[acs symposium series] synthesis and chemistry of agrochemicals volume 355 || synthesis and...

Chapter 3

Synthesis and Herbicidal Activity of Pyridazines Based

on 3-Chloro-4-methyl-6-[m-(trifluoromethyl)phenyl]pyridazine

Dale L. Shaner, Laurine M. Speltz, and Stephen S. Szucs

Agricultural Research Division, American Cyanamid Company, Princeton, NJ 08540

Greenhouse evaluation in a random herbicide screen showed that 3-chloro-4-methyl-6-[m-(trifluoromethyl)phenyl]pyridazine was sufficiently active to serve as a lead for a synthesis project. Related 3-chloropyridazines were prepared by a sequence based on the addition of acyl anion equivalents of substituted benzaldehydes to the appropriately substituted acrylate esters. Using 3-chloropyridazines as key intermediates, a variety of other 3-substituted-pyridazines were prepared. The effect of altering substitution at each position of the pyridazine and phenyl rings on herbicidal activity was examined.

The f i r s t p y r i d a z i n e f o r which p l a n t growth r e g u l a t i n g a c t i v i t y was patented was maleic hydrazide ( 1 ) . Since the i n t r o d u c t i o n of MH i n the l a t e 1940's, at l e a s t four other p y r i d a z i n e s have been developed as h e r b i c i d e s : Pyramin by BASF i n 1962, Kusakira by Sankyo i n 1970, Z o r i a l by Sandoz A. G. i n 1971 and py r i d a t e by Chemie L i n z i n 1976 ( 2 ) .

We f i r s t became i n t e r e s t e d i n p y r i d a z i n e s as h e r b i c i d e s when a number of p y r i d a z i n e s synthesized i n a CNS p r o j e c t at our Lederle d i v i s i o n were evaluated i n our primary h e r b i c i d e screen. One of these compounds, AC 228,764, c o n t r o l l e d eleven of the twelve weed species at 8 kg/ha i n the preemergence t e s t . A l l of the t e s t species were bleached, emerging white from the s o i l . In our secondary e v a l u a t i o n at 4 kg/ha, AC 228,764 c o n t r o l l e d ten out of eleven annual grass and broadleaf weed species w i t h s e l e c t i v i t y i n co t t o n , soybeans and r i c e . This spectrum of a c t i v i t y and crop

C < \ 'CH

AC 228,764

0097-6156/87/0355-0024$06.00/0 © 1987 American Chemical Society

Dow

nloa

ded

by U

NIV

OF

OK

LA

HO

MA

on

Oct

ober

29,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate:

Nov

embe

r 3,

198

7 | d

oi: 1

0.10

21/b

k-19

87-0

355.

ch00

3

In Synthesis and Chemistry of Agrochemicals; Baker, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1987.

3. SHANER ET AL. Synthesis and Activity of Pyridazines 25

s e l e c t i v i t y stimulated s u f f i c i e n t i n t e r e s t to designate the samp l e , 3-chloro-4-methyl-6- [m-( t r i f luoromethy1)phenylJpyridazine, as a lead f o r a synthesis p r o j e c t .

Based on a v a i l a b l e h e r b i c i d e data f o r r e l a t e d Cyanamid p y r i dazines and patented compounds, the f o l l o w i n g s t r u c t u r a l m o d i f i c a t i o n s were proposed: 1) s u b s t i t u t i o n of the c h l o r i n e at the 3-p o s i t i o n ; 2) replacement or d e r i v a t i z a t i o n of the 4-methyl group; 3) i n t r o d u c t i o n of s u b s t i t u e n t s at the 5 - p o s i t i o n ; 4) a l t e r n a t e s u b s t i t u t i o n i n the 6-phenyl r i n g as w e l l as re d u c t i o n to the corresponding c y c l o h e x y l d e r i v a t i v e s and replacement of the phenyl by h e t e r o c y c l e s ; and 5) o x i d a t i o n and q u a t e r n i z a t i o n of the n i t r o gens at p o s i t i o n s 1 and 2.

E s s e n t i a l l y every analog and d e r i v a t i v e prepared i n the proj e c t was u l t i m a t e l y derived from the corresponding 3 - c h l o r o - p y r i -dazine. With the exception of a few 3-ch l o r o p y r i d a z i n e s which o r i g i n a t e d from a F r i e d e l - C r a f t s a c y l a t i o n of benzene, the large m a j o r i t y of c h l o r o p y r i d a z i n e s were prepared by a sequence based on the a d d i t i o n of the masked a c y l anion equivalent of a benzaldehyde to the a p p r o p r i a t e l y s u b s t i t u t e d a c r y l a t e e s t e r .

a. £-TsOH, morpholine, THF b. KCN, H 20 c. R5CH=CHR4COOR, NaOMe, THF d. 70% HOAc e. N 2H 4-H 20, EtOH, ^ 0 f. B r 2 , g l HOAc g. P O C I 3

This procedure has p r e v i o u s l y been reported by Lederle chemists O, 4) and was used to prepare our o r i g i n a l screening sample. For preparing a s e r i e s of s u b s t i t u t e d phenyl analogs, the choice of benzaldehyde f i x e d the p o s i t i o n of the s u b s t i t u e n t and the choice of an a l k y l - or a r y l - s u b s t i t u t e d a c r y l a t e f i x e d the s u b s t i t u t i o n i n the 4- and/or 5 - p o s i t i o n . A l l intermediates i n t h i s sequence were r o u t i n e l y tested i n our h e r b i c i d e screens, but very few of these, i n c l u d i n g the dihydropyridazinones and the pyridazinones, showed any s i g n i f i c a n t a c t i v i t y .

Dow

nloa

ded

by U

NIV

OF

OK

LA

HO

MA

on

Oct

ober

29,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate:

Nov

embe

r 3,

198

7 | d

oi: 1

0.10

21/b

k-19

87-0

355.

ch00

3


26 SYNTHESIS AND CHEMISTRY OF AGROCHEMICALS

In a d d i t i o n to being evaluated i n t h e i r own r i g h t f o r comparison w i t h the lead, the 6 - ( s u b s t i t u t e d - p h e n y l ) - 3 - c h l o r o -p y r i d a z i n e s (R-Cl) were als o used as key intermediates f o r p r e paring analogs c o n t a i n i n g other s u b s t i t u e n t s i n the 3 - p o s i t i o n . Displacement by a v a r i e t y of a l k o x i d e s and amines gave the c o r r e s ponding 3-alkoxy- and 3-mono- or d i s u b s t i t u t e d a m i n o p y r i d a z i n e s . Hydrogenolysis over 10% palladium on carbon i n ethanol c o n t a i n i n g ammonium hydroxide gave the corresponding 3-hydro analog. For those p y r i d a z i n e s c o n t a i n i n g a phenyl group bearing a halogen or c e r t a i n o r t h o - s u b s t i t u e n t s , the 3-chloropyridazine was e i t h e r hy-drogenated over 10% palladium on carbon i n g l a c i a l a c e t i c a c i d or was converted to the 3-thiomethyl analog using a sodium mercaptide s a l t f o r subsequent Raney n i c k e l d e s u l f u r i z a t i o n .

R-Y (Y=F, I)

R-H R-OR R-NR'R"

6-CYCLOHEXYLPYRIDAZINES PYRIDAZINE N-OXIDES PYRIDAZINIUM SALTS

S i m i l a r l y when a displacement of a 3-chloropyridazine by ammonia or c e r t a i n a l k y l - s u b s t i t u t e d amines proceeded very slowly or r e s u l t e d i n very low y i e l d s , other 3-halopyridazines were used. The 3-iodopyridazines were prepared by heating the corresponding 3 - c h l o r o p y r i d a z i n e s with sodium iodide and h y d r i o d i c a c i d i n r e -f l u x i n g 2-butanone. The 3-bromopyridazines were prepared from the corresponding 3(2H)-pyridazinones by heating with phosphorous oxy-bromide. The 3 - f l u o r o p y r i d a z i n e s were prepared from the c o r r e s ponding 3-chloro intermediates by heating with potassium f l u o r i d e i n s u l f o l a n e at 190-200° (!5, 6).

A number of p y r i d a z i n e s were s e l e c t e d for f u r t h e r d e r i v a -t i z a t i o n based on t h e i r h e r b i c i d a l a c t i v i t y . P y r i d a z i n e s cont a i n i n g methoxy, substituted-amino, c h l o r o , and hydrogen i n the 3-p o s i t i o n were s e l e c t i v e l y reduced using platinum oxide i n t r i -f l u o r o a c e t i c a c i d to y i e l d the corresponding 6-cyclohexyl d e r i v a t i v e s ( 7 ) . Selected analogs were a l s o o x i d i z e d i n the 1-and/or 2-p o s i t i o n s using meta-chloroperbenzoic a c i d (8) and were quater-nized w i t h methyl iodide i n r e f l u x i n g a c e t o n i t r i l e (9) to

Dow

nloa

ded

by U

NIV

OF

OK

LA

HO

MA

on

Oct

ober

29,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate:

Nov

embe

r 3,

198

7 | d

oi: 1

0.10

21/b

k-19

87-0

355.

ch00

3



y i e l d the corresponding p y r i d a z i n e N-oxides and p y r i d a z i n i u m s a l t s .

For the purpose of comparing the pre- and postemergence data acquired i n a v a r i e t y of t e s t s over a two-year p e r i o d , the h e r b i c i d a l a c t i v i t y was expressed as an "averaged r a t i n g " over a spectrum of eight annual grass (Echinochloa c r u s - g a l l i , D i g i t a r i a spp., P h a l a r i s spp., S e t a r i a v i r i d i s and Avena fatua) and broad-l e a f (Ipomoea spp., B r a s s i c a kaber, and Sida spinosa) weed species common to most of the t e s t s . This averaged r a t i n g was determined f o r each pyr i d a z i n e by summing the r a t i n g given to each of the s e l e c t e d weed species and d i v i d i n g by the number of weeds t e s t e d , t y p i c a l l y e i g h t . The r a t i n g scale used i n the h e r b i c i d e e v a l u a t i o n ranged from zero, as observed by no e f f e c t r e l a t i v e to the c o n t r o l p l a n t , to nine, i n d i c a t i n g the death of the p l a n t .

Figure 1 compares the averaged r a t i n g s at 1 kg/ha of the lead p y r i d a z i n e (R^=C1) with other analogs s u b s t i t u t e d i n the 3-p o s i t i o n . The 3-hydro analog not only c o n t r o l l e d a l l species preemergence but a l s o had a higher l e v e l of postemergence a c t i v i t y . Although the 3-aminopyridazine had no detectable a c t i v i t y at 1 kg/ha, the dimethylamino analog gave preemergence c o n t r o l comparable to that of the 3-hydro analog and s i g n i f i c a n t l y increased the l e v e l of postemergence a c t i v i t y . The 3-methoxy analog a l s o showed higher l e v e l s of both pre- and postemergence a c t i v i t y i n comparison w i t h the lead. As a r e s u l t of these f i n d i n g s , a l l 3 - c h l o r o p y r i d a z i n e s c o n t a i n i n g s u b s t i t u t i o n i n the 6-phenyl r i n g were r o u t i n e l y converted to the 3-hydro, 3-dimethyl-amino, and 3-methoxy analogs.

One of the most i n t e r e s t i n g comparisons to evolve i n the p r o j e c t i n terms of a c t i v i t y and economics was the e f f e c t of changing s u b s t i t u e n t s at the 3 - p o s i t i o n f o r analogs c o n t a i n i n g an u n s u b s t i t u t e d phenyl group i n the 6 - p o s i t i o n (Figure 2). 3-Chloro-4-methyl-6-phenylpyridazine (R^=C1) gave the same l e v e l of weed c o n t r o l as the m-trifluoromethylphenyl lead. I n t e r e s t i n g l y , the 3-hydro analog d i d not produce the marked increase i n a c t i v i t y , p a r t i c u l a r l y i n the preemergence a p p l i c a t i o n as was observed f o r the m-trifluoromethylphenyl analog. However the same s i g n i f i c a n t increase i n a c t i v i t y i n both pre- and postemergence a p p l i c a t i o n s was observed for the unsubstituted-phenyl 3-methoxy and 3-dimethylaminopyridazines. The 3-methylaminopyridazine was n e a r l y as a c t i v e as the dimethylamino analog but the removal of the methyl s u b s t i t u t i o n (3-NH 2) or homologation (3-NHEt) r e s u l t e d i n a s i g n i f i c a n t r e d u c t i o n i n a c t i v i t y .

The most a c t i v e p y r i d a z i n e of the group was the 3-methoxy analog, AC 247,909. L i k e most of the a c t i v e p y r i d a z i n e analogs, preemergence a p p l i c a t i o n of AC 247,909 caused bl e a c h i n g . As the most a c t i v e postemergence p y r i d a z i n e h e r b i c i d e , AC 247,909 caused r a p i d n e c r o s i s , suggesting a p o t e n t i a l use as a contact-type h e r b i c i d e . As i n the 3-amino s e r i e s , an extension of the a l k y l c h a i n r e s u l t e d i n the l o s s of a c t i v i t y . Besides methyl, other s u b s t i t u e n t s introduced at the 3 - p o s i t i o n included a l k y l s u l f o n y l , cyano, carboxy, and amido. These p y r i d a z i n e s were i n a c t i v e at 1 kg/ha and i n some cases at 8 kg/ha.

The e f f e c t of s u b s t i t u t i o n at the 4- and 5 - p o s i t i o n s r e l a t i v e to AC 247,909 i s summarized i n Figure 3. Removal of the 4-methyl

Dow

nloa

ded

by U

NIV

OF

OK

LA

HO

MA

on

Oct

ober

29,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate:

Nov

embe

r 3,

198

7 | d

oi: 1

0.10

21/b

k-19

87-0

355.

ch00

3


00

PR

E

PO

ST

< z < o z I- <

4

2 -

o a.

Q.

CI

Figu

re 1

.

I B

r H

N

H,

NM

e2

SMe

OM

e

Herb

icid

al A

ctiv

ity

of 4

-Met

hy1-

6-Tm

-Ctr

iflu

oro

me th

y1)p

heny

l1py

rida

zine

s Su

bsti

tute

d in th

e 3-

Posi

tion

i s g 55

> z w » o > o w

>

Dow

nloa

ded

by U

NIV

OF

OK

LA

HO

MA

on

Oct

ober

29,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate:

Nov

embe

r 3,

198

7 | d

oi: 1

0.10

21/b

k-19

87-0

355.

ch00

3


PR

E P

OS

T

Lead

C

I I

F H

N

H2

NH

Me

NM

e2

NH

Et

OM

e O

Et

Me

Figu

re 2.

He

rbic

idal

Act

ivit

y of

4-M

ethy

l-6-

phen

ylpy

rida

zine

s Su

bsti

tute

d in th

e 3-

Posi

tion

Dow

nloa

ded

by U

NIV

OF

OK

LA

HO

MA

on

Oct

ober

29,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate:

Nov

embe

r 3,

198

7 | d

oi: 1

0.10

21/b

k-19

87-0

355.

ch00

3


PR

E P

OS

T

< x o z <

4 -

R5

«4

in

R4:

Me

H

H

Me

Et

CH

2O

Me

CH

2C

OO

Me

CH

2N

Me

2 C

H2P

h P

h

R5:

H

H

Me

Me

H

H

H

H

H

H

Figu

re 3

. He

rbic

idal

Act

ivit

y of

3-M

etho

xy-6

-phe

nylp

yrid

azin

es

Subs

titu

ted

in th

e 4-

and

5-P

osit

ions

X

w

g >

Dow

nloa

ded

by U

NIV

OF

OK

LA

HO

MA

on

Oct

ober

29,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate:

Nov

embe

r 3,

198

7 | d

oi: 1

0.10

21/b

k-19

87-0

355.

ch00

3


SHANER ET AL. Synthesis and Activity of Pyridazines 31

group r e s u l t e d i n poor h e r b i c i d a l a c t i v i t y at 2 kg/ha. Movement of the methyl from the 4- to the 5 - p o s i t i o n r e s u l t e d i n a s u b s t a n t i a l r e d u c t i o n i n a c t i v i t y , but the i n t r o d u c t i o n of a second methyl group at R_ r e s u l t e d i n a h e r b i c i d a l response n e a r l y i d e n t i c a l to that of ACT 247,909. Comparisons at lower rates showed that the 4,5-dimethyl analog was somewhat l e s s a c t i v e . This s l i g h t l y diminished a c t i v i t y f o r the 4,5-dimethyl analog was also observed i n the p a r a l l e l comparison between 3-dimethylaminopyridazines.

D e r i v a t i z a t i o n of the methyl group at g e n e r a l l y r e s u l t e d i n a s i m i l a r spectrum of weed c o n t r o l , but at lower l e v e l s of a c t i v i t y . Some examples include the e t h y l , methoxymethy1, c a r -bomethoxymethyl and dimethylaminomethyl. S u b s t i t u t i o n a t R, by be n z y l , phenyl, or t - b u t y l r e s u l t e d i n a complete l o s s of ner-b i c i d a l a c t i v i t y at 2 kg/ha.

The e f f e c t of monosubstitution i n the phenyl r i n g of se l e c t e d 3-methoxypyridazines i s shown i n Figure 4. In general subs t i t u e n t s i n the 6-phenyl r i n g decreased the l e v e l of a c t i v i t y across a spectrum of weeds i n the order meta _̂ ortho > para.

Both pre- and postemergence data from the monosubstituted phenyl analogs were evaluated using the Hansch 3X r e g r e s s i o n a n a l y s i s program. S i g n i f i c a n t equations were generated f o r the meta-substituted analogs. A high degree of c o r r e l a t i o n of both pre- and postemergence a c t i v i t y was obtained f o r a r e p r e s e n t a t i v e grass and broadleaf weed species as a f u n c t i o n of the independent v a r i a b l e s 11 and B^. Across a spectrum of weed species, none of the two dozen monosubstituted phenyl or the nine d i s u b s t i t u t e d phenyl analogs exceeded the a c t i v i t y , and c e r t a i n l y the cost e f f i c a c y , of the u n s u b s t i t u t e d phenyl analog, AC 247,909.

3 Wild Oats Preemergence: log (MW/EDoc) = 2.48 (+0.52) + 0.71 (+0.40) * - 0.34 (+0.22)

8 5 - - 9 n = 11 R 2 = 0.70 B 4

Postemergence: log (MW/EDg5) = 2.55 (+0.47) + 0.71 (+0.36) TT - 0.30 (+0.20) B 4

n = 10 R 2 = 0.76 Morningglory Preemergence log (MW/EDg5) = 2.08 (+0.40) + 0.59 (+0.30) * - 0.18 (+0.17) B 4

n = 11 R 2 = 0.72 Postemergence: log (MW/EDg5) = 2.88 (+0.36) + 0.45 (+0.28) * - 0.35 (+0.16) B 4

n = 11 R 2 = 0.78 where ED was the lowest estimated dose required to o b t a i n a r a t i n g or e i g h t .

Dow

nloa

ded

by U

NIV

OF

OK

LA

HO

MA

on

Oct

ober

29,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate:

Nov

embe

r 3,

198

7 | d

oi: 1

0.10

21/b

k-19

87-0

355.

ch00

3


SYNTHESIS AND CHEMISTRY OF AGROCHEMICALS

5

2 i E 0 1 o

0 1 o

u a.

a E

»sod[

V H / O J I I JL V O N I l V d

Dow

nloa

ded

by U

NIV

OF

OK

LA

HO

MA

on

Oct

ober

29,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate:

Nov

embe

r 3,

198

7 | d

oi: 1

0.10

21/b

k-19

87-0

355.

ch00

3



The s t r u c t u r e - a c t i v i t y r e l a t i o n s h i p developed for subs t i t u e n t s i n the 6-phenyl r i n g i n the 3-methoxy s e r i e s was p a r a l l e l e d i n the 3-chloro and 3-dimethylamino s e r i e s but not i n the 3-hydro s e r i e s (Figure 5). Conversion of AC 247,909 to i t s 2-oxide r e s u l t e d i n a r e d u c t i o n of preemergence a c t i v i t y and a complete l o s s of post a c t i v i t y at 1 kg/ha. S i m i l a r l y , l o s s of both pre and post a c t i v i t y was observed f o r the 2-oxides of both the 3* chloro-and the 3-hydrogen p y r i d a z i n e s r e l a t i v e to t h e i r r e s p e c t i v e parent p y r i d a z i n e s . Although m-trifluoromethy1 s u b s t i t u t i o n i n the phenyl of the 3-methoxypyridazine r e s u l t e d i n lower a c t i v i t y both pre and post, m-trifluoromethy1 s u b s t i t u t i o n i n the 3-hydro-p y r i d a z i n e r e s u l t e d i n a l e v e l of preemergence a c t i v i t y e q u i v alent to that of AC 247,909. This was unusual since very few of the 3-hydropyridazines showed a c t i v i t y at 4 kg/ha w i t h phenyl subs t i t u e n t s other than m-trifluoromethy1. Furthermore, instead of reducing a c t i v i t y as was observed f o r the 3-methoxy- and 3-chloro-p y r i d a z i n e s , o x i d a t i o n at the 2-nitrogen r e s u l t e d i n improved preemergence a c t i v i t y over that of AC 247,909. In a d d i t i o n , greenhouse t e s t s i n d i c a t e d that the 2-oxide AC 252,588 was s e l e c t i v e preemergence i n c o t t o n at 2 kg/ha.

< ) - 0 C H 3 •( X >

\ H C F / \ H 3 3 3

AC 247,909 AC 252,588 Two f i e l d candidates emerged from the synthesis p r o j e c t . AC

247,909 had both postemergence n o n - s e l e c t i v e a c t i v i t y and preemergence a c t i v i t y with s e l e c t i v i t y i n sunflowers. AC 252,588 had preemergence annual grass and broadleaf a c t i v i t y w i t h e x c e l l e n t s e l e c t i v i t y i n cotton. In the greenhouse, AC 252,588 was found to be more a c t i v e than Cotoran. In comparison w i t h Z o r i a l , AC 252,588 was two to three times l e s s a c t i v e across a spectrum of weeds but showed a greater margin of s e l e c t i v i t y i n c o t t o n at the rate necessary f o r weed c o n t r o l .

Both compounds were f i e l d t ested at a number of l o c a t i o n s . The l e v e l of a c t i v i t y observed i n the f i e l d t r i a l s , however, was not s u f f i c i e n t to warrant continued e v a l u a t i o n . Subsequent greenhouse t e s t i n g suggested that the f a i l u r e of AC 247,909 to perform i n the f i e l d may be due to photodecomposition i n postemergence t e s t s and to s o i l metabolism and v o l a t i l i t y i n preemergence t e s t s .

Although the synthesis program d i d not r e s u l t i n any commercial h e r b i c i d e s , two types of p y r i d a z i n e s were discovered which produced unexpected r e s u l t s , both i n the l e v e l and the type of a c t i v i t y . The f i r s t s e r i e s , which includes the 3-methoxy- and the 3-dimethylaminopyridazines, r e s u l t e d i n a high l e v e l of p o s t -emergence a c t i v i t y not observed i n the lead or i n the other 3-sub-s t i t u t e d - p y r i d a z i n e s . Secondly, based on a comparison with the N-oxides of other p y r i d a z i n e s , the N-oxide of the 3-hydropyridazine r e s u l t e d i n unexpectedly high preemergence a c t i v i t y , yet without p h y t o t o x i c i t y to c o t t o n .

Dow

nloa

ded

by U

NIV

OF

OK

LA

HO

MA

on

Oct

ober

29,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate:

Nov

embe

r 3,

198

7 | d

oi: 1

0.10

21/b

k-19

87-0

355.

ch00

3


SYNTHESIS AND CHEMISTRY OF AGROCHEMICALS

C O X E

O

I O I

z o

I o s o

2 o

X OC 01

V H / 9 * I I V 9 N I 1 V U

Dow

nloa

ded

by U

NIV

OF

OK

LA

HO

MA

on

Oct

ober

29,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate:

Nov

embe

r 3,

198

7 | d

oi: 1

0.10

21/b

k-19

87-0

355.

ch00

3


3. SHANER ET AL. Synthesis and Activity of Pyridazines

Several 3-alkoxy-4-methyl-6-phenylpyridazines, one of which is AC 247,909, have subsequently been disclosed as selective herbicides (10_). A patent covering novel pyridazines and pyridazine N-oxides has been assigned to American Cyanamid (11).

Acknowledgments

The authors acknowledge the following individuals who contributed to the synthesis and herbicide evaluations: R. L. Arotin, C. E. Augelli, R. E. Diehl, M. A. Guaciaro, A. W. Lutz, P. A. Odorisio, J. J. Pascavage, H. W. Turpenen, K. Umeda, B. L. Walworth, and D. L. Whitehead.

Literature Cited

1. Worthing, C. R., Ed. The Pesticide Manual; The British Crop Protection Council: Croydon, England, 1983.

2. Fletcher, W. W.; Kirkwood, R. C. Herbicides and Plant Growth Regulators; Granada Publishing Limited: London, 1982; Chapter 1.

3. Albright, J. D.; McEvoy, F. J.; Moran, D. B. J. Heterocyclic Chem. 1978, 15, 881.

4. McEvoy, F. J.; Albright, J. D. J. Org. Chem. 1979, 44, 4597. 5. Finger, G. C.; Starr, L. D.; Dickerson, D. R.; Gutowsky, H.

S.; Hamer, J. J. J. Org. Chem. 1963, 28, 1666. 6. Finger, G. C.; Kruse, C. W. J. Amer. Chem. Soc. 1956, 78,

6034. 7 Vierhapper, F. W.; Eliel, E. L. J. Org. Chem. 1975, 40, 2729. 8. Leclerc, G.; Wermuth, C. G. Bull. Soc. Chim. Fr. 1971, 1752. 9. Lund, H.; Lunde, P. Acta Chem. Scand. 1967, 21, 1067.

10. Jpn. Kokai Tokkyo Koho JP 59 01,469 [84 01,469]; Chem. Abstr. 1984, 101, 130699z.

11. Speltz, L. M.; Walworth, B. L. U.S. Patent 4 623 376, 1986.

RECEIVED September 8, 1987

Dow

nloa

ded

by U

NIV

OF

OK

LA

HO

MA

on

Oct

ober

29,

201

4 | h

ttp://

pubs

.acs

.org

P

ublic

atio

n D

ate:

Nov

embe

r 3,

198

7 | d

oi: 1

0.10

21/b

k-19

87-0

355.

ch00

3


[acs symposium series] synthesis and chemistry of agrochemicals volume 355 || synthesis and...

Documents