CA1136648A - Bromoacetamides - Google Patents

Abstract

Abstract of the Disclosure The invention relates to N-cyclopropyl-2-bromo-acetamide and N-alkyl derivatives thereof having fungicidal and bactericidal properties, and to the preparation of such novel compounds.

Description

~136648 Case 136-6864 Canada BROMOACETAMIDES
The invention relates to bromoacetamides possessing fungicidal and bactericidal properties.
Accordingly, the present invention provides novel bromoacetamides of formula I, cH2\ R
I /CH - N - CO - CH2Br wherein R is hydrogen, straight C2 4alkyl or branched C4alkyl .
R is preferably hydrogen or n-propyl.

The present invention also provides a process for producing a compound of formula I, which comprises 10 reacting a compound of formula II

CH
¦ ~CH - NH - R II

wherein R is as defined above with 2-bromo-acetylbromide.

The process of the invention may be carried out in a manner known E~ se for the production of haloacetamides.
15It may e.g. be effected in an inert organic medium, preferably in the presence of an acid acceptor, e.g. a trialkyl amine such as triethylamine.

113~648

- 2 - 136-6864 The preparation of the compound of formula I
wherein R is hydrogen, hereinafter designated compound Iat is preferably effec'~ed at reduced temperatures, especially from about -10 to about +5C, preferably at about 0CC.
The preparation of the compounds of formula I
wherein R is not hydrogen (compounds Ib) is preferably ' effected at moderate ternperature, e.g. from about 15 to 35C, more preferably from about 20 to 2SC.
The reaction is preferably effected under essentially 10 anhydrous conditions. Suitable inert organic media include halogenated hydrocarbons such as CH2C12 and, where any of the reactants or the acid acceptor are liquid at the reaction temperature, an excess thereof.
The compounds of formula I may be recovered and 15 refined by conventional means.
The compounds of formula II as well as 2-bromo-acetylbromide are also known or may be prepared by adapting procedures reported in the literature for the preparation of their known analogs.
The compounds of formula I are indicated for preventing or combatting fungi and bacteria in plants, seeds or soil.

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- 3 - 136-6864 The term "soil", as used herein is intended to embrace any conventional growing medium, whether natural or artificial.
The amount of compound of formula I to be applied to 5 attain the desired effect will, as will be appreciated, depend on various factors such as the locus to be treated,e.g.
whether a plant, soil or seed treatment is envisaged, the species of fungi or bacteria, mode of application, e.g.

whether the compound is applied as a foliar spray, a soil 10 treatment or a seed dressing, the conditions of the treatment such as the time of application, whether the treatment is prophylactic or therapeutic, the compound employed and the like.
However, in general, satisfactory results are 15 obtained when the compound is applied to a locus, e.g.
on crops or to soil, at a rate of from about O.l to lO, preferably about 0.2 to 5 kg (acti~Te ingredient)/hectare.
The treatment may be repeated as required, e.g. at 8 to 30 day intervals. When employed as a seed dressing, 20 satisfactory results are obtained when the compound-is employed at a rate of from about 0.05 to 0.5, preferably about O.l to 0.3 g/kg seed.

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- 4 - 136-6864 Fungi against which compounds I are particularly effective include those of the genus Fusarium sPP ., e.g.
F.o~ysporum f.s~ copersici in tomato F.oxvsporum f.sp.vasjnfectum in cotton F.oxysporum f.sp.cubense in banana F.solani in vegetables F.culmorum in cereals F.graminearum in cereals Verticillium ~., e.g. V. albo-atrum in a wide s~ectrum of 10 economically important crops such as cotton, hop, aifalfa and solanaceous crops; V.theobromae in banana;
ColletotriChum spp., e.g. C.lindemuthian~ in beans;
-Phytophthora s~., e.g. Ph.cactorum, Ph.~arasitica, andPh.cinnamomi. in susceptible plants;
15 Pythium spP., e.g. P.aphanidermatum in sugar beet;
Thielaviopsis basicola on a wide spectrum of crops;
Stereum spp., e.g. Stereum pur~ureum in pip and stone fruit trees; of the Order Ustilaginales, e.g. U.maYdis in corn;
Venturia spp., e.g. V. inaequalis in apples;
Phoma ~., e.g. Ph.betae on sugar beet; and Pyricularia spp., e.g. P.oryzae on rice.
Bacteria against which compounds I are particularly effective include those of the genus ~} ~

~. 1136648

- 5 - 136-6864 Xanthomonas spp., e.g. X.malvacearum in cotton, X.pelargonii in Pelargonium; and Pseudomonas spp., e.g.
P.tomato in tomato, P.syringae in susceptible plants.
Fungi and bacteria of the aforementioned genera cause considerable damage in agriculture, e.g. in tomato, cotton and cereal crops as well as in arboriculture and ornamentals, and are difficult to prevent or combat.
The compounds of the formula I are especially useful against Fusarium, Phytophthora, Ustilaginales, Pythium, Colletotrichum, Stereum, Thielaviopsis, Verticillium, Phoma, Venturia, Pyricularia, Pseudomonas and Xanthomonas.
The compounds may be employed as fungicidal and bactericidal composition comprising a compound of formula I and an inert fungicide or bactericide carrier.
In general, such compositions contain from about 0.01 to 90%, preferably from about 0.1 to 60% by weight of active agent. They may be in concentrate form, for dilution down prior to application, or in dilute, ready to apply form. As examples of particular forms may be given wettable powder, emulsion concentrate, dusting, spraying, granulate and delayed release forms, incorpora-ting conventional carriers and such other diluents and/or adjuvants conventional in the agro-chemical art. Emulsion concentrate forms generally contain from about 10 to 70~, preferably about 20 to 60~ by weight of active ingredient.

- 6 - 136-6864 Solid, especially particulate compositions are preferred.
The compositions particularly adapted for spraying, preferably include a surfactant such as a li~uid poly-glycol ether, 2 fatty alkyl sulphate or a lignin sulphonate.
~oreover, further fungicides, bacteriaidal or other beneficially-acting materials, such as insecticides, may be present in the formulations and are contemplated as urther e~bodiments of this invention.
- Concentrate forms of compositions for fungici~e use 10 genexally contain between about 2 and 80~, preferab].y between about 5 and 70~, by weight of a compound of formula I as active agent. Application forms of those compositions generally contain between about 0.01 and 10~, by weight of a compound of formula I as active agent.
The fungicidal/bactericidal activity of compounds of formula I is indicated by conventional tests such as described below:

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- 7 - 136-6864 Test method A: In vivo test employing Tomato ~ilt (Fusarium ox~sporun f.s~. lycoPersici) .

Lycopersicon esculentum cv. 'Rheinland's Ruhm' (tomato) is cultivated in a mixture of peat and sand in planter boxes for 10 days. Vapour-sterilized peat is infested with Fusarium-inoculum and the mixture then ~ treated by a soil mix method to give concentrations of 160, 40 and 10 ppm of active ingredient per volume of soil. After transfer of the treated, infested peat to 10 plastic pots of 6 cm diameter, the pots are planted with tomato seedlings from ~he planter boxes. The plants are - incubated at a temperature of 27C and G0-70% rH for 21 days. The efficacy of the active agent treatment is determined by comparing the degree of wili (symptoms) with 15 that of untreated, similarly inoculated check plants.
In the case of each of the compounds of Examples 1 - to 3, particularly in the case of the compounds of Examples 1 and 2, a fungicidal activity is observed.
An analogous test with simialr results is run on 20 Pythium aphanidermatum on cucumber and Phoma beta on sugar beet.

Test method B: In vitro test employing ~aydis (corn smut).

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~13664~

- 8 - 136-6&64 Different concentrations of the active ingredient are incorporated in malt agar plates to give concentrations of 0.8 to 200 ppm a.i.. The plates are then inoculated by spraying a spore suspension o~ U. maydis onto tllem or placing an agar plug containing the fungus in the centre of the plate. The plates are incuba~ed at room temperature for 2-5 days. The efficacy of the active agent treatm~nt is determined by comparing the growth of the fungus with that in untreated, similarly inoculated plates.
In the case of each of the compounds of Examples 1 to 3, particularly in the case of the compounds of Examples 1 and 2, fungicidal activity is observed.
Analogous tests with similar results are run on the follo~ing fungi/bacteria:
Venturia inaequalis, Pyricularia oryzae, Phyto~hthora cactorum, Stereum purpureum, Thielaviopsis basicola, Verticillium albo-atrum, Co]letotrichum lindemuthianum, Pseu~omonas tomato and Xanthomonas _ . . , ~elarqonii.

In addition to conventional carrier and surface-active materials, formulations of the compound of formuia I of the invention may also contain further additives with special purposes e.g. stabilizers, deactivators (for solid formu-25 lations on carriers with an active surface), agents for lmproving the adhesion to plants, corrosion inhibitors, ,, . ~

- 9 - 136-6864 anti-foaming agents and colorants.
Examples of the produc~ion of fungicide and bacteria-cides formulations are as follows:
a) Granulate 5 g of a compound of formula I e.g. 2-bromo-N-cyclo-propyl-acetamide or 2-bromo-N-cyclopropyl-N-n-propyl-acetamide are dissolved in 10 g of an aromatic solvent preferably with a boiling point within the range of 135-213C. The solution is sprayed onto 90 g of crushed, thoroughly sieved pumice ~grain size 0.3 - 1 mm) by a conventional technique.

b) Emulsion - Concentrate 25 Parts by weight of a compound of formula I, e.g.
2-bromo-N-cyclopropyl-acetamide or 2-bromo-N-cyclopropyl-N-n-propyl-acetamide are mixed with 30 parts by weight of iso-octyl phenyl octaglycol ether and 45 parts by weight of a petroleum fraction with a boiling range of 210-280C
(D2o:0.92). The concentrate is diluted with water to the desired concentration.
c) Wettable Powder -50 Parts by weight of a compound of formula I, e.g.
2-bromo-N-cyclopropyl-acetamide or 2-bromo-N-cyclopropyl-N-n-propyl-acetamide are mixed with 2 parts by weight of sodium lauryl sulphate, 3 parts by weight of sodiu~
lignin sulphonate and 45 parts by weight of ~aolinite.
The concentrate can be diluted with water to the desired ~ , .

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- 10 - 136-6864 concentration.

d) Seed dressinq 45 Parts by weight of a compound of formula I, e.g.
2-bromo-N-cyclopropyl-acetamide or 2-bromo-N-cyclopropy]-N-n-propyl-acetamide are mixed with 1.5 parts of diamyl-phenoldecaglycolether ethylene oxide adduct, 2 parts ofspindle oil, 51 parts of fine talcum and 0.5 parts of colorant rhodamin B. The mixture is ground in a contra-plex mill at 10,000 rpm until an average particle size of less than 20 microns is obtained. The resulting dry 10 seed dressing powder has good adherance and may be applied to seeds, e.g. by mixing for 2 to 5 minutes in a slowly turning vessel.
Other conventional forms such as paints useful in treating plant wounds are also contemplated.
In the following examples, which are illustrative of the invention, temperatures are in degrees in centigrade, and room temperature is 20 to 30C, unless indicated otherwise.

~13664,~

~ 136-6864 , Example 1 : 2-Bro~o-N-cyclo~ro~yl-ac2tamide 6.92 ml (0.1 mol) of cyclopropylamine is mixed with 13.9 ml (0.1 mol) triethyl~mine in 250 ml of methylene chloride and cooled to 0. 8.75 ml (0.1 mol) o 2-bromo-acetylbromide dissolved in 50 ml of methylene chloride is added dropwise, with stirring, over a period of 0.75 hou s, maintaining the temperature at 0 with external coolins.
The mixture is allowed to come to room temperature and stirred for an additional 18 hours. lhe reaction mixture is then ~orked up by washing t~ice with 50 ml portions of saturated aq. sodium bicarbonate solution, then 50 ml of brine, drying over anhydrous sodium sulphate, filtering and evaporating the filtrate in vacuo to obtain a tan solid which upon recrystallizing from hexane-methy-lene chloride (9:1) yields the title compound as a tan solid, m.p. 114-116.

Example 2 : 2-Bromo-N-cyclo~ro~yl-N-n-~ro~yl-acetamide 6 g (0.06 mol) of N-cyclopropyl~n-propylamine and 6.12 g (8.6 ml; 0.06 mol) of triethylamine in about ,,~

.:

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- 12 - 136-6~64 150 ml of methylene chloride is placed in a vessel equipped with a skirrer, a gas inlet and an addition funnel. 12.3 g (5.3 ml); 0.06 mol) of ~-bromo-acetyl-bromide in 20 ml of methylene chloride are added at 20 to 25 over a period of 40 min. under dry nitrogen gas with stirring and stirring is continued for an additional hour.
The mixture is then washed 3 times with 30 ml portions of 10~ hydrochloric acid, 3 times with 30 ml portions of 10 aq. sodium bicarbonate solution and twice with 30 ~ll 10 portions of brine, dried over anh. magnesium sulphate, and the solvent removed by evaporation to obtain crude title product which is refined by distilling at 100 at 0.2 mm Hg using a kugelrohr apparatus.
N-Cyclopropyl-n-propylamine used as starting 15 material is obtained by reaction of cyclopropylamine with propionyl chloride and reduction of the so obtained N-cyclopropyl-propylamide (m.p. 39-41) with borane in tetrahydrofuran.
Example 3 Following the procedure of Example 2, but in place 20 of the N-cyclopropyl-n-propylamine used therein, using an approximately equivalent amount of A~

.

a~ N-cyclopropyl--ethylamine;
b) N-cyclopropyl-n-butylamine or c) N-cyclopropyl-sec.butylamine there is accordingly obtained, respectively:

a) 2-bromo-N-cyclopropyl-N-ethyl-acetamide;
b) 2-bromo-N-cyclopropyl-~-n-butyl-acetamide and c) 2-bromo-N-cyclopropyl-N-sec.-butyl-acetamide.

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Claims (3)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A compound of formula I

wherein R is hydrogen, straight C2-4alkyl or branched C4alkyl.

2. The compound of Claim 1, in which R is H.

3. A process for the production of a compound of formula I as defined in Claim 1, which comprises reacting a compound of formula II

II

wherein R is as defined in Claim 1, with 2-bromo-acetylbromide.