Agricultural ureas and isoureas

This invention relates to ureas and isoureas which are useful as herbicides and plant growth regulants. In particular, compounds of the instant invention have demonstrated great selectivity.

BACKGROUND OF THE INVENTION 
This invention relates to ureas and isoureas and in particular their use as 
agricultural chemicals and particularly as herbicides. 
U.S. Pat. No. 4,127,405 teaches compounds which are useful for controlling 
weeds in wheat having the formula 
##STR1## 
wherein R.sub.1 is 
##STR2## 
R.sub.3 and R.sub.6 are independently hydrogen, fluorine, chlorine, 
bromine, iodine, alkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, 
nitro, trifluoromethyl, cyano, CH.sub.3 S(O).sub.n -- or CH.sub.3 CH.sub.2 
S(O).sub.n --; 
R.sub.4 is hydrogen, fluorine, chlorine, bromine or methyl; 
R.sub.5 is hydrogen, fluorine, chlorine, bromine, methyl or methoxy; 
R.sub.7 is hydrogen, fluorine, chlorine, bromine, alkyl of 1-2 carbon atoms 
or alkoxy of 1-2 carbon atoms; 
R.sub.8 is hydrogen, methyl, chlorine or bromine; 
R.sub.9 and R.sub.10 are independently hydrogen, methyl, chlorine or 
bromine; 
W and Q are independently oxygen or sulfur; 
n is 0, 1 or 2; 
X is hydrogen, chlorine, bromine, methyl, ethyl, alkoxy of 1-3 carbon 
atoms, trifluoromethyl, CH.sub.3 S-- or CH.sub.3 OCH.sub.2 --; and 
Y is methyl or methoxy; or their agriculturally suitable salts; provided 
that: 
(a) when R.sub.5 is other than hydrogen, at least one of R.sub.3, R.sub.4, 
R.sub.6 and R.sub.7 is other than hydrogen and at least two of R.sub.3, 
R.sub.4, R.sub.6 and R.sub.7 must be hydrogen; 
(b) when R.sub.5 is hydrogen and all of R.sub.3, R.sub.4, R.sub.6 and 
R.sub.7 are other than hydrogen, then all of R.sub.3, R.sub.4, R.sub.6 and 
R.sub.7 must be either chlorine or methyl; and 
(c) when R.sub.3 and R.sub.7 are both hydrogen, at least one of R.sub.4, 
R.sub.5 or R.sub.6 must be hydrogen. 
French Patent No. 1,468,747 discloses the following para-substituted 
phenylsulfonamides, useful as antidiabetic agents: 
##STR3## 
wherein R=H, halogen, CF.sub.3 or alkyl. 
Logemann et al. chem. Ab., 53, 18052 g (1959), disclose a number of 
sulfonamides, including uracil derivatives and those having the formula: 
##STR4## 
wherein R is butyl, phenyl or 
##STR5## 
and R.sub.1 is hydrogen or methyl. When tested for hypoglycemic effect in 
rats (oral doses of 25 mg/100 g), the compounds in which R is butyl and 
phenyl were most potent. The others were of low potency or inactive. 
Wojciechowski, J. Acta. Polon. Pharm. 19, p. 121-5 (1962) [Chem Ab., 59 
1633 e] describes the synthesis of 
N-[(2,6-dimethoxypyrimidin-4-yl)aminocarbonyl]-4-methylbenzenesulfonamide: 
##STR6## 
Based upon similarity to a known compound, the author predicted 
hypoglycemic activity for the foregoing compound. 
Netherlands Patent No. 121,788, published Sept. 15, 1966, teaches the 
preparation of compounds of Formula (i), and their use as general or 
selective herbicides, 
##STR7## 
wherein R.sub.1 and R.sub.2 may independently be alkyl of 1-4 carbon 
atoms; and 
R.sub.3 and R.sub.4 may independently be hydrogen, chlorine or alkyl of 1-4 
carbon atoms. 
Compounds of Formula (ii), and their use as antidiabetic agents, are 
reported in J. Drug. Res. 6, 123 (1974), 
##STR8## 
wherein R is pyridyl. 
The presence of undesired vegetation causes substantial damage to useful 
crops, especially agricultural products that satisfy man's basic food 
needs, such as soybeans, barley, wheat, and the like. The current 
population explosion and concomitant world food shortage demand 
improvements in the efficiency of producing these crops. Prevention or 
minimizing the loss of a portion of such valuable crops by killing, or 
inhibiting the growth of undesired vegetation is one way of improving this 
efficiency. 
A wide variety of materials useful for killing, or inhibiting (controlling) 
the growth of undesired vegetation is available; such materials are 
commonly referred to as herbicides. The need exists, however, for still 
more effective herbicides that destroy or retard weeds without causing 
significant damage to useful crops. 
SUMMARY OF THE INVENTION 
This invention relates to novel compounds of Formulas I, II, and III and 
their agriculturally suitable salts, suitable agricultural compositions 
containing them, and methods of using them as selective, as well as 
general herbicides having both pre-emergence and post-emergence activity. 
Some of the compounds are especially useful for controlling weeds in crops 
such as soybeans: 
##STR9## 
wherein W' is O or S; 
A' is H, Cl, Br, C.sub.1 -C.sub.4 alkyl, OCH.sub.3, NO.sub.2 or CF.sub.3 ; 
A is 
##STR10## 
where Q is O, S or 
##STR11## 
T is O or 
##STR12## 
where R.sup.III is H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.4 alkenyl; 
when 
Q is O or S then 
R.sup.I is C.sub.1 -C.sub.6 alkyl; C.sub.3 -C.sub.6 alkenyl; C.sub.3 
-C.sub.6 alkynyl; C.sub.2 -C.sub.6 alkyl substituted with 1-3Cl, F or Br, 
or one of CN or OCH.sub.3 ; C.sub.3 -C.sub.6 alkenyl substituted with 1-3 
Cl; C.sub.3 -C.sub.6 alkynyl substituted with Cl; C.sub.5 -C.sub.6 
cycloalkyl; cyclohexenyl; cyclohexyl substituted with 1-3 CH.sub.3 ; 
C.sub.4 -C.sub.7 cycloalkylalkyl or 
##STR13## 
where R.sub.7 and R.sub.8 are independently H, Cl, CH.sub.3 or OCH.sub.3 
; 
n is 0 or 1; and 
R.sub.9 is H or CH.sub.3 ; 
when Q is O then R.sup.I is CH.sub.2 CH.sub.2 OR.sub.15 ; CH.sub.2 
CH.sub.2 CH.sub.2 OR.sub.15 ; 
##STR14## 
where R.sub.15 is C.sub.2 H.sub.5, CH(CH.sub.3).sub.2, phenyl, CH.sub.2 
CH.sub.2 Cl, CH.sub.2 CCl.sub.3 ; --CH.sub.2 CH.sub.2 O--.sub.n' R.sub.16, 
##STR15## 
where R.sub.16 is CH.sub.3, C.sub.2 H.sub.5, CH(CH.sub.3).sub.2, phenyl, 
CH.sub.2 CH.sub.2 Cl, CH.sub.2 CCl.sub.3, and n' is 2 or 3; CH.sub.2 CN; 
##STR16## 
CH.sub.2 OR.sub.6 '; where R.sub.6 ' is C.sub.1 -C.sub.4 alkyl; provided 
R.sup.I has a total of .ltoreq.13 carbon atoms; when 
Q is 
##STR17## 
then R.sup.I is H; C.sub.1 -C.sub.6 alkyl; --CH.sub.2 CH.sub.2 OR.sub.10 
; --CH.sub.2 CH.sub.2 CH.sub.2 OR.sub.10 ; where R.sub.10 is CH.sub.3, 
CH.sub.3 CH.sub.2, CH(CH.sub.3).sub.2, or phenyl; C.sub.3 -C.sub.6 
alkenyl; C.sub.3 -C.sub.6 cycloalkyl; C.sub.5 -C.sub.6 cycloalkenyl; 
C.sub.6 cycloalkyl substituted with any one of 1-2 OCH.sub.3, 1-3 
CH.sub.3, --CH.sub.2 CH.sub.3 or CF.sub.3 ; C.sub.4 -C.sub.7 
cycloalkylalkyl; 
##STR18## 
where R' is H, C.sub.1 -C.sub.4 alkyl, OCH.sub.3, F, Cl, Br, CN, NO.sub.2 
or CF.sub.3 ; 
R" is H, CH.sub.3, Cl, F or Br; 
R.sub.7, R.sub.8 and R.sub.9 are as previously defined; R.sub.6 is H, 
C.sub.1 -C.sub.3 alkyl; CH.sub.2 CN; CH.sub.2 CH.sub.2 --CN or --CH.sub.2 
--CH.dbd.CH.sub.2 and R.sub.6 and R.sup.I may be taken together to form 
--(CH.sub.2).sub.4 --, --(CH.sub.2).sub.5 -- or --CH.sub.2 CH.sub.2 
O--CH.sub.2 CH.sub.2 --; 
with the proviso that when R.sub.6 is CH.sub.2 CH.sub.2 CN or CH.sub.2 CN, 
then R.sup.I is CH.sub.2 CH.sub.2 CN or CH.sub.2 CN; and R.sup.I and 
R.sub.6 have a total carbon atom count of .ltoreq.13; and when R.sup.I is 
OCH.sub.3 or OCH.sub.2 CH.sub.3 then R.sub.6 is CH.sub.3 or H; 
when 
A is 
##STR19## 
then R.sup.II is H, C.sub.1 -C.sub.6 alkyl; C.sub.3 -C.sub.6 alkenyl; 
phenyl; benzyl; benzyl or phenyl substituted with 1-2 Cl, 1-2 OCH.sub.3, 
1-2 CH.sub.3 ; C.sub.5 -C.sub.6 cycloalkyl; C.sub.4 -C.sub.7 
cycloalkylalkyl with the proviso that when T is .dbd.N--OR.sup.III, then 
R.sup.II must be C.sub.1 -C.sub.6 alkyl or C.sub.3 -C.sub.6 alkenyl; 
B is 
##STR20## 
where R.sub.4 is H or CH.sub.3 ; W is O or S; 
R.sub.5 is H, or CH.sub.3 ; with the proviso that either R.sub.4 or R.sub.5 
must be H; 
R.sup.IV is C.sub.1 -C.sub.6 alkyl or C.sub.3 -C.sub.4 alkenyl; 
R.sub.1 is 
##STR21## 
where Z is N, CH or C--F; 
X=H, Cl, --CH.sub.3, --OCH.sub.3 or --OCH.sub.2 CH.sub.3 ; 
Y=H; Cl; C.sub.1 -C.sub.4 alkyl; C.sub.1 -C.sub.4 alkyl substituted with 
--OCH.sub.3, --OC.sub.2 H.sub.5, --CN, --CO.sub.2 CH.sub.3, --CO.sub.2 
C.sub.2 H.sub.5, 
##STR22## 
or 1-3 atoms of F, Cl, Br; C.sub.3 -C.sub.4 alkenyl; 
--O--(CH.sub.2).sub.n' O--(C.sub.1 -C.sub.3 alkyl) where n' is 2 or 3; 
##STR23## 
where L is OH, --NH.sub.2, 
##STR24## 
--NH(C.sub.1 -C.sub.4 alkyl), --N(C.sub.1 -C.sub.4 alkyl).sub.2 or 
C.sub.1 -C.sub.6 alkoxy; SCN; --N.sub.3 ; NR.sub.11 R.sub.12 where 
R.sub.11 is H or CH.sub.3 and R.sub.12 is H, --OCH.sub.3, C.sub.1 -C.sub.4 
alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.3 -C.sub.4 alkenyl, C.sub.2 
-C.sub.3 alkyl substituted with OCH.sub.3 or OC.sub.2 H.sub.5, C.sub.1 
-C.sub.2 alkyl substituted with --CN, CO.sub.2 H, CO.sub.2 CH.sub.3 or 
CO.sub.2 C.sub.2 H.sub.5, and R.sub.11 and R.sub.12 can be taken together 
to form --CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 -- or CH.sub.2 CH.sub.2 
OCH.sub.2 CH.sub.2 --; --O--R.sub.9 where R.sub.9 is C.sub.1 -C.sub.4 
alkyl, C.sub.2 -C.sub.4 alkyl substituted with 1-3 atoms of F, Cl or Br, 
C.sub.1 - C.sub.2 alkyl substituted with cyano, C.sub.3 -C.sub.4 alkenyl, 
--CH.sub.2 C.tbd.CR.sub.13, 
##STR25## 
R.sub.13 is H, CH.sub.3 or CH.sub.2 Cl; SR.sub.14 ; where R.sub.14 is 
C.sub.1 -C.sub.4 alkyl, allyl, propargyl or C.sub.1 -C.sub.2 alkyl 
substituted with CN; with the proviso that when X and Y are both H, then 
R.sup.I and R.sup.II are less than 5 carbons; 
X.sub.1 =H, Cl, OCH.sub.3, OCH.sub.2 CH.sub.3 or CH.sub.3 ; 
Y.sub.1 =H, OCH.sub.3 or CH.sub.3 ; and 
X.sub.II =O or CH.sub.2 
and further provided that when A contains greater than 5 carbon atoms, then 
Y must contain .ltoreq.4 carbon atoms, and their agriculturally suitable 
salts. 
Preferred Compounds 
Preferred for reasons of higher activity and/or lower cost and/or greater 
ease of synthesis are compounds: 
(1) Of the Generic scope in which B is 
##STR26## 
More Preferred and in increasing order for reasons of higher activity 
and/or even lower cost and/or even greater ease of synthesis are 
compounds: 
(2) Preferred (1) in which W' is sulfur; 
(2a) Most Preferred (2) in which T is oxygen; 
(3) More Preferred (2a) in which R.sub.1 is 
##STR27## 
(4) More Preferred (3) where Q is O or S and R.sup.I is C.sub.1 -C.sub.4 
alkyl; C.sub.3 -C.sub.4 alkenyl; C.sub.3 -C.sub.4 alkynyl; C.sub.2 
-C.sub.3 alkyl substituted with CN, OCH.sub.3 or 1-3 F, Cl or Br; C.sub.3 
-C.sub.4 alkenyl substituted with 1-3 Cl; C.sub.3 -C.sub.4 alkynyl 
substituted with Cl; 
(5) More Preferred (3) in which Q is oxygen and R.sup.I is CH.sub.2 
CH.sub.2 OR.sub.15 ; CH.sub.2 CH.sub.2 CH.sub.2 OR.sub.15 ; 
##STR28## 
where R.sub.15 is CH.sub.2 CH.sub.3 ; CH.sub.2 CN; CH.sub.2 OR.sub.6 ' 
where R.sub.6 ' is CH.sub.3 or CH.sub.3 CH.sub.2 ; 
##STR29## 
(6) More Preferred (3) in which Q is 
##STR30## 
and R.sup.I is H, C.sub.1 -C.sub.4 alkyl, CH.sub.2 CH.sub.2 OR.sub.10, 
CH.sub.2 CH.sub.2 CH.sub.2 OR.sub.10 where R.sub.10 is CH.sub.3 or 
CH.sub.3 CH.sub.2 ; C.sub.3 -C.sub.4 alkenyl; CH.sub.2 CN; CH.sub.2 
CH.sub.2 CN; OCH.sub.3 or OCH.sub.2 CH.sub.3 ; R.sup.6 is H, C.sub.1 
-C.sub.2 alkyl, CH.sub.2 CN or CH.sub.2 CH.sub.2 CN and R.sub.6 and 
R.sup.I can be taken together to form --CH.sub.2 --.sub.4. 
(7) More preferred (3) in which R.sup.II is H or C.sub.1 -C.sub.3 alkyl; 
(8) More preferred (4), (5), (6) and (7) in which 
Z is CH or N; 
X is CH.sub.3 or CH.sub.3 O; and 
Y is C.sub.1 -C.sub.2 alkyl; C.sub.1 -C.sub.2 alkyl substituted with 
OCH.sub.3 ; OCH.sub.2 CH.sub.3, CN or 1-3 atoms of F, Cl or Br; 
##STR31## 
where L is NH.sub.2, OH, 
##STR32## 
N(CH.sub.3).sub.2, NHCH.sub.3, C.sub.1 -C.sub.2 alkoxy; SCN; N.sub.3 ; 
NR.sub.11 R.sub.12 where R.sub.11 is H or CH.sub.3 ; R.sub.12 is H, 
CH.sub.3, CH.sub.3 CH.sub.2, OCH.sub.3 ; OR.sub.9 where R.sub.9 is 
CH.sub.3, CH.sub.3 CH.sub.2 ; CH.sub.2 CH.dbd.CH.sub.2 or CH.sub.2 
C.tbd.CH; R.sub.9 is also C.sub.2 alkyl substituted with 1-3 F, Cl or Br; 
CH.sub.3 S; 
(9) More Preferred (3) in which A' is H, Cl or Br; 
(10) More Preferred (9) in which Q is O or S and R.sup.I is C.sub.1 
-C.sub.4 alkyl, CH.sub.2 CH.dbd.CH.sub.2 or CH.sub.2 CH.sub.2 Cl; 
(11) More Preferred (9) in which Q is O and R.sup.I is CH.sub.2 CH.sub.2 
OCH.sub.3, 
##STR33## 
CH.sub.2 OCH.sub.3 or CH.sub.2 OCH.sub.2 CH.sub.3 ; 
(12) More Preferred (9) in which Q is 
##STR34## 
and R.sup.I is H, C.sub.1 -C.sub.3 alkyl, OCH.sub.3 or OCH.sub.2 CH.sub.3 
and R.sub.6 is H or C.sub.1 -C.sub.2 alkyl; 
(13) More Preferred (9) in which R.sup.II is H or CH.sub.3 ; 
(14) More Preferred (10), (11), (12) and (13) in which A' is H; Y is 
CH.sub.3, OCH.sub.3, OCH.sub.2 CH.sub.3, OCH.sub.2 CF.sub.3, OCH.sub.2 
CH.dbd.CH.sub.2 or OCH.sub.2 C.tbd.CH; 
(15) More Preferred (8) in which A is 
##STR35## 
and Q is oxygen or sulfur and R.sup.I is CH.sub.3 or CH.sub.2 CH.sub.3 ; Q 
is 
##STR36## 
and R.sup.I is H, CH.sub.3 or OCH.sub.3 and R.sub.6 is CH.sub.3 ; R.sub.1 
is 
##STR37## 
and Y is CH.sub.3 or OCH.sub.3 ; 
(16) More Preferred (15) of Formula I; 
(17) More Preferred (15) of Formula II; 
(18) More Preferred (15) of Formula III. 
Equally More Preferred in increasing order and for reasons of higher 
activity and/or even lower cost and/or even greater ease of synthesis are: 
(19) Compounds of Preferred 1 in which W' is oxygen; 
(20) Compounds of More Preferred (19) in which T is oxygen; 
(21) More Preferred (20) in which R.sub.1 is 
##STR38## 
(22) More Preferred (21) where Q is O or S and R.sub.1 is C.sub.1 -C.sub.4 
alkyl; C.sub.3 -C.sub.4 alkenyl; C.sub.3 -C.sub.4 alkynyl; C.sub.2 
-C.sub.3 alkyl substituted with CN, OCH.sub.3 or 1-3 F, Cl or Br; C.sub.3 
-C.sub.4 alkenyl substituted with 1-3 Cl; C.sub.3 -C.sub.4 alkynyl 
substituted with Cl; 
(23) More Preferred (21) in which Q is oxygen and R.sup.I is CH.sub.2 
CH.sub.2 OR.sub.15 ; CH.sub.2 CH.sub.2 CH.sub.2 OR.sub.15 ; 
##STR39## 
where R.sub.15 is CH.sub.2 CH.sub.3 ; CH.sub.2 CN; CH.sub.2 OR.sub.6 ' 
where R.sub.6 ' is CH.sub.3 or CH.sub.3 CH.sub.2 ; 
##STR40## 
(24) More Preferred (21) in which Q is 
##STR41## 
and R.sup.I is H, C.sub.1 -C.sub.4 alkyl, CH.sub.2 CH.sub.2 OR.sub.10, 
CH.sub.2 CH.sub.2 CH.sub.2 OR.sub.10 where R.sub.10 is CH.sub.3 or 
CH.sub.3 CH.sub.2 ; C.sub.3 -C.sub.4 alkenyl; CH.sub.2 CN; CH.sub.2 
CH.sub.2 CN; OCH.sub.3 or OCH.sub.2 CH.sub.3 ; R.sup.6 is H, C.sub.1 
-C.sub.2 alkyl, CH.sub.2 CN or CH.sub.2 CH.sub.2 CN and R.sub.6 and 
R.sup.I can be taken together to form --CH.sub.2 --.sub.4. 
(25) More Preferred (21) in which R.sup.II is H or C.sub.1 -C.sub.3 alkyl; 
(26) More Preferred (22), (23), (24) and (25) in which 
Z is CH or N; 
X is CH.sub.3 or CH.sub.3 O; and 
Y is C.sub.1 -C.sub.2 alkyl; C.sub.1 -C.sub.2 alkyl substituted with 
OCH.sub.3 ; OCH.sub.2 CH.sub.3, CN or 1-3 atoms of F, Cl or Br; 
##STR42## 
where L is NH.sub.2, OH, 
##STR43## 
N(CH.sub.3).sub.2, NHCH.sub.3, C.sub.1 -C.sub.2 alkoxy; SCN; N.sub.3 ; 
NR.sub.11 R.sub.12 where R.sub.11 is H or CH.sub.3 ; R.sub.12 is H, 
CH.sub.3, CH.sub.3 CH.sub.2, OCH.sub.3 ; OR.sub.9 where R.sub.9 is 
CH.sub.3, CH.sub.3 CH.sub.2, CH.sub.2 CH.dbd.CH.sub.2 or CH.sub.2 
C.tbd.CH; R.sub.9 is also C.sub.2 alkyl substituted with 1-3 F, Cl or Br; 
CH.sub.3 S; 
(27) Preferred (21) in which A' is H, Cl or Br; 
(28) More Preferred (27) in which Q is O or S and R.sup.I is C.sub.1 
-C.sub.4 alkyl, CH.sub.2 CH.dbd.CH.sub.2 or CH.sub.2 CH.sub.2 Cl; 
(29) More Preferred (27) in which Q is O and R.sup.I is CH.sub.2 CH.sub.2 
OCH.sub.3, 
##STR44## 
CH.sub.2 OCH.sub.3 or CH.sub.2 OCH.sub.2 CH.sub.3 ; 
(30) More Preferred (27) in which Q is 
##STR45## 
and R.sup.I is H, C.sub.1 -C.sub.3 alkyl, OCH.sub.3 or OCH.sub.2 CH.sub.3 
and R.sub.6 is H or C.sub.1 -C.sub.2 alkyl; 
(31) More Preferred (27) in which R.sup.II is H or CH.sub.3 ; 
(32) More Preferred (28), (29), (30) and (31) in which A' is H; Y is 
CH.sub.3, OCH.sub.3, OCH.sub.2 CH.sub.3, OCH.sub.2 CF.sub.3, OCH.sub.2 
CH.dbd.CH.sub.2 or OCH.sub.2 C.tbd.CH; 
(33) More Preferred (27) in which A is 
##STR46## 
and Q is oxygen or sulfur and R.sup.I is CH.sub.3 or CH.sub.2 CH.sub.3 ; Q 
is 
##STR47## 
and R.sup.I is H, CH.sub.3 or OCH.sub.3 and R.sub.6 is CH.sub.3 ; R.sub.1 
is 
##STR48## 
and Y is CH.sub.3 or OCH.sub.3 ; 
(34) More Preferred (33) of Formula I; 
(35) More Preferred (33) of Formula II; 
(36) More Preferred (33) of Formula III. 
Specifically Preferred for reasons of highest activity and/or lowest cost 
and/or greatest ease of synthesis are: 
methyl 
3-[[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-thiophenec 
arboxylate 
methyl 
3-[[(4,6-dimethylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-thiopheneca 
rboxylate 
methyl 
3-[[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-thiop 
henecarboxylate 
methyl 
3-[[(4,6-dimethoxy-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-2-thiop 
henecarboxylate 
methyl 
3-[[(4,6-dimethyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-2-thioph 
enecarboxylate 
methyl 
3-[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-2- 
thiophenecarboxylate 
methyl 
3-[[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-furancarbo 
xylate 
methyl 
3-[[(4,6-dimethylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-furancarbox 
ylate 
methyl 
3-[[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-furan 
carboxylate 
methyl 
3-[[(4,6-dimethoxy-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-2-furan 
carboxylate 
methyl 
3-[[(4,6-dimethyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-2-furanc 
arboxylate 
methyl 
3-[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-2- 
furancarboxylate 
methyl 
2-[[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-3-thiophenec 
arboxylate 
methyl 
2-[[(4,6-dimethylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-3-thiopheneca 
rboxylate 
methyl 
2-[[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-3-thiop 
henecarboxylate 
methyl 
2-[[(4,6-dimethoxy-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-3-thiop 
henecarboxylate 
methyl 
2-[[(4,6-dimethyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-3-thioph 
enecarboxylate 
methyl 
2-[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-3- 
thiophenecarboxylate 
methyl 
2-[[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-3-furancarbo 
xylate 
methyl 
2-[[(4,6-dimethylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-3-furancarbox 
ylate 
methyl 
2-[[4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-3-furanc 
arboxylate 
methyl 
2-[[(4,6-dimethoxy-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-3-furan 
carboxylate 
methyl 
2-[[(4,6-dimethyl-1,3,5-triazin-2-yl)aminocarbonyl]-aminosulfonyl]-3-furan 
carboxylate 
methyl 
2-[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-3- 
furancarboxylate 
N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-2-(1-pyrrolidinylcarbon 
yl)-3-thiophenesulfonamide 
1-methylethyl 
3-[[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-thiophenec 
arboxylate 
2-propenyl 
3-[[(4-methoxy-6-methylpyrimidin-2-ylaminocarbonyl]aminosulfonyl]-2-thioph 
enecarboxylate 
1-methylethyl 
3-[[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-thiop 
henecarboxylate. 
Novel Intermediates 
Also novel and useful for the preparation of compounds of Formulas I, II 
and III are compounds of Formulas I', II' and III'. 
##STR49## 
wherein R.sup.I is H or M; 
M is a cation of an alkalii metal or of a tertiary amine of up to 12 carbon 
atoms; 
A', W', B, are as previously defined. 
Preferred and in increasing order for reasons of lower cost and/or greater 
ease of synthesis and/or higher activity of derived compounds are those 
intermediate 
(1) Compounds of formulas I', II' and III' in which W' is is sulfur, B is 
SO.sub.2 NHCONHR.sub.1, A' is H, Cl or Br and R.sub.1 is 
##STR50## 
(2) Compounds of Preferred (1) in which X is CH.sub.3 or OCH.sub.3 ; Y is 
CH.sub.3, OCH.sub.3, OCH.sub.2 CH.sub.3, OCH.sub.2 CF.sub.3, OCH.sub.2 
CH.dbd.CH.sub.2 or OCH.sub.2 --C.tbd.C--H; Z is CH or N; 
(3) Compounds of Preferred (2) in which Y is CH.sub.3 or OCH.sub.3 ; 
R.sub.1 is 
##STR51## 
A' is H; 
(4) Compounds of Preferred (3) of Formula I'; 
(5) Compounds of Preferred (4) of Formula II'; 
(6) Compounds of Preferred (5) of Formula III'; 
Equally Preferred in increasing order, for reasons of lower cost and/or 
greater ease of synethesis and/or higher activity of derived compound are 
those intermediate: 
(7) Compounds of formulas I', II' and III' in which W' is oxygen; B is 
SO.sub.2 NHCONHR.sub.1, A' is H, Cl or Br, and R.sub.1 is 
##STR52## 
(8) Compounds of Preferred (7) in which X is CH.sub.3 or OCH.sub.3 ; Y is 
CH.sub.3, OCH.sub.3, OCH.sub.2 CH.sub.3, OCH.sub.2 CF.sub.3, OCH.sub.2 
CH.dbd.CH.sub.2 or OCH.sub.2 C.tbd.C--H; and Z is CH or N; 
(9) Compounds of Preferred (8) in which Y is CH.sub.3 or OCH.sub.3 ; 
R.sub.1 is 
##STR53## 
A' is H; 
(10) Compounds of Preferred (9) of Formula I'; 
(11) Compounds of Preferred (9) of Formula II'; 
(12) Compounds of Preferred (9) of Formula III'; 
Specifically Preferred for reasons of lowest cost and/or greatest ease of 
synthesis and/or highest activity of desired compounds are: 
3-[[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-thiopheneca 
rboxylic acid 
3-[[(4,6-dimethylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-thiophenecar 
boxylic acid 
3-[[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-thioph 
enecarboxylic acid 
3-[[(4,6-dimethoxy-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-2-thioph 
enecarboxylic acid 
3-[[(4,6-dimethyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-2-thiophe 
necarboxylic acid 
3-[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-2-t 
hiophenecarboxylic acid 
3-[[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-furancarbox 
ylic acid 
3-[[(4,6-dimethylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-furancarboxy 
lic acid 
3-[[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-2-furanc 
arboxylic acid 
3-[[(4,6-dimethoxy-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-2-furanc 
arboxylic acid 
3-[[(4,6-dimethyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-2-furanca 
rboxylic acid 
3-[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-2-f 
urancarboxylic acid 
2-[[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-3-thiopheneca 
rboxylic acid 
2-[[(4,6-dimethylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-3-thiophenecar 
boxylic acid 
2-[[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-3-thioph 
enecarboxylic acid 
2-[[(4,6-dimethoxy-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-3-thioph 
enecarboxylic acid 
2-[[(4,6-dimethyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-3-thiophe 
necarboxylic acid 
2-[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-3-t 
hiophenecarboxylic acid 
2-[[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-3-furancarbox 
ylic acid 
2-[[(4,6-dimethylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-3-furancarboxy 
lic acid 
2-[[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]aminosulfonyl]-3-furanc 
arboxylic acid 
2-[[(4,6-dimethoxy-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-3-furanc 
arboxylic acid 
2-[[(4,6-dimethyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-3-furanca 
rboxylic acid 
2-[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]aminosulfonyl]-3-f 
urancarboxylic acid 
Also novel and useful for the preparation of compounds of Formulas I, II 
and III are compounds of Formulas I", II" and III" 
##STR54## 
wherein W is oxygen or sulfur; 
W' is oxygen or sulfur; 
A' is H, Cl, Br, C.sub.1 -C.sub.4 alkyl, OCH.sub.3, NO.sub.2 or CF.sub.3 ; 
R.sup.I is C.sub.1 -C.sub.6 alkyl; C.sub.3 -C.sub.6 alkenyl; C.sub.3 
-C.sub.6 alkynyl; C.sub.2 -C.sub.6 alkyl substituted with Cl, CN or 
OCH.sub.3 ; C.sub.3 -C.sub.6 alkenyl substituted with 1-3 Cl; C.sub.3 
-C.sub.6 alkynyl substituted with Cl; C.sub.5 -C.sub.6 cycloalkyl; 
cyclohexenyl; cyclohexyl substituted with 1-3 CH.sub.3 ; C.sub.4 -C.sub.7 
cycloalkylalkyl or 
##STR55## 
where R.sub.7 and R.sub.8 are independently H, Cl, CH.sub.3 or OCH.sub.3 
; 
n is 0 or 1; and 
R.sub.9 is H or CH.sub.3 ; CH.sub.2 CH.sub.2 OR.sub.15, CH.sub.2 CH.sub.2 
CH.sub.2 OR.sub.15, 
##STR56## 
where R.sub.15 is C.sub.2 H.sub.5, CH(CH.sub.3).sub.2, phenyl, CH.sub.2 
CH.sub.2 Cl, CH.sub.2 CCl.sub.3 ; --CH.sub.2 CH.sub.2 O--.sub.n, R.sub.16, 
##STR57## 
where R.sub.16 is CH.sub.3, C.sub.2 H.sub.5, CH(CH.sub.3).sub.2, phenyl, 
CH.sub.2 CH.sub.2 Cl, CH.sub.2 CCl.sub.3, and n' is 2 or 3; CH.sub.2 CN; 
##STR58## 
CH.sub.2 OR.sub.6 '; where R.sub.6 ' is C.sub.1 -C.sub.4 alkyl; provided 
R.sup.I has a total of .ltoreq.13 carbon atoms. 
Preferred in increasing order for reasons of lower cost and/or greater ease 
of synthesis and/or higher activity of desired compounds are those 
intermediate: 
(1) Compounds of formulas I", II" and III" in which W' is sulfur; W is 
oxygen; A' is H, Cl or Br; and R.sup.I is C.sub.1 -C.sub.4 alkyl; CH.sub.2 
CH.dbd.CH.sub.2 ; or CH.sub.2 CH.sub.2 Cl; CH.sub.2 CH.sub.2 OCH.sub.3 ; 
or 
##STR59## 
(2) Compounds of Preferred (1) in which R.sup.I is CH.sub.3 or CH.sub.2 
CH.sub.3 ; A.sup.I is H; 
(3) Compounds of Preferred (2) of Formula I"; 
(4) Compounds of Preferred (2) of Formula II"; 
(5) Compounds of Preferred (2) of Formula III". 
Equally Preferred in increasing order for reasons of lower cost and/or 
greater ease of synthesis and/or higher activity of derived compounds are 
those intermediate: 
(6) Compounds of formulas I", II", and III" in which W' is oxygen; W is 
oxygen; A' is H, Cl or Br; 
(7) Compounds of Preferred (6) in which R.sup.I is CH.sub.3 or CH.sub.2 
CH.sub.3 ; A.sup.I is H; 
(8) Compounds of Preferred (7) of Formula I". 
(9) Compounds of Preferred (7) of Formula II". 
(10) Compounds of Preferred (7) of Formula III". 
Specifically Preferred for reasons of lowest cost and/or greatest ease of 
synthesis and/or highest activity of desired compounds are: 
methyl 3-(isocyanatosulfonyl)-2-thiophenecarboxylate 
methyl 2-(isocyanatosulfonyl)-3-thiophenecarboxylate 
methyl 4-(isocyanatosulfonyl)-3-thiophenecarboxylate 
methyl 3-(isocyanatosulfonyl)-2-furancarboxylate 
methyl 2-(isocyanatosulfonyl)-3-furancarboxylate 
methyl 4-(isocyanatosulfonyl)-3-furancarboxylate 
Synthesis 
Many of the compounds of Formulas I-III are prepared as shown in Equation 3 
by the reaction of an appropriately substituted alkoxycarbonylthiophene or 
furan sulfonylisocyanate or sulfonylisothiocyanate with an appropriate 
aminopyrimidine or aminotriazine. These compounds of Formulas I-III can be 
converted to other compounds of Formulas I-III as will be shown in 
subsequent equations. 
The novel sulfonylisocyanates are important intermediates for the 
preparation of the compounds of this invention. Their synthesis is 
described in Equations 1 and 2. 
##STR60## 
A mixture of the appropriate sulfonamide, e.g. an 
2-alkoxycarbonyl-3-thiophene sulfonamide IV such as the methyl ester, 
which is known in the art, an alkyl isocyanate such as butyl isocyanate 
and a catalytic amount of 1,4-diaza[2.2.2]bicyclooctane (DABCO) in xylene 
or other inert solvent of sufficiently high boiling point (e.g. 
&gt;135.degree.) is heated to approximately 130.degree.-150.degree. C. 
Phosgene is added to the mixture until an excess of phosgene is present as 
indicated by a drop in the boiling point. After the mixture is cooled and 
filtered to remove a small amount of insoluble by-products, the solvent 
and alkyl isocyanate are distilled off in-vacuo leaving a residue which is 
the crude sulfonyl isocyanate V. In Equation 1, A', W' and CO.sub.2 
R.sup.I are as defined previously for structures I", II" and III". 
The novel sulfonylisothiocyanate intermediates of Formula V.sup.a, prepared 
according to Equations 2 and 2', are useful for the preparation of 
compounds of Formulas I-III where W.dbd.S. 
##STR61## 
The alkoxycarbonyl substituted sulfonamide is dissolved in 
dimethylformamide (DMF) with an equivalent amount of carbon disulfide and 
two equivalents of potassium hydroxide are added portionwise at room 
temperature. The mixture is stirred for 1-8 hours and diluted with 
ethylacetate, ethyl ether or similar aprotic solvent to cause the 
dipotassium salt of the dithiocarbamic acid to precipitate. The salt is 
isolated, dried and suspended in an inert solvent such as xylene, benzene, 
carbon tetrachloride or methylene chloride. Phosgene is added to the 
stirred suspension at below room temperature and the mixture stirred for 
1-3 hours. In place of phosgene, a chloroformic ester (e.g. methyl 
chloroformate), phosphorous pentachloride, sulfuryl chloride or thionyl 
chloride can be used. 
The sulfonylisothiocyanate which is formed is usually soluble in the 
solvent and is isolated by filtering off the insoluble potassium chloride 
and concentrating the filtrate. These isothiocyanates tend to be unstable 
and dimerize readily, (Equation 2') however, the dimers can be used 
Alternate routes to prepare sulfonylisothiocyanates are described by M. O. 
Lozinskii et al. in Organic Compounds: Reactions and Methods, Ed. by B. A. 
Kazanskii et al., Vol 22, p 188-197, Plenum Press, 1973 (Engl. Trans.) 
##STR62## 
in the same manner as the present isothiocyanates for the purposes of this 
invention. 
The synthetic method chosen for the preparation of compounds of Formulas 
I-III depends largely on the substituents QR.sup.I and R.sub.4. As shown 
in Equation 3, compounds of Formulas I-III wherein R.sup.I or A' are as 
defined for Equation 1, are conveniently prepared by reacting an 
appropriately substituted carbonyl thiophene or furan sulfonyl isocyanate 
or isothiocyanate of Formula V with an appropriately substituted 
aminopyrimidine or aminotriazine of Formula VI: 
##STR63## 
The reaction of Equation 3 is best carried out in inert aprotic organic 
solvents such as methylene chloride, tetrahydrofuran or acetonitrile, at 
ambient pressure and temperature. The mode of addition is not critical; 
however, it is often convenient to add the sulfonyl isocyanate or 
isothiocyanate to a stirred suspension of amine VI. Since such isocyanates 
and isothiocyanates are liquids, low melting solids or are readily soluble 
in solvents such as those listed above, their addition can be easily 
controlled. 
The reaction is generally exothermic. In some cases, the desired product is 
soluble in the warm reaction medium and on cooling crystallizes in pure 
form. Other products which are soluble in the reaction medium are isolated 
by evaporation of the solvent, trituration of the solid residue with 
solvents such as 1-chlorobutane or ethyl ether, and filtration. 
As shown in Equation 4, compounds of Formulas I-III, wherein W is S, A and 
A' are as previously defined and R.sub.5 is H, are altervatively prepared 
by the reaction of an appropriately substituted thiophene or furan 
sulfonamide with the appropriate triazine or pyrimidine isothiocyanate of 
Formula VIa. 
##STR64## 
The reaction of Equation 4 is best carried out by dissolving or suspending 
the sulfonamide and isothiocyanate in a polar solvent such as acetone, 
acetonitrile, ethyl acetate or methylethylketone, adding an equivalent of 
a base such as potassium carbonate and stirring the mixture at a 
temperature from ambient up to the reflux temperature for one to 
twenty-four hours. In some cases, the product precipitates from the 
reaction mixture and can be removed by filtration. The product is stirred 
in dilute mineral acid, filtered and washed with cold water. If the 
product does not precipitate from the reaction mixture, it can be isolated 
by evaporation of the solvent, trituration of the residue with dilute 
mineral acid and filtering off the insoluble product. 
The heterocyclic isothiocyanates which are used in the procedure of 
Equation 4 are prepared, for example, according to the method of Japan 
patent application Pub: Kokai No. 51-143686, June 5, 1976, or that of W. 
Abraham and G. Barnikow, Tetrahedron 29, 691-7 (1973). 
As shown in Equation 5, compounds of Formulas I-III, wherein A, A', 
R.sub.1, W', and R.sub.5 are as defined previously, and W is O, can be 
prepared by methylation of salts VII wherein M is an alkali metal cation 
such as sodium (derived from compounds of Formulas I-III wherein R.sub.4 
is hydrogen): 
##STR65## 
D being an incipient anion and n being an integer corresponding to the 
valence of D. 
The reaction of Equation 5 is best carried out in aprotic organic solvents 
such as tetrahydrofuran, dimethylformamide, or dimethylacetamide, at 
ambient pressure and temperature. Methylating agents VIII such as dimethyl 
sulfate or methyl iodide, can be employed. The desired product can be 
isolated by pouring the reaction mixture into water and filtering off the 
precipitated solid. 
As shown in Equation 6, compounds of Formulas I-III wherein A, A', R.sub.1, 
W', and R.sub.5 are as defined for Equation 5, and W is O or S, can also 
be prepared by the reaction of an appropriately substituted 
sulfonyl-N-methylcarbamyl chloride or sulfonyl-N-methylthiocarbamyl 
chloride of Formula IX with an appropriate aminopyrimidine or 
aminotriazine of Formula VI; 
##STR66## 
The preparation of ureas and thioureas, like those of Formula Ic, from 
amines and carbamyl chlorides and thiocarbamyl chlorides is well known to 
the art. The reaction can best be carried out by adding equivalent amounts 
of chloride IX and amine VI to an inert organic solvent, such as 
tetrahydrofuran, xylene, or methylene chloride, in the presence of an acid 
acceptor, such as triethylamine, pyridine, or sodium carbonate employing 
temperatures from 20.degree.-130.degree.. Soluble products can be isolated 
by filtering off the precipitated salts and concentration of the filtrate. 
Insoluble products can be filtered off and washed free of salts with 
water. 
The chlorides of Formula IX can be prepared by phosgenation or 
thiophosgenation of N-methylsulfonamide salts. The sulfonamide salt is 
added to an excess of phosgene or thiophosgene in an inert organic 
solvent, such as tetrahydrofuran, toluene, or xylene, whereupon, after 
removal of the excess phosgene, the chloride IX can be isolated or reacted 
in situ with the amine VI. 
The esters of Formulas I-III hydrolyze to the parent acid as shown in 
Equation 7. Alkali metal base catalyzed hydrolysis in aqueous methanol 
produces the alkali metal carboxylate from which the carboxylic acid is 
obtained by treatment with mineral acids such as HCl: 
##STR67## 
The reaction of Equation 7 is best carried out in a solution containing the 
compound being hydrolyzed, 2 to 10 parts of methanol, 10-50 parts of water 
and 2-10 equivalents of a base such as sodium or potassium hydroxide 
maintaining the temperature at 30.degree.-90.degree. C. for 3-24 hours. 
The reaction yields the soluble alkali metal salt of the carboxylic acid, 
which is suitable for the purposes of this invention. Conversion of these 
salts to the acid form is easily carried out by addition to the reaction 
medium of strong mineral acids, such as hydrochloric or sulfuric acid, 
causing the desired carboxylic acids to precipitate from solution. 
The acids of Formula Ie prepared as in Equation 7 wherein W is O can be 
converted to compounds of this invention where R.sup.I is a higher alkyl 
or substituted hydrocarbyl group, as already disclosed herein, by the 
reaction of salts of the parent acid with R.sup.I -halogen as shown in 
Equation 8. 
##STR68## 
The reaction of Equation 8 is of use where the intermediate compound 
R.sup.I -halogen contains a readily replaceable halogen as is the case for 
substituted or unsubstituted allylic or benzylic halides, 
.alpha.-halonitriles, or .alpha.-halocarbonyl compounds. 
The procedure of Equation 8 is best carried out in inert polar solvents 
such as tetrahydrofuran, acetonitrile or acetone by combining the 
appropriately substituted carboxylic acid and base such as triethylamine 
1,4-diaza[2,2,2]bicyclooctane adding the appropriate halide and heating 
the mixture to reflux with stirring for 1 to 16 hours. The reaction 
mixture can be evaporated to dryness and the residue triturated with 
water, filtered and washed with water to separate the desired product from 
the water soluble salt. 
The procedure of Equation 8 can also be used for the synthesis of compounds 
wherein R.sup.I -halogen of Equation 8 is of a less reactive species than 
described above. In these cases, the silver salt of the carboxylic acid is 
used rather than the amine salt. The silver salt which is precipitated by 
adding silver nitrate to an aqueous solution of the sodium salt of the 
acid of Formula Ie is combined with the appropriate R.sup.I -halide using 
the same solvents and conditions as shown above for the amine salt. 
When Q is NR.sub.6, the compounds can be prepared from the esters of this 
invention where R.sup.I is C.sub.1 -C.sub.4 (preferably C.sub.1) by the 
reaction of the esters with dialkylaluminum-N-alkylamide derivatives 
according to Equation 9; R.sup.I, A', W', R.sub.1, R.sub.4, R.sub.5 and 
R.sub.6 being as previously defined. 
##STR69## 
The intermediate alkylaminoaluminum compounds prepared according to A. 
Basha, M. Lipton and S. W. Weinreb, Tetrahedron Letters 4171 (1977), are 
comingled with a suspension of the esters in toluene or similar inert 
solvent and the mixture is refluxed for one to six hours. The product can 
be isolated by evaporation of the solvent, addition of methylene chloride 
and aqueous hydrochloric acid to decompose the residual reaction mass and 
extracting the desired product into methylene chloride. Evaporation of the 
methylene chloride yields the desired product in sufficiently pure form 
for the purpose of this invention. 
Compounds of Formula X, wherein Q is 
##STR70## 
A', W' and R.sub.4 are as previously defined in the general formula, which 
are useful as intermediates in Equation 4, are prepared as shown in 
Equation 10. 
##STR71## 
The conditions described for Equation 8 are suitable for the conversion of 
the esters of Formula IVa to the carboxamides as shown in Equation 10. 
The products of Equation 10 are especially useful for the preparation of 
compounds of Formulas I-III wherein Y has an ester substituent CO.sub.2 
(C.sub.1 -C.sub.6), by the route described in Equation 4. 
When Q is S, these compounds can be prepared from the esters of this 
invention wherein QR.sup.I is O(C.sub.1 -C.sub.4 alkyl) (preferably 
C.sub.1) by the reaction of the esters with the appropriate 
dialkylaluminum alkylthiolate according to Equation 11. 
##STR72## 
The intermediate aluminum thiolates can be prepared according to R. P. 
Hatch and S. W. Weinreb, Journal of Organic Chemistry, Vol. 42, 3960 
(1977). The reaction of the thiolate with the ester of this invention is 
best carried out in a neutral solvent such as toluene or xylene at reflux 
for one to three hours. Best results are obtained when the aluminum 
thiolate compound is present in excess of the stoichiometric amount 
required. 
Sulfonamides of Formula IVc are also converted from carboxylic acid esters 
to the thiolesters as shown in Equation 12 according to the method of R. 
P. Hatch and S. W. Weinreb as described for Equation 11 wherein R.sup.I, 
A', W' and R.sub.4 are as previously defined. 
##STR73## 
The conditions described for Equation 11 are suitable for the conversion 
of the sulfonamides of Formula IVc as shown in Equation 12. 
The products obtained by the procedure of Equation 12 are especially useful 
for the preparation of compounds of formulas I-III where Y has a 
substituent (CO.sub.2 C.sub.1 -C.sub.6) by the route described for 
Equation 4 and Q.dbd.S. 
An alternate route to prepare compounds where R.sup.I is bonded to Q 
(Q.dbd.O) at a secondary carbon involves the reaction of the appropriate 
dialkylaluminum alcoholate and an ester of this invention wherein R.sup.I 
is a lower primary alkyl group, preferably methyl, according to Equation 
13. 
##STR74## 
The reaction is carried out in a neutral solvent such as toluene with a 
boiling point sufficiently high to bring about the desired reaction during 
reflux. The dialkylaluminum alcoholate being present in greater than an 
equivalent amount to the ester for best yields. After refluxing for 1-15 
hours, the reaction mixture is decomposed with dilute hydrochloric acid 
and the product extracted into methylene chloride. Evaporation of the 
methylene chloride yields the desired compound sufficiently pure for the 
purposes of this invention. The product can be triturated with a solvent, 
e.g. 1-chlorobutane to remove impurities. 
Ketones wherein A is 
##STR75## 
and A', W', W, R.sub.1, R.sub.4 and R.sub.5 are as defined by the scope of 
this invention, are prepared according to Equation 14, from the carboxylic 
acids of Formula Ie whose preparation is described in Equation 7. 
##STR76## 
The reaction of an organolithium compound with a carboxylic acid to yield a 
ketone as in Equation 14 is described in the work of H. Gilman and P. R. 
Van Ess, JACS, 55, 1258 (1933); H. Gilman, W. Langham and F. W. Moore, 
ibid., 62 (1940); C. Tegner, Chem. Scand., 6, 782 (1952); J. F. Arens and 
D. A. Van Dorp, Rec. Trav., 65 338 (1946); 66, 759 (1947); C. H. Depuy, G. 
M. Dappen, K. L. Eilers and R. A. Klein, J. Org., 29, 2813 (1964). 
An excess of the organolithium compound in a suitable solvent such as 
diethyl ether, hexane, pentane or benzene is added to a solution or slurry 
of XI in a similar solvent at temperatures between -100.degree. and 
0.degree. C. The mixture is allowed to warm to room temperature and stir 
for 30 minutes. Aqueous acid is then added and the ketosulfonamide 
extracted into a suitable solvent to free it from salts followed by 
evaporation of the solvent. 
The synthesis of a wide variety of organolithium compounds by many 
different procedures is known in the art. A summary of methods with 
bibliography is contained in Organo-Metallic Compounds, G. E. Coates, John 
Wiley and Sons, 1960, p. 3-21. 
Oximes of the ketones of Formula XI, for example, can be prepared from the 
appropriate hydroxylamine derivative, wherein R.sup.III is as previously 
defined, and the ketone of Formula XI according to Equation 15. 
##STR77## 
A procedure such as that described in Preparative Organic Chemistry by G. 
Hilgetag and A. Martini, Ed., John Wiley and Sons, p. 513 is suitable for 
the preparation of the oximes of this invention. 
Compounds of Formulas I-III wherein B is 
##STR78## 
and W is O, are prepared by the sequence of reactions shown in Equation 
16. 
##STR79## 
The compounds of Formula XVII are prepared by adding an appropriate carbon 
tetrahalide to a solution of a compound of Formula XII and triphenyl 
phosphine in an inert aprotic solvent such as acetonitrile at about 
-10.degree. to 25.degree. and stirring at the designated temperature for 
10 to 48 hours. The carbamimidoyl halides of Formula XVI thus formed may 
be isolated by passing the reaction solution through a silica gel column 
to remove the triphenyl phosphine oxide and removal of the solvent by 
evaporation under reduced pressure. 
The compounds of Formula XVI can be converted to the corresponding 
compounds of Formula XVII by treating reaction mixture with a metal 
alkoxide, NaOR.sup.III, at -10.degree. to 25.degree. and stirring at 
ambient temperature for 2 to 24 hours. The crude products of Formula XVII 
are isolated by filtering off the precipitated metal halide and removing 
the solvent by evaporation under reduced pressure. Further purification 
may be accomplished by recrystallization or by column chromatography over 
silica gel. 
It will be understood that the compounds of Formula XVI are not necessarily 
converted directly to the compounds of Formula XVII, but may first form 
the carbodiimides of Formula XVIII. 
##STR80## 
Many compounds, particularly compounds in which the heterocyclic moiety is 
pyrimidinyl, may be prepared by the sequence of reactions shown in 
Equation 17. 
##STR81## 
The compounds of Formula XIX are prepared according to the procedure or R. 
Gompper and W. Hagele in Chemische Berichte 99, 2885-2899 (1966). 
The compounds of Formula XX are prepared from the compounds of Formula XIX 
with sulfuryl chloride in an inert organic solvent such as methylene 
chloride or chloroform at temperatures between -10.degree. and 80.degree.. 
They are isolated by removing the solvent under reduced pressure, and can 
be used without further purification. 
The compounds of Formula XXI are prepared in the following manner: The 
lithium salt of the appropriate aminoheterocycle is prepared from the 
aminoheterocycle with n-butyl lithium in a solvent such as 
tetrahydrofuran. To this salt solution is added the compound of Formula XX 
in tetrahydrofuran at a temperature of about -10.degree. to 10.degree.. 
The reaction mixture is then stirred at about 0.degree.-10.degree. for 
1/2-2 hours and at ambient temperature for 1/2-4 hours. The products of 
Formula XXI are isolated by filtering off the inorganic salts and removing 
the solvent under reduced pressure. Further purification can be done by 
recrystallization or by column chromatography on silica gel using a 
suitable eluent such as ethyl acetate. 
As shown in Equation 18, the compounds of Formula XXIV, wherein 
##STR82## 
and W.dbd.S can be prepared by reacting an appropriately substituted 
carbamimidothioic acid salt of Formula XXII with an alkylating agent of 
Formula XXIII. 
##STR83## 
wherein D is a sulfate or halogen, such as Cl, Br or I; M is an alkali or 
alkaline earth metal, and n is an integer corresponding to the valence of 
D. 
The reaction is best carried out in inert aprotic organic solvents such as 
tetrahydrofuran or diethyl ether at temperatures between 25.degree. and 
100.degree. C. and ambient pressure. The mode of addition is not critical; 
however, it is often convenient to add the alkylating agent in solution to 
a stirred suspension of the salt of Formula XXII. The product is isolated 
by evaporation of the solvent and can be purified by recrystallization 
from a solvent such as acetonitrile or ethanol. 
The metal salts of Formula XXII can be prepared by treating the 
corresponding sulfonylthiourea with a solution of an alkali metal or 
alkaline earth metal salt having an anion sufficiently basic to the proton 
(e.g. hydroxide, alkoxide, carbonate or hydride). 
When Z is N, the preferred procedure for the preparation of compounds of 
Formula XXIV is that shown in Equation 19. 
##STR84## 
A compound of Formula XXV is treated with an alkali metal (M') salt of the 
appropriately substituted heterocyclic amine at temperatures of 0.degree. 
to 100.degree. C. in a solvent such as dimethylformamide, 
dimethylsulfoxide or an ethereal solvent, such as tetrahydrofuran. 
Compounds of Formula XXV can be prepared according to the procedure of 
Chem. Ber. 99, 2885 (1966). 
Compounds of Formulas I-III wherein Y of group R.sub.1 contains 
##STR85## 
and L is OH can be prepared according to the procedure of Equation 20 
wherein A', W', X, R.sub.4, W and R.sub.5 are as defined previously; and 
Q' is C.sub.1 -C.sub.4 alkyl, OCH.sub.2, OCH.sub.2 CH.sub.2, 
##STR86## 
where R.sub.11 is as previously defined. 
##STR87## 
The reaction of Equation 20 is best carried out by suspending the compound 
being hydrolyzed in 10 to 100 parts of water with enough of a base such as 
sodium hydroxide or potassium hydroxide to obtain a pH 10 to 14, ideally a 
pH of 12, heating until a clear solution is obtained and then adjusting 
the pH to 1-3, preferably 3. The product is thus caused to precipitate in 
some instances and can be removed by filtration or it can be extracted 
into a polar organic solvent such as methylene chloride and isolated by 
evaporation of the solvent. 
Thiophene derivatives with sulfamoyl and alkoxycarbonyl substituents on 
adjacent carbon atoms are prepared by the methods taught by O. Hromatka 
and D. Binder, U.S. Pat. No. 4,028,373 and P. A. Rossy et al., U.S. Pat. 
No. 4,143,050. The analogous furan derivatives are prepared similarly or 
as taught in Belgian Pat. No. 871,772. 
Alternate methods of preparation of thiophene and furan sulfonamides with 
alkoxycarbonyl substituents adjacent to the sulfonamide are preferable in 
certain circumstances. For example, if one of the .alpha.-carbons is not 
substituted, chlorosulfonation of a furan or thiophene may give the 
undesired substituted sulfonyl chloride or a mixture of isomers. 
Regiospecific introduction of substituents may be achieved in many cases 
via ring metalation reactions. The use of such reactions has been reviewed 
by H. Gschwend and H. Rodriguez in "Organic Reactions", Vol. 26 (John 
Wiley & Sons, Inc., New York, 1979). Using these methods, the 
2-lithio-3-furancarboxylates or -thiophenecarboxylates may be generated 
from the corresponding acid and two equivalents of an alkyllithium in an 
inert, aprotic solvent such as an ether solvent. These intermediates are 
described in 
##STR88## 
Tetrahedron Letters 5051 (1980) and references therein. Treatment of these 
organolithium species with sulfur dioxide afford the corresponding 
2-sulfinate-3-carboxylate salts which are conveniently isolated by 
evaporation of the solvent. The lithium sulfinates are converted to the 
sulfonamides by reaction with an excess of chloramine in aqueous solution 
and isolated by acidification and extraction 
##STR89## 
into an organic solvent. Esterification of the resulting acids under 
standard conditions (e.g., methanol, sulfuric acid catalyst, 
25.degree.-65.degree. C., 1-24 h) yield the appropriate alkoxycarbonyl 
sulfonamides. 
Other isomeric furan and thiophene sulfonamides may be prepared through a 
sequence of these metalation reactions as shown below. The reaction of 
3-bromofurans or -thiophenes with alkyllithium reagents at low 
temperatures (preferably below -40.degree.) in an aprotic, inert solvent 
afford the corresponding 3-lithiofurans and -thiophenes via halogen-metal 
exchange. These may be quenched with sulfur dioxide to yield the 
3-sulfinic acid salts. They may be subsequently 
##STR90## 
converted to sulfonyl chlorides with a chlorinating agent, conveniently 
with a reagent such as N-chlorosuccinimide (NCS) in a suitable solvent 
such as acetic acid, preferably at ambient temperature. The 
##STR91## 
3-t-butylsulfonamide is then prepared upon reaction of the sulfonyl 
chloride with excess t-butylamine. Reaction of the sulfonamide with 
##STR92## 
two equivalents of an alkyllithium, as described above for the 
3-carboxylic acids, yield specifically the 2-lithio intermediates which 
are quenched with carbon dioxide to afford the 2-carboxylic acid salts. 
Esterification of the carboxylic acid and removal of the t-butyl group may 
be accomplished in one reaction by heating the above products in an 
alcohol solvent with acid catalyst (e.g. methanol, sulfuric acid). 
##STR93## 
For 3,4-disubstituted furan and thiophene sulfonamides, a modification of 
the above sequence is appropriate. A 4-bromo-3-t-butylsulfamoylthiophene 
or furan intermediate may be prepared by the methods outlined above 
beginning with the 3,4-dibromo compound. Reaction of these sulfonamides 
with 
##STR94## 
two equivalents of alkyllithium in preferably an ether solvent at low 
temperature (preferably less than -40.degree.) will afford the 3-lithio 
species via halogen-metal exchange. These may be subsequently quenched 
with carbon dioxide to yield the carboxylic acids which are then converted 
to the free sulfonamideesters as outlined above for the 2,3-disubstituted 
isomers. 
Compounds of structure XXIX wherein A is an aldehyde group and A' does not 
equal --NO.sub.2 are prepared by the procedure of Equation 21. 
##STR95## 
Following the procedure of R. Kanazawa and T. Tokoroyama, Synthesis, 526 
(1976), a solution of sodium bis-(2-methoxyethoxy)aluminum hydride in THF 
is reacted with one equivalent of morpholine. To this solution at 
-40.degree. C. is added a methyl ester of Formula XXVIII and the solution 
is allowed to warm to 25.degree. C. The product is isolated by addition of 
aqueous acid and extraction into ether or methylene chloride. Evaporation 
of the solvent and crystallization or column chromatography on silica gel 
affords the aldehyde XXX. 
Aldehydes of Formula XXX may also be prepared from the esters of treatment 
with diisobutylaluminum hydride according to the procedures of E. 
Winterfeldt, Synthesis, 617 (1975). 
Compounds of Formulas I, II and III may also be prepared by the reaction of 
the appropriately substituted thiophene or furan sulfonamides with the 
appropriate heterocyclic isocyanate using the methods described in 
co-pending applications U.S. Ser. No. 098,725 and U.S. Ser. No. 098,722, 
filed Nov. 30, 1979. 
The synthesis of heterocyclic amines has been reviewed in "The Chemistry of 
Heterocyclic Compounds" a series published by Interscience Publ., New York 
and London. 2-Aminopyrimidines are described by D. J. Brown in The 
Pyrimidines, Vol. XVI of this series. The 2-amino-1,3,5-triazines are 
reviewed by K. R. Huffman and in The Triazines of this same series. The 
synthesis of triazines are also described by F. C. Schaefer, U.S. Pat. No. 
3,154,547 and by K. R. Huffman and F. C. Schaeffer, J. Org. Chem. 28, 
1816-1821 (1963). 
The preparation of the aminoheterocycles described by Formula XXX varies 
according to the definition of Y.sub.1 and X.sub.II. 
##STR96## 
Braker, Sheehan, Spitzmiller and Lott, J. Am. Chem. Soc. 69, 3072 (1947) 
describe the preparation of 
6,7-dihydro-4-methoxy-5H-cyclopentapyrimidin-2-amine by the following 
sequence of reactions. 
##STR97## 
Similarly, 6,7-dihydro-4-methyl-5H-cyclopentapyrimidin-2-amine can be 
prepared by the condensation of 2-acetylcyclopentanone with guanidine 
carbonate, but preferably under acidic conditions, removing the water 
formed. 
##STR98## 
Shrage and Hitchings, J. Org. Chem. 16, 1153 (1951) describe the 
preparation of 5,6-dihydro-4-methylfuro[2,3-d]pyrimidin-2-amine by the 
following sequence of reactions. 
##STR99## 
5,6-Dihydro-4-methoxyfuro[2,3-d]pyrimidin-2-amine can be prepared by the 
method of Braker et al. J. Am. Chem. Soc. 69, 3072 (1947), using 
5,6-dihydro-4-hydroxyfuro[2,3-d]pyrimidin-2-amine [Svab, Budesinski and 
Vavrina, Collection Czech. Chem. Commun. 32, 1582 (1967)]. 
##STR100## 
Caldwell, Kornfeld and Donnell, J. Am. Chem. Soc. 63, 2188 (1941), describe 
the preparation of 6,7-dihydro-5H-cyclopentapyrimidin-2-amine by the 
following sequence of reactions. 
##STR101## 
Fissekis, Myles and Brown, J. Org. Chem. 29, 2670 (1964), describe the 
preparation of 2-amino-4-hydroxy-5-(2-hydroxyethyl)pyrimidine which can be 
converted to 5,6-dihydrofuro[2,3-d]pyrimidin-2-amine by dehydration. 
##STR102## 
Agriculturally suitable salts of compounds of Formulas I-III are also 
useful herbicides and can be prepared by a number of ways known to the 
art. For example, metal salts can be made by treating compounds of 
Formulas I-III with a solution of alkali or alkaline earth metal salt 
having a sufficiently basic anion (e.g., hydroxide, alkoxide, carbonate or 
hydride). Quaternary amine salts can be made by similar techniques. 
Salts of compounds of Formulas I-III can also be prepared by exchange of 
one cation to another. Cationic exchange can be effected by direct 
treatment of an aqueous solution of a salt of a compound of Formulas I-III 
(e.g., alkali metal or quuaternary amine salt) with a solution containing 
the cation to be exchanged. This method is most effective when the desired 
salt containing the exchanged cation is insoluble in water, e.g., a copper 
salt, and can be separated by filtration. 
Exchange may also be effected by passing an aqueous solution of a salt of a 
compound of Formulas I-III (e.g., an alkali metal or quaternary amine 
salt) through a column packed with a cation exchange resin containing the 
cation to be exchanged. In this method, the cation of the resin is 
exchanged for that of the original salt and the desired product is eluted 
from the column. This method is particularly useful when the desired salt 
is water soluble, e.g., a potassium, sodium or calcium salt. 
Acid addition salts, useful in this invention, can be obtained by reacting 
a compound of Formulas I-III with a suitable acid, e.g., p-toluenesulfonic 
acid, trichloroacetic acid or the like. 
The compounds of this invention and their preparation are further 
illustrated by the following examples wherein temperatures are given in 
degrees centigrade. 
The desired product is underscored at the top of each example.