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The Practical Side
C H A P T E R
XI
The Practical Side
I. Introduction It is b e y o n d the scope of this treatise to delve deeply into the practical side of o z o n e organic c h e m i s t r y . This is d o n e to a considerable degree e l s e w h e r e (29,32,589,932-938). It is a p p r o p r i a t e , h o w e v e r , that selected topics and e x a m p l e s at least be called to the attention of the r e a d e r , and this is the p u r p o s e of this c h a p t e r . T h e c h a p t e r begins with a brief discussion of n e w e r ozonation techniques and selected examples of the use of o z o n e in synthesis and structural proof. T h e use of o z o n e in the purification of w a t e r , the refining of w o o d p u l p , p o l y m e r grafting, e t c , is then briefly c o n s i d e r e d . T h e c h a p t e r closes with the a d v e r s e side of o z o n e chemistry: air pollution, the danger of fluorocarbons and other s u b s t a n c e s to the o z o n e layer, r u b b e r degradation, toxic effects, e t c . I I . Techniques S o m e of the techniques of ozonolysis and ozonation have already been d i s c u s s e d , especially the conversion of peroxidic to nonperoxidic ozonolysis p r o d u c t s (Vol. I, C h a p t e r VIII). Excellent recent sources (935-936a) of routine ozonation t e c h n i q u e s , including o z o n e generation, and ozonation a p p a r a t u s and p r o c e d u r e s (935) h a v e already been referenced. S o m e w h a t older sources are also still important (32,933). In this section emphasis will be given to certain special techniques which either h a v e already p r o v e d to be of unusual importance and utility or show great p r o m i s e . T h e first is the use of o z o n e in the a b s e n c e of molecular oxygen (939, 939a). This t e c h n i q u e , in combination with determination of molecular oxygen as an ozonation p r o d u c t (243,258,574), has been of inestimable value in m e c h a n i s m studies, especially t h o s e concerning the competition b e t w e e n ozonolysis and epoxidation (Vol. I, C h a p t e r XI), the competition 355
356
XI
T H E PRACTICAL SIDE
b e t w e e n ozonolysis and quinone production (Chapters V and VI), and the c o u r s e of ozonation of amines and o t h e r nucleophiles (Chapter VII), hetero double b o n d s (Chapter VIII), and saturated groupings (Chapter IX). A n o t h e r technique that is continually gaining in importance is ozonation at very low t e m p e r a t u r e s (110,923,940-943), sometimes in matrices (944). T h e s e studies are leading to the identification of k e y , unstable intermediates in ozonation via low t e m p e r a t u r e spectroscopy of various t y p e s . Such studies at medium low t e m p e r a t u r e s also are very important (259a,469,945 -952). It is reasonable to predict that the most important adv a n c e s in the future will c o m e from improved t e c h n i q u e s for extremely low-temperature studies coupled with q u a n t u m mechanical calculations. A new technique that is being developed rapidly and becoming increasingly useful in small-scale syntheses is " d r y o z o n a t i o n " (48,145,468,829843,903). This p r o c e d u r e already has b e e n discussed in considerable detail in Chapter IX, Section V I I I , A and C h a p t e r X , Sections III and IV. As shown t h e r e , these reactions are in general more regio- and stereoselective than reactions carried out in solution. It has been suggested that this selectivity is due to the molecules being closely p a c k e d in the a d s o r b e d layer, so that o z o n e attack o c c u r s preferentially at e x p o s e d terminal positions (833 -835). A n o t h e r suggestion is that an actual interaction b e t w e e n the silica and substrate o c c u r s , which c a u s e s the o z o n e attack to involve a s o m e w h a t altered species (48). T h e r e are disadvantages to this m e t h o d , h o w e v e r , in that it is not easily monitored and so far can be used only on a small scale. This would be o v e r c o m e to some extent if o z o n e solutions rather than gaseous o z o n e could be e m p l o y e d , but this disrupts the a d s o r b e d m o n o l a y e r and dec r e a s e s regioselectivity. A c o m p r o m i s e that can be used with c o m p o u n d s having hydroxyl functional groups e m p l o y s the hydrogen succinate of the substrate, which is more strongly a d s o r b e d than the substrate itself, and Freon-11 solutions of ozone (835a). It would be amiss not to mention u n d e r special techniques the use of nucleophiles, especially p h o s p h i t e s , to generate singlet oxygen through ozonation. This is discussed thoroughly in C h a p t e r V I I , Section III. In passing, the following t w o items a p p e a r worthy of mention. Ultramicro ozonolysis m e t h o d s have been described using quantities of 1 0 0 500 ng of c o m p o u n d to be ozonized and chromatographic analysis (953956). Teflon tubing and joints have long been used in ozonation setups, and it has been a s s u m e d that they are inert to o z o n e . Recently, h o w e v e r , it has been reported that some o z o n e attack d o e s o c c u r very slowly, producing difluoromethanal ( C F 0 ) and c a r b o n dioxide in small a m o u n t s . (957). T h e o z o n e attack is thought to o c c u r at terminal olefinic groups in the poly2
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Synthesis
357
mer. T h e degree to which these are p r e s e n t and the c o n s e q u e n t o z o n e at tack o c c u r s is so slight, h o w e v e r , that it can be ignored in most experi ments.
III. Synthesis An effort has been m a d e in this treatise, especially in this v o l u m e , to call attention to the synthetic utility associated with ozonation of various c o m p o u n d t y p e s in the c h a p t e r s dealing explicitly with these t y p e s . It s e e m s a p p r o p r i a t e , h o w e v e r , to call attention to some of this again and to include a limited n u m b e r of additional e x a m p l e s , especially from the recent literature regarding olefins. In Vol. I, C h a p t e r I V , it w a s s h o w n that alkyl substituents increase the reactivity of an olefinic double bond t o w a r d o z o n e . This principle has fre quently been used in selective ozonolysis. In o n e such e x a m p l e (958), an endocyclic double bond w a s cleaved in preference to an exocyclic double b o n d . In a n o t h e r instance an exocyclic double bond w a s cleaved in pref e r e n c e to an endocyclic double b o n d which w a s a part of an a , /3-unsaturated k e t o n e system (959). O d i n o k o v et al. (959a) have s h o w n that Ε dou ble b o n d s are selectively a t t a c k e d in preference to Ζ double b o n d s in cyclic p o l y e n e s . T h e reasons for this are discussed in Vol. I, C h a p t e r I V , Section II. In C h a p t e r s VI (Sections I and V I , B) and VII (Section II, D) of Vol. I, intramolecular interactions b e t w e e n protic, nucleophilic functional groups and carbonyl moieties to p r o d u c e heterocycles w e r e described. T h e s e reactions have obvious synthetic possibilities. Recently, such reac tions have been used in the synthesis of c y c l o p h o s p h a m i d e derivatives of t y p e s 1026 and 1027, as shown in S c h e m e 112 (960-963, see also 963a). A n o t h e r interesting variation, involving a hydrazine type is also shown at the b o t t o m of S c h e m e 112 (964). T y p e s 1026a and 1027a show antitumor activity (963). T w o o t h e r e x a m p l e s in which intramolecular interactions play a role in the synthesis of heterocyclics are w o r t h y of reference (965, 966). In Vol. I, C h a p t e r V I I , Section II, Β " a m m o z o n o l y s i s " and " c y a n o z o n o l y s i s " were discussed. T h e s e interesting reactions also h a v e obvious utility in the synthesis of heterocyclics, including oxaziridines and α-hy d r o x y carboxylic acids. C h a p t e r VIII in Vol. I is the c h a p t e r that discusses the various reagents used to c o n v e r t peroxidic to nonperoxidic ozonolysis p r o d u c t s . Dimethyl sulfide is o n e of the most widely used reducing agents for conversion to
358
XI
O
THE
PRACTICAL
SIDE
Ο
NHR'
V v
NHR' Ρ
G(CH ) CH=CH a
a
Ο
RN
2
G(CH ) C=0
2
2
2
Η
R'
R' Ο Ν—CHOH V \ Ρ CH
Ο. N—CHOOH V \ Ρ CH
(C H ) P 6
5
3
2
2
R^N
G-CH
R,N
2
G-CH 1027
1026
R = C l C H C H ; R ' = H o r C1CH CH CH a:G = 0 b : G = Ν I R a
a
2
Ν—NH
v
2
Ρ / \
R2N
0-CH CH=CH 8
v
^/
2
Ρ
Η Ν—Ν
/ \/
\
Ο
\\
C—Η
R,N 0 - C H
2
2
Η O
2
Η Η \ Ο Ν -N \ W / Ρ CHOOH / \ / R N O-CH,
Η O
2
ν
\/ \
Ρ
/
RN
2
a
SCHEME
Η Ν—Ν
\/
CHOH
0-CH
2
11 2
aldehydes and k e t o n e s or derivatives thereof (189,967-969; see also Vol. I, C h a p t e r V I I I , Section I). In o n e p r o c e d u r e methyl orthoformate also w a s e m p l o y e d , and the p r o d u c t s w e r e acetals which could be either hydrolyzed to aldehydes or ozonized further to methyl e s t e r s , both in high yield (967; see also C h a p t e r I X , Section V, D). An e x a m p l e is outlined in S c h e m e 113. In one instance ozonation w a s performed with the dimethyl sulfide present in situ (970). It is doubtful that this would often be successful, h o w e v e r , since dimethyl sulfide itself is readily attacked by o z o n e (Chap ter VII, Section IV). In regard to a n o t h e r reducing agent, lithium aluminum hydride, by which ozonides are reduced through the aldehyde or k e t o n e stage to alco hols, a new study (977) has indicated that the ozonide reduction involves a
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Synthesis
359
simple hydride attack at a peroxidic o x y g e n , analogous to other nucleophilic reductions of peroxidic ozonolysis p r o d u c t s , r a t h e r than the complicated m e c h a n i s m proposed by Story et al. (Vol. I, C h a p t e r V I I I , Section I). Reduction at the carbonyl stage a c c o u n t s for the labeling results o b s e r v e d , as well as the stereoselectivity found in certain cases (971). S c h e m e 113 includes the two-step c o n v e r s i o n of an olefin to ester moieties via acetal groupings. This also has been accomplished in one operation, without a reduction s t e p , by ozonizing in the p r e s e n c e of either a n h y d r o u s hydrogen chloride (972) or boron trifluoride (973-975). The reaction c o u r s e for the hydrogen chloride experiments undoubtedly w a s as shown in the lower part of S c h e m e 113 (972). Such a s c h e m e should also be valid for the boron trifluoride e x p e r i m e n t s , but the data presented (973-975) leave the reaction c o u r s e uncertain. A s pointed out in Vol. I, C h a p t e r X , Section I, ozonolysis of substituted vinyl chlorides in methanol yields methyl esters from both sides of the double b o n d . This has recently b e e n s h o w n to be t r u e , in quantitative yields, for vinyl 1,2-dichloro c o m p o u n d s (976). N o t only is this of import a n c e in syntheses but also in the destruction of certain insecticide pollutants (976).
RCHO
•
RCH(OR')
RCH=CHR
I OR' SCHEME
I OR' 113
2
360
XI
THE
PRACTICAL
SIDE
Simple ozonolysis p r o c e d u r e s have resulted in the synthesis, for the first time, of malonic and dimethylmalonic anhydrides (977). T h e starting materials w e r e ketene dimers, as outlined in E q . (112). R 0=C
R C = CR
0=C
2
'C=0
+ R COO 2
•
Peroxides
V
R = Η or Me
(112) Odinokov et al. (978,979, see also 979a) have reported the remarkable conversion of cyclic olefins to dicarboxylic acids with 1 equivalent of o z o n e , using oxygen as the carrier, in ether-type solvents (diethyl ether, d i o x a n e , tetrahydrofuran, or ethyl acetate), followed by t r e a t m e n t with Lindlar catalyst ( P d — C a C 0 — P b O ) and h y d r o g e n . This is astonishing, not only in view of the fact that 1 equivalent of o z o n e generally results in oxidation only to the a l d e h y d e - a c i d stage, but also in that catalytic hydrogenation did not bring about reduction. O d i n o k o v et al. (979), how ever, stated that hydrogen w a s essential and could not be replaced by ni trogen. Likewise, the ether-type solvent w a s n e c e s s a r y . In most cases 2 equivalents of methanol also w e r e p r e s e n t , but w e r e not required. Odinokov et al. (979) claim to h a v e identified the peroxidic ozonolysis products in the case of cyclooctene as 1028b in the p r e s e n c e of m e t h a n o l , and 1029 in its a b s e n c e . With methanol alone (no ethereal solvent), the p r o d u c t w a s 1028a (979). Obviously, molecular o x y g e n entered the reac tion in the p r e s e n c e of the ethereal-type solvents. Peroxides 1028b and 1029 were c o n v e r t e d to octanedioic acid by t r e a t m e n t with hydrogen and Lindlar catalyst, but 1028a w a s not. According to O d i n o k o v et al. (979) the p r o c e s s involves hydrogen transfer, as outlined in S c h e m e 114. The origin of 1028a is obvious (see Vol. I, C h a p t e r s V and V I I , Section II, for m e t h o x y alkyl h y d r o p e r o x i d e - a l d e h y d e interactions), but the role of oxygen in producing 1028b and 1029 is unclear and highly unusual, to say the least, as is also the role of hydrogen in the decomposition of 1028b and 1029. In contrast to these results, O d i n o k o v and c o - w o r k e r s (959a,980) re ported o t h e r ozonolyses in which Lindlar catalyst and hydrogen con verted the peroxidic ozonolysis p r o d u c t s to a l d e h y d e s . T h e difference w a s said to be due to the ethereal-type solvent used in the ozonations to carboxylic acids (979). Odinokov and co-workers (959a,978-988a) have published a series of p a p e r s on the ozonolysis of cyclic and acyclic olefins in which they h a v e described conversion of the various peroxidic ozonolysis p r o d u c t s to p o lyfunctional peroxidic and nonperoxidic p r o d u c t s by various m e a n s . 3
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361
Synthesis
HC 3
CH I
I
o (o )
ο I ο
ο ι ο
2
CH3OH (Et O) a
I
CH
o
CH3O
dioxane
2
X
(CH ) a
(
1028a : G = Η 1028b : G = OH Pd—CaCO,—PbO
i.e., 1028b
/(CH,) HC-
.CH
(CH ) 2
θ'
°
HC (CH ) 2
I
HO-C
Os/°
Ο
6
C-OH II
ο
(
1029 H
^ O H - 0 > \ 2
Pd—CaCO,—PbO
Vo -HO 0 x/
C
CH
(CH ) a
SCHEME
X 6
114
S o m e of the results are straightforward and a p p e a r to be useful for synthe sis; o n e e x a m p l e is a step in the synthesis of certain sex p h e r o m o n e s (988a). O t h e r s , like the o n e already m e n t i o n e d , are surprising and must be verified before a c c e p t a n c e . Recently, a commercial p r o c e s s has gone into operation for the synthe sis of N y l o n 12, in which the first step is selective ozonolysis of cyclododecatriene (988b). An important use of ozonolysis in synthesis is to effect ring contraction via an aldol-type condensation following the ozonolysis (e.g., 989-991). An e x a m p l e is shown in E q . (113) (989).
362
XI
THE
PRACTICAL
SIDE
A n o t h e r useful synthetic operation involves the ozonation of silyloxyalkenes (992,993). T h e enolate double bond is m o r e reactive than m o s t other double b o n d s and can be cleaved by o z o n e selectively, as outlined at the top of S c h e m e 115, in a synthesis of 1030. Since either the kinetic or the t h e r m o d y n a m i c enolate of u n s y m m e t r i c a l k e t o n e s (e.g., 1031) can be trapped as the trialkylsilyloxy derivative, either can be ozonized, as s h o w n in S c h e m e 115 with 1032a and 1032b (992,993). Ozonolysis of the kinetic enolate derivative (e.g., 1032a) m a k e s possible oxidative cleavage of an unsymmetrical ketone away from the m o r e highly alkylated side (see also 994). In some cases " a n o m a l o u s " ozonations o c c u r , involving purely electrophilic o z o n e attack without double-bond cleavage (see e x a m p l e s in Vol. I, Chapter X I , Section III, B) (992,993). K e t o n e s , such as 1 0 3 1 , h a v e also b e e n converted to enolates by o t h e r m e a n s , and the resulting double b o n d cleaved by o z o n e (995,996). In regard to p r o c e d u r e s of synthetic importance discussed in Vol. I, thermal and photolytic decompositions of ozonides and other peroxidic ozonolysis p r o d u c t s (Chapters VIII and IX) are obvious e x a m p l e s . C h a p t e r IX in Vol. I deals largely with so-called a n o m a l o u s ozonolysis of ally lie and a , /^-unsaturated carbonyl c o m p o u n d s . S o m e examples of the importance of this reaction in synthesis w e r e mentioned in Vol. I, C h a p t e r IX, Section I, and discussed in this v o l u m e , C h a p t e r V I , Section
COOH 1031
1032a
COOH
SCHEME
115
///
Synthesis
363
1036 SCHEME
116
II, C. T h e s e reactions involved the preparation and ozonolysis of a-benzylidene and furfurylidene derivatives of cyclic k e t o n e s with resultant cleavage of the ring. This p r o c e d u r e also can be of importance in ring contraction (see 935 for other e x a m p l e s and references). A similar type of operation e m p l o y s ozonolysis of a - h y d r o x y m e t h y l e n e k e t o n e s (997), as outlined at the top of S c h e m e 116. Such a reaction also occurs with cyclic dienes possessing conjugated e x o methylene groups (e.g., 1033). By the use of special conditions, h o w e v e r , simple cleavage of the methylene groups (e.g., to 1034) can be favored (998). T w o o t h e r a n o m a l o u s o z o n o l y s e s , analogous to those described in Vol. I, C h a p t e r IX, are also outlined in S c h e m e 116. T h e one with 1035 (999) involves an
364
XI
THE
PRACTICAL
SIDE
allylic-type a n o m a l o u s ozonolysis (Vol. I, C h a p t e r I X , Section II), while that with 1036 (1000) is of the a , β-unsaturated carbonyl type (Vol. I, C h a p t e r IX, Section III). C h a p t e r XI in Vol. I deals with epoxide formation and o t h e r noncleavage reactions of o z o n e . H e r e , t o o , applications to synthesis should be apparent. In C h a p t e r III of this volume the importance of exhaustive ozonolysis of aromatic c o m p o u n d s , both in synthesis and structure elucidation, w a s dis c u s s e d . A new and interesting e x a m p l e leading to a large-ring polylactone is s h o w n in E q . (114) (1001). T h e yield w a s s o m e w h a t less than the sta tistical 2 5 % (see C h a p t e r III).
a:
DO
d)o
(114)
3
(2) M e S 2
O ^ O
In C h a p t e r V I I , Section V, A, ozonation of selenides to p r o d u c e selenoxides w a s described. An important synthetic application of this ozonaδ '
A
Η
Λ
+
Se—R
.x^-ci
R*/ Η
Η R
V Η R
R \
Η / C=C / \ Η R
+
S e —R V Η R
1037
1038
+
^ ^
(
^
r
*(CH ) a
^OOEt
O-O Η / \ / Η ΗC C c / \ ^"(CH τ τ χ) A Η
t
SeC H 8
HOSeR
2
s
^COOEt
N
2
1039
SeC H fi
NaBH
HO-C H
v 2
-(CH
^ ^ C O O E t 2
1040 SCHEME
117
4
s
V
Water,
Wastewater,
and Sewage
Purification
365
tion is syn elimination of the selenoxide group and hydrogen to p r o d u c e unsaturation. T h e m e c h a n i s m is outlined in S c h e m e 117 (1037—> 1038) (1002). This technique has been utilized by Clark and H e a t h c o c k (993) in a separate synthesis of 1030 (Scheme 115). M a n y other e x a m p l e s are listed in an excellent review by Clive (1002). This reaction has been c o m b i n e d with ozonolysis of a double bond in one operation, as outlined in Scheme 117 (1039 - > 1040) (1003). Finally, ozonation u n d e r strong-acid conditions has been used to introd u c e carbonyl groups into the 6- and 7-positions of steroids, as illustrated in E q . (115) (1004).
(115) O t h e r e x a m p l e s of syntheses involving o z o n e can be found in other reviews (272,510,935-936a, 1005,1006). IV. Analysis and Proof of Structure T h e most important use of ozonolysis for many y e a r s w a s in proof of structure of c o m p o u n d s bearing double and triple b o n d s . T h e r e are many examples of this in other reviews (29,32,935,936,1006). In C h a p t e r III, Section V the important exhaustive ozonolysis of aromatic rings w a s discussed. This has been used in both structural and configurational proofs. Earlier in this c h a p t e r m i c r o t e c h n i q u e s were cited, which can be used in structural proofs (953-956,1007,1008) as well as in determinations of degree of unsaturation (1008a). Recently, interesting results concerning ozonolysis of corrins have been reported (1009), which h a v e been useful at least in confirming assigned s t r u c t u r e s . V. Water, Wastewater, and Sewage Purification Probably the most important use of o z o n e today is in the purification of w a t e r for drinking p u r p o s e s , the cleaning u p of sewage w a t e r before discharge into the e n v i r o n m e n t and r e u s e , and the r e m o v a l of industrial chemical w a s t e s from industrial w a t e r s before r e e n t r a n c e into rivers and
366
XI
THE PRACTICAL
SIDE
s t r e a m s . Although o z o n e has b e e n used for w a t e r purification for nearly 100 y e a r s , principally in E u r o p e , it has only recently received the attention it d e s e r v e s in the United States (WW; see also Vol. I, C h a p t e r I, Section I). T h e largest o z o n e generation plant for w a t e r purification in the world is said to be in East M o s c o w (WW). In recent years many p a p e r s concerning o z o n e in w a t e r purification have been published. It is b e y o n d the scope of this b o o k to include a c o m prehensive discussion or bibliography. Only a few representative articles will be listed, dealing with disinfection, color, o d o r and taste control, and removal of dissolved material in sewage and w a s t e w a t e r (WW-W22). O t h e r s can be found elsewhere (589,933,937,938), and in bibliographies listed in the references cited in this section, as well as in o t h e r sections of this v o l u m e , especially C h a p t e r III (Sections IV and V ) , C h a p t e r IV (Section V, E ) , C h a p t e r VIII (Section I, C, 5), and C h a p t e r IX (Sections I V , A, VI and VII), and in Vol. I, C h a p t e r I, Section I). B e c a u s e of the danger of producing chlorinated h y d r o c a r b o n s and o t h e r carcinogenic substances during the t r e a t m e n t of w a s t e w a t e r by chlorination (727,1010,1015,1016,1018-1020,1022-1024), o z o n e a p p e a r s destined to b e c o m e the m e t h o d of choice for w a t e r purification. Burleson et al. (1023, W24) have shown that the mutagenicity and carcinogenicity of various poly aromatic amines and h y d r o c a r b o n s , certain alkylating agents, pesticides, and selected other s u b s t a n c e s are completely destroyed by ozonation (see C h a p t e r s V - V I I I for the chemistry involved). It w a s pointed out, h o w e v e r , that care must be taken with benzidine and certain h y d r a z i n e s , which yield transient m u t a g e n s on partial ozonation. O z o n e a p p e a r s to be more efficient in the destruction of organic materials in w a t e r at an alkaline p H ( > 9 . 0 ) (456,919 -921,1022,1025,1026). This is thought to be due to catalytic decomposition of o z o n e , resulting in the generation of hydroxyl radicals, which are powerful oxidants (Chapter X , Section V I , D). Such a p r o c e s s d o e s not a p p e a r to be as practical for the purification of municipal waters as a n o t h e r p r o c e s s that also generates hydroxyl radicals. This method involves a combination of o z o n e and U V radiation and s h o w s promise of being superior both in disinfection and in destruction of organic waste and industrial materials in w a t e r (727,1027, 1028), including water-soluble p o l y m e r s (1028a). Although some attention has been given to identification of the actual p r o d u c t s obtained from the ozonation of organic pollutants in w a t e r (e.g., 33,115,117,126,456,727,1021,1027,1029), most of the studies in the literature have dealt largely with sewage and o t h e r w a s t e w a t e r s and have merely determined the biological oxygen d e m a n d (BOD) and chemical oxygen d e m a n d (COD) reduction realized by o z o n e t r e a t m e n t . Although this has been useful, m u c h more study of the organic chemistry involved is greatly n e e d e d .
VIII
The Ozone Layer
Controversy
367
VI. Pulping and Bleaching of Wood T h e separation of lignin from cellulose in w o o d and the bleaching of the resulting w o o d p u l p , as well as the clean-up of the effluents from these p r o c e s s e s , are very important p r o b l e m s in the p a p e r industry, especially since the traditional m e t h o d s involving alkali followed by chlorine and chlorine dioxide result in excessive w a s t e and pollution (1030-1032a). F o r this r e a s o n , considerable attention is being given to the use of o z o n e for these p u r p o s e s (1031,1032). Lignin is a phenolic-type, high-molecular-weight material readily at tacked by o z o n e (155,782,1030,1033; see also C h a p t e r III, Section IV). O z o n e can be used to delignify w o o d , but the cellulose is considerably degraded simultaneously (776-782). This is b e c a u s e ^-glycosides are readily attacked by o z o n e , m o r e so than α-glycosides (Chapter IX, Sec tion V, D). T h e problem still awaits solution. O t h e r references are avail able in a n o t h e r review (1034). VII. Miscellaneous Uses Ozonation has been used for grafting and o t h e r modifications of natural and synthetic polymers (821,1034,1035), oxidation of coal and car bon (1036-1040a), and m a n y o t h e r p u r p o s e s discussed else where (1006,1034,1036). VIII. The Ozone Layer Controversy O z o n e in the a t m o s p h e r e that w e b r e a t h e is harmful to u s , as briefly discussed in Section IX. O z o n e in the s t r a t o s p h e r e , h o w e v e r , is thought to be essential to life as we k n o w it. Life on land apparently did not begin until the o z o n e layer w a s formed, and it is thought that destruction of or a decline in the o z o n e layer will bring on serious climatic and health haz a r d s , particularly a dramatic increase in skin c a n c e r (1041). T h e danger of a large d e c r e a s e in the concentration of ozone in the stratosphere c a u s e d by the release of F r e o n s (aerosols) into the at m o s p h e r e w a s mentioned in Vol. I (page 1) and in this v o l u m e , C h a p t e r X , Section V I , Ε . T h e first warning of this danger c a m e from Molina and Rowland (924,1042) in 1974. Since t h e n , many p a p e r s h a v e been p u b lished on the subject, only a few of which can be cited h e r e . S o m e cham pion, or at least take seriously, the theory (1043-1050), while others belit tle, cast d o u b t u p o n , or minimize the importance of this problem (925,1050-1057). As pointed out in Vol. I (page 1), m a n y other possible c o n t a m i n a n t s , for e x a m p l e , h y d r o g e n chloride from volcanos (1058), ex-
368
XI
THE PRACTICAL
SIDE
pected to bring about the same effect have also been cited. An excellent, highly readable account of this c o n t r o v e r s y has been written by Dotto and Schiff (1041). It t o o , h o w e v e r , h a s been accused of bias (1058a). [For ad ditional references, see Graedel and F a r o w (1059) and references in papers cited in the preceding discussions.] T h e danger c o m e s largely from the k n o w n U V light decomposition of chlorofluorocarbons (Freons), to p r o d u c e chlorine a t o m s , and the chain reaction involving the destruction of o z o n e by chlorine a t o m s [ E q s . (105) and (106), C h a p t e r X , Section V I , E ] . T h o s e w h o believe that there h a s been overreaction to the problem cite the uncertainties involved, espe cially the time factor, the ability of o z o n e to regenerate itself, and the im portance of chain-breaking reactions (1041). T h e c o n t r o v e r s y has been bitter b e c a u s e of the fiancial loss suffered by the multimillion dollar fluorochloromethane industry as a c o n s e q u e n c e of the theory (1041). IX. The Negative Side of Ozone Organic Chemistry A. O Z O N E IN A I R P O L L U T I O N It has been k n o w n for a long time, as a result of the pioneering studies of Haagen-Smit (1060-1063), that o z o n e is present in photochemical smog. T h e principal reactions involved are outlined in E q s . (116)—(121) (1064-1065). Many others also apparently o c c u r 1066). NO
ο
2
+ o
2
o
3
RH
+
hv
•
NO
+
Μ
•
o
+
NO
+
O
R.
+ o
2
ROO-
+ o
2
3
NO
+ ο
(116)
+
(117)
+ o
2
•
R.
•
ROO-
RO-
Μ
+
2
(118)
-OH
(119) (120)
4
o
3
(121)
The literature in this field is v o l u m i n o u s , and it is b e y o n d the scope of this b o o k to d o m o r e than refer to reviews w h e r e the work is summarized (934,1059,1064-1065a,1066a, 1067-1069). Along with o z o n e various o t h e r irritants are p r o d u c e d , some via reactions of o z o n e with h y d r o c a r b o n s . T h e s e in turn, along with o z o n e itself, are h a z a r d o u s to both plants (1070) and animals (1071).
IX
Negative
Side of Ozone Organic
Chemistry
369
Although this is a problem of great c o n c e r n , it a p p e a r s that control is difficult, due largely to h u m a n n a t u r e (1071a). B. E F F E C T S O F O Z O N E O N SYSTEMS: TOXICITY
BIOLOGICAL
In Section I X , A , the o c c u r r e n c e of o z o n e in polluted air w a s discussed briefly. T h e toxicity of o z o n e and/or p r o d u c t s from o z o n e reacting with o t h e r pollutants therefore is of great c o n c e r n . Again, it is beyond the scope of this b o o k to discuss t h e s e important problems in detail, and only r e v i e w s , both short (1072) and long (1070,1071,1073-1074), are cited; most of the important references can be found therein. Of particular interest to o z o n e organic chemistry are recent studies on the reactions of o z o n e with cellular s u b s t a n c e s such as unsaturated and polyunsaturated fatty acids and lipids u n d e r conditions resembling those in cells (929,930,1074-1081). Although ozonolysis of the double b o n d s by the Criegee m e c h a n i s m (Vol. I) a p p e a r s to be the major reaction c o u r s e , there is evidence that radicals also are p r o d u c e d (930 \ see also C h a p t e r X , Section VI, F). T h e source is u n c e r t a i n , as is also the possiblity of competing autoxidation initiated by o z o n e (929,930,1076,1076a). C. D E G R A D A T I O N O F R U B B E R :
ANTIOZONANTS
A n o t h e r important side effect of air pollution is the degradation of rubb e r and o t h e r elastomers by o z o n e in the air. In fact, r u b b e r is often used as a specific reagent for measuring o z o n e in air quantitatively (1082,1083). M u c h has been written on the subject of the action of o z o n e on r u b b e r and o t h e r e l a s t o m e r s , beginning with the w o r k of Harries (1084) (see also Vol. I, C h a p t e r I, Section II). Only a few of these studies are cited here (438, 481,482,1083,1085-1089). O t h e r references can be found in these p a p e r s , especially (438), (482), and (1088). T h e r e a p p e a r s to be little reason to doubt that the major o z o n e attack involves ozonolysis of the double b o n d s (Vol. I), although it has b e e n suggested that ozone-initiated autoxidation at allylic centers also o c c u r s (1085). Of greatest interest concerning the degradation of r u b b e r and o t h e r elastomers by o z o n e is the p r e v e n t i o n or retardation of this action by m e a n s of antiozonants (e.g., 436-438,478,480-484,1083,1086,10901094). T h e r e are m a n y t y p e s of a n t i o z o n a n t s , s e c o n d a r y phenylenediamines (Chapter V I I , Section II) being a m o n g the best. T h e m e c h a n i s m of antiozonant action still a p p e a r s to be speculative (438,1086,1094). There are at least four principal theories (438,1094). T h e first is the scavenger m e c h a n i s m which simply suggests that o z o n e reacts with the antiozonant
370
XI
THE
PRACTICAL
SIDE
faster than with the elastomer. T h e second is similar in that it p r o p o s e s that the antiozonant not only reacts with o z o n e faster than the e l a s t o m e r d o e s , but that the p r o d u c t s of the reaction form a protective film. T h e third m e c h a n i s m postulates that the antiozonant reacts with e l a s t o m e r ozonation fragments, thereby effectively relinking t h e m and healing the fractures. M u r r a y and Story (438,1086) convincingly point out flaws in all these theories and suggest a fourth, namely, that the antiozonant reacts with the Criegee zwitterion or the ozonide p r o d u c e d by ozonolysis (Vol. I) and, t h e r e b y , provides a protective coating on the elastomer surface, which is not readily penetrated by o z o n e . In the most recent w o r k on the p r o b l e m , h o w e v e r , Andries et al. (1094) found no spectral evidence for the M u r r a y - S t o r y m e c h a n i s m (1086), at least with antiozonants of the Ν , Ν ' - d i a l k y l p h e n y l e n e d i a m i n e t y p e . Their studies indicated a combination of the first t w o m e c h a n i s m s (scavenger and protective film, without participation of the e l a s t o m e r itself).
XI
The Practical Side
I. Introduction It is b e y o n d the scope of this treatise to delve deeply into the practical side of o z o n e organic c h e m i s t r y . This is d o n e to a considerable degree e l s e w h e r e (29,32,589,932-938). It is a p p r o p r i a t e , h o w e v e r , that selected topics and e x a m p l e s at least be called to the attention of the r e a d e r , and this is the p u r p o s e of this c h a p t e r . T h e c h a p t e r begins with a brief discussion of n e w e r ozonation techniques and selected examples of the use of o z o n e in synthesis and structural proof. T h e use of o z o n e in the purification of w a t e r , the refining of w o o d p u l p , p o l y m e r grafting, e t c , is then briefly c o n s i d e r e d . T h e c h a p t e r closes with the a d v e r s e side of o z o n e chemistry: air pollution, the danger of fluorocarbons and other s u b s t a n c e s to the o z o n e layer, r u b b e r degradation, toxic effects, e t c . I I . Techniques S o m e of the techniques of ozonolysis and ozonation have already been d i s c u s s e d , especially the conversion of peroxidic to nonperoxidic ozonolysis p r o d u c t s (Vol. I, C h a p t e r VIII). Excellent recent sources (935-936a) of routine ozonation t e c h n i q u e s , including o z o n e generation, and ozonation a p p a r a t u s and p r o c e d u r e s (935) h a v e already been referenced. S o m e w h a t older sources are also still important (32,933). In this section emphasis will be given to certain special techniques which either h a v e already p r o v e d to be of unusual importance and utility or show great p r o m i s e . T h e first is the use of o z o n e in the a b s e n c e of molecular oxygen (939, 939a). This t e c h n i q u e , in combination with determination of molecular oxygen as an ozonation p r o d u c t (243,258,574), has been of inestimable value in m e c h a n i s m studies, especially t h o s e concerning the competition b e t w e e n ozonolysis and epoxidation (Vol. I, C h a p t e r XI), the competition 355
356
XI
T H E PRACTICAL SIDE
b e t w e e n ozonolysis and quinone production (Chapters V and VI), and the c o u r s e of ozonation of amines and o t h e r nucleophiles (Chapter VII), hetero double b o n d s (Chapter VIII), and saturated groupings (Chapter IX). A n o t h e r technique that is continually gaining in importance is ozonation at very low t e m p e r a t u r e s (110,923,940-943), sometimes in matrices (944). T h e s e studies are leading to the identification of k e y , unstable intermediates in ozonation via low t e m p e r a t u r e spectroscopy of various t y p e s . Such studies at medium low t e m p e r a t u r e s also are very important (259a,469,945 -952). It is reasonable to predict that the most important adv a n c e s in the future will c o m e from improved t e c h n i q u e s for extremely low-temperature studies coupled with q u a n t u m mechanical calculations. A new technique that is being developed rapidly and becoming increasingly useful in small-scale syntheses is " d r y o z o n a t i o n " (48,145,468,829843,903). This p r o c e d u r e already has b e e n discussed in considerable detail in Chapter IX, Section V I I I , A and C h a p t e r X , Sections III and IV. As shown t h e r e , these reactions are in general more regio- and stereoselective than reactions carried out in solution. It has been suggested that this selectivity is due to the molecules being closely p a c k e d in the a d s o r b e d layer, so that o z o n e attack o c c u r s preferentially at e x p o s e d terminal positions (833 -835). A n o t h e r suggestion is that an actual interaction b e t w e e n the silica and substrate o c c u r s , which c a u s e s the o z o n e attack to involve a s o m e w h a t altered species (48). T h e r e are disadvantages to this m e t h o d , h o w e v e r , in that it is not easily monitored and so far can be used only on a small scale. This would be o v e r c o m e to some extent if o z o n e solutions rather than gaseous o z o n e could be e m p l o y e d , but this disrupts the a d s o r b e d m o n o l a y e r and dec r e a s e s regioselectivity. A c o m p r o m i s e that can be used with c o m p o u n d s having hydroxyl functional groups e m p l o y s the hydrogen succinate of the substrate, which is more strongly a d s o r b e d than the substrate itself, and Freon-11 solutions of ozone (835a). It would be amiss not to mention u n d e r special techniques the use of nucleophiles, especially p h o s p h i t e s , to generate singlet oxygen through ozonation. This is discussed thoroughly in C h a p t e r V I I , Section III. In passing, the following t w o items a p p e a r worthy of mention. Ultramicro ozonolysis m e t h o d s have been described using quantities of 1 0 0 500 ng of c o m p o u n d to be ozonized and chromatographic analysis (953956). Teflon tubing and joints have long been used in ozonation setups, and it has been a s s u m e d that they are inert to o z o n e . Recently, h o w e v e r , it has been reported that some o z o n e attack d o e s o c c u r very slowly, producing difluoromethanal ( C F 0 ) and c a r b o n dioxide in small a m o u n t s . (957). T h e o z o n e attack is thought to o c c u r at terminal olefinic groups in the poly2
///
Synthesis
357
mer. T h e degree to which these are p r e s e n t and the c o n s e q u e n t o z o n e at tack o c c u r s is so slight, h o w e v e r , that it can be ignored in most experi ments.
III. Synthesis An effort has been m a d e in this treatise, especially in this v o l u m e , to call attention to the synthetic utility associated with ozonation of various c o m p o u n d t y p e s in the c h a p t e r s dealing explicitly with these t y p e s . It s e e m s a p p r o p r i a t e , h o w e v e r , to call attention to some of this again and to include a limited n u m b e r of additional e x a m p l e s , especially from the recent literature regarding olefins. In Vol. I, C h a p t e r I V , it w a s s h o w n that alkyl substituents increase the reactivity of an olefinic double bond t o w a r d o z o n e . This principle has fre quently been used in selective ozonolysis. In o n e such e x a m p l e (958), an endocyclic double bond w a s cleaved in preference to an exocyclic double b o n d . In a n o t h e r instance an exocyclic double bond w a s cleaved in pref e r e n c e to an endocyclic double b o n d which w a s a part of an a , /3-unsaturated k e t o n e system (959). O d i n o k o v et al. (959a) have s h o w n that Ε dou ble b o n d s are selectively a t t a c k e d in preference to Ζ double b o n d s in cyclic p o l y e n e s . T h e reasons for this are discussed in Vol. I, C h a p t e r I V , Section II. In C h a p t e r s VI (Sections I and V I , B) and VII (Section II, D) of Vol. I, intramolecular interactions b e t w e e n protic, nucleophilic functional groups and carbonyl moieties to p r o d u c e heterocycles w e r e described. T h e s e reactions have obvious synthetic possibilities. Recently, such reac tions have been used in the synthesis of c y c l o p h o s p h a m i d e derivatives of t y p e s 1026 and 1027, as shown in S c h e m e 112 (960-963, see also 963a). A n o t h e r interesting variation, involving a hydrazine type is also shown at the b o t t o m of S c h e m e 112 (964). T y p e s 1026a and 1027a show antitumor activity (963). T w o o t h e r e x a m p l e s in which intramolecular interactions play a role in the synthesis of heterocyclics are w o r t h y of reference (965, 966). In Vol. I, C h a p t e r V I I , Section II, Β " a m m o z o n o l y s i s " and " c y a n o z o n o l y s i s " were discussed. T h e s e interesting reactions also h a v e obvious utility in the synthesis of heterocyclics, including oxaziridines and α-hy d r o x y carboxylic acids. C h a p t e r VIII in Vol. I is the c h a p t e r that discusses the various reagents used to c o n v e r t peroxidic to nonperoxidic ozonolysis p r o d u c t s . Dimethyl sulfide is o n e of the most widely used reducing agents for conversion to
358
XI
O
THE
PRACTICAL
SIDE
Ο
NHR'
V v
NHR' Ρ
G(CH ) CH=CH a
a
Ο
RN
2
G(CH ) C=0
2
2
2
Η
R'
R' Ο Ν—CHOH V \ Ρ CH
Ο. N—CHOOH V \ Ρ CH
(C H ) P 6
5
3
2
2
R^N
G-CH
R,N
2
G-CH 1027
1026
R = C l C H C H ; R ' = H o r C1CH CH CH a:G = 0 b : G = Ν I R a
a
2
Ν—NH
v
2
Ρ / \
R2N
0-CH CH=CH 8
v
^/
2
Ρ
Η Ν—Ν
/ \/
\
Ο
\\
C—Η
R,N 0 - C H
2
2
Η O
2
Η Η \ Ο Ν -N \ W / Ρ CHOOH / \ / R N O-CH,
Η O
2
ν
\/ \
Ρ
/
RN
2
a
SCHEME
Η Ν—Ν
\/
CHOH
0-CH
2
11 2
aldehydes and k e t o n e s or derivatives thereof (189,967-969; see also Vol. I, C h a p t e r V I I I , Section I). In o n e p r o c e d u r e methyl orthoformate also w a s e m p l o y e d , and the p r o d u c t s w e r e acetals which could be either hydrolyzed to aldehydes or ozonized further to methyl e s t e r s , both in high yield (967; see also C h a p t e r I X , Section V, D). An e x a m p l e is outlined in S c h e m e 113. In one instance ozonation w a s performed with the dimethyl sulfide present in situ (970). It is doubtful that this would often be successful, h o w e v e r , since dimethyl sulfide itself is readily attacked by o z o n e (Chap ter VII, Section IV). In regard to a n o t h e r reducing agent, lithium aluminum hydride, by which ozonides are reduced through the aldehyde or k e t o n e stage to alco hols, a new study (977) has indicated that the ozonide reduction involves a
///
Synthesis
359
simple hydride attack at a peroxidic o x y g e n , analogous to other nucleophilic reductions of peroxidic ozonolysis p r o d u c t s , r a t h e r than the complicated m e c h a n i s m proposed by Story et al. (Vol. I, C h a p t e r V I I I , Section I). Reduction at the carbonyl stage a c c o u n t s for the labeling results o b s e r v e d , as well as the stereoselectivity found in certain cases (971). S c h e m e 113 includes the two-step c o n v e r s i o n of an olefin to ester moieties via acetal groupings. This also has been accomplished in one operation, without a reduction s t e p , by ozonizing in the p r e s e n c e of either a n h y d r o u s hydrogen chloride (972) or boron trifluoride (973-975). The reaction c o u r s e for the hydrogen chloride experiments undoubtedly w a s as shown in the lower part of S c h e m e 113 (972). Such a s c h e m e should also be valid for the boron trifluoride e x p e r i m e n t s , but the data presented (973-975) leave the reaction c o u r s e uncertain. A s pointed out in Vol. I, C h a p t e r X , Section I, ozonolysis of substituted vinyl chlorides in methanol yields methyl esters from both sides of the double b o n d . This has recently b e e n s h o w n to be t r u e , in quantitative yields, for vinyl 1,2-dichloro c o m p o u n d s (976). N o t only is this of import a n c e in syntheses but also in the destruction of certain insecticide pollutants (976).
RCHO
•
RCH(OR')
RCH=CHR
I OR' SCHEME
I OR' 113
2
360
XI
THE
PRACTICAL
SIDE
Simple ozonolysis p r o c e d u r e s have resulted in the synthesis, for the first time, of malonic and dimethylmalonic anhydrides (977). T h e starting materials w e r e ketene dimers, as outlined in E q . (112). R 0=C
R C = CR
0=C
2
'C=0
+ R COO 2
•
Peroxides
V
R = Η or Me
(112) Odinokov et al. (978,979, see also 979a) have reported the remarkable conversion of cyclic olefins to dicarboxylic acids with 1 equivalent of o z o n e , using oxygen as the carrier, in ether-type solvents (diethyl ether, d i o x a n e , tetrahydrofuran, or ethyl acetate), followed by t r e a t m e n t with Lindlar catalyst ( P d — C a C 0 — P b O ) and h y d r o g e n . This is astonishing, not only in view of the fact that 1 equivalent of o z o n e generally results in oxidation only to the a l d e h y d e - a c i d stage, but also in that catalytic hydrogenation did not bring about reduction. O d i n o k o v et al. (979), how ever, stated that hydrogen w a s essential and could not be replaced by ni trogen. Likewise, the ether-type solvent w a s n e c e s s a r y . In most cases 2 equivalents of methanol also w e r e p r e s e n t , but w e r e not required. Odinokov et al. (979) claim to h a v e identified the peroxidic ozonolysis products in the case of cyclooctene as 1028b in the p r e s e n c e of m e t h a n o l , and 1029 in its a b s e n c e . With methanol alone (no ethereal solvent), the p r o d u c t w a s 1028a (979). Obviously, molecular o x y g e n entered the reac tion in the p r e s e n c e of the ethereal-type solvents. Peroxides 1028b and 1029 were c o n v e r t e d to octanedioic acid by t r e a t m e n t with hydrogen and Lindlar catalyst, but 1028a w a s not. According to O d i n o k o v et al. (979) the p r o c e s s involves hydrogen transfer, as outlined in S c h e m e 114. The origin of 1028a is obvious (see Vol. I, C h a p t e r s V and V I I , Section II, for m e t h o x y alkyl h y d r o p e r o x i d e - a l d e h y d e interactions), but the role of oxygen in producing 1028b and 1029 is unclear and highly unusual, to say the least, as is also the role of hydrogen in the decomposition of 1028b and 1029. In contrast to these results, O d i n o k o v and c o - w o r k e r s (959a,980) re ported o t h e r ozonolyses in which Lindlar catalyst and hydrogen con verted the peroxidic ozonolysis p r o d u c t s to a l d e h y d e s . T h e difference w a s said to be due to the ethereal-type solvent used in the ozonations to carboxylic acids (979). Odinokov and co-workers (959a,978-988a) have published a series of p a p e r s on the ozonolysis of cyclic and acyclic olefins in which they h a v e described conversion of the various peroxidic ozonolysis p r o d u c t s to p o lyfunctional peroxidic and nonperoxidic p r o d u c t s by various m e a n s . 3
///
361
Synthesis
HC 3
CH I
I
o (o )
ο I ο
ο ι ο
2
CH3OH (Et O) a
I
CH
o
CH3O
dioxane
2
X
(CH ) a
(
1028a : G = Η 1028b : G = OH Pd—CaCO,—PbO
i.e., 1028b
/(CH,) HC-
.CH
(CH ) 2
θ'
°
HC (CH ) 2
I
HO-C
Os/°
Ο
6
C-OH II
ο
(
1029 H
^ O H - 0 > \ 2
Pd—CaCO,—PbO
Vo -HO 0 x/
C
CH
(CH ) a
SCHEME
X 6
114
S o m e of the results are straightforward and a p p e a r to be useful for synthe sis; o n e e x a m p l e is a step in the synthesis of certain sex p h e r o m o n e s (988a). O t h e r s , like the o n e already m e n t i o n e d , are surprising and must be verified before a c c e p t a n c e . Recently, a commercial p r o c e s s has gone into operation for the synthe sis of N y l o n 12, in which the first step is selective ozonolysis of cyclododecatriene (988b). An important use of ozonolysis in synthesis is to effect ring contraction via an aldol-type condensation following the ozonolysis (e.g., 989-991). An e x a m p l e is shown in E q . (113) (989).
362
XI
THE
PRACTICAL
SIDE
A n o t h e r useful synthetic operation involves the ozonation of silyloxyalkenes (992,993). T h e enolate double bond is m o r e reactive than m o s t other double b o n d s and can be cleaved by o z o n e selectively, as outlined at the top of S c h e m e 115, in a synthesis of 1030. Since either the kinetic or the t h e r m o d y n a m i c enolate of u n s y m m e t r i c a l k e t o n e s (e.g., 1031) can be trapped as the trialkylsilyloxy derivative, either can be ozonized, as s h o w n in S c h e m e 115 with 1032a and 1032b (992,993). Ozonolysis of the kinetic enolate derivative (e.g., 1032a) m a k e s possible oxidative cleavage of an unsymmetrical ketone away from the m o r e highly alkylated side (see also 994). In some cases " a n o m a l o u s " ozonations o c c u r , involving purely electrophilic o z o n e attack without double-bond cleavage (see e x a m p l e s in Vol. I, Chapter X I , Section III, B) (992,993). K e t o n e s , such as 1 0 3 1 , h a v e also b e e n converted to enolates by o t h e r m e a n s , and the resulting double b o n d cleaved by o z o n e (995,996). In regard to p r o c e d u r e s of synthetic importance discussed in Vol. I, thermal and photolytic decompositions of ozonides and other peroxidic ozonolysis p r o d u c t s (Chapters VIII and IX) are obvious e x a m p l e s . C h a p t e r IX in Vol. I deals largely with so-called a n o m a l o u s ozonolysis of ally lie and a , /^-unsaturated carbonyl c o m p o u n d s . S o m e examples of the importance of this reaction in synthesis w e r e mentioned in Vol. I, C h a p t e r IX, Section I, and discussed in this v o l u m e , C h a p t e r V I , Section
COOH 1031
1032a
COOH
SCHEME
115
///
Synthesis
363
1036 SCHEME
116
II, C. T h e s e reactions involved the preparation and ozonolysis of a-benzylidene and furfurylidene derivatives of cyclic k e t o n e s with resultant cleavage of the ring. This p r o c e d u r e also can be of importance in ring contraction (see 935 for other e x a m p l e s and references). A similar type of operation e m p l o y s ozonolysis of a - h y d r o x y m e t h y l e n e k e t o n e s (997), as outlined at the top of S c h e m e 116. Such a reaction also occurs with cyclic dienes possessing conjugated e x o methylene groups (e.g., 1033). By the use of special conditions, h o w e v e r , simple cleavage of the methylene groups (e.g., to 1034) can be favored (998). T w o o t h e r a n o m a l o u s o z o n o l y s e s , analogous to those described in Vol. I, C h a p t e r IX, are also outlined in S c h e m e 116. T h e one with 1035 (999) involves an
364
XI
THE
PRACTICAL
SIDE
allylic-type a n o m a l o u s ozonolysis (Vol. I, C h a p t e r I X , Section II), while that with 1036 (1000) is of the a , β-unsaturated carbonyl type (Vol. I, C h a p t e r IX, Section III). C h a p t e r XI in Vol. I deals with epoxide formation and o t h e r noncleavage reactions of o z o n e . H e r e , t o o , applications to synthesis should be apparent. In C h a p t e r III of this volume the importance of exhaustive ozonolysis of aromatic c o m p o u n d s , both in synthesis and structure elucidation, w a s dis c u s s e d . A new and interesting e x a m p l e leading to a large-ring polylactone is s h o w n in E q . (114) (1001). T h e yield w a s s o m e w h a t less than the sta tistical 2 5 % (see C h a p t e r III).
a:
DO
d)o
(114)
3
(2) M e S 2
O ^ O
In C h a p t e r V I I , Section V, A, ozonation of selenides to p r o d u c e selenoxides w a s described. An important synthetic application of this ozonaδ '
A
Η
Λ
+
Se—R
.x^-ci
R*/ Η
Η R
V Η R
R \
Η / C=C / \ Η R
+
S e —R V Η R
1037
1038
+
^ ^
(
^
r
*(CH ) a
^OOEt
O-O Η / \ / Η ΗC C c / \ ^"(CH τ τ χ) A Η
t
SeC H 8
HOSeR
2
s
^COOEt
N
2
1039
SeC H fi
NaBH
HO-C H
v 2
-(CH
^ ^ C O O E t 2
1040 SCHEME
117
4
s
V
Water,
Wastewater,
and Sewage
Purification
365
tion is syn elimination of the selenoxide group and hydrogen to p r o d u c e unsaturation. T h e m e c h a n i s m is outlined in S c h e m e 117 (1037—> 1038) (1002). This technique has been utilized by Clark and H e a t h c o c k (993) in a separate synthesis of 1030 (Scheme 115). M a n y other e x a m p l e s are listed in an excellent review by Clive (1002). This reaction has been c o m b i n e d with ozonolysis of a double bond in one operation, as outlined in Scheme 117 (1039 - > 1040) (1003). Finally, ozonation u n d e r strong-acid conditions has been used to introd u c e carbonyl groups into the 6- and 7-positions of steroids, as illustrated in E q . (115) (1004).
(115) O t h e r e x a m p l e s of syntheses involving o z o n e can be found in other reviews (272,510,935-936a, 1005,1006). IV. Analysis and Proof of Structure T h e most important use of ozonolysis for many y e a r s w a s in proof of structure of c o m p o u n d s bearing double and triple b o n d s . T h e r e are many examples of this in other reviews (29,32,935,936,1006). In C h a p t e r III, Section V the important exhaustive ozonolysis of aromatic rings w a s discussed. This has been used in both structural and configurational proofs. Earlier in this c h a p t e r m i c r o t e c h n i q u e s were cited, which can be used in structural proofs (953-956,1007,1008) as well as in determinations of degree of unsaturation (1008a). Recently, interesting results concerning ozonolysis of corrins have been reported (1009), which h a v e been useful at least in confirming assigned s t r u c t u r e s . V. Water, Wastewater, and Sewage Purification Probably the most important use of o z o n e today is in the purification of w a t e r for drinking p u r p o s e s , the cleaning u p of sewage w a t e r before discharge into the e n v i r o n m e n t and r e u s e , and the r e m o v a l of industrial chemical w a s t e s from industrial w a t e r s before r e e n t r a n c e into rivers and
366
XI
THE PRACTICAL
SIDE
s t r e a m s . Although o z o n e has b e e n used for w a t e r purification for nearly 100 y e a r s , principally in E u r o p e , it has only recently received the attention it d e s e r v e s in the United States (WW; see also Vol. I, C h a p t e r I, Section I). T h e largest o z o n e generation plant for w a t e r purification in the world is said to be in East M o s c o w (WW). In recent years many p a p e r s concerning o z o n e in w a t e r purification have been published. It is b e y o n d the scope of this b o o k to include a c o m prehensive discussion or bibliography. Only a few representative articles will be listed, dealing with disinfection, color, o d o r and taste control, and removal of dissolved material in sewage and w a s t e w a t e r (WW-W22). O t h e r s can be found elsewhere (589,933,937,938), and in bibliographies listed in the references cited in this section, as well as in o t h e r sections of this v o l u m e , especially C h a p t e r III (Sections IV and V ) , C h a p t e r IV (Section V, E ) , C h a p t e r VIII (Section I, C, 5), and C h a p t e r IX (Sections I V , A, VI and VII), and in Vol. I, C h a p t e r I, Section I). B e c a u s e of the danger of producing chlorinated h y d r o c a r b o n s and o t h e r carcinogenic substances during the t r e a t m e n t of w a s t e w a t e r by chlorination (727,1010,1015,1016,1018-1020,1022-1024), o z o n e a p p e a r s destined to b e c o m e the m e t h o d of choice for w a t e r purification. Burleson et al. (1023, W24) have shown that the mutagenicity and carcinogenicity of various poly aromatic amines and h y d r o c a r b o n s , certain alkylating agents, pesticides, and selected other s u b s t a n c e s are completely destroyed by ozonation (see C h a p t e r s V - V I I I for the chemistry involved). It w a s pointed out, h o w e v e r , that care must be taken with benzidine and certain h y d r a z i n e s , which yield transient m u t a g e n s on partial ozonation. O z o n e a p p e a r s to be more efficient in the destruction of organic materials in w a t e r at an alkaline p H ( > 9 . 0 ) (456,919 -921,1022,1025,1026). This is thought to be due to catalytic decomposition of o z o n e , resulting in the generation of hydroxyl radicals, which are powerful oxidants (Chapter X , Section V I , D). Such a p r o c e s s d o e s not a p p e a r to be as practical for the purification of municipal waters as a n o t h e r p r o c e s s that also generates hydroxyl radicals. This method involves a combination of o z o n e and U V radiation and s h o w s promise of being superior both in disinfection and in destruction of organic waste and industrial materials in w a t e r (727,1027, 1028), including water-soluble p o l y m e r s (1028a). Although some attention has been given to identification of the actual p r o d u c t s obtained from the ozonation of organic pollutants in w a t e r (e.g., 33,115,117,126,456,727,1021,1027,1029), most of the studies in the literature have dealt largely with sewage and o t h e r w a s t e w a t e r s and have merely determined the biological oxygen d e m a n d (BOD) and chemical oxygen d e m a n d (COD) reduction realized by o z o n e t r e a t m e n t . Although this has been useful, m u c h more study of the organic chemistry involved is greatly n e e d e d .
VIII
The Ozone Layer
Controversy
367
VI. Pulping and Bleaching of Wood T h e separation of lignin from cellulose in w o o d and the bleaching of the resulting w o o d p u l p , as well as the clean-up of the effluents from these p r o c e s s e s , are very important p r o b l e m s in the p a p e r industry, especially since the traditional m e t h o d s involving alkali followed by chlorine and chlorine dioxide result in excessive w a s t e and pollution (1030-1032a). F o r this r e a s o n , considerable attention is being given to the use of o z o n e for these p u r p o s e s (1031,1032). Lignin is a phenolic-type, high-molecular-weight material readily at tacked by o z o n e (155,782,1030,1033; see also C h a p t e r III, Section IV). O z o n e can be used to delignify w o o d , but the cellulose is considerably degraded simultaneously (776-782). This is b e c a u s e ^-glycosides are readily attacked by o z o n e , m o r e so than α-glycosides (Chapter IX, Sec tion V, D). T h e problem still awaits solution. O t h e r references are avail able in a n o t h e r review (1034). VII. Miscellaneous Uses Ozonation has been used for grafting and o t h e r modifications of natural and synthetic polymers (821,1034,1035), oxidation of coal and car bon (1036-1040a), and m a n y o t h e r p u r p o s e s discussed else where (1006,1034,1036). VIII. The Ozone Layer Controversy O z o n e in the a t m o s p h e r e that w e b r e a t h e is harmful to u s , as briefly discussed in Section IX. O z o n e in the s t r a t o s p h e r e , h o w e v e r , is thought to be essential to life as we k n o w it. Life on land apparently did not begin until the o z o n e layer w a s formed, and it is thought that destruction of or a decline in the o z o n e layer will bring on serious climatic and health haz a r d s , particularly a dramatic increase in skin c a n c e r (1041). T h e danger of a large d e c r e a s e in the concentration of ozone in the stratosphere c a u s e d by the release of F r e o n s (aerosols) into the at m o s p h e r e w a s mentioned in Vol. I (page 1) and in this v o l u m e , C h a p t e r X , Section V I , Ε . T h e first warning of this danger c a m e from Molina and Rowland (924,1042) in 1974. Since t h e n , many p a p e r s h a v e been p u b lished on the subject, only a few of which can be cited h e r e . S o m e cham pion, or at least take seriously, the theory (1043-1050), while others belit tle, cast d o u b t u p o n , or minimize the importance of this problem (925,1050-1057). As pointed out in Vol. I (page 1), m a n y other possible c o n t a m i n a n t s , for e x a m p l e , h y d r o g e n chloride from volcanos (1058), ex-
368
XI
THE PRACTICAL
SIDE
pected to bring about the same effect have also been cited. An excellent, highly readable account of this c o n t r o v e r s y has been written by Dotto and Schiff (1041). It t o o , h o w e v e r , h a s been accused of bias (1058a). [For ad ditional references, see Graedel and F a r o w (1059) and references in papers cited in the preceding discussions.] T h e danger c o m e s largely from the k n o w n U V light decomposition of chlorofluorocarbons (Freons), to p r o d u c e chlorine a t o m s , and the chain reaction involving the destruction of o z o n e by chlorine a t o m s [ E q s . (105) and (106), C h a p t e r X , Section V I , E ] . T h o s e w h o believe that there h a s been overreaction to the problem cite the uncertainties involved, espe cially the time factor, the ability of o z o n e to regenerate itself, and the im portance of chain-breaking reactions (1041). T h e c o n t r o v e r s y has been bitter b e c a u s e of the fiancial loss suffered by the multimillion dollar fluorochloromethane industry as a c o n s e q u e n c e of the theory (1041). IX. The Negative Side of Ozone Organic Chemistry A. O Z O N E IN A I R P O L L U T I O N It has been k n o w n for a long time, as a result of the pioneering studies of Haagen-Smit (1060-1063), that o z o n e is present in photochemical smog. T h e principal reactions involved are outlined in E q s . (116)—(121) (1064-1065). Many others also apparently o c c u r 1066). NO
ο
2
+ o
2
o
3
RH
+
hv
•
NO
+
Μ
•
o
+
NO
+
O
R.
+ o
2
ROO-
+ o
2
3
NO
+ ο
(116)
+
(117)
+ o
2
•
R.
•
ROO-
RO-
Μ
+
2
(118)
-OH
(119) (120)
4
o
3
(121)
The literature in this field is v o l u m i n o u s , and it is b e y o n d the scope of this b o o k to d o m o r e than refer to reviews w h e r e the work is summarized (934,1059,1064-1065a,1066a, 1067-1069). Along with o z o n e various o t h e r irritants are p r o d u c e d , some via reactions of o z o n e with h y d r o c a r b o n s . T h e s e in turn, along with o z o n e itself, are h a z a r d o u s to both plants (1070) and animals (1071).
IX
Negative
Side of Ozone Organic
Chemistry
369
Although this is a problem of great c o n c e r n , it a p p e a r s that control is difficult, due largely to h u m a n n a t u r e (1071a). B. E F F E C T S O F O Z O N E O N SYSTEMS: TOXICITY
BIOLOGICAL
In Section I X , A , the o c c u r r e n c e of o z o n e in polluted air w a s discussed briefly. T h e toxicity of o z o n e and/or p r o d u c t s from o z o n e reacting with o t h e r pollutants therefore is of great c o n c e r n . Again, it is beyond the scope of this b o o k to discuss t h e s e important problems in detail, and only r e v i e w s , both short (1072) and long (1070,1071,1073-1074), are cited; most of the important references can be found therein. Of particular interest to o z o n e organic chemistry are recent studies on the reactions of o z o n e with cellular s u b s t a n c e s such as unsaturated and polyunsaturated fatty acids and lipids u n d e r conditions resembling those in cells (929,930,1074-1081). Although ozonolysis of the double b o n d s by the Criegee m e c h a n i s m (Vol. I) a p p e a r s to be the major reaction c o u r s e , there is evidence that radicals also are p r o d u c e d (930 \ see also C h a p t e r X , Section VI, F). T h e source is u n c e r t a i n , as is also the possiblity of competing autoxidation initiated by o z o n e (929,930,1076,1076a). C. D E G R A D A T I O N O F R U B B E R :
ANTIOZONANTS
A n o t h e r important side effect of air pollution is the degradation of rubb e r and o t h e r elastomers by o z o n e in the air. In fact, r u b b e r is often used as a specific reagent for measuring o z o n e in air quantitatively (1082,1083). M u c h has been written on the subject of the action of o z o n e on r u b b e r and o t h e r e l a s t o m e r s , beginning with the w o r k of Harries (1084) (see also Vol. I, C h a p t e r I, Section II). Only a few of these studies are cited here (438, 481,482,1083,1085-1089). O t h e r references can be found in these p a p e r s , especially (438), (482), and (1088). T h e r e a p p e a r s to be little reason to doubt that the major o z o n e attack involves ozonolysis of the double b o n d s (Vol. I), although it has b e e n suggested that ozone-initiated autoxidation at allylic centers also o c c u r s (1085). Of greatest interest concerning the degradation of r u b b e r and o t h e r elastomers by o z o n e is the p r e v e n t i o n or retardation of this action by m e a n s of antiozonants (e.g., 436-438,478,480-484,1083,1086,10901094). T h e r e are m a n y t y p e s of a n t i o z o n a n t s , s e c o n d a r y phenylenediamines (Chapter V I I , Section II) being a m o n g the best. T h e m e c h a n i s m of antiozonant action still a p p e a r s to be speculative (438,1086,1094). There are at least four principal theories (438,1094). T h e first is the scavenger m e c h a n i s m which simply suggests that o z o n e reacts with the antiozonant
370
XI
THE
PRACTICAL
SIDE
faster than with the elastomer. T h e second is similar in that it p r o p o s e s that the antiozonant not only reacts with o z o n e faster than the e l a s t o m e r d o e s , but that the p r o d u c t s of the reaction form a protective film. T h e third m e c h a n i s m postulates that the antiozonant reacts with e l a s t o m e r ozonation fragments, thereby effectively relinking t h e m and healing the fractures. M u r r a y and Story (438,1086) convincingly point out flaws in all these theories and suggest a fourth, namely, that the antiozonant reacts with the Criegee zwitterion or the ozonide p r o d u c e d by ozonolysis (Vol. I) and, t h e r e b y , provides a protective coating on the elastomer surface, which is not readily penetrated by o z o n e . In the most recent w o r k on the p r o b l e m , h o w e v e r , Andries et al. (1094) found no spectral evidence for the M u r r a y - S t o r y m e c h a n i s m (1086), at least with antiozonants of the Ν , Ν ' - d i a l k y l p h e n y l e n e d i a m i n e t y p e . Their studies indicated a combination of the first t w o m e c h a n i s m s (scavenger and protective film, without participation of the e l a s t o m e r itself).