The Preparation of Standards for Aldicarb (Temik) Metabolism Study J o h n A. Durden, Jr., William J. Bartley, a n d John F. Stephen
The synthesis of 18 compounds of the general structure CH,XC(CH&R (where X is S, SO, or SOr and R is peracetic acid
CH3SH
+ BrC(CH&COOH
CH3SOC(CH3)nCOOH TiA
NaOH
___f
CH3SC(CH3)zCOOH
.1
6OCh
(excess)
T?A
CH,SC(CH&CONHOH < HzNOH CHaSC(CH3)ZCOCl + "2 CHsSC(CH,),CONH? THA
TAm
peracetic acid
peracetic acid
I
excess
I
excess
r-----l
1 equiv.
CH3SO?C(CH&CONHOH CH3SOC(CH&CONHOH TzHA
TIHA
456 J. AGR. FOOD CHEM., VOL. 18, NO. 3, 1970
1
1 equiv.
j. CH3SO?C(CH3),CONH? CH~SOC(CH~)ZCONH? T2Am
TIAm
Table I. Nmr Spectral Data of Aldicarb Metabolites and Related Standards CHa-X-C (CH3 ) 2-R Chemical Shifts (6) _______ -X-C(CH~)LCHa-CH_=NOH 1.35 and 1.43 2.41 so -CH=NOH ~
Compound TiO'* TLO"
TIAmh T2Amb TAP TiAl' TJAI'
2.78 2.70 3.12 2.09 2.53 2.93 1.96 2.51 2 96
DTI"
2.53
TIN* TiNb TAmb
-R (7.51) ( 7.32)
so so,
1.48 1 . 5 3 and 1 . 6 8 1.77 1.51 1 . 2 9 a n d 1.63 1.66 1.22 1 . 2 1 and 1 . 2 6 1.38
-C=N -C=N -CONH? (6.80) -CONE? -CONHa PCH2-0H - - (3.36), - (3.28) _____ -C&OH (3 . 6 6 ) , ( 4_ _._9_ _7 )
so
1 . 4 4 a n d 1 53
-CH=NOCNH? -
SO2
so
SOY
S
so SO? S
-
-
-Ck2-OH
-
(3.80). (3.50) __..__ 0 (7 82). (6 55) ..____
0 2.97 2.13 2.62 3.08 2.03 2.58 3.13
DT? TAc" TiAcC T Aci
THA' TIHA T HA " Aceto11i'-dr.
so2
-CH=NOCNH2 (7 87), (6.53) __.__ -COOH-( 1 1 5y) -COOH (1 1 09) PCOOH --CONHOH -CONHOH PCONHOH
1.62 1.50 1.51 1.61 1.47 1.49aiid1.50 1.64
S
so so2 S
so SO2
~
CDCIJ. 'D>O.
Again, due to competing sulfone formation, the sulfoxide alcohol (TIAl) was difficult to prepare in pure form. At room temperature with 1 equivalent of TAL and with 0.9 equivalent of peracetic acid, the product was a 70:30 mixture of sulfoxide and sulfone, respectively. At 0" C the product contained 3 to 5 % of sulfone. The use of sodium rnetaperiodate, a reagent reported t o give a high degree of selectivity in the sulfide to sulfoxide oxidation (Leonard and Johnson, 1962) gave results similar to those obtained with peracetic acid at 0 " C. TIAl was obtained in high purity by a reaction
However, the hydroxamic acid sulfoxide (TIHA) was obtained in a 1 :llmixture with its corresponding sulfone (T2HA), as indicated- by spectral and tlc data. The mixture was satisfactory for use as a tlc standard. The "desmethyl aldicarb" derivative, 2-methyl-2-(methylthi0)propionaldehyde 0-carbamoyloxime, DT, and the corresponding sulfoxide DTI, and sulfone DT?, were prepared according to Equation 2. No difficulty was encountered in the synthesis of DT and DT?, but DT1, like the preceding hydroxamic acid? TIHA, was obtained as a mixture with the corresponding sulfone. CHsSC(CHZ)?CH=NOH
COCln
CH3SC(CH,)?CH=NOCOCl
h"s + CH3SC(CH&CH=NOCONHz
TO
DT
I peracetic acid excess
1
CHySOK(CH3)2CH=NOCONHz
I equiv.
CH3SOC(CH3)2CH=NOCONH:!
DT2
DTi
The propanol derivatives (TAI, TIAl, and T2Al) were prepared according to Equation 3. ___~~_____
C H BSC(CHd2COCl
LAlHs
_____
C H 3SC(CH &CH?OH
TAI
I
1 peracetic acid
excess
(3 1
1 equiv.
-30' C
CHaSO&(CH&CHyOH
TzAI
CHaSOC(CH,),CHzOH
TlAl J. AGR. FOOD CHEM., VOL. 18, NO. 3, 1970 457
involving slightly less than one equivalent of peracetic acid at -4O”to -30°C. The following compounds described in this paper were identified as metabolites of aldicarb in cotton plants (Bartley et ul., 1970) (Table I); T1O, T20, TIN, T,Am. TIAI, TIAc. and T?Ac. In each case, sufficient quantities of these materials were synthesized for the required toxicological studies. The nmr spectra of these compounds are summarized in Ta ble I. ACKNOWLEDGMENT
The authors are indebted to G. E. O’Dell, E. B. Shamlin, and H. W. Stollings for invaluable technical assistance, Gratitude is also expressed to H. R. Joyce for infrared, C. B. Strow for nmr, and W. J. Lambdin and B. E. Wilkes for the high-resolution mass spectra.
458 3. AGR. FOOD CHEM., VOL. IS, NO. 3,
1970
LITERATURE
Bartley, W. J., Andrawes. N. R., Chancey. E. L.. Bagley, W. P., Spurr, H. W., J. AGR.FOODCHEM. 18, 446 ( 1970). Coppedge, J. R., Lindquist, D. A,. Bull, D. L.. Dorough H. W., J. AGR.FOODCHEM.15, 902 (1967). Hurd, C. D., in “Inorganic Synthesis,” H. S. Booth. Ed., Vol. I. p. 87-89, McGraw-Hill, New York, 1939. l i l i i . . Teclitrol. GotheizLarsson, E., Monies, L., Trans. Cl~ctlmer.~ burg, (Sweden). No. 47, 9 (1945); Chem. Abstr. 40, 2795 (1946). Leonard, N. J.. Johnson, C. R.; J . Org. Clzem. 27, 282 (1962). Metcalf, R. L., Fukuto. T. R., Collins. C.. Borck, K.. Burk, J., Reynolds, H. T., Osman. M. F.. J. AGR.FOODCHESI.14, 579 (1 966). Payne, L. K., Stansbury, H. A., Weiden, M. H. J.. J. AGR.FOOD CHEW14, 356 (1966). Smissman, E. E.. J . Amer. Chem. Soc. 76, 5805 (1954).
Receired for recieiv October 31, 1969. Accepted Fehrrini:v 18, 1970.
