Synthesis and Chemistry of Agrochemicals - ACS Publications

Chapter 7 α-Trichloroethylstyrene

Oxides

A New Class of Grass Herbicides 1

1

1

L. D. Markley , E. J. Norton,L. L. Smith, Jr. , and P. S. Zorner

2

1

Dow Chemical Company, Midland, MI 48674 Dow Chemical Company, Walnut Creek, CA 94598

Downloaded by UNIV LAVAL on May 9, 2016 | http://pubs.acs.org Publication Date: November 3, 1987 | doi: 10.1021/bk-1987-0355.ch007

2

Tridiphane, the active ingredient in Dow's new herbicide, TANDEM , is being developed for postemergent grass and broadleaf control in corn. When used in combination with triazine herbicides such as atrazine, it enhances their weed activity by decreasing the rate of glutathione conjugation. Tridiphane is a member of a unique class of α-trichloroethylstyrene oxides discovered by The Dow Chemical Company. The synthesis and herbicidal activity of this group of compounds will be reviewed.

Tridiphane, 2-(3,5-dichlorophenyl)-2-(2,2,2-trichloroethyl)oxirane, ^ is the active ingredient in Dow's new herbicide, TANDEM, which is being developed for postemergent weed control in corn. The material is the outgrowth of many years of research in The Dow Chemical Company in the o

Tridiphane

area of a-trichloroethylstyrenes and their epoxides as potential herbicides. The project had its beginning in Dow in the early sixties when by random 0097-6156/87/0355-0074$06.00/0 © 1987 American Chemical Society

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

7. MARKLEYETAL.

a-Trichlorotthylstyrtnt Oxides

75


screening, a-(2,2,2-trichloroethyl)styrene, 2, was shown to possess good levels of preemergent herbicidal activity, most effective on grass weeds(1).

CCI

3

It is of historical interest to note that M.S. Kharasch and co-workers (2) h a d previously reported preparing 2_ in their pioneering studies of the addition of halogenated hydrocarbons to olefins. In this case ( S c h e m e I), Kharasch a d d e d bromotrichloromethane to a-methylstyrene with either light or acetyl peroxide as the free-radical initiator, a n d under the reaction conditions elimination of hydrogen bromide o c c u r r e d , resulting in the formation of a-(2,2,2-trichloroethyl) styrene 2. T h e light or peroxide-initiated SCHEME 1 Br

2

additions were often limited in that poor yields of one-to-one adducts were obtained a n d cheaper raw materials such as c a r b o n tetrachloride gave considerably lower yields than the c o r r e s p o n d i n g brominated materials.


76

SYNTHESIS AND CHEMISTRY OF AGROCHEMICALS

In the early sixties, a redox catalyst system for the addition of halogenated hydrocarbons to olefins was discovered at Dow (3). T h e addition was carried out in the presence of a mixture of cuprous chloride a n d an amine such as piperidine or cyclohexylamine (Scheme II). Essentially quantitative yields of the one-to-one adducts could be obtained a n d the new catalyst system worked as well with c a r b o n tetrachloride as bromotrichloromethane. Independently, M. Asscher and D. Vofsi (4) found a similar catalyst system.


S c h e m e II

2 W i t h the discovery in Dow that 2_ possessed good herbicidal activity, a series of aromatic-substituted analogs were prepared a n d tested. In general o n e could c o n c l u d e from this work that the meta-substituted analogs were the most active, while the c o r r e s p o n d i n g ortho-substituted derivatives were

x essentially inactive and the para-substituted ones were intermediary. Three of the best c o m p o u n d s included the m-nitro $ m-trifluoromethyl 4_and m-chloro 5 derivatives.


7. MARKLEYETAL.

a-Trichlorotthylstyrtnt Oxidts


3

77

4

5

A g r e e n h o u s e c o m p a r i s o n of preemergent grass weed activity of these c o m p o u n d s is given in Table I. In addition, their effect on corn and s o y b e a n s at s o m e w h a t higher rates is included as a measure of crop selectivity. TABLE I Preemergent Herbicidal Activity

Barnyard Grass

% Crabgrass

W e e d Control* Yellow Johnson Foxtail Grass

X/lbs/Acre

1.0 0.50

1.0

1.0 0.50

H

50

40

80

40

99

95

100

100

0

0

95

90

9 5 90

90

90

95

95

100 95

N0 CF CI

3

2

0.50

8 0 70 0

0

1.0 0.50

Corn

Soybean

2

1

2

1

80

80

90

85

0

0

0

0

0

0

0

0

100 100

50

0

0

0

90

95

85

50

30

90

'Ratings were made two weeks after application

O n e can see from these results that the original lead, 2± is considerably less active than the three substituted analogs with the exception of its highly injurious effect on corn. The m-nitro-a-(2,2,2-trichloroethyl) styrene_3 was quite safe on c o r n , however, its s p e c t r u m of weed activity was quite narrow. m-Chloro-a(2,2,2-trichloroethyl) styrene_5 has been field tested a n d s h o w n to provide g o o d annual grass control and upon incorporation in the soil also inhibits yellow nutsedge by destroying the growing points of this difficult-to-control perennial weed (5). Over the years a general laboratory procedure as outlined in S C H E M E III has been developed for the preparation of the desired a-(2,2,2-trichloroethyl)


78


styrenes. As s h o w n , t h e needed a-methylstyrenes c a n b e prepared by classical routes involving Grignard chemistry a n d dehydration of t h e 3° carbinol is accomplished with catalytic amounts of strong acids such as ptoluenesulfonic acid. T h e addition of carbon tetrachloride or bromotrichloromethane to t h e subsitited a-methylstyrene has remained essentially the s a m e as first discovered. T h e final step involves elimination of hydrogen chloride or bromide a n d in many cases c a n be accomplished using catalytic a m o u n t s of cuprous chloride a n d heat. Lewis acids such as antimony pentachloride have also been used.(6).


S C H E M E III

General Procedure for Synthesis of (a-2,2,2-trichloroethyl) styrenes CH

3

OH

CH

3


7. MARKLEYETAL.

79

a-Trichlorotthyktyrtnt Oxides

Discussions between Dow chemists a n d biologists concerning the m o d e of action of this unique class of herbicides led to the synthesis and screening of 2-phenyl-2-(2,2,2-trichloroethyl)oxirane, & The epoxide w a s f o u n d to be twice as active as the olefin, 2, w h e n applied preemergently and t h e type of activity of t h e t w o materials were similar (7). A series of


cci

3

aromatic substituted -phenyl epoxides were prepared a n d again t h e metasubstituted derivatives were t h e most active herbicides while the orthosubstituted analogs h a d little activity. T h e para-substituted c o m p o u n d s were of intermediary activity (8). It w a s later shown that t h e olefins are oxidized in plant tissue to t h e epoxides. Greenhouse c o m p a r i s o n s of t h e most active epoxides_7-9_as well as 6_are given in TABLE II. As shown t h e epoxides

CCI3

> have greater herbicidal activity than their corresponding olefins in TABLE I, however, more crop damage, especially to c o r n , is also exhibited by the oxiranes. Under field conditions, the m-trifluoromethyl 8.and m-chloro 9. epoxides were s h o w n to effectively control grass weeds at application rates w h e r e soybeans were quite tolerant.

7

8

_9



80

TABLE II Preemergent Herbicidal Activity


% Barnyard Grass X/lbs/Acre 0.50 H N0 CF CI

2

3

0.25

Crabgrass 0.50

0.25

W e e d Control* Yellow Johnson Foxtail Grass

Corn

Soybean

0.50 0.25 0.50 0.25

2

1

2

98

1

98

90

90

20

95

60

25

15

97

20

40

0

95

30

0

0

50

0

50 40

0

10 0

95

95

100

95

95

95

95

95

100 95

50

40

95

95

100

95

85

75

90

90

90 85

60

40


T h e epoxides were prepared from the corresponding olefins either by oxidation with various peracids s u c h as peracetic acid or m-chloroperbenzoic acid or in a two-step procedure via the halohydrin ( S C H E M E IV). T h e direct epoxidation procedure is preferred due to the generally low yields of halohydrins obtained in the second m e t h o d . The halohydrins are active herbicides and will be discussed in a future publication (9).

S C H E M E IV Preparation of Epoxides

X2—Br2,Cl2


7. MARKLEYETAL.

81

a-Trichlorotthylstyrtnt Oxidts


Since the meta-substituted epoxides were the most active herbicides, we next chose to look at the 3,5-disubstituted c o m p o u n d s . T h e first c o m p o u n d prepared was the 3,5-dichloro derivative, tridiphane, T. Its precursor, a(2,2,2-trichloroethy 1)-3,5-dichlorostyrene, showed very little preemergent

activity while tridiphane possessed excellent levels of activity and m u c h to our surprise was safe on both corn and soybeans. As can be seen in TABLE III, tridiphane performs at rates in the greenhouse comparable to standards such as alachlor a n d trifluralin. TABLE III Preemergent Herbicidal Activity

% Barnyard Grass

Crabgrass

Weed Yellow Foxtail

Control* Johnson Grass

Herb/lbs/A .125 .0625 .125 .0625

.125 .0625 .125 .0625

Tridiphane

98

85

100

70

100

100

100

98

Alachlor

70

60

80

20

100

95

70

30

Trifluralin

75

60

98

35

98

25

80

20

Corn 2

Soybean

1

2

1

0

0

0

0

0

0

0

0

0

0

50 35


With the discovery that the 3,5-dichloro analog was very active (10), a variety of 3,5-disubstituted c o m p o u n d s were prepared and tested. The 3,5-dimethyl epoxide 10 exhibited g o o d activity in the greenhouse but under field conditions did not give season-long weed control while the 3-chloro-5-fluoro derivative 11^ was somewhat more active than tridiphane.

10

11



82


Tridiphane was field tested for several years as a preemergent grass herbicide for corn a n d soybeans. Even t h o u g h it performed well in c o m p a r i s o n to standards such as alachlor, it was d e c i d e d that in order to c o m p e t e in the mature corn herbicide market we would have to offer the grower a truly unique product. T h e discovery that tridiphane could synergize triazine herbicides postemergently c a m e at a most o p p o r t u n e t i m e a n d was m a d e initially in the field as o p p o s e d to the greenhouse. In the field test, tridiphane a n d atrazine were applied separately to 3-4 leaf grass w e e d s and to corn a n d the two materials were also applied in c o m b i n a t i o n (TABLE IV). From greenhouse testing it was known that tridiphane inhibited the growth of w e e d s w h e n applied postemergently, however, in time the w e e d s would regrow. It was also not surprising to find atrazine ineffectual on grass w e e d s in as m u c h as it is used for broadleaf w e e d control. It was surprising to see the dramatic synergistic effect w h e n the two materials were applied in c o m b i n a t i o n .

T A B L E IV Postemergent Field Test

%

Treatment/lbs/Acre Tridiphane

0.50

Atrazine Tridiphane a n d Atrazine

0.5 + 1.0 + 2.0 +

Weed

Control*

Barnyard Grass

Johnson Grass

Corn

0

7

0

1.0

39

20

0

2.0

44

65

7

1.0

0

0

0

2.0

47

33

0

1.0 1.0 1.0

76 90 98

32 93 95

0 0 3

• R a t i n g s w e r e m a d e 4 w e e k s after application With this discovery, intensive work was carried out in both the g r e e n h o u s e a n d field to better define the breadth of the s y n e r g i s m . It was found that the tridiphane-triazine c o m b i n a t i o n was effective in controlling not only grassy w e e d s but broadleaf w e e d s as well — including velvetleaf, a broadleaf w e e d atrazine alone d o e s not control effectively. Laboratory studies have s h o w n that tridiphane slows d o w n the rate of glutathione conjugation of atrazine in giant foxtail, the major route of detoxification of triazine herbicides in foliar tissue (11) as shown in T A B L E V (12,13).


7. MARKLEY ET AL. Cl Ν I EtNH

2^

83

a-Trichloroethylstyrene Oxides SG Ν I

GST +GSH

N ^ N H- {

N < ^ N I I

• EtNH ^

Atrazine

Ν^

NH - (

Glutathione Conjugate

TABLE V


Detoxification of Atrazine in Giant Foxtail % Atrazine R e m a i n i n g in Leaf After Application T i m e (Hrs)

Atrazine

Tridiphane + Atrazine

6

80

86

24

50

72

72

28

73

T h e major route of detoxification of tridiphane in corn has also been s h o w n to be glutathione conjugation.

Glutathione Conjugate GSH = y - G l u - C y s - G l y GST = Glutathione-S-transferase Enzyme

W e have synthesized the glutathione conjugate of tridiphane and s h o w n it to be inactive as a herbicide; however, G. L. L a m o u r e u x and D. G. R u s n e s s (14,15) have found it to be an effective inhibitor of atrazine glutathione conjugation in vitro. Tridiphane is a unique molecule in m a n y ways. It is certainly not a typical epoxide in its chemical reactivity. As s h o w n in S C H E M E V, it can be heated in glacial acetic acid at 1 0 0 ° C for eight hours with little or no change.


84



SCHEME V Reactions of Tridiphane

12

13

O n e c a n open the epoxide, however, by treating it with s o d i u m acetate in acetic acid at 8 5 ° C for 48 hours and obtain the gylcol acetate, 12, in quantitative yield. Treatment of tridiphane with one equivalent of s o d i u m m e t h o x i d e in methanol at room t e m p e r a t u r e causes hydrogen chloride elimination and formation of the vinyl epoxide, 13, w h i c h has little herbicidal activity. In contrast to s o d i u m methoxide, s o d i u m methylthiolate readily o p e n s the epoxide ring giving the /Mhioalcohol, 14 in quantitative yield. M a n y related c o m p o u n d s have been synthesized and tested at Dow both as herbicides a n d triazine synergists. Replacement of one of the chlorines in the trichloromethyl group with other substituents as s h o w n below

cci -x 2

CI X = H, C H , CN, C O N H , C 0 E t , C O C H , C F , etc. 3

2

2

3

3

resulted in c o m p o u n d s with varying levels of herbicidal activity. It was d i s a p p o i n t i n g , however, to find that none of the c o m p o u n d s were as effective as tridiphane in synergizing atrazine. Replacement of one of the


T. MARKLEYETAL.

85

a-Trichloroethylstyrene Oxides


h y d r o g e n s on the unsubstituted carbon in the epoxide ring as in 15 or on the c a r b o n adjacent to the trichloromethyl g r o u p as in 16 with either a chlorine or a methyl g r o u p resulted in c o m p o u n d s devoid of herbicidal

15

16 Ζ = CI, C H

3

activity. S o m e of the most active herbicidal analogs of tridiphane m a d e w e r e heterocyclic derivatives as s h o w n below.

17

M a n y pyridine c o m p o u n d s as well as primidines were synthesized and s c r e e n e d . T h e most active material is the direct pyridine analog, 17, w h i c h possessed activity equivalent to tridiphane. (16). T h e success of the project is d u e in part to the extraordinary efforts of m a n y Dow scientists. Synthetic chemists w h o have m a d e m a n y of the c o m p o u n d s include Κ. E. Arndt, D. L. Decker, L. D. Markley, S. D. M c G r e g o r , L. R. Morris, E. J . Norton, T. M. Ozretich, R. G. Pews, J . M. R e n g a , R. B. Rogers and J . M. Soper. Early-stage g r e e n h o u s e biologists including B. C. Gerwick, T. W . H o l m s e n , P. G. Ray, L. L. Smith, Jr. a n d P. S. Zorner have evaluated the materials as herbicides as well as d e t e r m i n e d the basis for the tridiphane-triazine s y n e r g i s m . In s u m m a r y , with the discovery in Dow that a-(2,2,2-trichloroethyl) styrene possessed unique preemergent herbicidal activity a n d the synthesis a n d evaluation of close to one t h o u s a n d related materials, a new product, tridiphane, the active ingredient in T A N D E M * will enter the marketplace in 1986. Tridiphane will be the first postemergent grass herbicide for use in corn a n d will be used in c o m b i n a t i o n with triazine herbicides s u c h as atrazine and cyanazine.


86



Literature Cited 1.

Mussell, D.R., U.S. Patent 3 373 011, 1968.

2.

Kharasch, M.S.; Simon E.; Nudenberg, W. J. Org. Chem., 1953, 18, 328.

3.

Decker, D.L.; Moore, C.; Tousignant, W.F. U.S. Patent 3 454 657, 1969.

4.

Asscher, M.; Vofsi, D. J. Chem. Soc, 1963, 1887.

5.

Barrons, K.C.; Smith L.L.; Holmsen, T.W. U.S. Patent 4 086 081, 1978.

6.

Markley, L.D. U.S. Patent 4 188 436, 1980.

7.

Ozretich, T.M. U.S. Patent 3 719 465, 1973.

8.

Ozretich, T.M. U.S. Patent 4 018 801, 1977.

9.

Markley, L.D. U.S. Patent 3 972 913, 1976.

10.

Markley, L.D.; Norton, E.J. U.S. Patent 4 211 549, 1980.

11.

Frear, D. S.; Still, G.G. Phytochemistry 1970, 9, 2123.

12.

Zorner, P.S.; Olson, G.L. Proc. North Central Weed Control Conference, December 8, 1981, p. 15.

13.

Zorner, P.S. Proc. Southern Weed Science Society, 38th Annual Meeting, 1985, p. 484.

14.

Lamoureux, G.L.; Rusness, D.G. Proc. 188th National ACS Meeting, 1984.

15.

Lamoureux, G.L.; Rusness, D.G. Pestic. Biochem. Physiol., 1986, 26, 323.

16.

Markley, L.D.; Soper J.M. U.S. Patent 4 474 602, 1984.

RECEIVED

July 20, 1987


Synthesis and Chemistry of Agrochemicals - ACS Publications

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