Synthesis and Herbicidal Activity of Pyrrolopyridylimidazolinones

Chapter 11

Synthesis and Herbicidal Activity of Pyrrolopyridylimidazolinones John Finn, Nina Quinn, and Brad Buckman

Downloaded by PENNSYLVANIA STATE UNIV on June 22, 2012 | http://pubs.acs.org Publication Date: December 7, 1991 | doi: 10.1021/bk-1991-0443.ch011

Agricultural Research Division, American Cyanamid Company, P.O. Box 400, Princeton, NJ 08540

A series of imidazolinylpyrrolopyridinecarboxylic acids was synthesized and found to possess potent herbicidal activity. Synthetic approaches are described that allow for the preparation of a variety of analogs in both the [2,3-b] and [3,2-b] pyrrolopyridine series. The herbicidal activities of compounds within each series are compared and structure-activity relationships are identified.

Introduction. Since their discovery, the imidazolinone herbicides have been the focus of much synthetic activity at American Cyanamid. This is due to their ability to control a broad spectrum of weeds at very low rates (e.g. 0.08-0.5 kg/Ha). The original discovery of the imidazolinone class of herbicides was described in detail by Los (I). His chapter describes the chemistry leading to the development of several compounds that are the active ingredients in commercial products. These include: AC 222,293 (imazamethabenz) for control of mustard and wild oats in wheat, AC 243,997 (imazapyr), a total vegetation herbicide, and AC 252,214 (imazaquin), a broad spectrum herbicide for use in soybeans. An additional commercial compound AC 263,499 (imazethapyr) also used primarily for weed control in soybeans has been described (2). The satisfactory performance of these products has spurred interest in the discovery of other novel members of the imidazolinone class with good herbicidal properties.

0097-6156/91/0443-0133S06.00/0 © 1991 American Chemical Society

In Synthesis and Chemistry of Agrochemicals II; Baker, D., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1991.

134

SYNTHESIS AND CHEMISTRY OF AGROCHEMICALS Π

This chapter reports the synthesis and herbicidal activity of pyrrolopyridylimidazolinones. Interest in this series began with the potent activity and crop selectivity demonstrated by other hetero-fused pyridylimidazolinones. Of these compounds, the furo[2,3-6]pyridine series in particular displayed herbicidal behavior comparable to AC 252,214 Q). The bioisosteric replacement of nitrogen for the furano oxygen results in the pyrrolopyridine series which would therefore be likely to give an active set of herbicides. In addition, a QSAR study (4) predicted that both the pyrrolo[2,3-6]pyridine and pyrrolo[3,2-6]pyridine series should demonstrate good herbicidal activity. Downloaded by PENNSYLVANIA STATE UNIV on June 22, 2012 | http://pubs.acs.org Publication Date: December 7, 1991 | doi: 10.1021/bk-1991-0443.ch011

Synthesis At the outset of this project,we were faced with the need to develop appropriate synthetic routes to highly substituted pyrrolopyridines in both the [2,3-6] and [3,2b] series. In both series, efforts centered on developing methods for the synthesis of pyrrolopyridine diesters, because the conversion of these diesters to their corresponding imidazolinone acids was expected to be readily accomplished using known methodology. Pvrrolo[2.3-fr1pvridine Imidazolinones One of the known methods for constructing the pyrrolo[2,3-6]pyridine ring system involves the treatment of a 2chloro-3-(2-cWoroethyl)pyridine with a secondary arnineQ). Application of this method to the synthesis of the parent pyrrolo[2,3-6]pyridine-5,6-diester required the preparation of the appropriate tetrasubstituted pyridine. Following the general procedure described by Meth-Cohn(6), treatment of acylaniline 1 with Vilsmeier's reagent afforded quinoline 2 in modest yield. Oxidation of the quinoline ring with ozone in methanol-trimethylorthoformate with sulfuric acid catalysis provided the desired pyridine diester 3 in excellent yield. The use of the methanoltrimethylorthoformate -H2SO4 solvent system in the ozone reaction proved to be an improvement over the more commonly used acetic acid, providing a cleaner and faster oxidation. This is likely due to the conversion of the α,β unsaturated aldehyde intermediate I, which is only slowly oxidized by ozone to the corresponding dimethoxyacetal Π, where the electron-rich enol double bond is reactive toward ozone. Treatment of 3 with dimethylamine afforded the desired dihydropyrrolo[2,3-6]pyridine 4 in low yield. The major side product isolated from this reaction was olefin 5. This finding is consistent with that reported by YakhontovCD, who noted yields of the dihydropyrrolopyridine variedfrom5% to 53% for reactions of chloropyridines with dialkyl amines, with the elimination to

14%


IL FINN ET AL.

135

Pyrrotopyruiylimidazolwo

vinyl pyridines as the major side reaction. Despite the relative low yield of this step, the synthesis of the dihydtopyrrolopyridine was amenable to scale-up allowing the multigram preparation of 4.

O

CH 0

C

H

3


3

The dihydropynolo[2,3-6]pyridine diester 4 was readily oxidized with DDQ in dioxane to the aromatic pyrrolo[2,3-6]pyridine diester 6 in good yield (75%). Chlorination of 6 with NCS-benzoylperoxide in carbon tetrachloride was regioselective, affording 7 in modest yield. CH 0 < 3

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CH C H 3 0 2 C

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6 CH CH Another route was needed for the preparation of alkyl and alkoxy substituted analogs in the pyrrolo[2,3-6]pyridine series. An attractive route was utilization of the highly functionalized hetero[2,3-6]pyridine intermediate available from the Dieckmann condensation of a diester intermediateQ). The pyridine tetraesters 12 required by this route were readily prepared in three steps. Michael addition of 8 to 9 followed by intramolecular ring closure afforded pyridine 10, which was converted to the 6-chloropyridine 11 by phosphorous oxychloride. Treatment of the 6-chloropyridine triester 11 with sarcosine and sarcosine esters at room temperature afforded a series of 6-aminopyridines 12a-c. 3

Ο

4

4

%

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11

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i Ο

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l)N»OMe 2)(CH,) COCI

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,

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11. FINN ET AL

141

PyrrotopyrUylimidozolinones

Herbicidal Activity Both series of 2-irnidazolinylpyrrolopyridine-3-carboxylic acids possess considerable herbicidal activity, with fair to good soybean safety. The biological data for these compounds are displayed in Tables 1 and 2. These tables illustrate two different measures of herbicidal activity. First is the rate required for broad spectrum weed control; for purposes of comparison, this is the rate required for complete kill (8 or 9 rating on a 0-9 scale) of at least seven of the ten weeds used in the tertiary screen. Second is a measure of gross herbicidal activity, compiled by noting the number of weeds killed (8 or 9 rating) at all six rates tested: PRE tested between 1/64-1/2 kg/Ha; POST tested between 1/32-1 kg/Ha. There were 10 weeds per rate, and 60 represents the maximum score. This number is defined as the weed kill index (WKI). The ten weed species used for both of these ratings were: purple nutsedge,fieldbindweed, quackgrass, matricaria, velvedeaf, morningglory, barnyard grass, foxtail, ragweed, and wild oats. Pyrrolor2.3-fr1pyridines The herbicidal activity for thefivecompounds tested in this series is shown in Table 1. As a class, the pyrrolo[2,3-Z?]pyndines display good herbicidal activity, with four out of the five compounds achieving broad spectrum preemergence control at rates between 0.125 and 0.500 kg/Ha. Crop safety is observed in soybeans for all compounds in this series. The unsubstituted aromatic pyrrolo[2,3-fc]pyridine is the most active member of the series, exhibiting the highest weed kill index rating both pre- and postemergence. Slightly less active are the dihydro analog and the 2-methyl analog. The overall ranking for activity is: R = H > dihydro > 2-Me > 3-C1 > MeO.

Table 1 : Preemergence and Postemergence Weed Control bv Imidazolinylpyrrolor2.3-61pyridinecarboxylic Acids

ο Preemergence Control Rate (kg/Ha) Η 0.250 >0.500 3-MeO 0.250 dihydro 0.500 3-C1 0.125 2-Me

Weed Kill Index 34 5 24 13 30

Postemergence Control Rate (kg/Ha) 1.00 >1.00 1.00 >1.00 >1.00

Weed Kill Index 30 7 27 16 17



142

SYNTHESIS AND CHEMISTRY OF AGROCHEMICALS Π

Pvrrolor3.2-fe1pvridines The herbicidal activity for compounds in the pyrrolo[3,2&]pyridine series is shown in Table 2. The five most active members in this series are compared. The other three members in this series, the dihydro analog, the Nhydroxy-2-phenyl compound and the N-methoxy-2-phenyl compound, are less active and are not included. All five of the compounds in Table 2 are very active; they exhibit broad spectrum weed control both pre and post at rates between 0.032 and 0.250 kg/Ha. Crop safety is observed in soybean for all compounds.The Nmethoxypyrrolo[3,2-Z>]pyridine 32a is among the most active herbicides prepared to date in the imidazolinone series and has a broad-spectrum control rate of0.032 (or 1/32) kg/Ha both pre- and post-emergence. The other four members, while less active than 32a are still very active herbicides. The structure-activity relationships in this series are: Ri= OMe = Me > C H 2 C H C H 2 O ; R2= Η > CI = Me > dihydro > phenyl.

Table 2: Preemergence and Postemergence Weed Control bv Imidazolinvlpvrrolor3.2-blpvridinecarboxvlic Acids

El MeO allyloxy Me MeO MeO

£2

Η Η Η 2-Me 3-Cl

Premergence

Postemergence

Control Rate Weed Kill Index (kg/Ha) 0.032 51 0.125 39 0.032 49 0.250 31 0.064 39

Control rate Weed Kill ikg/Hal Index 0.032 50 34 0.250 0.063 45 39 0.250 0.125 35

In comparision to other members of the imidazolinone series, the pyrrolopyridines are quite active. In Table 3, two of the more active compounds in this series, 32a and 32b, are compared to A C 252,214. The broad spectrum weed control demonstrated by these compounds is comparable to this commercial standard. All three compounds display crop safety in soybeans. Summary A new series of compounds, the pyrrolopyridylimidazolinones were prepared. The synthetic routes to these compounds allowed preparation of a variety of analogs in both the [2,3-fc] and [3,2-fc] pyrrolopyridine series. Excellent herbicidal activity was found for a number of compounds especially in the [3,2-fc] series.


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Pyrrolopyridylimidazolinones


Table 3: Postemergence Weed Control by 32a, 32h and A C 252.214.

wild oats ragweed foxtail barnyard morning glory velvetleaf matricaria quackgrass bindweed p. nutsedge

32a at 0.032fkg/Ha> 9 7 9 9 9 9 8 9 6 8

32b at 0.25(kg/Ha} 9 3 6 4 7 6 2 8 4 9

AC 252,214 at 0.125fkg/Ha) 9 6 9 6 6 6 6 9 9 9

Acknowledgments The authors acknowledge Pierre Marc and Laura Quakenbush for their efforts in the biological evaluation of the compounds described in this chapter. Literature Cited 1. Los, M., American Chemical Society Symposium Series ,1984,255, 29-44. 2. Peoples, T. R., Wang,T.,Fine, R.R.,Orwick,P.L.,Graham, S.E. and Kirkland,K., Proceedings of the British Crop Protection Conf.-Weeds, 1985,1,99. 3. Los, M., Ladner,D.W. and Cross, B., U.S. Patent 4,650,514, 1987. 4. Ladner,D.W. and Cross, B., IUPAC Int. Congress of Pest. Chem., August 1986, paper # 1C-07. 5. Yakhontov, L. N. and Rubtsov, M.V. J. Gen. Chem. USSR (English Trans.), 1960, 30, 3269. 6. Meth-Cohn, O., Narine,B. and Tarnowski, B., J. Chem. Soc.Perkin Trans. 1, 1981,1520. 7. Willette, R. E., Advances in Heterocyclic Chem.,l968, 9, 54-56. 8. Los, M. U. S. Patent 4,798,619, 1989. 9. Azimov, V. A. and Yakhontov, L. N., Khim. Geterotsikl. Soedin,. 1977, 10,1425. 10. Clark, R. E. and Repke, D. B., Heterocycles, 1984, 22, 195. 11. Clemo, G. R. and Swan, G. Α., J. Chem. Soc., 1945, 603.

RECEIVED December15,1989


Synthesis and Herbicidal Activity of Pyrrolopyridylimidazolinones

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