Synthesis and Chemistry of Agrochemicals III - American Chemical

Chapter 8

Discovery of a New Class of Herbicides: Sulfonyl Carboxamides 1

S. I. Alvarado, A. D. Crews , P. J . Wepplo, R. F. Doehner, T. E. Brady, D. M . Gange, and D. L. Little

Downloaded by IOWA STATE UNIV on October 18, 2014 | http://pubs.acs.org Publication Date: September 22, 1992 | doi: 10.1021/bk-1992-0504.ch008

Agricultural Research Division, American Cyanamid Company, P.O. Box 400, Princeton, NJ 08543-0400 A potential new class of herbicides of the structural type shown below which inhibit acetohydroxy acid synthase has been discovered at the Agricultural Research Division of American Cyanamid. The Level of herbicidal activity is increased by

addition of halogens to the aromatic portion of the structure while crop selectivity is improved with addition of alkyl or alkoxy groups on the aromatic moiety. A scheme of synthetic methodology as well as a description of structure activity relationships will be given. As part of a general program aimed at the synthesis of imidazolinone analogues which are described by the generic structure below, N-sulfonation was investigated.

Hydrolysis of the sulfonation product afforded a diamide which exhibited excellent herbicidal activity. 1

Corresponding author

0097-6156/92/0504-O075$06.00A) © 1992 American Chemical Society In Synthesis and Chemistry of Agrochemicals III; Baker, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1992.

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SYNTHESIS AND CHEMISTRY OF AGROCHEMICALS III

COOH


H3O

1

The herbicidal activity was followed up with an analogue program which replaced the heterocyclic aromatic nucleus with simple alkyl groups and thus, delivered the sulfonyl carboxamides as a new class of AHAS inhibiting herbicides (7, 2). Preparation of Sulfonyl Carboxamides Sulfonyl carboxamides are prepared by one of the five general methods described below. From N-arylsulfonylimidazolinones. Sulfonylations of imidazolinones 1 with arylsulfonyl chlorides (Scheme I) were performed using pyridine, sodium hydride or triethylamine, in methylene chloride, tetrahydrofuran or a mixture of both. The reactions were usually performed at room temperature, but in some instances were carried out atreflux,and generally required 6 to 18 hours to complete. The intermediates 2 were generally not isolated or purified, but were hydrolyzed directly to N-acylsulfonylcarboxamides 3 by treatment with dilute HCl(aq). However, intermediates 2 could be easily isolated when sodium hydride was employed as a base. Generally the hydrolysis of 2 required only a few minutes at room temperature to afford the desired products 3, which typically could be purified by crystallization from ethanol/water or methylene chloride/hexanes. R

.1

/ ArS0 CI 2

j

base solvent*

-R

2

R - f

o

SOo

o

AT RC(OEt) xylenes reflux

NH OC 2

• NH

H*0

3

ArS0 NHCO

2

2

R: H , C H

.NHCOR

3

R R : H, Alkyl, Cycloalkyl, Spiroalkyl 1§

2

Scheme I

In Synthesis and Chemistry of Agrochemicals III; Baker, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1992.

8. ALVARADOETAL.

New Class of Herbicides: Sulfonyl Carboxamides

Imidazolinones of type 1 were prepared by reaction between aminoamides 4 and triethylorthoformate or triethylorthoacetate (Scheme I). This method was used to prepare a major protion of the carboxamides studied in this effort.


From a-Aminosulfonylcarboxamides. A second general method for preparation of sulfonylcarboxamides (Scheme II) involvedreactionof amine salts 5, or the corresponding zwitterions 6, and electrophilic reagents. This reaction was carried out with acid chlorides, carboxylic acid anhydrides, alkyl or arylisocyanates, arylsulfonylisocyanates, and arylsulfonyl chlorides. In general, thereactionoutlined in Scheme II was carried out by the addition of a base to a solution of compound 5 or 6 in a suitable solvent, followed by the addition of an electrophilic reagent. Ri

ArS0 NHCO -j—NHCHO 2

R,

****

ArS0 NHCO-|-NH3%l 2

R

q »

R

1

ArS0 NCO-|-NH3* 2

R

2

Electrophilic Reagent Base Solvent

5

2

6

ArS0 NHCO-|-NHR 2

R

2

7 Ar = Substituted phenyl, 8-quinolinyl Electrophilic Reagents = R-COCI, R-NCO, ArNCO, ArS0 NCO, ArS0 CI 2

2

Scheme II

From Azlactones. Another general method for preparation of sulfonylcarboxamides 3 involved treatment of azlactones 10 (Scheme HI), with arylsuifonylamide sodium salts 11. Azlactones 10 were readily prepared from amino acids 8 via their N-acetyl derivatives 9 using standard literature procedures (5). Azlactones 10 also reacted with other nucleophiles, such as hydrazine, to afford hydrazides 12, which by reaction with an arylsulfonyl chloride gave sulfonyl hydrazides 13. R

i

Ri

H N-LC00H —^2

1 3 , ™ , ^ , , *

2

R I 8

2

EtoN/toluene

^ AcNH-l-COOH , R | 9

D C C

CH Cl2 2

2


77

78

SYNTHESIS AND CHEMISTRY OF AGROCHEMICALS III

NH NH 2

1

? NH -NH-CO-4-NHAc

2

10

•

2

R ArS0 NHNa

2

12

2

1 1

JArS0 CI 2

R

.1

^ r

1

ArS0 NH-CO-J-NHAc

ArS0 NH-NH-CO-j-NHAc R* 2 13

2


R

2

R

2

3 R , R = H, Alkyl 1

2

Scheme III

From N-arylsulfonylhydantoins. An interesting method for preparation of sulfonylcarboxamides 16 from hydantoins 14 was also developed (Scheme IV), and successfully utilized to introduce the modifications of the N-acetyl moiety indicated by reaction of intermediates 15 with nucleophiles. H

H R

'

1

' R

V - 2 + ArS0 CI 2

/

—

•

°Y

N N

N

R

1

R

R

A 2

2

L 0

H

0

ArSOjf

14

1

ArS0 HN-CO-UlH-CO-Nu R 2

15

16 Nu: CH 0-, CH S", NH NH , (CH ) NH 3

3

2

2

3

2

Scheme IV

From Mixed Anhydrides. This general method (Scheme V) involved generation of mixed anhydrides 17 in situ, with subsequent reaction with the sodium salt of an arylsulfonamide 11. . « i i i I * ™ , CIC00R AcNH-4-COOH R

2

9

CO-0-COOR

ArS0 NH*Na

3

+

2

3 R

•

R

1+ 2 AcNH 17

_

11

CO-NH-SO.Ar R ^ R , AcNH 3

Scheme V

Herbicidal Activity While some sulfonyl carboxamides possessed non-selective herbicidal activity, others had selectivity in corn, wheat, barley or rice. These materials had both pre- and postemergence activity, primarily on broadleaf and composite weeds. The latter activity nicely complemented the imidazolinone weed spectrum.


8. ALVARADO ET AL.

New Class of Herbicides: Sulfonyl Carboxamides

Sulfonyl carboxamides possessing the S configuration were found to be solely responsible for both AHAS inhibition and herbicidal activity. The R isomers were totally inactive. This contrasts with the imidazolinone series, wherein the R isomers are 2X to 8X more active than the S isomers both in vivo and in vitro. Structure-Activity Relationships The structure-activity discussion will center on the effects of structure modification of three main regions depicted as A, B and C below.


B

S0 — 2

NH-CO-

NH--CO-R3

Region A. Of phenyl substitution patterns investigated, the most interesting and active were those containing methyl, methoxy or halogen, while other substituents such as branched alkyls, benzoyl and hydroxy yielded analogues with little or no herbicidal activity. Crop safety of the active analogues was influenced by the particular aromatic substitution pattern. Halogen substitution in general enhanced herbicidal activity at the expense of crop selectivity. Alkyl substitution of the aromatic ring afforded compounds having selectivity in the small grain crops. Region B. Of the analogues prepared, the methyl/isopropyl combination was found to be optimal for herbicidal activity. The S -isomer of the methyl/isopropyl combination was the active isomer both against the isolated AHAS enzyme and in whole plants, while the corresponding R -isomer is virtually devoid of activity. Region C. Of the many different substitutions for the acetyl group which were made, none yielded a significant improvement in the level of biological activity. Replacement of the acetyl group with larger aliphatic acyl groups, yielded analogues with equivalent enzymatic activity, but with diminished whole plant activity. Replacement by benzoyl almost abolished the activity, while replacement by methoxycarbonyl or methylcarbamoyl maintained both enzyme and whole plant activity. However, n-butylcarbamoyl substitution afforded an analogue with a potent AHAS inhibitor but was inactive on the whole plant Conclusions The sulfonyl carboxamides are a new class of AHAS inhibiting pre- and postemergence herbicides discovered at the Agricultural Research Division of American Cyanamid Company. Five basic methods for synthesis of the carboxamides have been defined. Structure-activity relationships which define optimum substitution patterns for crop selectivity have been determined.


79

80

SYNTHESIS AND CHEMISTRY OF AGROCHEMICALS ffl

Literature Cited 1. 2. 3.

Alvarado, S. I., U.S. Patent 4,883,914, 1989. Alvarado, S. I., U.S. Patent 4,992,094, 1991. Suda, K.; Hino, F. Chem.Pharm.Bull.,1985,33 (2), 882.


RECEIVED March25,1992


Synthesis and Chemistry of Agrochemicals III - American Chemical

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