Journal of Agricultural and Food Chemistry 0 Copyright 1974 by the American Chemical Society
Volume 22, Number 6 Novem berlDecem ber 1974
Synthesis and Herbicidal Activity of Pyrrolidinecarboxanilides William J. Pyne,* Steve S.Szabo,l and Robert E. Holm
A series of pyrrolidinecarboxanilides and pyrrolidinethiocarboxanilides has been prepared and found to be herbicidally active. Substitution of methyl groups in the cis configuration a t the 2 and 5 positions of the pyrrolidine ring of the carboxanilides increased the herbicidal activity, while methyl groups in the trans configuration reduced or eliminated the activity. In general, the thiocarboxanilides were less active than the
corresponding carboxanilides. Pyrrolidinecarboxanilides were very active inhibitors of the Hill reaction and the degree of inhibition correlated with the accumulation of nitrite in tissue. cis2,5-Dimethyl-l-pyrrolidinecarboxanilide,one of the most herbicidally active compounds in the series, has undergone extensive field testing and is being developed as a selective corn herbicide.
Synthesis and biological evaluation of a series of pyrrolidine and alkylpyrrolidinecarboxanilides were initiated after several were found to have pre- and postemergence herbicidal activity. Synthesized compounds were evaluated in standard greenhouse herbicide tests and in special tests using isolated chloroplasts and excised leaf sections. From this work one compound, cis-2,5-dimethyl-l-pyrrolidinecarboxanilide ( l ) , has been selected for further development and commercialization.
@ YH-C-
9
cFJ
cis-2,5-Dimethylpyrrolidinewas synthesized from the corresponding pyrrole using the procedures of Overberger e t al. (1955) and Hill and Chan (1965). trans-2,5-Dimethylpyrrolidine was prepared by the method of Evans (1951). Pyrrolidinecarboxanilides and thiocarboxanilides were synthesized by reaction of the appropriate phenyl isocyanate or thioisocyanate and the desired pyrrolidine in benzene (eq 1).The various pyrrolidinecarboxanilides are listCH 9 -
N CH,
-
L+
1
Compound 1, known by the trade name Rowtate, has been field tested for 2 years as a selective corn herbicide. In these tests, Rowtate has controlled broadleaf and certain grassy weeds in corn a t 2-3 kgfha, depending on soil type.
ed in Tables I-IV with yields, melting points, and preemergence and postemergence herbicidal activity ratings on broadleaf weeds and grasses. Compounds 1 through 74 were prepared by the following method given for cis-2,5-dimethyl-l-pyrrolidinecarboxanilide (1). Phenyl isocyanate (11 g, 0.092 M ) was allowed to react in 100 ml of anhydrous benzene with cis-2,5-dimethylpyrrolidine (9.1 g, 0.092 M ) . This mixture was heated to reflux for 3 hr, cooled, and filtered; the solvent was removed a t reduced pressure. The residual solid was crystallized from a benzene-petroleum ether mixture to give 13 g (64% yield) of a solid melting a t 119-120".
MATERIALS AND METHODS
Phenyl isocyanates and thioisocyanates were purchased from commercial sources or were prepared by the reaction of phosgene and the appropriate aniline in ethyl acetate. Diamond Shamrock Corporation, T. R. Evans Research Center, Painesville, Ohio 44077. Boyce Thompson Institute for Plant Research, Inc., Yonkers, N. Y. 10701. 921
PYNE e t al.
Table I. Structures, Chemical Properties, a n d Biological Activities of the cis -2,5-Dimethyl- 1-pyrrolidinecarboxanilides
Rating no." Preemergent
Postemergent
Yield, No. -
1 2 3 4 5 6
7 8 9 10
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
31 32 33 34 35 36 37 38 39
40 41 42 43 44
45 46 47
X
70
MP, "C
Broadleaf
Grass
Broadleaf
Grass
H 2 -F 3 -F 4 -F 2-CF3 3 -C F3 4 -CF3 3 -c1 4 -c1 3 -Br 4 -Br 3 -I 4 -I 4 -CN 3 -NO2 4 -NO2 3-CH3 4 -CH3 4 -CF30 2 -CH30 3 -CH30 4 -CH30 3 -CH3S 4 -CH3S 3,4 -C12 2,5 4212 2,4 -Br2 2,5 -Br, 2,6-Br2 2,4-F2 2,s-F~ 3,4-F2 3-C1, 4 - F 3-CH3, 4 - F 3 -F, 4 -CH3 3-CF3, 4 - F 3,4-(CH3)2 2-F, 4,5-C12 3 -C1, 4-Br 3-CF3, 4-Br 3-CF3, 4-C1 4 -(CH,),CNHC02 4 -CH3C(CH3)H 4-(CH3)3C 2,3,4,5 -F, 2,3,5,6 -F4 3 -C1, 4 -CH30
65 100 80 75 28 85 65 81 84 70 88 83 87 41 84 98 76 100 82 56 61 80 80 84 78 42 78 74 80 54 61 60 73 96 88 76 81 71 61 65 63 20 63 97 58 24 87
119-120 125- 127b 117- 118 135 128- 129 129-130 123-125 118- 119 148- 149 102-103 131- 132 103- 105 134-135 160-161 130-131 114-116 73-75 130- 13 1 143- 145 69 106 110-112 82 108 137- 138 55 70-71 62-63 171-172 78-80 64-65 107- 108 113-115 99- 100 123- 125 115-116 112- 113 103- 104 127- 129 124- 125 110 80 115-117 128 102-104 163-166 115-116
5 5 5 5 0 3 3 1 1 2 3 2 3 3 0 0 1 3 2 0 0 0 2 1 2 0 0 0 0 1 5 6 3 4 4 2 0 2 0 2 2 2 0 0 0
0 1 3 3 0 3 0 0 0 2 0 0 0
7 7 8 7
5 4 4 3 0 3 2 5 5 2 3 3 0 2
0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 1 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0
0 6 5 8 7 5 7 6 8 6 2 2 7 4 4 4 5 5 5 4 8 1 0 0 0 3 8 7 5 6 6 4 3 4 4 4 5 2 3 0 0 0 2
1 0 4 2 2 2 2 1 0 0 2 1 0 0 0 5 2 6 3 3 2 2 0 2 3 0 0 0 3 0 0 0
1
Ratings range from 0 to 9 with 0 indicating no weed control a t the highest rate tested (17.92 kg/ha) and 9 representing weed control at 0.07 kg/ha. Control of broadleaf weeds and grasses a t each rating level had to be at least 50% for preemergent application and 80% for postemergent application. See Materials and Methods for complete rating table. Determined at 0.2 mm. Q
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J. Agr. Food Chern., Vol. 22, No. 6,1974
PYRROLIDINECARBOXANILIDES
Table 11. Structures, Chemical Properties, and Biological Activities of the trans -2,5-Dimethyl- 1-pyrrolidinecarboxanilides
Rating no." Preemergent
P o s temergent
Yield, No.
X
cic
MP, "C
48 49
2 -F 3 -F 4 -F 3 -.CF3 3 -c1 4 -c1 2,5-F, H 3,4 -c1,
63 73 72 80 84 100 48 85 83
91-93 142-143 149-150 115-117 135-137 151- 152 105-107 143 147-148
50 51
52 53 54 55 56
Broadleaf
Grass
Broadleaf
Grass
Ratings range from 0 to 9 with 0 indicating no weed control a t the highest rate tested (17.92 kg/ha) and 9 representing weed control at 0.07 kg/ha. Control of broadleaf weeds and grasses at each rating level had to be at least 50% for preemergent application and 80% for postemergent application. See Materials and Methods for complete rating table. (1
Table 111. Structures, Chemical Properties, and Biological Activities of the Pyrrolidinecarboxanilides
Rating no. a Preemergent
Postemergent
Yield, X
9%
MP, "C
Broadleaf
3 -c1 4 -c1 3,4 -c1, 3 -CF, 2,5-F2
91 91 100 78 67 68
180- 181 143- 144 167-168 179- 180 160-161 69-70
2 1 3 1 3 1
No.
09 70 71 72 73
74
H
Grass
Broadleaf
Grass
5 3 3
2
4
2 0 1
3 3
2 1
Ratings range from 0 to 9 with 0 indicating no weed control at the highest rate tested (17.92 kg/ha) and 9 representing weed control a t 0.07 kg/ha. Control of broadleaf weeds and grasses at each rating level had to be a t least 50% for preemergent application and 80% for postemergent application. See Materials and Methods for complete rating table. (1
Compounds 75 through 82 were synthesized by the following general procedure outlined for cis-2,5-dimethyl-lpyrrolidinethiocarboxanilide (77). cis-2,5-Dimethylpyrrolidine (9.9 g, 0.1 M ) was allowed to react in 100 ml of anhydrous benzene with phenyl isothiocyanate (13.5 g, 0.1 M ) . After the slightly exothermic reaction subsided, the reaction mixture was heated a t reflux for 3 hr and cooled, and the solvent removed a t reduced pressure. The residual solid was crystallized from a pentane-benzene mixture to give 14 g (60% yield) of a solid melting a t 104-105". Structures of novel carboxanilides were verified by quantitative elemental analysis of carbon, hydrogen, and nitrogen (accuracy within =to.3%), by infrared spectroscopy, and by nmr analysis.
Test formulations were prepared by mixing 20 ml of an acetone solution containing 0.083 g of the test compound with 20 ml of water containing 0.01 g of Triton X-155 surfactant ("Triton" is a registered trademark). The resultant formulations contained 2080 ppm of test compound in 50% by volume of acetone and 0.025% by weight of surfactant. Appropriate lower concentrations were obtained by diluting the stock formulation with 50% aqueous acetone containing 0.025% surfactant. The pre- and postemergence tests were run in 23 cm X 23 cm X 5 cm aluminum pans containing 3.8 cm of composted soil. Seeds of buckwheat (Fagopyrum esculentum Moench), turnip (Brassica rapa L.), zinnia (Zinnia elegans Jacq.), browntop millet ( P a n i c u m ramosum L.), peJ. A g r . Food Chem., Vol. 22, No. 6,1974
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PYNE et al.
Table IV. Structures, Chemical Properties, and Biological Activities of the Pyrrolidinethiocarboxanilides
Rating no. a Preemergent Postemergent Geometrical isomer Broadleaf G r a s s Broadleaf G r a s s
Yield, No.
%
MP, "C
X
Y
75
93
76 77 78 79 80 81
80 60 94 98 90 83 68
149-150 120- 12 1 104- 105 104-105 123-125 109-110 141- 143 78-79
H 3-CF3
H 2,5-(CH3)2 2,5 -(CH3)2 2,s -(CH3)2 2,5 -(CH,)2 2,5 -(CH3)2 2,5 -(CH3)2 2,5 -(CH3)2
82
H 3 -F 3 -F 2 -F 3-CF3 2 -F
Cis Cis Cis Trans Trans Trans Cis
2 0 2 3 0 0 0
2
2 0 0 0 0 0 0 0
2 6
2 0 0 3
5 3 0 0 0
0 0 0
2
0
Ratings range from 0 to 9 with 0 indicating no weed control a t the highest rate tested (17.92 kg/ha) and 9 representing weed control a t 0.07 kg/ha. Control of broadleaf weeds and grasses a t each rating level had to be a t least 50% for preemergent application and 80% for postemergent application. See Materials and Methods for complete rating table.
rennial ryegrass ( L o l i u m perenne L.),and sorghum (Sorg h u m uulgare Pers.) were planted about 1 cm deep in onehalf of the tray. The trays were transferred to the greenhouse where the test species were allowed to grow until one true leaf was present on the slowest growing species (zinnia). This required 7-14 days depending on the time of the year. The other one-half of the tray was planted with the same six species and the tray was sprayed with 40 ml of the stock solution so that the soil surface and plants were uniformly covered. Application rates varied from 17.92 to 0.07 kg/ha. The tests were evaluated 2 weeks after treatment and assigned ratings, as listed in Tables I-IV, according to the following scheme rating number
test rate kg/ ha
nn,
