# Patent

## Title
Pyridazinylurea N-oxide plant regulators

## Abstract

Novel hydroxyalkylesters of N-phosphonomethylglycine have been identified which prove to be effective gametocides.

## Background
This invention concerns compounds that have been found to be active as gametocides. These compounds are derivatives of N-phosphonomethylglycine, which is usually called glyphosate.

An effective gametocide is a compound that, when applied to a plant during sexual maturity, is capable of killing or effectively terminating the development of a plant's male gametes while leaving the plant's female gametes, or at least a significant proportion of them, capable of undergoing cross fertilization with subsequent high yields of fertile, viable hybrid seed.

Many compounds are capable of killing the male gametes of a plant, indeed almost any systemic herbicide is effective in this role. However most also kill the female gametes and the rest of the plant and are therefore ineffective gametocides. Additionally, while some compounds can be applied at rates such that substantially only the gametes are affected, most are found to be fairly non-discriminating regarding the sex of the gametes destroyed.

A requirement of the ideal gametocide, therefore, is that the application level at which male gametes are effectively destroyed should be significantly lower than that required to destroy also the female gametes. Thus a gametocide should be capable of being spray applied in the field without extraordinary precautions against accidental overdoses.

Other desirable characteristics may be dictated by the plant to be treated. As an example, wheat is by nature self-pollinating as the male and female gametes are found inside the same flower which remains closed until the male gametes release their pollen onto the female gametes to fertilize them. Thus, when the flower opens fertilization is normally essentially complete. For a gametocide to be useful on wheat it must, besides killing the male gametes, not interfere with the opening of the flower when the female gametes are ready to be fertilized such that fertilization by pollen from other wheat plants, perhaps of a different strain, can occur.

The utility of gametocides lies in precisely this area of plant hybridization. By causing pollination of one variety of a plant species by a different variety of the same species, a hybrid plant is obtained. By careful selection of the parents, hybrids can be obtained with specific combinations of desirable traits such as plant size, grain yield disease resistance, herbicide tolerance, climatic adaptation, plant growth regulator response, and so on.

Hybridization utilizing cytoplasmic male sterility is available and is often used to produce commercial hybrid corn seed. However, techniques using the cytoplasmic male sterility system can take years to develop lines to the point that commercial quantities of hybrid seed can be produced. Use of an effective gametocide significantly reduces this development time by fifty percent or more.

Some plants, such as corn, can be relatively easily hybridized without resort to genetic techniques because the organ containing the male gametes are exposed and can easily be removed. These systems leave the female gametes, when ready for fertilization, accessible to any foreign corn pollen that is deposited thereon. As indicated above, however, this is not the case with plants such as wheat in which the male and female gametes develop together inside the same closed flower.

The significance of an effective gametocide is therefore that it provides a tool for the development of advantageous hybrids of plants that hitherto have been very difficult to cross-pollinate.

The present invention provides a group of novel compounds that are found to possess the gametocidal utility described above. The best of these gametocides are very effective in the production of high yields of fertile hybrid seed.

Many derivatives of N-phosphonomethylglycine have been described in the patent and scientific literature. These compounds have been described in terms of their herbicidal, plant growth regulating or sucrose deposition enhancing characteristics.

Typical examples of this type of art include U.S. Pat. Nos. 3,799,758, 3,853,530, 4,140,513, 3,970,695, 4,047,926 and 4,035,176.

None of these patents however teach any gametocidal activity or the specific compounds that provide one aspect of the present invention.

Other patents have been published showing compounds claimed to have gametocidal activity. These include U.S. Pat. No. 4,345,934 (1-aryl-1,4-dihydro-4-oxo(thio)pyridazines) and European Patent Application No. 0029265 (azetidine derivatives). None however have been found or described that are glyphosate derivatives.

The compounds of the present invention have the formula ##STR1## wherein R is hydrogen; a C.sub.1 -C.sub.4 alkyl, hydroxyalkyl or chloroalkyl; or a C.sub.2 -C.sub.6 alkoxyalkyl group; R' is a hydroxyalkyl group having from 2 to 8 carbon atoms and from 1-6 hydroxyl groups; R" is hydrogen or R'; and X is hydrogen or --COCF.sub.3 ; as well as agronomically acceptable salts of such compounds.

The R' substituent is a hydroxyalkyl group and can contain from 1-6 hydroxyl groups. Generally it is found that better results are obtained when two or more hydroxyl groups are present. Thus preferred derivatives include glyceryl esters which may be esterified via the 1-, 2-, or the 3- hydroxyl group.

The preferred group R is also hydrogen but compounds having other R groups can be used. Such groups include alkyl, hydroxyalkyl and haloalkyl having from 1 to 4 carbon atoms and one or two halogen or hydroxyl groups. The preferred halogen is chlorine though bromine, fluorine or iodine could also be used. Alkoxy alkyls having a total of 2 to 6 carbon atoms, such as ethoxyethyl, can also be used.

In addition to the above compounds it is possible to use their agronomically acceptable salts. As will be noted the compounds of the invention are potentially amphoteric. Thus an acid such as hydrochloric acid can protonate the basic nitrogen atom or, if R or R" is hydrogen, a salt can be formed at one of these acidic hydrogens by reaction with a suitable base. In point of fact the use of a salt, particularly one in which the salt is formed by reaction with a base, is preferred since such salts are generally much more water-soluble than the corresponding acid. This makes application of the compounds significantly easier in practice.

Agronomically acceptable salts are salts in which the salt-forming moiety that reacts with the glyphosate derivative does not have any ecologically unacceptable consequences for the plant, the soil or the general environment. Acid that may form acceptable salts include hydrochloric acid, phosphoric acid and trifluoro acetic acid and bases include the alkali metal hydroxides and those based on the "onium" ions such as ammonium, organoammonium, sulfonium, sulfoxonium, phosphonium and oxonium.

The invention also comprises a process for the production of hybrid plants including monocotylodons such as rice, wheat, oats, barley and the like as well as dicotylodons such as soybeans. This process comprises applying a compound of the invention to a first plant species in an amount that is effective to sterilize essentially all the male gametes of the plant while leaving a significant proportion of the female gametes capable of fertilization; causing the female gamates to be fertilized by pollen from a second plant; and thereafter harvesting the hybridized seeds.

A secondary consequence of sterility in wheat is that the heads open so as to expose the female gametes. As a result they are fully accessible to pollen introduced from outside. Of course, if hybridization is planned, it is relatively easy to arrange that the pollen comes from a different wheat line.

The gametocide should preferably be applied after initiation of sexual development, but prior to sexual maturity, that is before pollen is shed from the anthers. Generally application in wheat should occur when the spike or head length is from 1 to 9 cm. and preferably 4 to 7 cm. in length. In other plants application should preferably be when the plants have reached a corresponding degree of sexual maturity.

The gametocides of the present invention when applied under optimum conditions kill essentially all, that is at least 95%, of all male gametes, while leaving a significant portion, by which is meant at least 40%, and often 60% or more of the female gametes capable of fertilization and the rest of the plant affected as little as possible.

The most preferred products achieve the desired effect over a wide range of application levels. This is referred to as showing a wide "application window". This is of course highly desirable when working in the field as accidental overdoses can easily occur. As will be noted the best compounds of the invention leave as much as 70% of the female gametes viable and have only a slight stunting effect on the plant as a whole.

The stunting effect is the result of the compounds having some phytotoxic activity that, at the levels of application used in connection with the present invention, is manifested by a reduction in the size of the plant and perhaps by a minor amount of chlorosis. Clearly the preferred gametocides of the invention are those in which these phytotoxic side effects are minimized.

The critical test for a gametocide is of course to apply it to a crop before fertilization occurs so as to kill the male gametes, allow cross fertilization with pollen from a second line, harvest the resulting seed, and grow this seed. This tests the extent to which the cross pollination has resulted in a viable hybrid. This, of course, takes a long time and makes the identification of an effective group of gametocides a difficult task. To cope with this problem a series of screens have been developed. The first screen, which can occur in a growth chamber or in a greenhouse during appropriate seasons, involves applying the gametocide and observing the effect on the plant. Those that eventually show good gametocidal activity are found to cause the flower to open wide (something that normally occurs only after the pollen from the male gametes is ready for discharge and fertilization has already occurred. This is known as showing "open head morphology". Parallel with this the best gametocides show only slight stunting of the plant.

Gametocides that survive this first screen are then subjected to the second screen in which they are applied to plants growing in a field. The rows are planted such that the treated rows can be fertilized by pollen from untreated rows of a different line. The seed from the cross-pollinated plants is harvested, planted and grown to assess the viability and degree of hybridization of the seed.

In a final evaluation, treated plants are followed to determine the degree of out-crossing that has occurred and the fertility of the resulting seed.

As will be seen from the data presented below, it is found that gametocides that perform well on the first screen generally show overall gametocidal activity. The compounds of the invention can be prepared by standard techniques known in the art such as those described in U.S. Pat. Nos. 4,053,505 and 4,218,235 processes.

In a modification of the process of U.S. Pat. No. 4,053,505 to illustrate a specific production sequence the glyceryl ester of glyphosate is prepared by reacting the ethyl ester of N-(dichlorophosphinyl-methyl) N-trifluoroacetyl glycine with 2,3-dibenzyloxypropyl alcohol in the presence of a base (triethylamine). This reaction product is then hydrolyzed using caustic soda and then acidified to generate the unesterified carboxylic acid group. Finally the benzyl ether groups are removed to yield hydroxyl groups using hydrogen and a 10% palladium on charcoal reduction catalyst with the reactant dissolved in acetic acid solution. This reaction sequence actually produces the isomer mixture employed in Example 1.

This Example details the gametocidal activity of a compound according to the invention on spring wheat in a growth chamber.

The awned hard red spring wheat cultivar "Anza" was grown in a growth chamber set at 70% humidity, and 21.degree. C. (16 hour day, 8 hour night) until termination of the experiment. Light intensity was 800 uE. Seven seeds per six inch pot were planted in a soilless medium of Metro-Mix200 supplemented with 93 g Osmocote (14-14-14) Controlled Release Fertilizer, 93 g Peters (14-7-7) Slow Release Fertilizer, 17 g Micromax Micronutrients per cubic foot of Metro-Mix200. Approximately 10-14 days after planting, pots were thinned to six plants per pot. Chemical treatments were foliar applied using an enclosed track sprayer chamber consisting of a compressed air reservoir equipped with a manual speed adjustment and field sprayer nozzle (4002E). This method simulates actual field spraying techniques. The test consisted of using three rates on three dates in an aqueous carrier solution containing 0.2% Tween20 (a commercial surfactant) sprayed at a rate equivalent to 2805 liters/hectare. Untreated controls were included for comparison. After spike emergence and before anthesis, glassine bags were placed over approximately 12-15 heads per pot to prohibit all but self-pollination. When seeds were large enough to be easily seen and stigmas senesced (approximately 4  weeks after heading), bagged and unbagged spikes were evaluated for the number of seed set and observations on phytotoxicity recorded.

The compound was a glycerol ester of N-phosphonomethyl glycine. Analysis showed the compound to be a mixture of two isomers as follows: ##STR2##

The treatment dates, evaluation parameters and terminology explanations are as follows: time of bagging. heads]) seeds/head]/[total # heads]) Spraydates Dates:          (Spike Length) ______________________________________ Planted = 8-16  D1 = 9-20 (1.76 cm) Heading = 10-01 D2 = 9-24 (4.92 cm) Bagging = 10-01 D3 = 9-26 (7.3 cm) thru 10-17 ______________________________________

The mean % male sterility was determined to be as follows: Spray Date Rate    D1               D2     D3 ______________________________________ 5.6    79               100    100 11.2    87               100    100 16.8    (No Heads)       100     86 ______________________________________ Control: Out of 80 bagged spikes from 6 pots, 4 spikes (5%) were sterile.

The detailed results on which this is based are shown on Table I. __________________________________________________________________________ Tot. Bagged      Unbagged   Ht. Rate: Rep* Comments      Hds. No. PS(P100 + PP) No. PS(P100 + PP) (cm) Notes __________________________________________________________________________ 5.6 Kg/H Date:D1 1  MOD.STUNT,SK + AWN 24 16  100(100 + 0) 8  100(100 + 0) 35 SL.HEAD DIS.,SL.DEV.                               DISTORTION ONE HD. EPINASTY 2  SL.YELLOWER   23 12  58(33 + 25) 11 45(0 + 45) 45 L.Hds. Date:D2 1  SL.STUNT,SL.DEV. 17 6   100(50 + 50) 11 99(90 + 9) 35 DIST., CUP SHAPED 2  SL.DEV.       21 13  99(84 + 15) 8  87(87 + 0) 43 MOST NOT FULLY OUT OF BOOT Date:D3 1  SL.TO         21 9   100(100 + 0) 12 100(100 + 0) 40 MOD.STUNT,SL.DEV. 2  SL.STUNT      21 10  100(70 + 30) 11 99(90 + 9) 35 SIX HEADS TOTALLY IN BOOT NOT SCORED 11.2 Kg/H Date:D1 1  SD,MOD.TO SEV. 21 16  74(62 + 12) 5  60(60 + 0) 37 SPOTTY FERT. STUNT,YELLOWING OF LLVS + HDS, 10/8 = 10H 2  SEV.STUNT,NO HDS. 13 6   100(100 + 0) 7  100(100 + 0) 20 DEFORMED HDS. Date:D2 1  SL.STUNT,FEWER 12 2   100(100 + 0) 10 100(100 + 0) 26 ALL STILL IN HDS/POT,SL.DEV.                            BOOT, MANY CUP SHAPED 2  SL.STUNT,NO HDS. 12 2   100(100 + 0) 10 100(100 + 0) 24 NONE OUT OF BOOT, CUP SHAPED Date:D3 1  SL.STUNT,NO HDS. 11 6   100(100 + 0) 5  100(100 + 0) 30 NONE FULLY EMERGED,SL.DEV.                            OUT OF BOOT, LVS HAVE PURPLE TINGE 2  SL.STUNT,SL.DEV. 8 6   100(100 + 0) 2  100(50 + 50) 30 SIX PLANTS 10/8 = 20H                                 FULLY IN BOOT 1.68 Kg/H Date:D1 1  SEV.STUNT,NO HDS, 1 1   0(0 + 0) 0  0(0 + 0) 15 ONLY ONE HD. YELLOW-GREEN                               EMERGED-REST COLOR                                      OF PLANT DEAD 2  SEV.STUNT,     0 0   0(0 + 0) 0  0(0 + 0) 25 NO HEADS YELLOWING,NO HDS Date:D2 1  SL.TO MOD.STUNT, 9 1   100(100 + 0) 8  100(100 + 0) 20 NONE FULLY FEW HDS                                    OUT OF BOOT 2  MOD.STUNT,FEW HDS 6 1   100(100 + 0) 5  100(100 + 0) 17 CUP SHAPED, IN BOOT, NO HDS.OUT                        FEW HEADS Date:D3 1  SL.STUNT,SL.DEV 14 9   77(77 + 0) 5  80(80 + 0) 35 MANY HEADS SILL INSIDE BOOT 2  SL.STUNT,SL.DEV 21 9   100(100 + 0) 12 100(100 + 0) 33 NONE FULLY OUT OF __________________________________________________________________________ BOOT *Replication No.

From the above it can be seen that the compound showed excellent male sterility through if the application is made too early there is a reduction in normal spikes appearing from the boot.

The same compound as was evaluated in Example 1 was tested in the field on three different wheat varieties on five different dates (D1-D5) and at four different levels. The observations were reported in terms of height, vegetative damage (0=Plot completely damage; 100=No damage to plot), percent sterility, grain yield (in grams of seed per three foot row), and in percentage of seed obtained that was in fact hybridized.

The varieties and the spray dates were as follows: Spike Spray   Length        Calendar Variety     Date    Range         Date ______________________________________ DK 235      D1      1-2 mm        May 9 D2      10-20 mm      May 17 D3      22-32 mm      May 19 D4      30-40 mm      May 21 D5      35-45 mm      May 23 McNair 1003 D1      4 mm          May 9 D2      12-20 mm      May 18 D3      25-28 mm      May 19 D4      30-43 mm      May 23 D5      38-62 mm      May 24 Vona        D1      4 mm          May 9 D2       8-14 mm      May 16 D3      10-17 mm      May 18 D4      18-32 mm      May 21 D5      24-54 mm      May 23 ______________________________________

Field grown winter wheat plants were used to examine potential gametocide activity. The procedures for evaluating the gametocide were as follows.

Experimental plots were four feet long and seven rows wide consisting of both male and female rows. The female rows or spray rows were the center three rows and consisted of cultivars that contained either the Rht1 or Rht2 dwarfing gene. These rows were bordered by two rows, which were male rows or the pollen source. The male rows contained a mixture of cultivars varying in date of anthesis that did not contain either of the dwarfing genes and were of "normal" height.

All of the cultivars were seeded with a Marliss grain drill at a rate of 112 Kg per hectare which is standard for the area and growing conditions. No herbicide was applied to the plots and minor weeding was done by hand. Fall application of fertilizer consisted of 28, 140, and 140 Kg per hectare of nitrogen, phosphorus, and potassium as ammonium nitrate, superphosphate, and muriate potash, respectively. In the early spring at greenup of the wheat an additional 56 Kg of nitrogen per hectare was applied as a 28% nitrogen solution (UAN) adjusted to pH6 with concentrated HCl. Di-syston 8 (1.17 liters/hectare was applied on 19 April for aphid and greenbug control. Malathion (1.12 Kg ai/hectare) and Bayleton 50% WP (0.2 Kg ai/hectare) was applied with an aerial application of 46.75 liters/hectare at the late boot stage of development to control insects and leaf rust, respectively.

The experimental design consisted of a split-split plot design with cultivars as main blocks and dates of application as sub-blocks. Compounds and rates were randomized within the splits. The field layout grouped the treatment combinations such that the treatments applied on the same date were adjacent. Timing of application was based on spike length and ranged from double ridge to spikes lengths equal to 5 cm which would make the stage of plant development in the early jointing to early boot stage. Spikes were excised from a sample of the most mature tillers at regular intervals and the spike lengths were used to monitor ear development.

Treatments were foliarly applied to the female rows using a spray boom mounted to a high-clearance tractor with a single spray nozzle directly above each of the spray rows. Treatment chemicals were formulated in water and included 0.2% Tween20 as a surfactant. Applications were made with a solvent volume equivalent to approximately 701.25 liters per hectare.

Data collection: Glassine bags were placed on 25-30 spikes per plot to determine the level of male sterility. The glassine bags (5-8 bags/day) were placed on the spikes after head emergence but prior to anthesis (anther extrusion). The bags were stapled and left in place to prevent all but self-pollination from occurring. About four weeks later after the seeds were in a soft-hard dough stage of development the bags were collected and scored for seed set. Three classifications of seed set were used in scoring the bags: 100% sterility--no seed set on the spike, partial sterility--<15% seed set or approximately 1-5 seeds per spike, or fertile spikes-->15% seed set. After anthesis, observations were made on vegetative damage, "open heads", spike distortion, and head emergence. Prior to harvest culm height was measured by determining an average culm height for each plot.

Grain yield was determined by hand harvesting the entire female plot and threshing with a Vogel thresher. A sub-sample of the grain was used in a GA test (40 mg/pot) to determine hybrid seed set. Plants were scored for responsiveness to GA approximately two weeks after seeding. Hybrid seed produced by crossing pollen from the male rows onto the sterile female stigmas will have elongated internodes after being grown in the GA solution. Only plots that had shown significant male sterility under bagged heads were tested for hybrid seed set.

The results obtained were as follows: ______________________________________ Ste- ril- Grain  Hybrid Rate       Height  Vegetative ity  Yield  Seed Kg/H       cm      Damage    %    G/Meter (%) ______________________________________ McNair 1003 66      100.0     1.8  98.4    0 (Control) Spray Date: D2 1.68       50      35.0      74.0 36.3    9 Spray Date: D3 1.68 EQ    57      48.3      4.3  54.6    4 3.36 EQ    53      43.3      50.0 38.4   35 5.04 EQ    43      36.7      75.3 15.5   28 6.72 EQ    34      12.5      88.0 2.1    34 Spray Date: D4 1.68 EQ    66      95.0      9.3  87.0    5 3.36 EQ    59      56.7      63.7 45.1   41 5.04 EQ    46      36.7      84.0 19.8   52 6.72 EQ    39      11.7      93.3 3.0    62 Spray Date: D5 1.68 EQ    63      91.7      4.0  76.3    4 3.36 EQ    57      73.3      46.0 62.3   36 5.04 EQ    47      66.7      63.3 36.7   50 6.72 EQ    42      46.7      76.3 19.5   44 DK235-CMS Spray Date: D2 60      100.0     99.2 61.9   69 Spray Date: D4 62      100.0     98.2 55.4   81 VAR: DK235 62      100.0     4.1  115.2   0 (Control) Spray Date: D2 1.68 EQ    49      61.7      60.0 62.8    3 3.36 EQ    29      7.5       82.0 6.9     2 5.04 EQ    30      3.5       90.5 1.7     7 6.72 EQ    28      2.0       92.0 .0     -- Spray Date: D3 1.68 EQ    59      98.3      10.3 116.5   3 3.36 EQ    53      71.7      55.0 61.1   11 5.04 EQ    40      41.7      69.3 27.9   16 6.72 EQ    36      17.3      79.0 15.6   11 Spray Date: D4 1.68 EQ    63      100.0     5.3  115.1   0 3.36 EQ    61      100.0     31.7 95.7    3 5.04 EQ    59      100.0     32.7 83.5   10 6.72 EQ    57      80.0      31.7 75.4    9 Spray Date: D5 1.68 EQ    65      100.0     8.3  119.0   0 3.36 EQ    58      96.7      48.7 69.8   11 5.04 EQ    59      85.0      75.0 58.7   23 6.72 EQ    51      70.0      86.3 29.9   42 VONA-CMS Spray Date: D2 59      100.0     98.0 49.4   79 Spray Date: D4 59      100.0     97.0 52.2   77 VONA (Control) 59      100.0     2.0  87.3   -- Spray Date: D2 1.68 EQ    46      63.3      42.7 39.2    6 3.36 EQ    27      3.0       90.0 .4     15 5.04 EQ    25      .0        92.5 .1     31 Spray Date: D3 1.68 EQ    34      26.7      84.0 11.2    6 Spray Date: D4 1.68 EQ    51      100.0     22.0 66.6    6 3.36 EQ    36      15.0      88.0 7.0    27 5.04 EQ    33      3.5       93.5 1.3     8 Spray Date: D5 1.68 EQ    59      100.0     .0   97.2    2 3.36 EQ    54      100.0     13.0 78.6    3 5.04 EQ    53      76.7      36.7 47.4   15 6.72 EQ    43      50.0      54.0 26.0   14 ______________________________________

This Example shows that the compound evaluated in Examples 1 and 2 has gametocidal activity also in rice.

The rice cultivar S-201 (Japanicum rice) was grown in a greenhouse set at ambient conditions with no additional lighting. Ten to twelve seeds per six inch holeless pot were planted in a soilless medium of Metro-Mix200 supplemented with Oscomote (14-14-14) Controlled Release Fertilizer, Peters (14-7-7) Slow Release Fertilizer and Micromax Micronutrients. Pots were then covered with a sheet of cellophane to reduce soil evaporation. The cellophane was removed 4-5 days after the seedlings had emerged. Pots were later thinned to six plants per pot. Eight weeks after planting 0.12 g of Sequestrene Fe was added to each pot after the appearance of Fe deficiency. Fourteen weeks after planting 1.5 g of Peters (20-19-18) Soluble Fertilizer was added to each pot. Chemical treatments were foliar applied using an atomizer and compressed air in a test using four rates on four dates in a 15 ml carrier solution of 100% H20-0.2% Tween20.* Untreated controls were included for comparisons. Approximately twenty-one weeks after planting, plants were evaluated for percentage seed set and observations on vegetative phytotoxicity recorded. Pot:    Pot number PS:     Percent sterility where sterility is equal to the approximate percentage of kernels in the green panicles which were sterile. Panicle Observations: N = normal appearing panicle, W = white panicle where panicle is totally sterile and appears to have dried up. Emergence of panicle from the boot: fully emerged-  panicle totally out of the boot 0       fully emerged- only partial emergence of panicle from boot 0 emerged- no panicles emerged from boot Vegetative Damage: VD = vegetative damage LF TIP CHL = leaf tip chlorosis SL = slight, SEV = severe, MOD = moderate, V SL = very slight Treatment with the compound occurred as follows: Rates:      2.8, 5.6, 8.4 and 11.2 Kg/H Dates:      Planted = July 2 Spraydates D1 = Sept. 10 D2 =       Sept. 17 D3 =       Sept. 19 D4 =       Sept. 19 D5 =       Sept. 20 Heading Date = Sept. 21 Results: Table III contains the detailed observations. ______________________________________

Summary:

The compound tested was an active male sterilant on rice. Early applications (D1-approximately 1-cm panicle length) at high rates (5.6-11.2 Kg/H) resulted in a reduction in plant height, severe vegetative damage, and a failure of the majority of the panicles to emerge from the boot. Even at the 2.8 Kg/H rate there was a significant reduction in the number of panicles per pot on the D1 spray date.

Later dates [D2-D4(late boot)] of application showed slight to moderate vegetative damage depending on the rate, but the vegetative damage was significantly less than the D1 applications. __________________________________________________________________________ Pot PS  Panical Obs.    Vegetative Damage __________________________________________________________________________ Rate: 0.0 Kg/H Date: 1  949 0%  17N-ALL FULLY EMERG NO VD, SOME LF TIP CHL Date: 2  950 0%  21N-ALL FULLY EMERG NO VD, SOME LF TIP CHL Date: 3  951 0%  26N-ALL FULLY EMERG NO VD, SOME LF TIP CHL, MANY NEW TILLERS Date: 4  952 0%  16N-ALL FULLY EMERG NO DV, SOME LF TIP CHL Rate: 2.8 Kg/H Date: D1 940 >90% 4N-) FULLY EMERG SL.VD, LF TIP CHL, MANY NEW TILLERS 918 <50% 3W, 8N-MOST HAVE EMERG SL.VD, V.SL.LF TIP CHL, MANY NEW TILLERS 908 100% 1W, 3N-0 FULLY EMERG SL.VD, LF TIP NEC, MANY NEW TILLERS Date: D2 943 >50% 1W, 17N-0 EMERG NO VD, LF TIP CHL 902 <50% 1W, 12N-MANY NOT NO VD, THIN STAND, LF TIP CHL FULLY EMERG 925 >50% 14N-0 FULLY EMERG NO VD, LF TIP CHL Date: D3 915 >50% 4W, 13N-MOST HAVE EMERG VD = 0 TO V.SL. 933 <75% 2W, 19N-MOST HAVE EMERG NO VD, LF TIP CHL 924 <50% 3W, 11N-SEVERAL EMERGED NO VD, LF TIP CHL Rate: 2.8 Kg/H Date: D4 911 >50% 17N-0 FULLY EMERG SL, VD, LF TIP CHL, A FEW NEW TILLERS 945 <50% 3W, 14N-2 HAVE EMERG SL.VD, LF TIP CHL, MANY NEW TILLERS 932 <75% 2W, 15N-MANY FULLY V.SL.VD, LF TIP CHL, MANY NEW TILLERS EMERG Rate: 5.6 Kg/H Date: D1 939 100% 4N-0 EMERG      SL. VD, LF TIP CHL 907    NO PANICLES     MOD. VD, CHL 919    NO PANICLES     MOD. VD, CHL Date: D2 926 >50% 2W, 13N-0 FULLY EMERG NO VD, SL. CHL 941 100% 1W, 16N-0 FULLY EMERG V. SL. VD, SL. CHL 904 >50% 5W, 9N-0 FULLY EMERG NO VD, LF TIP CHL Date: D3 921 >50% 7W, 7N-0 FULLY EMERG SL. VD, LF TIP CHL 913 >50% 10W, 5N-2 HAVE EMERG SL. VD, LF TIP CHL 934 100% 7W, 7N-0 FULLY EMERG NO VD, LF TIP CHL Date: D4 910 >75% 7W, 7N-0 FULLY EMERG SL.VD, LF TIP CHL.F FEW NEW TILLERS 930 >75% 3W, 10N-0 FULLY EMERG SL.VD, SL. CHL, A FEW NEW TILLERS 946 <>50% 11W, 9N-0 FULLY EMERG V.SL.VD, LF TIP CHL, MANY NEW TILLERS Rate: 8.4 Kg/H Date: D1 937    NO PANICLES     SEV. VD, NECR 906    NO PANICLES     SEV. VD, NECR 917    NO PANICLES     SEV. VD, CHL, LF TIP NECR Date: D2 903 100% 4W, 8N-0 FULLY EMERG V. SL. VD, LF TIP CHL 928 >75% 2W, 11N-1 EMERGED V. SL. VD, SOME CHL 942 100% 8W, 5N-0 EMERG  V. SL. VD, LF TIP CHL Date: D3 935 >90% 9W, 5N-0 FULLY EMERG SL. VD, LF TIP CHL 914 100% 10W, 7N-0 FULLY EMERG V. SL. VD, LF TIP CHL 922 100% 5W, 13N-0 EMERG MOD. VD, LF TIP NECR Date: D4 948 100% 8W, 6N-0 FULLY EMERG SL. VD, SOME CHL, A FEW NEW TILLERS 931 100% 7N-0 EMERG      SL. VD, CHL 909 100% 2W, 1N-0 EMERG  SL. VD, CHL Rate: 11.2 Kg/H Date: D1 938    NO PANICLES     SEV. VD, NECR 920    NO PANICLES     SEV. VD, NECR. 905    NO PANICLES     SEV. VD, CHL, LF TIP NECR Date: D2 944 > 50% 7W, 9N-A FEW EMERG V. SL. VD, LF TIP CHL 927 100% 1W, 5N-0 EMERG SEV SL. VD, SOME CHL DISEASE 901 >90% 2W, 8N-0 EMERG  NO VD, LF TIP CHL Date: D3 923 100% 14W, 2N-0 FULLY EMERG SL. VD, LF TIP CHL SEV DISEASE 936 >90% 6W, 9N-0 FULLY EMERG SL. VD, LF TIP CHL 916 100% 10N-0 EMERG SEV V. SL. VD, SOME CHL DISEASE Rate: 11.2 Kg/H Date: D4 912 100% 7W, 10N-0 EMERG SL. VD, CHL 947 100% 5W, 6N-0 EMERG  SL. VD, SOME CHL 929 100% 2W, 2N-0 EMERG  SL. VD, CHL __________________________________________________________________________

This Example shows the application of the compound tested in Examples 1 to 3 is a gametocide for dicotyledonous plants such as soybeans.

A field experiment was conducted in which 1.12 and 5.6 Kg/H of the compound was applied to (cv Nathan, MGV) soybean at first flower appearance (on August 10). Pollen was sampled on August 29 and viability was measured using the I-KI starch test. The 1.12 Kg/H rate contained 75-95% viable pollen compared to a control. No viable pollen was detected in plants treated at the 5.6 Kg/H rate. Observations on November 2 indicated the plants treated at the higher rate were functionally sterile, i.e., they had few or no pods.

This Example details the evaluation of the herbicidal activity of (A) the bis(2-hydroxyethyl)ester of glyphosate and (B) the mono (2-hydroxyethyl)ester of glyphosate.

The procedure used was the same as that described in Example 2. The evaluation was conducted on the same varieties of wheat and spraying was performed on the same spray dates.

The results obtained are set forth on Table IV. ______________________________________ Vegeta-                Hybrid Rate      Height  tive     Sterility Yield  Seed Kg/H      cm      Damage   %      G/Meter (%) ______________________________________ A DK235   62      100.0    4.1    115.2  -- Control Spray Date: D2 1.68 EQ   53      93.3     15.3   79.5   2 3.36 EQ   46      21.7     63.3   28.1   8 5.40 EQ   31      3.5      84.5   2.2    2 6.72 EQ   28      3.5      80.5   2.4    4 Spray Date: D3 1.68 EQ   58      93.3     2.0    100.1  1 3.36 EQ   51      55.0     44.0   62.8   11 5.40 EQ   43      25.0     58.7   30.6   11 6.72 EQ   35      11.7     70.0   9.6    21 Spray Date: D4 1.68 EQ   65      100.0    6.7    106.4  0 3.36 EQ   62      98.3     9.3    89.4   2 5.40 EQ   60      93.3     20.7   95.5   0 6.72 EQ   55      70.0     22.3   70.9   8 Spray Date: D5 1.68 EQ   64      100.0    2.0    117.2  1 3.36 EQ   63      100.0    8.0    104.9  1 5.40 EQ   58      71.7     29.3   73.8   4 6.72 EQ   58      48.3     31.7   62.6   8 B DK235   62      100.0    4.1    115.2  -- Control Spray Date: D2 1.68 EQ   55      100.0    19.3   89.4   2 3.36 EQ   45      35.0     56.0   43.5   3 5.40 EQ   38      15.0     81.3   22.7   7 6.72 EQ   34      10.7     85.0   6.4    11 Spray Date: D3 1.68 EQ   62      98.3     5.0    121.2  1 3.36 EQ   55      98.3     43.3   84.2   3 5.40 EQ   52      71.7     52.3   61.0   6 6.72 EQ   50      45.0     58.7   35.0   6 Spray Date: D4 1.68 EQ   60      100.0    2.7    102.8  2 3.36 EQ   65      100.0    9.3    112.4  0 5.40 EQ   62      100.0    32.2   97.3   5 6.72 EQ   59      98.3     35.3   90.8   26 Spray Date: D5 1.68 EQ   62      96.7     12.0   123.1 3.36 EQ   62      100.0    15.3   107.6 5.40 EQ   61      100.0    23.7   93.1 6.72 EQ   59      98.3     65.7   66.9 A McNair 1003 60      100.0    1.8    98.4   -- Control Spray Date: D2 1.68 EQ   58      62.5     27.5   50.9   -- 3.36 EQ   42      35.0     93.0   16.0   13 5.40 EQ   36      7.5      97.0   3.1    35 6.72 EQ   27      5.0      100.0  .9     14 Spray Date: D3 1.68 EQ   63      75.0     .0     70.6   1 3.36 EQ   54      40.0     23.3   46.2   26 5.40 EQ   46      23.3     66.7   18.3   30 6.72 EQ   37      9.0      76.3   5.7    18 Spray Date: D4 1.68 EQ   66      88.3     .7     80.7   2 3.36 EQ   66      88.3     16.7   64.4   14 5.40 EQ   51      25.0     51.7   29.5   16 6.72 EQ   51      31.7     52.3   30.2   31 Spray Date: D5 1.68 EQ   63      100.0    .0     102.5  0 3.36 EQ   62      90.0     7.3    85.6   2 5.40 EQ   61      78.3     16.3   67.8   13 6.72 EQ   52      50.0     46.3   44.5   30 C McNair 1003 66      100.0    1.8    98.4   -- Control Spray Date: D2 1.68 EQ   58      65.0     56.0   51.3   16 3.36 EQ   46      30.0     70.5   27.4   10 5.40 EQ   45      25.0     96.0   21.5   10 6.72 EQ   35      10.0     90.0   5.9    14 Spray Date: D3 1.68 EQ   65      95.0     .0     91.0   2 3.36 EQ   60      53.3     10.0   65.6   7 5.40 EQ   56      38.3     46.0   42.3   25 6.72 EQ   52      33.3     74.3   24.6   32 Spray Date: D4 1.68 EQ   66      96.7     1.7    83.3   3 3.36 EQ   61      85.0     39.7   73.1   15 5.40 EQ   55      68.3     61.7   41.6   45 6.72 EQ   54      63.3     72.3   38.6   40 Spray Date: D5 1.68 EQ   61      98.3     1.7    85.7   0 3.36 EQ   61      91.7     9.7    77.9   5 5.40 EQ   61      80.0     34.7   77.5   14 6.72 EQ   57      66.7     41.7   62.5   22 ______________________________________

The following Example summarizes the field and growth chamber results in the evaluation of several candidate gametocides applied to wheat. The evaluation procedures were essentially those described in Examples 1 and 2 above.

The compounds tested conformed to the following formula. ##STR3##

The compounds tested (A through E) had specific formulae as follows: Compound R.sup.1    R.sup.2 R.sup.3 __________________________________________________________________________ A.sup.(1) H          H ##STR4## B.sup.(2) .sup..sym. [NH.sub.3CH(CH.sub.3).sub.2 ] H ##STR5## C      C.sub.2 H.sub.5 COCF.sub.3 ##STR6## D.sup.(3) H          H ##STR7## and ##STR8## E.sup.(3) H          H ##STR9## and ##STR10## __________________________________________________________________________ .sup.(1) with 0.4/mole NaCl and 0.4/mole H.sub.2 O .sup.(2) with 0.75/mole of H.sub.2 O .sup.(3) mixture of isomers with structures indicated

The gametocidal activity and plant toxicity results are set forth in Table V. ______________________________________ Growth Compound           Field          Chamber ______________________________________ A       2.24 Kg/H  moderate activity, -- slight toxicity 8.96 Kg/H  very active, toxicity B       2.24 Kg/H  moderate activity, 7.28 Kg/H slight toxicity Active 4.48 Kg/H  very active, slight toxicity C                  --             3.36 Kg/H Active D       5.6 Kg/H   slight activity, -- low toxicity E       2.24 Kg/H  moderate activity, -- slight toxicity 4.48-      active, toxic  -- 6.72 Kg/H ______________________________________

The following example was designed to evaluate the potential for retention of female fertility in wheat. Winter wheat cultivars were planted and evaluated as for Example 2. In this example, large plots, 1.5.times.1.5M were treated with the themical when the heads of the plants had reached 6 cm in length. %           %      % VEG  PLANT SEEDS  MALE   GRAIN FEMALE HYBRID CULTIVAR SCORE HEIGHT PER HEAD STERILITY YIELD FERTILITY SEED __________________________________________________________________________ B393 Control 100  80    24.3    0     877  100     0 Treated 85  65    0.2    99     379   43    80 Vona Control 100  81    34      0     913  100     0 Treated 48  49    6.9    80      92   10    80 Auburn Control 100  87    34      0     1159 100    NT Treated 70  67    6.1    82     470   40    NT McNair 1003 Control 100  91    30      0     1019 100    NT Treated 50  57    2.8    91     138   13    NT Titan Control 100  94.5  33      0     990  100    NT Treated 90  82.75 1.8    95     454   46    NT __________________________________________________________________________

This example demonstrates the relative field performance of 3 derivatives described in this invention. Winter wheat plants were cultivated and evaluated as described in Example 2. Compounds were sprayed when the heads of the plants had reached 4 cm in length at a rate equivalent to 4.5 lbs./A of compound A. Compound        R ______________________________________ A               --CH.sub.2.CH(OH).CH.sub.2 OH B               --CH.sub.2 --CH.sub.2 --OH C               --CH.sub.2 --CH.sub.2 --CH.sub.2 --OH ______________________________________

The compounds used conform to the following formula: ##STR11## %      GRAIN % CULM  VEG  MALE   YIELD HYBRID COMPOUND GENOTYPE HEIGHT SCORE STERILITY (GMS) SEED __________________________________________________________________________ Controls B393   62    100   4     115   0 McNair 1003 66    100   2     98    0 A       B393   59    85   75     15   23 McNair 1003 47    67   63     37   50 B       B393   61    100  24     93    5 McNair 1003 55    68   62     42   45 C       B393   58    72   29     74    4 McNair 1003 61    78   16     68   13 __________________________________________________________________________

## Claims

1. A process for the production of hybrid seed which comprises applying to a plant, at a time after initiation of sexual development, but before sexual maturity, a compound having the formula: wherein R is hydrogen or a C.sub.1 -C.sub.4 alkyl; R.sup.1 is a hydroxyalkyl group having from 2 to 8 carbon atoms, 1 to 6 hydroxyl groups and 0 or 1 --O--CH.sub.n [phenyl].sub.3-n substituent wherein n is from 0 to 3; R.sup.11 is hydrogen; and X is hydrogen or a --COCF.sub.3 group; as well as agronomically acceptable salts of such compounds wherein said compound is applied in a quantity sufficient to render at least 95% of the plants' male gametes sterile while leaving at least 40% of the female gametes viable, causing the female gametes to be fertilized with pollen from a different cultivar of the same plant variety, and subsequently harvesting hybrid seed from said plant.

2. A process according to claim 1 in which the plant is a monocotylodon.

3. A process according to claim 2 in which the plant is wheat.

4. A process for hybridizing wheat which comprises applying an effective amount of a glyceryl monoester of glyphosate to a wheat plant, at a time from 2 to 20 days before flower opening, so as to kill at least 95% of the male gametes while leaving at least 40% of the female gametes viable, pollinating the wheat using pollen from a different cultivars and later harvesting the hybridized seed produced thereby.