70 Products of Peracid Oxidation of S-Alkyl Phosphorothiolate Pesticides Downloaded via IOWA STATE UNIV on January 5, 2019 at 20:18:32 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
YOFFI SEGALL1 and JOHN E. CASIDA Pesticide Chemistry and Toxicology Laboratory, Department of Entomological Sciences, University of California, Berkeley,CA94720
Biooxidation is an essential activation process for some organothiophosphorus neurotoxicants (1). m-Chloroperoxybenzoic acid (MCPBA) has been used to mimic some of these reactions but without identifying the products derived from phosphorothiolates (2,3). We observed that S-alkyl phosphorothiolates react with MCPBA to form a new and unexpected class of phosphinyloxysulfonates via a novel rearrangement process (Eq. 1).
Peracid oxidation of S-alkyl phosphorothiolates (1) appears to proceed by initial formation of S-oxides (2) which undergo spontaneous and very rapid rearrangement, via phosphoranoxide intermediates, to the corresponding sulfenate esters (3) that are 1Current address: Israel Institute for Biological Research, Ness-Ziona, P.O.B. 19, Israel.
0097-615 6/81/0171-03 37$05.00/ 0 © 1981 American Chemical Society
Quin and Verkade; Phosphorus Chemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1981.
PHOSPHORUS CHEMISTRY
338
further oxidized to the oxysulfinate (4) and oxysulfonate esters (5) (Eq. 1). With equimolar MCPBA very l i t t l e starting material undergoes reaction because most of the oxidant is used up in con version of 3 and 4 to 5. As a result the most extensively oxidiz ed product (5) is strongly favored. These generalizations are based on studies with four S-alkyl phosphorothiolate pesticides (6a, 7a, 7b, 8) and related compounds as follows:
The oxidation rate with excess peracid decreases in the order ϋ Jjk 7J> >> 6a; the first three compounds react readily below -30°C whereas 6a requires > 10°C for significant reaction in 24 hr. The nitrogen free electrons of 7ji and 7b may facilitate their oxidation by increasing the polarizability of the sulfur. >
>
Profenofos (6a) and its derivatives were selected for detailed examination. Sulfonate ester 6b is obtained pure in 86% yield on reacting 6a with five equivalents of MCPBA in ethanol-free chloro form at 25 C for 8 hr followed by rapidly extracting the solution with aqueous NaHS0 and NaHC03 at 0°C. Similar treatment at 25°C for 5 min results in complete hydrolysis of 6b to J>£ and propylsulfonic acid. NMR studies (Table I) suggest conversion of the phosphorothiolate to a phosphate. Thus, on going from 6ji to 6b there is a significant high field shift in the ^Ip NMR signals and downfield shifts in the and -^C signals of the α-methylene bonded to sulfur. In addition, neither the proton nor the carbon of the ^-methylene in 6b is coupled with the phosphorus. Three minor phosphorus-containing products formed on oxidation of 6a are: the acid 6c (δ P -6.82 ppm in CDC1 ); the 3-chlorobenzoyl U
3
3 l
3
Quin and Verkade; Phosphorus Chemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1981.
70.
SEGALL
AND
S-AlkyI Phosphorothiolate
CASiDA
TABLE I .
Pesticides
339
NMR S p e c t r a l D a t a f o r 6 a a n d 6b (CDC1 > 3
C h e m i c a l s h i f t s d e n o t e d a s f o l l o w s : "^H f o r d i a s t e r e o t o p i c p r o t o n s o f t h e m e t h y l e n e d i r e c t l y bonded t o s u l f u r ( d o w n f i e l d o f TMS); 13c f o r c a r b o n d i r e c t l y bonded t o s u l f u r (TMS); l p a r e n e g a t i v e when u p f i e l d o f 1% t r i m e t h y l p h o s p h a t e i n C,D, (6 P = 0 ) . 3
3
1
6b
6a δ ppm
Nucleus
δ ppm
^31p_nucleus
^31p~nucleus
2.91
9.3 Hz
3.49
none
13
c
33.44
9.0 Hz
55.18
none
31
p
+22.91
-
-21.77
31 e s t e r 6e (δ Ρ - 1 6 . ^ J ) ; t h e d i a s t e r e o m e r i c p y r o p h o s p h a t e 6^ (two l i n e s centered a t δ Ρ - 2 2 . 7 4 , Δδ 0.03 ppm). Comparable o x i d a t i o n o f £ (δ P +31.28 i n a c e t o n e , r e f e r e n c e d t o 1% t r i m e t h y l p h o s p h a t e i n CDCI3) y i e l d s t h e a n a l o g o u s d i e t h y l p h o s p h o r i c a c i d (δ P + 1 . 8 0 ) , d i e t h y l 3 - c h l o r o b e n z o y l o x y p h o s p h a t e (δ P -10.30) and t e t r a e t h y l p y r o p h o s p h a t e (one l i n e a t δ ^ P - 1 0 . 7 8 ) . M i x e d a n h y d r i d e 6b i s a s u l f o n y l a t i n g r a t h e r t h a n a p h o s p h o r y l a t i n g a g e n t . Thus, h y d r o l y s i s w i t h H 0 g i v e s a c i d 6c and p r o p y l s u l f o n i c a c i d i n w h i c h t h e 0 isotope i s incorporated o n l y i n t h e s u l f o n i c a c i d ( E q . 2 ) . Compound 61) r e a c t s w i t h e i t h e r a l c o h o l s (methanol, e t h a n o l , sec-butanol) o r L - c y s t e i n e t o y i e l d a c i d 6 c and w i t h t r i e t h y l a m i n e t o g i v e t h e a n i o n o f 6c, p r o b a b l y v i a p r o p y l s u l f e n e (4) ( E q . 2 ) . 3
3
1
1
3 1
3
1 8
2
1
C
2 5°v H
/?
u
Y
ArO^
H
\ s 0
2
C
3
H
ι · 2 0 Λ
ArO^
7
6b
\)H 6c
Eq. 2
-(C H ) N 2
5
3
-(C H ) NH 2
5
3
HOS0 C H 2
3
7
)H O 2
v y
+
Ρ
9
ArO
0-S0 -CHCH CH 2
2
3
ArO
0 S=CHCH CH 2
2
3
0"
Phosphoramidothiolates 7a a n d 7b w i t h MCPBA y i e l d t h e r m a l l y u n s t a b l e p r o d u c t s i n c o n t r a s t t o t h e more s t a b l e 6b o b t a i n e d on o x i d a t i o n o f 6a. N e u t r a l aqueous h y d r o l y s i s o f t h e r e a c t i o n p r o d u c t s o f Ta t h e n d e r i v a t i z a t i o n w i t h d i a z o m e t h a n e y i e l d s many
Quin and Verkade; Phosphorus Chemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1981.
340
PHOSPHORUS
CHEMISTRY
compounds, i n c l u d i n g 10 a n d JUL i d e n t i f i e d b y MS a n d NMR. These products i n d i c a t e involvement o f both t h e -SCH3 a n d -NH2 g r o u p s i n t h e o x i d a t i o n and d e c o m p o s i t i o n p r o c e s s e s . Phosphorotrithiol a t e 8 (6 P +66.40 ppm i n CDCI3) r e a c t s a l m o s t i n s t a n t l y w i t h MCPBA (3-4 e q u i v a l e n t s ) a t -30°C t o g i v e r e a r r a n g e d p r o d u c t s (δ P +0.50, -7.60 a n d -17.00) t h a t do n o t c o n t a i n a n y d i r e c t P-S bond a s t h e i r p r o t o n c o u p l e d and d e c o u p l e d ^ P NMR s i g n a l s are i d e n t i c a l t o each o t h e r . 3 1
3 1
3
The b i o l o g i c a l p r o p e r t i e s o f a p h o s p h o r o t h i o l a t e S^-oxide p r e s u m a b l y depend i n p a r t on t h e r e l a t i v e r a t e a t w h i c h i t r e a c t s as a p h o s p h o r y l a t i n g a g e n t a s opposed t o t h e r a t e i t r e a r r a n g e s to t h e p h o s p h i n y l o x y s u l f e n a t e ( E q . 3 ) . A s i m p l e e x p e r i m e n t . . , phosphorothiolate A
mfojo] oct,vot,on
·*·
[phosphorothiolottl ι Ζ L
S-ox.d.
hydrolate(t)
J
. , . phosphorylated w
»
Α
hydrolai.L)
deactivation
phosphinyloxysulfenote
Eq. 3
M0 2
hydrolysis products
i l l u s t r a t e s t h i s p o i n t . On o x i d a t i o n o f j>a i n e t h a n o l t h e o n l y p h o s p h o r u s p r o d u c t i s o l a t e d i s t h e d i e t h y l e s t e r 6d u n d o u b t e d l y obtained from p h o s p h o r y l a t i o n o f e t h a n o l by the S-oxide i n t e r m e d i a t e ; p h o s p h o r o t h i o l a t e 6a by i t s e l f does n o t r e a c t w i t h e t h a n o l a n d p h o s p h i n y l o x y s u l f o n a t e 6b g i v e s t h e a c i d 6 c . T h u s , i f the S-oxide a c t i v a t i o n p r o d u c t i s formed on m i x e d - f u n c t i o n o x i d a s e (mfo) a c t i v a t i o n w i t h i n t h e c e l l i t may i m m e d i a t e l y phosphorylate s e n s i t i v e s i t e s such as h y d r o l a s e s i n c l u d i n g a c e t y l c h o l i n e s t e r a s e . However, when t h e S - o x i d e i s f o r m e d i n a n e n v i r o n m e n t where r e arrangement occurs f a s t e r than p h o s p h o r y l a t i o n t h e o v e r a l l r e s u l t i s the d e a c t i v a t i o n process o f h y d r o l y s i s . T h i s h y p o t h e s i s war r a n t s c a r e f u l c o n s i d e r a t i o n i n e v a l u a t i n g t h e t o x i c o l o g y and metabolism o f S_-alkyl phosphorothiolate p e s t i c i d e s . Acknowledgment S u p p o r t e d i n p a r t b y G r a n t 5 P01 ES00049 f r o m t h e N a t i o n a l Institutes of Health.
Literature Cited 1. 2. 3. 4.
Eto, M. "Organophosphorus Pesticides: Organic and Biological Chemistry," CRC Press, Cleveland, 1974. Bellet, E. M.; Casida, J . E. J . Agric. Food Chem. 1974, 22, 207. Eto, M.; Okabe, S.; Ozoe, Y.; Maekawa, K. Pestic. Biochem. Physiol. 1977, 7, 367. Michalski, J.; Radziejewski, C.; Skrzypczyński, Z. J . Chem. Soc. Chem. Comm. 1976, 762.
RECEIVED
July 7, 1981.
Quin and Verkade; Phosphorus Chemistry ACS Symposium Series; American Chemical Society: Washington, DC, 1981.
