivalents of o z o n e ( r e q u i r i n g passage of 5 - 6 m o l e e q u i v a l e n t s ) , f o l lowed b y oxidative w o r k u p (1:1 1 0 % sodium hydroxide: 3 0 % hydrogen p e r o x i d e ) l e d to benzo[r,s,t~\pentaphene-5,8-dione ( 1 2 ) ( 1 4 % ), p h t h a l i c acid ( 1 3 ) ( 4 % ) , p-terphenyl-2,2',3',2"-tetracarboxylic acid-2',3'-anhydride (14) ( 1 0 % ) , and 2-(o-carboxyphenyl)-l,10-phenanthrenedicarb o x y l i c a c i d a n h y d r i d e ( 1 5 ) ( 3 % ) , w i t h a 5 6 % r e c o v e r y of u n r e a c t e d 7, as s h o w n b e l o w . r
+
+
o
7
2,
12
13
14
15
OOH-
3, H 0 * 3
Mayo; Oxidation of Organic Compounds Advances in Chemistry; American Chemical Society: Washington, DC, 1968.
65.
MORICONI
A N D SALCE
Polycyclic
69
Aromatics
O z o n a t i o n of p e n t a p h e n e ( 1 1 ) ( s h o w n b e l o w ) i n m e t h y l e n e c h l o r i d e at — 78 ° C . w i t h one m o l e e q u i v a l e n t of o z o n e l e d to a p e r o x i d i c m i x t u r e w h i c h o n o x i d a t i v e w o r k u p l e d to 2 , 2 ' - b i n a p h t h y l - 3 , 3 ' - d i c a r b o x a l d e h y d e (16)
( 1 6 % ) , 2,2'-binaphthyl-3,3'-dicarboxylic acid (17)
phthalic acid ( 1 3 ) ( 2 % ) ; a c i d ) gave 16 ( 2 5 % ) . ered.
(16%),
and
r e d u c t i v e w o r k u p ( s o d i u m i o d i d e i n acetic
I n b o t h cases, 2 8 %
of u n r e a c t e d 11 w a s recov
O z o n a t i o n of 11 w i t h 4 m o l e e q u i v a l e n t s of o z o n e f o l l o w e d b y
o x i d a t i v e w o r k u p gave 2,2',4,4',5,5'-hexacarboxybiphenyl
(18)
(53%)
a n d p h t h a l i c a c i d ( 1 3 ) ( 9 % ).
18
Summary and Conclusions T a b l e I s u m m a r i z e s the d a t a n o w a v a i l a b l e f r o m o u r l a b o r a t o r y o n the o z o n a t i o n of c a r c i n o g e n i c p o l y c y c l i c a r o m a t i c h y d r o c a r b o n s 1 - 7 a n d the n o n c a r c i n o g e n , 11. A l l the c o m p o u n d s h a v e at least one K r e g i o n ( w i t h s i m i l a r electronic i n d i c e s , 3.16-3.41/?). D e s p i t e some i n i t i a l l y e n c o u r a g i n g results w h i c h suggested that u n s u b s t i t u t e d p o l y c y c l i c aromatics of i n c r e a s i n g c a r c i n o g e n i c a c t i v i t y d i d react m o r e s t r o n g l y w i t h ozone at the K - r e g i o n a n d to a c o r r e s p o n d i n g l y lesser degree at the L - r e g i o n (20, 23, 28), w e h a v e o b s e r v e d several exceptions.
Mayo; Oxidation of Organic Compounds Advances in Chemistry; American Chemical Society: Washington, DC, 1968.
70
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OF
ORGANIC
COMPOUNDS
III
I n t h e i r s t u d y of p r o t e i n b i n d i n g as a necessary, b u t not sufficient, p r e r e q u i s i t e f o r h y d r o c a r b o n carcinogenesis, H e i d e l b e r g e r a n d M o l d e n h a u e r (16)
h a v e e x p e r i m e n t a l l y d e m o n s t r a t e d that 2, 3, a n d 6 w e r e
b o u n d to s k i n p r o t e i n to a large a n d a p p r o x i m a t e l y e q u a l extent.
A
p o r t i o n of this tissue i n t e r a c t i o n most p r o b a b l y occurs at the K - r e g i o n ( 9 ) , i n a c c o r d a n c e w i t h the t h e o r e t i c a l s p e c u l a t i o n of the P u l l m a n s 32).
(30,
Thus, any direct correlation between carcinogenicity and reactivity
to ozone w o u l d result i n p r e d o m i n a n t e l e c t r o p h i l i c ozone attack at the C o m p o u n d s 2, 3, a n d 6,
K - r e g i o n of these three -|—|—|—f- carcinogens.
h o w e v e r , r e a c t e d w i t h ozone e x c l u s i v e l y at the L - a n d M - r e g i o n s . C e r t a i n l y 3 w a s not a p r i v i l e g e d c o m p o u n d (30)
i n w h i c h the L - r e g i o n w a s
p r o t e c t e d f r o m attack b y ozone. T h e lesser carcinogens b e n z o [c] p h e n a n t h r e n e benz[a,/]anthracene (24)
(4)
(20)
( + ),
(l)
(19)
( + ), d i -
and dibenz[a,K]anthracene
(5)
(-)—f-) r e a c t e d w i t h ozone p r e d o m i n a n t l y at the K - r e g i o n . R e l a
tive to 6, this response to ozone is the r e v e r s a l of w h a t w o u l d h a v e b e e n p r e d i c t e d b y the electronic t h e o r y of carcinogenesis. Both benzo[r,s,t]pentaphene
( 7 ) a n d 6 are + + H—h
carcinogens,
a n d some i d e n t i t y of response to e l e c t r o p h i l i c ozone w o u l d be p r e d i c t e d . Y e t the f u s i o n of a b e n z e n e r i n g to the 1,2-bond i n 6 has e n h a n c e d the K - r e g i o n a c t i v i t y of 7 to ozone ( 1 3 %
t o t a l of 14 a n d 1 5 ) , l o w e r e d the
T a b l e I.
O z o n a t i o n of P o l y c y c l i c
Pu llman-Pullman Electronic Indices'
1
Polycyclic
Aromatic
Pentaphene (11) Benzo [c] phenanthrene (1) D i b e n z [A,/] anthracene (4) D i b e n z \a,h~\ anthracene (5) 7,12-Dimethylbenz [ a ] anthracene 3-Methylcholanthrene (3) Benzo [a] pyrene (6) Benzo [r,s t] pentaphene (7) 9
K-Region
(2)
L-Region
5.56
3.23 3.41 3.31 3.30
5.66 5.69
3.16 3.16
Ozone-Poly cyclic Mole Ratio
1.0 0.6 1.0 1.0 1.0 1.5 1.0 3.5
" See Ref. 2. "Reaction conditions: ozonation at — 7 8 ° C . in methylene chloride or 3:1 methylene chloride: methanol, followed by alkaline hydrogen peroxide workup (unless otherwise stated). Ozonation of 7 and 11 also produced 13 (4% and 2%, respectively). These yields are not included in either K- or L - region product totals since the site of ozone attack to produce 13 is unknown. l-(o-Carboxyphenyl)-2-naphthoic acid. 1,4-Dimethyl-3-hydroxymethyl-2-phenylnaphthalene-2 -carboxylic acid. Yield of biphenyl from the presumed primary ozonation product, 2,2',3,4,5-pentacarboxybiphenyl. 0
d
/
c
Mayo; Oxidation of Organic Compounds Advances in Chemistry; American Chemical Society: Washington, DC, 1968.
65.
MORICONI
Polycyclic
A N D SALCE
r e a c t i v i t y of the L - r e g i o n ( 1 4 %
71
Aromatics
of 1 2 ) , a n d decreased the o v e r - a l l ease
of o z o n a t i o n of 7 r e l a t i v e to 6. T h e y i e l d s of K - r e g i o n cleavage p r o d u c t s , u n d e r the same c o n d i t i o n s of o z o n a t i o n v a r y f r o m 0 - 4 5 %
(Table I).
E v e n c o n s i d e r i n g the e x p e r i
m e n t a l errors i n v o l v e d i n o z o n a t i o n a n d o x i d a t i v e w o r k u p , there is n o s i m p l e , observable c o r r e l a t i o n b e t w e e n the P u l l m a n s ' t h e o r e t i c a l K - r e g i o n values a n d the r e a c t i v i t y of these sites to e l e c t r o p h i l i c ozone. A l t h o u g h three of the c o m p o u n d s l i s t e d i n T a b l e L - r e g i o n s , the most potent carcinogens
I have
( 2 , 3, 6, a n d 7) d o not.
formal Two
( 6 a n d 7) c a n be c o n s i d e r e d to h a v e s u c h sites w h o s e a c t i v i t y has b e e n suppressed b y a f u s e d r i n g , a n d t w o ( 2 a n d 3 ) are essentially s u b s t i t u t e d at the L - r e g i o n . T h u s , the o z o n a t i o n results for these f o u r c o m p o u n d s , summarized in Table
I, cannot
t r u l y be c o n s i d e r e d
L-region quinoid
p r o d u c t s . D e s p i t e this, the r e l a t i v e y i e l d s of s u c h q u i n o n e s c l e a r l y s h o w a n inverse r e l a t i o n s h i p b e t w e e n the theoretical, p r e d i c t e d l o w L - r e g i o n a c t i v i t y a n d the course of the ozone reaction. T o s u m u p , a c o m p a r i s o n of the o b s e r v e d r e l a t i v e r e a c t i v i t y of 7 a n d 11 to ozone w i t h that p r e d i c t e d b y P u l l m a n s ' t h e o r e t i c a l calculations (30, 32), a n d a n analysis of a l l the a v a i l a b l e o z o n a t i o n d a t a l e a d us to c o n c l u d e that there is no s i m p l e , consistent c o r r e l a t i o n b e t w e e n c a r c i n o Aromatic
Hydrocarbons
Actual % Yields of K- and L-Region Ozonation Products
b
Total K-Region Cleavage Products 32 30 42 45 14* 4 0 13' c
C
L-Region Quinoid Products 0 0 10 0 29 32 27-30* 14' 9
h
% Recovery Unreacted Polycyclic Aromatic 28 40 32.5 0 0 0 60-65 56
Carcinogen Potency 0
+ + ++ ++++ ++++ ++++ ++++
Total yield of 14 and 15. ' Composed of 23% of benz[a]anthracene-7,12-dione and 6% of 1,2-anthraquinonedicarboxylic acid. Composed of 15% of 8,9-dimethylbenz[a]anthracene-7,12-dione and 18% of 1,2dimethylanthraquinone. Undoubtedly the yields of primary ozonization products, 9-methylbenz[a]anthracene-7,12-dion-8-acetic acid, and 2-methyl-5,6-dicarboxyanthraquinon-1-acetic acid are higher. No alkaline hydrogen peroxide workup required. Compound 12. r
,l
1
J
Mayo; Oxidation of Organic Compounds Advances in Chemistry; American Chemical Society: Washington, DC, 1968.
72
OXIDATION
O F ORGANIC
COMPOUNDS—HI
g e n i c i t y , K - a n d L - r e g i o n a d d i t i v i t y t o w a r d s ozone, a n d the P u l l m a n s ' electronic t h e o r y of carcinogenesis. F i n a l l y , even t h e o b s e r v a t i o n (14, 21) that the m e t a b o l i c reactions l i k e l y to b e r e l a t e d to the course of these ozone reactions are those of detoxification rather t h a n of c a r c i n o g e n i c r e s p o n s i b i l i t y is n o t w i t h o u t exception—cf., e.g., the seven m e t a b o l i c o x i d a t i o n p r o d u c t s of 5 (22) to the single o z o n a t i o n p r o d u c t (24).
Acknowledgment T h i s research e x t e n d i n g over a d e c a d e w a s e n t i r e l y s u p p o r t e d b y U . S . P u b l i c H e a l t h Service grants f r o m t h e N a t i o n a l C a n c e r Institute, t h e most recent of w h i c h h a v e b e e n CA-07808-01-3. T h i s p a p e r c o n c l u d e s t h e series e n t i t l e d " O z o n o l y s i s of P o l y c y c l i c A r o m a t i c s " [ P a p e r I, (34); Paper X I V , (26)].
Literature Cited
(1) Badger, G. M., J. Chem. Soc. 1949, 456. (2) Ibid., 1950, 1809. (3) Badger, G. M., Campbell, J. E., Cook, J. W., Raphael, R. A., Scott, A. I., J. Chem. Soc. 1950, 2326. (4) Bailey, P. S., J. Am. Chem. Soc. 78, 3811 (1956). (5) Bailey, P. S., Mainthia, S. B., J. Org. Chem. 23, 1089 (1958). (6) Bailey, P. S., Ashton, J. B., J. Org. Chem. 22, 98 (1957). (7) Bailey, P. S., Kolsaker, P., Sinha, B., Ashton, J. B., Dobinson, F., Batterbee, J. E., J. Org. Chem. 29, 1400 (1964). (8) Bailey, P. S., Bath, S. S., Dobinson, F., Garcia-Sharp, F. J., Johnson, C. D., J. Org. Chem. 29, 697 (1964). (9) Bhargava, P. M., Heidelberger,C.,J.Am. Chem. Soc. 78, 3671 (1956). (10) Cook, J. W., Hieger, I., Kennaway, E. L., Mayneord, W. J., Proc. Roy. Soc. (London)B111,455 (1932). (11) Copeland, P. G., Dean, R. E., McNeil, D., J. Chem. Soc. 1961, 1232. (12) Copeland, P. G., Dean, R. E., McNeil, D., Chem. Ind. 1959, 329. (13) Coulson, C. A., Advan. Cancer Res. 1, 1 (1953). (14) Cromwell, N. H., Am. Scientist 53, 213 (1965). (15) Danheux, C., Hanoteau, L., Martin, R. H., Van Binst, G., Bull. Soc. Chim. Belges 72, 2891 (1963). (16) Heidelberger, C., Moldenhauer, M. G., Cancer Res. 16, 442 (1956). (17) Johnson, C. D., Bailey, P. S., J. Org. Chem. 29, 703 (1964). (18) Lacassagne, A., Zajdela, F., Buu-Hoi, N. P., Chalvet, O., Compt. Rend. 244, 273 (1957). (19) Moriconi, E. J., Salce, L., Taranko, L. B., J. Org. Chem. 29, 3297 (1964). (20) Moriconi, E. J., Taranko, L. B., J. Org. Chem. 28, 1831 (1963). (21) Ibid., p. 2526. (22) Ibid., p. 2526, footnote 4. (23) Moriconi, E. J., O'Connor, W. F., Rakoczy, B., J. Org. Chem. 27, 3618 (1962). (24) Moriconi, E. J., O'Connor, W. F., Schmitt, W. J., Cogswell, G. W., Furer, B. P., J. Am. Chem. Soc. 82, 3441 (1960). (25) Moriconi, E. J., O'Connor, W. F., Rakoczy, B., J. Am. Chem. Soc. 83, 4618 (1961).
Mayo; Oxidation of Organic Compounds Advances in Chemistry; American Chemical Society: Washington, DC, 1968.
65.
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AND
SALCE
Polycyclic
Aromatics
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(26) Moriconi, E. J., Salce, L., J. Org. Chem. 32, 2829 (1967). (27) Moriconi, E. J., O'Connor, W. F., Wallenberger, F. T., J. Am. Chem. Soc. 81, 6466 (1959). (28) Moriconi, E. J., O'Connor, W. F., Taranko, L. B., Arch. Biochem. Biophys. 83, 283 (1959). (29) Newman, M. S., Otsuka, S., J. Nat. Cancer Inst. 21, 721 (1958). (30) Pullman, A., Pullman, B., Advan. Cancer Res. 3, 117 (1955). (31) Ibid., pp. 141-144. (32) Pullman, A., Pullman, B., "La Cancerisation par les Substances Chimiques et la Structure Moleculaire," Masson et Cie, Paris, 1955. (33) Roitt, I. M., Waters, W. A., J. Chem. Soc. 1949, 3060. (34) Schmitt, W. J., Moriconi, E. J., O'Connor, W. F., J. Am. Chem. Soc. 77, 5640 (1955). (35) Unseren, E., Fieser, L. F., J. Org. Chem. 27, 1386 (1962). (36) Vollmann, H., Becker, H., Correll, M., Streeck, H., Ann. 531, 1 (1937). (37) Wibaut, J. P., DeBoer, Th. J., Konikl. Ned. Akad. Wetenschap. 59, 421 (1956). (38) Wibaut, J. P., DeBoer, Th. J., Rec. Trav. Chim. 78, 183 (1959). RECEIVED
October 20, 1967.
Mayo; Oxidation of Organic Compounds Advances in Chemistry; American Chemical Society: Washington, DC, 1968.