EP4558468A2 - Nitrification inhibiting heterocycles - Google Patents

Nitrification inhibiting heterocycles

Info

Publication number
EP4558468A2
EP4558468A2 EP23843911.1A EP23843911A EP4558468A2 EP 4558468 A2 EP4558468 A2 EP 4558468A2 EP 23843911 A EP23843911 A EP 23843911A EP 4558468 A2 EP4558468 A2 EP 4558468A2
Authority
EP
European Patent Office
Prior art keywords
nhch
mmol
haloalkyl
ethynyl
alkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP23843911.1A
Other languages
German (de)
French (fr)
Inventor
Peter BAAS
Steve Brown
Adel Hamza
David M. Jones
Muhammad M. KHALIFA
David Mann
Jeffrey Petkus
John C. ROHANNA
Greg SCHULENBERG
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Corteva Agriscience LLC
Original Assignee
Corteva Agriscience LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Corteva Agriscience LLC filed Critical Corteva Agriscience LLC
Publication of EP4558468A2 publication Critical patent/EP4558468A2/en
Pending legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P15/00—Biocides for specific purposes not provided for in groups A01P1/00 - A01P13/00
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/08—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with oxygen as the ring hetero atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/58—1,2-Diazines; Hydrogenated 1,2-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system

Definitions

  • Nitrogen is an essential element for plant health.
  • bound nitrogen for plant nutrition can be present in the form of ammonium compounds or nitrates.
  • the ammonium form of nitrogen is preferred because it is readily incorporated into plants.
  • nitrate nitrogen must be reduced to ammonium by the plant before it can be used – an energetically costly process.
  • Ammonium nitrogen, having a positive charge, is tightly bound to growing media.
  • Nitrogen in the form of nitrate is negatively charged, water soluble, not tightly bound to growing media and is readily washed out.
  • Ammonia-oxidizing bacteria of the genera Nitrosomonas and Nitrobacter oxidize ammonium nitrogen to nitrate nitrogen via nitrite nitrogen. This process is known as nitrification. The extent of nitrification is dependent on the temperature, type of growing medium, pH, moisture content and biological activity. The nitrification process leads to ammonium nitrogen loss and nitrate nitrogen creation. As much as half of applied nitrogen fertilizer is lost within a year, and an undesirable concentration of nitrate in the groundwater is promoted by this process.
  • the inhibition of nitrification is particularly important, and is generally considered to consist in selective inhibition of the growth of the above-mentioned bacteria strains.
  • the incorporation of certain chemical compounds in critical quantities into growing media are known to have a pronounced effect on nitrification – the conversion of reduced nitrogen such as ammonia or ammonium ions into higher oxidized forms, particularly into the nitrate form.
  • Prevention of such nitrification in growing media is known to be beneficial and desirable from the economic and agronomic points of view since it enhances plant health, enhances crop yields, and lessens nitrate runoff.
  • nitrification inhibitors including linoleic acid, a-linoleic acid, methyl-p- coumarate, methyl ferulate, MHPP, Karanjin, brachialacton, 2-chloro-6-trichloromethylpyridine (nitrapyrin), dicyandiamide, 3,4-dimethylpyrazole phosphate, 4-amino-1,2,4-triazole hydrochloride, 1-amido-2-thiourea, 2-amino-4-chloro-6-methylpyrimidine, 5-ethoxy-3- trichloromethyl-1,2,4-thiodiazole, 2-sulfanilamidethiazole, 3,5-dimethyltetrahydro-1,3,5- thiadiazine-2-thione (dazomet).
  • Nitrification inhibition has been disclosed in the following publications: US 3,494,757 and US 3,635,690, German Laid Open Application DOS 2,745,833 and GB 1,592,516. See also U.S. 3,050,380 Goring; GB 970,663 Watkins; US 3,533,774 Nault; US 4,673,429 Rieber, et al; US 4,925,476 Wagner et al; US 2015/0052960 Makin et al; US 2017/0036969 Nave et al; US 2020/0352162 Cunningham et al; WO 2015/158853 Nave et al; WO 2020/002472 Cunningham et al; WO 2020/020765 Nesvadba et al; WO 2020/020777 Nesvadba et al.
  • nitrification inhibitors lack traits that are beneficial to their users.
  • dazomet is known to have a very non-specific action and attack non-target bacteria in growing media, especially in soil.
  • Nitrification inhibition is also useful for lowering the production of nitrate in growing media – particularly in soil – thereby reducing the amount unwanted nitrate in groundwater.
  • Methods of employing the compounds include applying to and/or incorporating into growing media (e.g., soil) an effective amount of nitrification-inhibiting alkynyl heterocycle.
  • growing media e.g., soil
  • Preferred compounds include an ethynyl-thiazole, an ethynyl-oxazole, an ethynyl-isoxazole, or mixtures thereof.
  • growing medium and growing media are defined as materials in which plants grow.
  • Exemplary growing media include, but are not limited to, soil, perlite, pumice, vermiculite, zeolite, compost, peat moss, coconut coir, sand, silt, clay, water, bark, sawdust, water, and limestone.
  • Exemplary growing media may be outdoor-soil-based or hydroponic.
  • alkyl refers to a C 1 – C 6 branched or unbranched group consisting of carbon and hydrogen atoms.
  • Alkyl groups include for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i- butyl, s-butyl, t-butyl and the like.
  • alkoxy refers to a O-C 1 – C 6 group where the oxygen atom is connected to a C 1 – C 6 branched or unbranched alkyl group.
  • Alkoxy groups include for example methoxy, ethoxy, propoxy, iso-propoxy, butoxy, iso-butoxy, sec-butoxy, tert-butoxy and the like.
  • thioalkyl refers to a S-C 1 – C 6 group, branched or unbranched, where the sulfur atom is connected to a C 1 – C 6 alkyl group.
  • Thioalkyl groups include for example thiomethyl, thioethyl, thiopropyl, thioisopropyl, thiobutyl, thioisobutyl, thiosecbutyl, thiotertbutyl, and the like.
  • cycloalkyl refers to a C3 – C6 group where the carbon atoms form a carbocyclic ring.
  • Cycloalkyl groups include for example cyclopropane, cyclobutane, cyclopentane, cyclohexane and the like.
  • alkenyl refers to a C 2 – C 6 to a branched or unbranched group consisting of carbon and hydrogen atoms and having one or more double bonds between carbon atoms.
  • Alkenyl groups include for example ethylene, propene, 1-butene, 2-butene, isobutene and the like.
  • cycloalkenyl refers to a C 3 – C 6 where the carbon atoms for a carbocyclic ring and contain one or two double bonds.
  • Cycloalkenyl groups include for example cyclopropene, cyclobutene, cyclopentene, cyclohexene, cyclopentadiene, 1,4-cyclohexadiene and the like.
  • halo refers to halogen atoms such as F, Cl, Br, and I.
  • haloalkyl refers to a C 1 – C 6 branched or unbranched alkyl group where one or more hydrogen atoms has been replaced with a halogen atom.
  • Haloalkyl groups include for example fluoromethyl, difluoromethyl, trifluoromethyl, chloroethyl, bromoethyl, iodobutyl, dichloroethyl, and the like.
  • haloalkoxy refers to a C 1 – C 6 group where the oxygen atom is connected to a C 1 – C 6 branched or unbranched alkyl group where one or more hydrogen atoms has been replaced with a halogen atom.
  • Halolkoxy groups include for example trifluoromethoxy, difluoroethoxy, chloropropoxy, bromo-iso-propoxy, dibromobutoxy, and the like.
  • haloalkenyl refers to a C 2 – C 6 to a branched or unbranched group consisting of carbon and hydrogen atoms where one or more hydrogen atoms has been replaced with a halogen atom and having one or more double bonds between carbon atoms.
  • Haloalkenyl groups include for example 1-chloroethylene, 3,3-difluoropropene, 4-bromo-1-butene, and the like.
  • N-oxide includes any compound which has at least one tertiary nitrogen atom that is oxidized to an N-oxide moiety. N-oxides may be formed for example through oxidation of tertiary amines, such as pyridine, by hydrogen peroxide.
  • salts and agriculturally acceptable salts include hydrofluorides, hydrochlorides, hydrobromides, hydroiodides, nitrates, hydrogensulfates, sulfates, dihydrogenphosphates, hydrogenphosphates, phosphates, carbonates, bicarbonates, oxalates, and C 1 – C 6 branched or unbranched alkanoates – such as formates, acetates, n-propionates, i-propionates, and the like.
  • carrier includes a liquid or solid carrier.
  • a carrier may include an organic or inorganic carrier.
  • Exemplary liquid carriers include, but are not limited to: water; petroleum fractions or hydrocarbons, such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils, such as soybean oil, rapeseed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; esters of monoalcohols or dihydric, trihydric, or other lower polyalcohols (4-6 hydroxy containing), such as 2-ethyl hexyl stearate, n- butyl oleate, isopropyl myristate, propylene glycol dioleate, di-octyl succinate, di-butyl adipate, di-octyl phthalate and the like; esters of mono, di and polycarboxylic acids and the like; toluene;
  • Exemplary solid carriers include, but are not limited to: silicas, silica gels, silicates, talc, kaolin, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, ground synthetic materials, pyrophyllite clay, attapulgus clay, kieselguhr, calcium carbonate, bentonite clay, Fuller's earth, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, lignin, ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas, cereal meal, tree bark meal, wood meal, nutshell meal, cellulose powders, and mixtures thereof.
  • Fertilizers including but limited to, fertilizers comprising ammonia may be used as carriers.
  • exemplary fertilizers comprise, but are not limited to, anhydrous ammonium, ammonium salts such as ammonium nitrate, calcium ammonium nitrate, ammonium sulfate nitrate, ammonium sulfate or ammonium phosphate; organic ammonia sources, such as manure, biogas, worm castings, compost, seaweed or guano; urea-containing fertilizers such as, urea, formaldehyde urea, urea ammonium nitrate solution, urea sulfur, urea ammonium sulfate, or other urea-based fertilizers.
  • surfactant or surfactants include, but are not limited to: the alkali metal salts, alkaline earth metal salts and ammonium salts of fatty acids or of aromatic sulfonic acids (e.g., lignosulfonic acids, phenolsulfonic acids, naphthalenesulfonic acids, and dibutylnaphthalenesulfonic acid); alkyl- and alkylarylsulfonates; alkyl sulfates, lauryl ether sulfates and fatty alcohol sulfates; salts of sulfated hexa-, hepta- and octadecanols; salts of fatty alcohol glycol ethers; condensates of sulfonated naphthalene and its derivatives with formaldehyde; condensates of naphthalen
  • adjuvant includes agriculturally acceptable adjuvants.
  • exemplary agriculturally acceptable adjuvants include, but are not limited to, antifreeze agents, antifoam agents, compatibilizing agents, sequestering agents, neutralizing agents and buffers, corrosion inhibitors, colorants, odorants, penetration aids, wetting agents, spreading agents, dispersing agents, thickening agents, freeze point depressants, antimicrobial agents, crop oil (concentrates), adhesives (for instance, for use in seed treatment formulations), surfactants, protective colloids, emulsifiers, tackifiers, and mixtures thereof.
  • Exemplary agriculturally acceptable adjuvants include, but are not limited to, crop oil concentrates (e.g., 85% mineral oil + 15% emulsifiers); nonylphenol ethoxylates; benzylcocoalkyldimethyl quaternary ammonium salts; blends of petroleum hydrocarbon, alkyl esters, organic acids, and anionic surfactants; C 9 -C 11 alkylpolyglycoside; phosphate alcohol ethoxylates; natural primary alcohol (C 12 -C 16 ) ethoxylate; di-sec-butylphenol EO-PO block copolymers; polysiloxane-methyl cap; nonylphenol ethoxylate+urea ammonium nitrates; emulsified methylated seed oils; tridecyl alcohol (synthetic) ethoxylates (e.g., 8 EO); tallow amine ethoxylates (e.g., 15 EO); and PEG(
  • Exemplary agriculturally acceptable adjuvants include, but are not limited to, thickening agents (i.e., thickeners).
  • Exemplary thickeners include, but are not limited to, polysaccharides (e.g., xanthan gum), organic and inorganic sheet minerals, and mixtures thereof.
  • Exemplary agriculturally acceptable adjuvants include, but are not limited to, antifoam agents.
  • Exemplary antifoam agents include, but are not limited to, silicone emulsions, long-chain alcohols, fatty acids, fatty acid salts, organofluorine compounds, and mixtures thereof.
  • Exemplary agriculturally acceptable adjuvants include, but are not limited to, antifreeze agents.
  • Exemplary antifreeze agents include, but are not limited to ethylene glycol, propylene glycol, urea, glycerol, and mixtures thereof.
  • Exemplary agriculturally acceptable adjuvants include, but are not limited to, colorants.
  • Exemplary colorants include, but are not limited to, the dyes known under the names Rhodamine B, pigment blue 15:4, pigment blue 15:3, pigment blue 15:2, pigment blue 15:1, pigment blue 80, pigment yellow 1, pigment yellow 13, pigment red 112, pigment red 48:2, pigment red 48:1, pigment red 57:1, pigment red 53:1, pigment orange 43, pigment orange 34, pigment orange 5, pigment green 36, pigment green 7, pigment white 6, pigment brown 25, basic violet 10, basic violet 49, acid red 51, acid red 52, acid red 14, acid blue 9, acid yellow 23, basic red 10, basic red 108, and mixtures thereof.
  • Exemplary agriculturally acceptable adjuvants include, but are not limited to, adhesives.
  • Exemplary adhesives include, but are not limited to, polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, tylose, and mixtures thereof.
  • an agriculturally effective amount of compound is an amount of compound that produces a measurable effect on one or more of: ammonium nitrogen, nitrification inhibition, nitrate formation, increased plant health, increased plant growth, increased plant or crop yield, bacteria of the genera Nitrosomonas and Nitrobacter.
  • compound or “compounds” comprise chemicals defined by molecular structure formulas and/or chemical names as well as their tautomers, salts, N-oxides, and stereoisomers.
  • Compounds described herein are nitrification inhibitors.
  • One or more compounds described herein may be incorporated into a composition comprising other ingredients such as carriers, surfactants, and adjuvants.
  • the composition optionally may include a source of ammonia.
  • Sources of ammonia include anhydrous ammonia, urea, urea-ammonium nitrate, and manure.
  • the compound or composition may be mixed directly with the ammonia source.
  • the mixture of compound or composition and ammonia source may be applied directly to a growing medium, such as soil.
  • the compound or composition and the ammonia source may be applied separately to the growing medium, such as soil.
  • the compound or composition and the ammonia source may be applied separately and simultaneously.
  • a compound or composition may be applied before planting or after planting.
  • a compound or composition may be applied pre- emergence or post-emergence.
  • a nitrification inhibiting composition or method provided herein comprises one or more of the following compounds and agriculturally acceptable salts, tautomers, stereoisomers, and N-oxides thereof: R 1 R 1 R 1 N O N R N S 4 N R3 R2 R3 R2 R 3 R 2 Formula I Formula II Formula III, where R 1 -R 4 are independently H, ethynyl, trimethylsilyl-ethynyl, C 1 – C 6 alkoxy, C 1 – C 6 thioalkyl, C 1 – C 6 alkyl, C 3 – C 6 cycloalkyl, C 1 – C 6 alkenyl, C 3 – C 6 cycloalkenyl, C 1 – C 6 haloalkyl, C 1 – C 6 haloalkenyl, C 1 – C 6 haloal
  • R 11 and R 14 are independently C ⁇ C, C ⁇ C-TMS, C ⁇ CMe, OEt, OMe, OCF 3 , OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R 11 and R 14 is C ⁇ C or C ⁇ C-TMS.
  • R 12 – R 13 are H.
  • R 21 and R 24 are independently C ⁇ C, C ⁇ C-TMS, C ⁇ CMe, OEt, OMe, OCF 3 , OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R 21 and R 24 is C ⁇ C or C ⁇ C-TMS.
  • R 22 , R 23 , and R 25 are H.
  • R 32 R N 33 R 31 N R34 Formula VI where R 31 and R 33 are independently C ⁇ C, C ⁇ C-TMS, C ⁇ CMe, OEt, OMe, OCF 3 , OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R 31 and R 33 is C ⁇ C or C ⁇ C-TMS.
  • R32, and R34 are H.
  • R 42 N R 43 R 41 N R44 Formula VII where R 41 and R 43 are independently C ⁇ C, C ⁇ C-TMS, C ⁇ CMe, OEt, OMe, OCF 3 , OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R 41 and R 43 is C ⁇ C or C ⁇ C-TMS.
  • R 42 and R 44 are H.
  • R 51 R 52 Formula VIII, where R 51 , R 52 , and R 53 are independently H, C ⁇ C, C ⁇ C-TMS, C ⁇ CMe, OEt, OMe, OCF 3 , OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R 51 , R 52 , or R 53 is C ⁇ C or C ⁇ C-TMS.
  • R 63 R 61 R 62 Formula IX where R 61 , R 62 , and R 63 are independently H, C ⁇ C, C ⁇ C-TMS, C ⁇ CMe, OEt, OMe, OCF 3 , OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R 61 , R 62 , or R 63 is C ⁇ C or C ⁇ C-TMS.
  • R 71 N N R 72 R 74 R 73 Formula X where R 71 , R 72 , R 73 , and R 74 are independently H, C ⁇ C, C ⁇ C-TMS, C ⁇ CMe, OEt, OMe, OCF 3 , OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R 71 , R 72 , R 73 , or R 74 is C ⁇ C or C ⁇ C-TMS.
  • a nitrification inhibiting compound, composition, or method provided herein comprises a compound selected from the group consisting of Si N O N O , , O O Si N O N O , , O O N N N S , S O , S , S N S , , S N ⁇ y E / o N, PO ⁇ I — ( o / ⁇ ⁇ N ⁇ H ⁇ V i A / ⁇ , , , , , , , , , S N O N O O O N N , , , , H Cl , , , , , , , , , , , , Sa , H N" UL , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
  • a nitrification inhibiting compound, composition, or method provided herein comprises a compound selected from the group consisting of S N O N O N , , , , and agriculturally acceptable salts, N-oxides, stereoisomers, and tautomers thereof.
  • a nitrification inhibiting compound is selected from the group consisting of compounds in Table 1, and agriculturally acceptable salts, N-oxides, stereoisomers, and tautomers thereof.
  • Application of Nitrification Inhibitor Compounds to Soil In certain aspects provided herein one or more nitrification inhibitor compounds or compositions are mixed with a source of ammonia.
  • Sources of ammonia include, but are not limited to, anhydrous ammonium, ammonium salts, such as ammonium nitrate, calcium ammonium nitrate, ammonium sulfate nitrate, ammonium sulfate or ammonium phosphate; organic ammonia sources, such as manure, biogas, worm castings, compost, seaweed or guano; urea-containing fertilizers such as, urea, formaldehyde urea, urea ammonium nitrate solution, urea sulfur, urea ammonium sulfate, or other urea-based fertilizers.
  • anhydrous ammonium such as ammonium nitrate, calcium ammonium nitrate, ammonium sulfate nitrate, ammonium sulfate or ammonium phosphate
  • organic ammonia sources such as manure, biogas, worm castings, compost, seaweed or guano
  • one or more of the nitrification inhibitor compounds or compositions are mixed with anhydrous ammonia, which is then injected into the soil.
  • the compound or composition is injected separately into the growing medium at the time of anhydrous ammonia application.
  • the amount of compound or composition present in the anhydrous ammonia mixture, or directly injected, may be adjusted so that an agriculturally effective amount of the nitrification-inhibiting compound or composition is spread.
  • the nitrification inhibitor compound or composition is mixed with fertilizers such as urea-ammonium nitrate solution to form a urea-ammonium nitrate nitrification-inhibitor mixture.
  • mixtures may also include other ingredients such as herbicides, insecticides, fungicides, and safeners.
  • Such mixtures may be applied at rates of from about 10 to about 70 gallons per acre depending on the fertilizer strength and concentration as well as the target amount of nitrogen per acre.
  • the amount of compound or composition present in the treated mixture may be adjusted so that an agriculturally effective amount of the compound or composition is spread.
  • the nitrification compound or composition is impregnated on dry urea. The amount of compound or composition impregnated will depend upon the application rate of the urea. For example, urea may be spread at a rate of from about 200 to about 700 pounds per acre.
  • An amount of compound or composition may be impregnated on dry urea so that the compound or composition is spread at an agriculturally effective amount.
  • the compound or composition is spread as part of a manure slurry mixture.
  • the compound or composition may be mixed with manure prior to application or may be separately applied.
  • the amount of compound or composition present in a manure slurry may be adjusted so that an agriculturally effective amount of compound or composition is spread.
  • a compound or composition may be applied to a growing medium at a rate of from about 50 grams per acre to about 4 kilograms per acre.
  • a compound may be applied to a growing medium at the following rates: 50-60 grams/acre; 60-70 grams/acre; 70-80 grams/acre; 80-90 grams/acre; 90-100 grams/acre; 100-120 grams/acre; 120-140 grams/acre; 140-160 grams/acre; 160-180 grams/acre; 180-200 grams/acre; 200-225 grams/acre; 225-250 grams/acre; 250-275 grams/acre; 275-300 grams/acre; 300-350 grams/acre; 350-400 grams/acre; 400-450 grams/acre; 450-500 grams/acre; 500-550 grams/acre; 550-600 grams/acre; 600-650 grams/acre; 650-700 grams/acre; 700-750 grams/acre; 750-800 grams/acre; 800-850 grams/acre; 850-900 grams/acre; 900-950 grams/acre; 950-1000 grams/acre; 1.0-1.1 kilograms/acre; 1.1-1.2 kilograms/acre; 1.2-1.3 kilograms/acre; 1.3-1.4 kilograms/acre;
  • reaction mixture was cooled to RT, EtOAc (30 mL) was added, filtered through a pad of celite, the filtrate was washed with brine (20 mL), dried over anhydrous Na 2 SO 4 , filtered, and concentrated under reduced pressure.
  • reaction mixture was cooled to RT, EtOAc (30 mL) was added, filtered through a pad of celite, the filtrate was washed with brine (20 mL), dried over anhydrous Na 2 SO 4 , filtered, and concentrated under reduced pressure.
  • reaction mixture was cooled to RT, EtOAc (150 mL) was added and filtered through pad of celite and filtrate was washed with brine (20 mL), dried over anhydrous Na 2 SO 4 , filtered, and concentrated under reduced pressure.
  • Furan-2-carbaldehyde SM-C (0.5 g, 6.41 mmol) was then added into the reaction mixture at -78 °C and stirred for 5h at RT. After completion of the reaction, the reaction mixture was quenched with aq. NH 4 Cl (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na 2 SO 4 , filtered, and concentrated under reduced pressure.
  • the vial was placed in a heating block that was warmed to 80 oC and the solution was stirred for 20 h. After the reaction time, the vial was opened to air and aqueous Na 2 CO 3 was added (4 mL). The crude product was extracted with CH 2 Cl 2 and purified by flash chromatography on silica gel.
  • General Procedure F To a 20 mL vial, sodium alkoxide (1.0 equiv.) was charged. Then a solution of aryl halide (1.0 equiv.) in THF (0.2 M concentration of substrate) was added. The vial was placed in a heating block that was warmed to 50 oC and the solution was stirred for 20 h.
  • the contents were sealed and degassed with nitrogen and the overall reaction concentration was 0.2M. With stirring, ethynyltrimethylsilane (2 equiv) was added neat and the contents were heated to 60 o C overnight for 18 hours. The reaction was quenched with AcOH (10 equiv), the product mass was observed by LCMS. The contents were diluted with EtOAc and partitioned between 2.5 M KHCO3 (2 x) and brine then dried over MgSO 4 . The contents were condensed by rotoary evaporation and the residue was purified by silica-gel chromatography eluting with hexanes/EtOAc 10-100% over 10 minutes to yield the product.
  • Biological Testing Compound Preparation Compounds were dissolved in DMSO at 0.1 mM concentrations.
  • Soil Slurry Preparation Two different soils were sourced from Kalamazoo, Michigan (loamy fine sand) and Windfall, Indiana (clay loam). After collection soils were sieved at 2 mm and stored at 4 °C for no more than 6 months.
  • the slurry is prepared by weighing out 143 grams of field moist soil per liter of nitrification media with a chlorate block (0.8 ⁇ M K 2 HPO 4 ; 0.1 ⁇ M KH 2 PO 4 ; 0.5 ⁇ M(NH 4 ) 2 SO 4 ; 10 ⁇ M NaClO 3 ) and stirring it in a Pyrex dish for 5 minutes.
  • Experimental Approach While stirring, 900 ⁇ L of slurry was pipetted into a 96 deep well plate. After slurry addition, 9 ⁇ L of 0.1 mM stock solution of a compound or solvent control (i.e., DMSO) was immediately added to the designated well to bring the final concentration to 0.1 ⁇ M.
  • a compound or solvent control i.e., DMSO
  • a sealing mat was placed on top of the plate and mixed by inverting the plates three times. Plates were incubated for 48 hours at 28°C while shaking sideways at 225 rpm. After 48 hours the plate was spun down at 3,000 rpm for 15 minutes and the supernatant was analyzed for nitrite concentrations using the colorimetric Griess assay. Nitrification rates were determined by the total amount of nitrite formed over the incubation period. Nitrification inhibition was determined by normalizing the nitrification rate by the DMSO control. The relative inhibition of tested compounds was additionally normalized to the reference nitrification inhibitor nitrapyrin. Results are shown in Table 3. Table 3 Inhibition of Soil Nitrification.

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Abstract

Heterocyclic alkynes useful for nitrification inhibition as well as methods of using heterocyclic alkynes for nitrification inhibition and crop yield enhancement are described.

Description

Nitrification Inhibiting Heterocycles This application claims priority to U.S. Provisional Patent Application No.63/369,015, filed July 21, 2022, which is hereby incorporated herein by reference in its entirety. Background Nitrogen is an essential element for plant health. In growing media (e.g., soil), bound nitrogen for plant nutrition can be present in the form of ammonium compounds or nitrates. The ammonium form of nitrogen is preferred because it is readily incorporated into plants. In contrast, nitrate nitrogen must be reduced to ammonium by the plant before it can be used – an energetically costly process. Ammonium nitrogen, having a positive charge, is tightly bound to growing media. Nitrogen in the form of nitrate is negatively charged, water soluble, not tightly bound to growing media and is readily washed out. Ammonia-oxidizing bacteria of the genera Nitrosomonas and Nitrobacter oxidize ammonium nitrogen to nitrate nitrogen via nitrite nitrogen. This process is known as nitrification. The extent of nitrification is dependent on the temperature, type of growing medium, pH, moisture content and biological activity. The nitrification process leads to ammonium nitrogen loss and nitrate nitrogen creation. As much as half of applied nitrogen fertilizer is lost within a year, and an undesirable concentration of nitrate in the groundwater is promoted by this process. Therefore, the inhibition of nitrification is particularly important, and is generally considered to consist in selective inhibition of the growth of the above-mentioned bacteria strains. The incorporation of certain chemical compounds in critical quantities into growing media are known to have a pronounced effect on nitrification – the conversion of reduced nitrogen such as ammonia or ammonium ions into higher oxidized forms, particularly into the nitrate form. Prevention of such nitrification in growing media is known to be beneficial and desirable from the economic and agronomic points of view since it enhances plant health, enhances crop yields, and lessens nitrate runoff. A number of nitrification inhibitors are known including linoleic acid, a-linoleic acid, methyl-p- coumarate, methyl ferulate, MHPP, Karanjin, brachialacton, 2-chloro-6-trichloromethylpyridine (nitrapyrin), dicyandiamide, 3,4-dimethylpyrazole phosphate, 4-amino-1,2,4-triazole hydrochloride, 1-amido-2-thiourea, 2-amino-4-chloro-6-methylpyrimidine, 5-ethoxy-3- trichloromethyl-1,2,4-thiodiazole, 2-sulfanilamidethiazole, 3,5-dimethyltetrahydro-1,3,5- thiadiazine-2-thione (dazomet). Nitrification inhibition has been disclosed in the following publications: US 3,494,757 and US 3,635,690, German Laid Open Application DOS 2,745,833 and GB 1,592,516. See also U.S. 3,050,380 Goring; GB 970,663 Watkins; US 3,533,774 Nault; US 4,673,429 Rieber, et al; US 4,925,476 Wagner et al; US 2015/0052960 Makin et al; US 2017/0036969 Nave et al; US 2020/0352162 Cunningham et al; WO 2015/158853 Nave et al; WO 2020/002472 Cunningham et al; WO 2020/020765 Nesvadba et al; WO 2020/020777 Nesvadba et al. These references and other references cited in this application, the disclosures of which are hereby incorporated herein by reference in their entirety. Some conventional nitrification inhibitors lack traits that are beneficial to their users. For example, dazomet is known to have a very non-specific action and attack non-target bacteria in growing media, especially in soil. A need still exists for nitrification inhibitors which exhibit nitrification inhibition while lacking less beneficial traits. Summary It has been found that certain alkynyl-heterocycles are useful in controlling nitrification. Specifically, certain ethynyl-thiazoles, ethynyl-oxazoles, and ethynyl-isoxazoles have been found to inhibit nitrification. Such inhibition is useful because it promotes more efficient nitrogen uptake by plants – enhancing crop yields. Nitrification inhibition is also useful for lowering the production of nitrate in growing media – particularly in soil – thereby reducing the amount unwanted nitrate in groundwater. Methods of employing the compounds include applying to and/or incorporating into growing media (e.g., soil) an effective amount of nitrification-inhibiting alkynyl heterocycle. Preferred compounds include an ethynyl-thiazole, an ethynyl-oxazole, an ethynyl-isoxazole, or mixtures thereof. Detailed Description As used herein growing medium and growing media are defined as materials in which plants grow. Exemplary growing media include, but are not limited to, soil, perlite, pumice, vermiculite, zeolite, compost, peat moss, coconut coir, sand, silt, clay, water, bark, sawdust, water, and limestone. Exemplary growing media may be outdoor-soil-based or hydroponic. As used herein alkyl refers to a C1 – C6 branched or unbranched group consisting of carbon and hydrogen atoms. Alkyl groups include for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i- butyl, s-butyl, t-butyl and the like. As used herein alkoxy refers to a O-C1 – C6 group where the oxygen atom is connected to a C1 – C6 branched or unbranched alkyl group. Alkoxy groups include for example methoxy, ethoxy, propoxy, iso-propoxy, butoxy, iso-butoxy, sec-butoxy, tert-butoxy and the like. As used herein thioalkyl refers to a S-C1 – C6 group, branched or unbranched, where the sulfur atom is connected to a C1 – C6 alkyl group. Thioalkyl groups include for example thiomethyl, thioethyl, thiopropyl, thioisopropyl, thiobutyl, thioisobutyl, thiosecbutyl, thiotertbutyl, and the like. As used herein cycloalkyl refers to a C3 – C6 group where the carbon atoms form a carbocyclic ring. Cycloalkyl groups include for example cyclopropane, cyclobutane, cyclopentane, cyclohexane and the like. As used herein alkenyl refers to a C2 – C6 to a branched or unbranched group consisting of carbon and hydrogen atoms and having one or more double bonds between carbon atoms. Alkenyl groups include for example ethylene, propene, 1-butene, 2-butene, isobutene and the like. As used herein cycloalkenyl refers to a C3 – C6 where the carbon atoms for a carbocyclic ring and contain one or two double bonds. Cycloalkenyl groups include for example cyclopropene, cyclobutene, cyclopentene, cyclohexene, cyclopentadiene, 1,4-cyclohexadiene and the like. As used herein halo refers to halogen atoms such as F, Cl, Br, and I. As used herein haloalkyl refers to a C1 – C6 branched or unbranched alkyl group where one or more hydrogen atoms has been replaced with a halogen atom. Haloalkyl groups include for example fluoromethyl, difluoromethyl, trifluoromethyl, chloroethyl, bromoethyl, iodobutyl, dichloroethyl, and the like. As used herein haloalkoxy refers to a C1 – C6 group where the oxygen atom is connected to a C1 – C6 branched or unbranched alkyl group where one or more hydrogen atoms has been replaced with a halogen atom. Halolkoxy groups include for example trifluoromethoxy, difluoroethoxy, chloropropoxy, bromo-iso-propoxy, dibromobutoxy, and the like. As used herein haloalkenyl refers to a C2 – C6 to a branched or unbranched group consisting of carbon and hydrogen atoms where one or more hydrogen atoms has been replaced with a halogen atom and having one or more double bonds between carbon atoms. Haloalkenyl groups include for example 1-chloroethylene, 3,3-difluoropropene, 4-bromo-1-butene, and the like. The term N-oxide includes any compound which has at least one tertiary nitrogen atom that is oxidized to an N-oxide moiety. N-oxides may be formed for example through oxidation of tertiary amines, such as pyridine, by hydrogen peroxide. As used herein salts and agriculturally acceptable salts include hydrofluorides, hydrochlorides, hydrobromides, hydroiodides, nitrates, hydrogensulfates, sulfates, dihydrogenphosphates, hydrogenphosphates, phosphates, carbonates, bicarbonates, oxalates, and C1 – C6 branched or unbranched alkanoates – such as formates, acetates, n-propionates, i-propionates, and the like. As used herein carrier includes a liquid or solid carrier. In some aspects, a carrier may include an organic or inorganic carrier. Exemplary liquid carriers include, but are not limited to: water; petroleum fractions or hydrocarbons, such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils, such as soybean oil, rapeseed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; esters of monoalcohols or dihydric, trihydric, or other lower polyalcohols (4-6 hydroxy containing), such as 2-ethyl hexyl stearate, n- butyl oleate, isopropyl myristate, propylene glycol dioleate, di-octyl succinate, di-butyl adipate, di-octyl phthalate and the like; esters of mono, di and polycarboxylic acids and the like; toluene; xylene; petroleum naphtha; crop oil; acetone; methyl ethyl ketone; cyclohexanone; trichloroethylene; perchloroethylene; ethyl acetate; amyl acetate; butyl acetate; propylene glycol monomethyl ether and diethylene glycol monomethyl ether; methyl alcohol; ethyl alcohol; isopropyl alcohol; amyl alcohol; ethylene glycol; propylene glycol; glycerine; N-methyl-2- pyrrolidinone; N;N-dimethyl alkylamides; dimethyl sulfoxide; and liquid fertilizers, as well as mixtures thereof. Exemplary solid carriers include, but are not limited to: silicas, silica gels, silicates, talc, kaolin, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, ground synthetic materials, pyrophyllite clay, attapulgus clay, kieselguhr, calcium carbonate, bentonite clay, Fuller's earth, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, lignin, ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas, cereal meal, tree bark meal, wood meal, nutshell meal, cellulose powders, and mixtures thereof. Fertilizers, including but limited to, fertilizers comprising ammonia may be used as carriers. Exemplary fertilizers comprise, but are not limited to, anhydrous ammonium, ammonium salts such as ammonium nitrate, calcium ammonium nitrate, ammonium sulfate nitrate, ammonium sulfate or ammonium phosphate; organic ammonia sources, such as manure, biogas, worm castings, compost, seaweed or guano; urea-containing fertilizers such as, urea, formaldehyde urea, urea ammonium nitrate solution, urea sulfur, urea ammonium sulfate, or other urea-based fertilizers. As used herein surfactant or surfactants (e.g., wetting agents, tackifiers, dispersants, emulsifiers) include, but are not limited to: the alkali metal salts, alkaline earth metal salts and ammonium salts of fatty acids or of aromatic sulfonic acids (e.g., lignosulfonic acids, phenolsulfonic acids, naphthalenesulfonic acids, and dibutylnaphthalenesulfonic acid); alkyl- and alkylarylsulfonates; alkyl sulfates, lauryl ether sulfates and fatty alcohol sulfates; salts of sulfated hexa-, hepta- and octadecanols; salts of fatty alcohol glycol ethers; condensates of sulfonated naphthalene and its derivatives with formaldehyde; condensates of naphthalene or of the naphthalene sulfonic acids with phenol and formaldehyde; polyoxyethylene octylphenol ether; ethoxylated isooctyl-, octyl- or nonylphenol, alkylphenyl or tributylphenyl polyglycol ether; alkyl aryl polyether alcohols; isotridecyl alcohol; fatty alcohol/ethylene oxide condensates; ethoxylated castor oil; polyoxyethylene alkyl ethers or polyoxypropylene alkyl ethers; lauryl alcohol polyglycol ether acetate; sorbitol esters; lignosulfite waste liquors and proteins; denatured proteins, polysaccharides (e.g., methylcellulose); hydrophobically modified starches; and polyvinyl alcohol, polycarboxylates, polyalkoxylates, polyvinyl amine, polyethyleneimine, polyvinylpyrrolidone, and copolymers thereof. As used herein adjuvant includes agriculturally acceptable adjuvants. Exemplary agriculturally acceptable adjuvants include, but are not limited to, antifreeze agents, antifoam agents, compatibilizing agents, sequestering agents, neutralizing agents and buffers, corrosion inhibitors, colorants, odorants, penetration aids, wetting agents, spreading agents, dispersing agents, thickening agents, freeze point depressants, antimicrobial agents, crop oil (concentrates), adhesives (for instance, for use in seed treatment formulations), surfactants, protective colloids, emulsifiers, tackifiers, and mixtures thereof. Exemplary agriculturally acceptable adjuvants include, but are not limited to, crop oil concentrates (e.g., 85% mineral oil + 15% emulsifiers); nonylphenol ethoxylates; benzylcocoalkyldimethyl quaternary ammonium salts; blends of petroleum hydrocarbon, alkyl esters, organic acids, and anionic surfactants; C9-C11 alkylpolyglycoside; phosphate alcohol ethoxylates; natural primary alcohol (C12-C16) ethoxylate; di-sec-butylphenol EO-PO block copolymers; polysiloxane-methyl cap; nonylphenol ethoxylate+urea ammonium nitrates; emulsified methylated seed oils; tridecyl alcohol (synthetic) ethoxylates (e.g., 8 EO); tallow amine ethoxylates (e.g., 15 EO); and PEG(400) dioleate-99. Exemplary agriculturally acceptable adjuvants include, but are not limited to, thickening agents (i.e., thickeners). Exemplary thickeners include, but are not limited to, polysaccharides (e.g., xanthan gum), organic and inorganic sheet minerals, and mixtures thereof. Exemplary agriculturally acceptable adjuvants include, but are not limited to, antifoam agents. Exemplary antifoam agents include, but are not limited to, silicone emulsions, long-chain alcohols, fatty acids, fatty acid salts, organofluorine compounds, and mixtures thereof. Exemplary agriculturally acceptable adjuvants include, but are not limited to, antifreeze agents. Exemplary antifreeze agents, include, but are not limited to ethylene glycol, propylene glycol, urea, glycerol, and mixtures thereof. Exemplary agriculturally acceptable adjuvants include, but are not limited to, colorants. Exemplary colorants include, but are not limited to, the dyes known under the names Rhodamine B, pigment blue 15:4, pigment blue 15:3, pigment blue 15:2, pigment blue 15:1, pigment blue 80, pigment yellow 1, pigment yellow 13, pigment red 112, pigment red 48:2, pigment red 48:1, pigment red 57:1, pigment red 53:1, pigment orange 43, pigment orange 34, pigment orange 5, pigment green 36, pigment green 7, pigment white 6, pigment brown 25, basic violet 10, basic violet 49, acid red 51, acid red 52, acid red 14, acid blue 9, acid yellow 23, basic red 10, basic red 108, and mixtures thereof. Exemplary agriculturally acceptable adjuvants include, but are not limited to, adhesives. Exemplary adhesives include, but are not limited to, polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, tylose, and mixtures thereof. As used herein an agriculturally effective amount of compound is an amount of compound that produces a measurable effect on one or more of: ammonium nitrogen, nitrification inhibition, nitrate formation, increased plant health, increased plant growth, increased plant or crop yield, bacteria of the genera Nitrosomonas and Nitrobacter. As used herein “compound” or “compounds” comprise chemicals defined by molecular structure formulas and/or chemical names as well as their tautomers, salts, N-oxides, and stereoisomers. Compounds described herein are nitrification inhibitors. One or more compounds described herein may be incorporated into a composition comprising other ingredients such as carriers, surfactants, and adjuvants. The composition optionally may include a source of ammonia. To enhance plant health and/or improve crop yields, the compound or composition may be applied to a growing medium with or without a source of ammonia. Sources of ammonia include anhydrous ammonia, urea, urea-ammonium nitrate, and manure. The compound or composition may be mixed directly with the ammonia source. The mixture of compound or composition and ammonia source may be applied directly to a growing medium, such as soil. The compound or composition and the ammonia source may be applied separately to the growing medium, such as soil. The compound or composition and the ammonia source may be applied separately and simultaneously. The compound or composition and the ammonia source may be applied separately and sequentially. Sequential application of a compound or composition and a source of ammonia may take place within 24 hours, within 1 to 3 days, within 1 to 5 days, within one week, within two weeks, within three weeks, or within four weeks; between one week and two weeks, between one week and three weeks, or between one week and four weeks; between two weeks and three weeks, or between two weeks and four weeks. A compound or composition may be applied before planting or after planting. A compound or composition may be applied pre- emergence or post-emergence. In certain aspects a nitrification inhibiting composition or method provided herein comprises one or more of the following compounds and agriculturally acceptable salts, tautomers, stereoisomers, and N-oxides thereof: R1 R1 R1 N O N R N S 4 N R3 R2 R3 R2 R3 R2 Formula I Formula II Formula III, where R1-R4 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, wherein at least one of R1 – R4 is C≡C or C≡C-TMS. R1 R1 R1 S N O N R N 4 N R3 R2 R3 R2 R3 R2 Formula I Formula II Formula III, where R1 – R4 are independently H, C≡C, C≡C-TMS, C≡CMe, OEt, OMe, OCF3, OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R1 – R4 is C≡C or C≡C-TMS. N R N 14 R11 R13 R12 Formula IV, where R11 - R14 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, wherein at least one of R11 – R14 is C≡C or C≡C-TMS. N R N 14 R11 R13 R12 Formula IV, where R11 and R14 are independently C≡C, C≡C-TMS, C≡CMe, OEt, OMe, OCF3, OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R11 and R14 is C≡C or C≡C-TMS. R12 – R13 are H. R23 R22 R24 R21 N R25 Formula V, where R21 - R24 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, wherein at least one of R21 – R24 is C≡C or C≡C-TMS. R23 R22 R24 R21 N R25 Formula V, where R21 and R24 are independently C≡C, C≡C-TMS, C≡CMe, OEt, OMe, OCF3, OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R21 and R24 is C≡C or C≡C-TMS. R22, R23, and R25 are H. R32 R N 33 R31 N R34 Formula VI, where R31 – R34 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, wherein at least one of R31 – R34 is C≡C or C≡C-TMS. R32 R N 33 R31 N R34 Formula VI, where R31 and R33 are independently C≡C, C≡C-TMS, C≡CMe, OEt, OMe, OCF3, OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R31 and R33 is C≡C or C≡C-TMS. R32, and R34 are H. R42 N R43 R41 N R44 Formula VII, where R41 – R44 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, wherein at least one of R41 – R44 is C≡C or C≡C-TMS. R42 N R43 R41 N R44 Formula VII, where R41 and R43 are independently C≡C, C≡C-TMS, C≡CMe, OEt, OMe, OCF3, OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R41 and R43 is C≡C or C≡C-TMS. R42 and R44 are H. S N R53 R51 R52 Formula VIII, where R51, R52, and R53 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, wherein at least one of R51, R52, or R53 is C≡C or C≡C-TMS. S N R53 R51 R52 Formula VIII, where R51, R52, and R53 are independently H, C≡C, C≡C-TMS, C≡CMe, OEt, OMe, OCF3, OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R51, R52, or R53 is C≡C or C≡C-TMS. O N R63 R61 R62 Formula IX, where R61, R62, and R63 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, wherein at least one of R61, R62, or R63 is C≡C or C≡C-TMS. O N R63 R61 R62 Formula IX, where R61, R62, and R63 are independently H, C≡C, C≡C-TMS, C≡CMe, OEt, OMe, OCF3, OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R61, R62, or R63 is C≡C or C≡C-TMS. R71 N N R72 R74 R73 Formula X, where R71, R72, R73, and R74 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, wherein at least one of R71, R72, R73, or R74 is C≡C or C≡C-TMS. R71 N N R72 R74 R73 Formula X, where R71, R72, R73, and R74 are independently H, C≡C, C≡C-TMS, C≡CMe, OEt, OMe, OCF3, OH, I, Cl, F, methyl, ethyl, cyclopropyl, propyl, SMe, CN, benzyl, acetyl, vinyl, wherein at least one of R71, R72, R73, or R74 is C≡C or C≡C-TMS. In certain aspects a nitrification inhibiting compound, composition, or method provided herein comprises a compound selected from the group consisting of Si N O N O , , O O Si N O N O , , O O N N N S , S O , S , S N S , , S N \ y E / o N, PO \ I — ( o / \ \ N \ HÁ V i A /\ , , , , , , , , , , S N O N O O N N , , , , HCl , , , , , , , , , , Sa , , HN" UL , , , , , , , , , , , , , , , , , , , , , and agriculturally acceptable salts, N-oxides, stereoisomers, and tautomers thereof. In certain aspects a nitrification inhibiting compound, composition, or method provided herein comprises a compound selected from the group consisting of S N O N O N , , , , and agriculturally acceptable salts, N-oxides, stereoisomers, and tautomers thereof. In certain aspects a nitrification inhibiting compound is selected from the group consisting of compounds in Table 1, and agriculturally acceptable salts, N-oxides, stereoisomers, and tautomers thereof. Application of Nitrification Inhibitor Compounds to Soil In certain aspects provided herein one or more nitrification inhibitor compounds or compositions are mixed with a source of ammonia. Sources of ammonia include, but are not limited to, anhydrous ammonium, ammonium salts, such as ammonium nitrate, calcium ammonium nitrate, ammonium sulfate nitrate, ammonium sulfate or ammonium phosphate; organic ammonia sources, such as manure, biogas, worm castings, compost, seaweed or guano; urea-containing fertilizers such as, urea, formaldehyde urea, urea ammonium nitrate solution, urea sulfur, urea ammonium sulfate, or other urea-based fertilizers. In certain aspects provided herein, one or more of the nitrification inhibitor compounds or compositions are mixed with anhydrous ammonia, which is then injected into the soil. In other aspects, the compound or composition is injected separately into the growing medium at the time of anhydrous ammonia application. The amount of compound or composition present in the anhydrous ammonia mixture, or directly injected, may be adjusted so that an agriculturally effective amount of the nitrification-inhibiting compound or composition is spread. In certain aspects provided herein, the nitrification inhibitor compound or composition is mixed with fertilizers such as urea-ammonium nitrate solution to form a urea-ammonium nitrate nitrification-inhibitor mixture. These mixtures may also include other ingredients such as herbicides, insecticides, fungicides, and safeners. Such mixtures may be applied at rates of from about 10 to about 70 gallons per acre depending on the fertilizer strength and concentration as well as the target amount of nitrogen per acre. For example, the amount of compound or composition present in the treated mixture may be adjusted so that an agriculturally effective amount of the compound or composition is spread. In certain aspects provided herein, the nitrification compound or composition is impregnated on dry urea. The amount of compound or composition impregnated will depend upon the application rate of the urea. For example, urea may be spread at a rate of from about 200 to about 700 pounds per acre. An amount of compound or composition may be impregnated on dry urea so that the compound or composition is spread at an agriculturally effective amount. In certain aspects provided herein, the compound or composition is spread as part of a manure slurry mixture. The compound or composition may be mixed with manure prior to application or may be separately applied. The amount of compound or composition present in a manure slurry may be adjusted so that an agriculturally effective amount of compound or composition is spread. A compound or composition may be applied to a growing medium at a rate of from about 50 grams per acre to about 4 kilograms per acre. A compound may be applied to a growing medium at the following rates: 50-60 grams/acre; 60-70 grams/acre; 70-80 grams/acre; 80-90 grams/acre; 90-100 grams/acre; 100-120 grams/acre; 120-140 grams/acre; 140-160 grams/acre; 160-180 grams/acre; 180-200 grams/acre; 200-225 grams/acre; 225-250 grams/acre; 250-275 grams/acre; 275-300 grams/acre; 300-350 grams/acre; 350-400 grams/acre; 400-450 grams/acre; 450-500 grams/acre; 500-550 grams/acre; 550-600 grams/acre; 600-650 grams/acre; 650-700 grams/acre; 700-750 grams/acre; 750-800 grams/acre; 800-850 grams/acre; 850-900 grams/acre; 900-950 grams/acre; 950-1000 grams/acre; 1.0-1.1 kilograms/acre; 1.1-1.2 kilograms/acre; 1.2-1.3 kilograms/acre; 1.3-1.4 kilograms/acre; 1.4-1.5 kilograms/acre; 1.5-1.6 kilograms/acre; 1.6-1.7 kilograms/acre; 1.7-1.8 kilograms/acre; 1.8-1.9 kilograms/acre; 1.9-2.0 kilograms/acre; 2.0-2.2 kilograms/acre; 2.2-2.4 kilograms/acre; 2.4-2.6 kilograms/acre; 2.6-2.8 kilograms/acre; 2.8-3.0 kilograms/acre; 3.0-3.2 kilograms/acre; 3.2-3.4 kilograms/acre; 3.4-3.6 kilograms/acre; 3.6-3.8 kilograms/acre; and 3.8-4.0 kilograms/acre. Experimental General Synthesis Procedures General Procedure 1 To a stirred solution of the heterocyclic (1 equiv) 0.7 g, 3.95 mmol, in EtOAc (0.2 mmolar ) were added TEA (4 equiv.) and CuI (5 mol%) at RT (room temperature) and the reaction mixture was degassed with argon for 5 min, followed by addition of TMS-acetylene (4.5 equiv.) and bis(triphenylphosphine)palladium chloride (15 mol%). The reaction mixture was stirred at 50 °C for 16h. After completion of the reaction (monitor by TLC), the reaction mixture was filtered through celite pad, the filtrate was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography using 10 - 20% EtOAc in petroleum ether to afford the desired products. General Procedure 2 To a stirred solution of the ethynyl TMS heterocycle (1.0 eq) in methanol (0.2 mmolar) was added 1 equiv. potassium carbonate. The reaction was stirred at room temperature until completion of the reaction (monitor by TLC). The reaction mixture was filtered through celite pad, the filtrate was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography using 10 - 20% EtOAc in petroleum ether to afford the desired products. General Procedure 3 Aldehyde (1.0 equiv.) was a dissolved in anhydrous methanol (0.2-0.5 mM) and charged with cesium carbonate (1.0 equiv.) and cooled to 0-5 degrees C. Dimethyl (l-diazo-2-oxopropyl) phosphonate (1.0 equiv.) was added dropwise after which the reaction was allowed to stir for 1- 18h after which the crude mixture was concentrated onto silica gel and purified directly by flash silica gel chromatography to provide the desired alkyne. Synthesis Procedures 12780973 Trimethylsilylacetylene, (1.5 mL, 10.81 mmol), bis(triphenylphosphine)palladium(II) chloride (79 mg, 0.113 mmol) and copper(I) iodide (4.29 mg, 0.023 mmol) was added to a degassed solution of methyl 2-bromo-1,3-thiazole-5-carboxylate (500 mg, 2.252 mmol) and Et3N (1.4 mL, 9.68 mmol) in EtOAc (2.0 mL). The mixture was heated to 50 °C for 7h before cooling to 25 °C and filtering the reaction mixture through celite. The solvent was evaporated under reduced pressure to obtain the desired product. 12791843 To a solution of 1-(4-(trifluoromethyl)-2-((trimethylsilyl)ethynyl)thiazol-5-yl)ethan-1-one (0.4 g, 1.37 mmol) in MeOH (5 mL) was added NaBH4 (0.025 g, 0.68 mmol) at 0 °C and stirred for 1h at same temperature. Water (10 mL) added to reaction mixture and extracted with DCM, washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 20 - 25% EtOAc in petroleum ether to afford 0.2 g (65%) of target an off white solid; M P 73 – 77 °C; 1H NMR (400 MHz, CDCl3) δ 5.48 – 5.45 (m, 1H), 3.50 (s, 1H), 2.44 – 2.43 (m, 1H), 1.60 – 1.58 (m, 3H); 19F NMR (376 MHz, CDCl3) δ -60.41; ESIMS m/z 222.07 ([M+H]+). 12791845 To a solution of 4-(trifluoromethyl)-2-((trimethylsilyl)ethynyl)thiazole-5-carboxamide 0.2 g, 0.68 mmol) in THF-H2O mixture (3:1) (5 mL) was added LiOH.H2O (0.03 g, 0.68 mmol) and the reaction mixture was stirred for 2h at RT. The reaction mixture was acidified with 1N HCl and extracted with DCM. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 60 - 70% EtOAc in petroleum ether to afford 0.035 g (23%) of target, a pale brown solid; M P 134 - 138 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.39 (s, 1H), 8.14 (s, 1H), 5.24 (s, 1H); 19F NMR (376 MHz, CDCl3) δ -60.27; ESIMS m/z 221.06 ([M+H]+). 12791847 To a solution of ethyl 2-((trimethylsilyl)ethynyl)thiazole-5-carboxamide 0.1 g, 0.44 mmol) in THF-H2O mixture (3:1) (5 mL) was added LiOH.H2O (0.02 g, 0.44 mmol) and the reaction mixture was stirred for 2h at RT. The reaction mixture was acidified with 1N HCl and extracted with DCM. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford 0.03 g (44%) of target, a pale brown solid; M P 178 - 182 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.40 (s, 1H), 8.26 (s, 1H), 7.80 (s, 1H), 5.08 (s, 1H); ESIMS m/z 153.01 ([M+H]+). 12791857 To a solution of 1-(2-ethynylthiazol-5-yl)ethan-1-one (0.1 g, 0.66 mmol) in MeOH (3 mL) was added NaBH4 (0.013 g, 0.33 mmol) at 0 °C and stirred for 1h at same temperature. Water (10 mL) added to reaction mixture and extracted with DCM, washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 20 - 25% EtOAc in petroleum ether to afford 0.09 g (89%) of target, a brown solid; M P 72 – 76 °C; 1H NMR (400 MHz, CDCl3) δ 7.64 (s, 1H), 5.21 – 5.15 (m, 1H), 3.45 (s, 1H), 2.20 – 2.19 (m, 1H), 1.63 – 1.60 (m, 3H); ESIMS m/z 154.03 ([M+H]+). 12791863 To a solution ethyl 2-ethynylthiazole-5-carboxylate (1.4 g, 5.53 mmol) in THF:H2O mixture (3:1) (15 mL) was added LiOH.H2O (0.28 g, 6.64 mmol) and the reaction mixture was stirred at RT for 16h. The reaction mixture was acidified with 1N HCl (pH ~ 2) and was extracted with DCM. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford 0.8 g (72%) of target, a black solid; M P 195 - 199 °C; 1H NMR (400 MHz, DMSO-d6) δ 13.30 (brs, 1H), 8.54 (s, 1H), 5.02 (s, 1H); ESIMS m/z 153.99 ([M+H]+). 12791865 To a solution of 2-ethynylthiazole-5-carboxylic acid (0.25 g, 1.63 mmol) in DMF (5 mL) was added HATU (0.745 g, 1.96 mmol), DIPEA (0.315 g, 2.45 mmol), NH4Cl (0.1 g, 1.96 mmol) and the reaction mixture was stirred for 16h at RT. The reaction mixture was diluted with water (20 mL) and was extracted with EtOAc. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 50 - 60% EtOAc in petroleum ether to afford 0.17 g (66%) of target, an off white solid; M P 162 - 166 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 1H), 7.88 (s, 1H), 7.65 (s, 1H), 5.02 (s, 1H); ESIMS m/z 153.02 ([M+H]+). 12791867 To a solution of 2-ethynylthiazole-4-carboxylic acid (0.25 g, 1.63 mmol) in DMF (5 mL) was added HATU (0.93 g, 2.45 mmol), DIPEA (0.42 g, 3.26 mmol), 2-methylbut-3-yn-2-amine (0.16 g, 1.96 mmol) and the reaction mixture was stirred for 16h at RT. The reaction mixture was diluted with water (20 mL) and was extracted with EtOAc. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 30 - 40% EtOAc in petroleum ether to afford 0.16 g (45%) of target, an off white solid; M P 101 - 105 °C; 1H NMR (400 MHz, CDCl3) δ 8.13 (s, 1H), 7.40 (brs, 1H), 3.53 (s, 1H), 2.38 (s, 1H), 1.76 (s, 3H), 1.75 (s, 3H); ESIMS m/z 219.07 ([M+H]+). 12791869 To a solution of 2-ethynylthiazole-4-carboxylic acid (0.25 g, 1.63 mmol) in DMF (5 mL) was added HATU (0.93 g, 2.45 mmol), DIPEA (0.42 g, 3.26 mmol), 2-methylbut-3-yn-2-amine (0.16 g, 1.96 mmol) and the reaction mixture was stirred for 16h at RT. The reaction mixture was diluted with water (20 mL) and was extracted with EtOAc. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 30 - 40% EtOAc in petroleum ether to afford the product, an off white solid (0.17 g, 54%); M P 121 - 125 °C; 1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 7.47 (brs, 1H), 4.25 - 4.23 (m, 2H), 3.54 (s, 1H), 2.27 - 2.26 (m, 1H); ESIMS m/z 191.03 ([M+H]+). 12795389 To a solution of 2-bromo-N-(2-methylbut-3-yn-2-yl)thiazole-4-carboxamide (0.4 g, 1.46 mmol) in toluene (5 mL) was added CuI (0.03 g, 0.14 mmol) followed by the addition of DIPEA (0.37 g, 2.93 mmol), PdCl2(PPh3)2 (0.05 g, 0.07 mmol), TMS acetylene (0.18 g, 1.75 mmol) under argon atmosphere and the reaction mixture was stirred at 70 °C for 16h. The reaction mixture was cooled to RT, EtOAc (30 mL) was added, filtered through a pad of celite, the filtrate was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 5 - 10% EtOAc in petroleum ether to afford 0.12 g (28%) of target, a brown liquid; FT-IR 1666.53 cm-1 (C=O stretching present); 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.41 (brs, 1H), 2.38 (s, 1H), 1.74 - 1.73 (m, 6H), 0.30 (s, 9H); ESIMS m/z 291.01 ([M+H]+). 12795393 To a solution of 2-bromo-N-(prop-2-yn-1-yl)thiazole-4-carboxamide (0.4 g, 1.46 mmol) in toluene (5 mL) was added CuI (0.03 g, 0.14 mmol) followed by the addition of DIPEA (0.37 g, 2.93 mmol), PdCl2(PPh3)2 (0.05 g, 0.07 mmol), TMS acetylene (0.18 g, 1.75 mmol) under argon atmosphere and the reaction mixture was stirred at 70 °C for 16h. The reaction mixture was cooled to RT, EtOAc (30 mL) was added, filtered through a pad of celite, the filtrate was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 5 - 10% EtOAc in petroleum ether to afford 0.12 g (28%) of target, a pale brown solid (0.11 g, 25%); M P 79 - 83 °C; 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.48 (brs, 1H), 4.24 - 4.21 (m, 2H), 2.26 - 2.24 (m, 1H), 0.30 (s, 9H); ESIMS m/z 263.08 ([M+H]+). 12806737 To a stirred solution of 1-(2-((trimethylsilyl)ethynyl)thiazol-4-yl)prop-2-yn-1-one (0.2 g, 0.80 mmol) in MeOH (2 mL) was added K2CO3 (1 mg, cat.) at RT. The reaction mixture was stirred at RT for 5 minutes. After completion of the reaction, the reaction mixture was poured in ice water (5 mL), acidified with 1N HCl (2 mL, pH ~4) and extracted with EtOAc. Combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10 % EtOAc in petroleum ether eluent to afford the product, a pale brown solid (0.032 g, 27%); M P 126 - 130 °C; 1H NMR (400 MHz, CDCl3) δ 8.33 (s, 1H), 3.56 (s, 1H), 3.50 (s, 1H); ESIMS m/z 162.08 ([M+H]+). 12806745 To a stirred solution of (E)-1-(2-((trimethylsilyl)ethynyl)thiazol-4-yl)but-2-en-1-one (0.2 g, 0.80 mmol) in MeOH (2 mL) was added K2CO3 (1 mg, cat.) at RT. The reaction mixture was stirred at RT for 5 minutes. After completion of the reaction, the reaction mixture was poured in ice water (5 mL), acidified with 1N HCl (2 mL, pH ~4) and extracted with EtOAc. Combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10 % EtOAc in petroleum ether eluent to afford a pale brown solid (0.025 g, 17%); M P 111 - 115 °C; 1H NMR (400 MHz, CDCl3) δ 8.33 (s, 1H), 7.23 - 7.14 (m, 1H), 6.77 - 6.72 (m, 1H), 3.63 (s, 1H); 2.03 (t, J = 3.4 Hz, 3H); ESIMS m/z 178.09 ([M+H]+). 12806753 To a stirred solution of 1-(2-((trimethylsilyl)ethynyl)thiazol-5-yl)prop-2-yn-1-one (1.2 g, 5.76 mmol) in DCM (15 mL) was added DMP (3.17 g, 7.49 mmol) at 0 °C. The reaction mixture was stirred at RT for 3h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 24g) using 10 - 20% EtOAc in petroleum ether eluent to afford the product, a brown solid (0.2 g, 50%); M P 78 - 82 °C; 1H NMR (400 MHz, CDCl3) δ 8.50 (s, 1H), 3.45 (s, 1H), 0.30 (s, 9H); ESIMS m/z 234.11 ([M+H]+). 12806761 To a stirred solution of (E)-1-(2-((trimethylsilyl)ethynyl)thiazol-4-yl)but-2-en-1-one (0.2 g, 0.80 mmol) in MeOH (2 mL) was added K2CO3 (1 mg, cat.) at RT. The reaction mixture was stirred at RT for 5 minutes. After completion of the reaction, the reaction mixture was poured in ice water (5 mL), acidified with 1N HCl (2 mL, pH ~4) and extracted with EtOAc. Combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10 % EtOAc in petroleum ether eluent to afford target (0.025 g, 21%), a pale brown solid (0.025 g, 17%); M P 111 - 115 °C; 1H NMR (400 MHz, CDCl3) δ 8.33 (s, 1H), 7.23 - 7.14 (m, 1H), 6.77 - 6.72 (m, 1H), 3.63 (s, 1H); 2.03 (t, J = 3.4 Hz, 3H); ESIMS m/z 178.09 ([M+H]+). 12811457 1 mL MeOH was added to N-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5-carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C and the reaction was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF, the filtrate was concentrated under low temperature to get product (40 mg, 86%), a yellow solid. 12811461 1 mL MeOH was added to N-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5-carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C and the reaction was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF, the filtrate was concentrated under low temperature to get product (40 mg, 83%), a brown solid. 12811465 Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidephenyl)benzamide (150 mg, 0.54mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cul (21 mg, 0.11 mmol), NEt3 (1.5 ml) in 4.5 mL of THF. The reaction was stirred at 50 °C for 2h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 5:1) to give the product, a yellow solid. 12811467 Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidephenyl)benzamide (150 mg, 0.54mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cul (21 mg, 0.11 mmol), NEt3 (1.5 ml) in 4.5 mL of THF. The reaction was stirred at 50 °C for 2h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 5:1) to give the product, a yellow solid. 12811469 Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidephenyl)benzamide (150 mg, 0.54mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cul (21 mg, 0.11 mmol), NEt3 (1.5 ml) in 4.5 mL of THF. The reaction was stirred at 50 °C for 2h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 5:1) to give the product, a yellow solid. 12811471 Under N2, 2-bromo-N-methylthiazole-5-carboxamide (0.54mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cul (21 mg, 0.11 mmol), NEt3 (1.5 ml) in 4.5 mL of THF. The reaction was stirred at 50 °C for 2h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 5:1) to give the product N-methyl-2- ((trimethylsilyl)ethynyl)thiazole-5-carboxamide, a brown solid (63%).1H NMR (400 MHz, CDCl3) δ 8.10 (s, 1H), 6.14 (s, 1H), 3.01 (d, J = 4.8 Hz, 3H), 0.29 (s, 9H).13C NMR (101 MHz, 155-156 °C. 12811481 1 mL MeOH was added to N-methyl-2-((trimethylsilyl)ethynyl)thiazole-5-carboxamide (0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C and the reaction was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF, the filtrate was concentrated under low temperature to get product provide the desired product, a brown solid (55 mg, 98%) 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 6.25 (s, 1H), 3.57 (s, 1H), 3.01 (d, J = 4.9 Hz, 3H).13C NMR (101 MHz, CDCl3) δ 160.22, 150.49, 142.97, 136.16, 84.05, 75.97, 26.90. ESIMS m/z 167 ([M+H]+). Mp, 118-119 °C. 12811473 1 mL MeOH was added to N-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5-carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C and the reaction was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF, the filtrate was concentrated under low temperature to get product (40 mg, 86%), a brown solid. 12811475 1 mL MeOH was added to N-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5-carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C and the reaction was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF, the filtrate was concentrated under low temperature to get product (40 mg, 86%), a brown solid. 12811477 1 mL MeOH was added to N-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5-carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C and the reaction was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF, the filtrate was concentrated under low temperature to get product (40 mg, 86%), a brown solid.1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 5.70 (s, 1H), 4.01 - 3.92 (m, 1H), 3.56 (s, 1H), 1.70 - 1.61 (m, 2H), 1.54 - 1.45 (m, 2H), 0.95 (t, J = 7.4 Hz, 6H).13C NMR (101 MHz, CDCl3) δ 159.30, 150.41, 142.57, 136.71, 83.90, 76.03, 67.98, 53.11, 27.48, 10.29. ESIMS m/z 223 ([M+H]+). Mp, 81-82 °C. 12811479 Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidephenyl)benzamide (150 mg, 0.54mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cul (21 mg, 0.11 mmol), NEt3 (1.5 ml) in 4.5 mL of THF. The reaction was stirred at 50 °C for 2h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 5:1) to give the product 1 (161mg, 64%), a brown solid. 12811481 Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidephenyl)benzamide (150 mg, 0.54mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cul (21 mg, 0.11 mmol), NEt3 (1.5 ml) in 4.5 mL of THF. The reaction was stirred at 50 °C for 2h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 5:1) to give the product 1 (114 mg, 72%), a brown solid. 12811485 Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidephenyl)benzamide (150 mg, 0.54mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cul (21 mg, 0.11 mmol), NEt3 (1.5 ml) in 4.5 mL of THF. The reaction was stirred at 50 °C for 2h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 5:1) to give the product 1 (150 mg, 49%), a white solid. 12776911 To a solution of ethyl 2-bromooxazole-4-carboxylate L-a (1.5 g, 6.81 mmol) in toluene (10 mL) was added CuI (0.13 g, 0.0.68 mmol), DIPEA (1.75 g, 13.62 mmol), PdCl2(PPh3)2 (0.24 g, 0.34 mmol) and trimethylsilylacetylene (1 g, 10.21 mmol) under argon atmosphere and the reaction mixture was stirred at 50 °C for 16h. The reaction mixture was cooled to RT, EtOAc (150 mL) was added and filtered through pad of celite and filtrate was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 5 - 10% EtOAc in petroleum ether to afford 0.8 g (50%) of target, a brown liquid; FT-IR 1737.89 cm-1 (C=O stretching present); 1H NMR (400 MHz, CDCl3) δ 8.16 (s, 3H), 4.39 (q, J = 7.2 Hz, 2H), 1.38 (t, J = 7.2 Hz, 3H), 0.27 (s, 9H); ESIMS m/z 238.22 ([M+H]+). 12776913 To a solution of 2-ethynyloxazole-4-carboxylic acid (0.8 g, 3.37 mmol) in THF-H2O mixture (3:1) (10 mL) was added LiOH.H2O (0.14 g, 3.37 mmol) and the reaction mixture was stirred for 2h at RT. The reaction mixture was acidified with 1N HCl and extracted with DCM. The organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to afford 0.6 g (86%) of target, a brown solid; M P 161 – 165 °C; 1H NMR (400 MHz, DMSO-d6) δ 13.35 (bs, 1H), 8.83 (s, 1H), 4.95 (s, 1H); ESIMS m/z 138.16 ([M+H]+). 12776915 To a solution of 2-ethynyloxazole-4-carboxylic acid (0.1 g, 0.72 mmol) and amine input (0.073 g, 0.87 mmol) in DMF (3 mL), was added HATU (0.42 g, 1.09 mmol) and DIPEA (0.19 g, 1.44 mmol) at 0 °C and the reaction mixture was stirred for 16h at RT. The reaction mixture diluted with water (20 mL), was extracted with EtOAc. The organic layer was washed with ice water, brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 30 - 35% EtOAc in petroleum ether to afford 0.08 g (54%) of target, a brown solid. 12776921 To a solution of 2-ethynyloxazole-5-carboxylic acid (0.35 g, 2.55 mmol) and amine input (0.318 g, 3.83 mmol) in DMF (5 mL), was added HATU (1.45 g, 3.82 mmol) and DIPEA (0.98 g, 7.66 mmol) at 0 °C and the reaction mixture was stirred for 16h at RT. The reaction mixture diluted with water (30 mL), was extracted with EtOAc. The organic layer was washed with ice water, brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 20 - 25% EtOAc in petroleum ether to afford 0.240 g (46%) of product, an off white solid; M P 133 – 137 °C; 1H NMR (400 MHz, CDCl3) δ 7.70 (s, 1H), 6.30 (s, 1H), 3.33 (s, 1H), 2.41 (s, 1H), 1.75 (s, 6H); ESIMS m/z 203.13 ([M+H]+). 12776925 To a solution of ethyl ethyl 2-iodooxazole-5-carboxylate h1 (2.5 g, 9.36 mmol) in toluene (25 mL) was added CuI (0.178 g, 0.93 mmol), DIPEA (2.4 g, 18.72 mmol), PdCl2(PPh3)2 (0.33 g, 0.468 mmol) and trimethylsilylacetylene (1.8 g, 18.72 mmol) under argon atmosphere and the reaction mixture was stirred at 50 °C for 16h. The reaction mixture was cooled to RT. EtOAc (100 mL) was added and filtered through pad of celite and filtrate was washed with brine (30 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 5 - 10% EtOAc in petroleum ether to afford 1 g (45%) of product, a brown liquid; FT-IR 1733.07 cm-1 (C=O stretching present); 1H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 4.39 (q, J = 7.2 Hz, 2H), 1.38 (t, J = 7.2 Hz, 3H), 0.28 (s, 9H); ESIMS m/z 238.15 ([M+H]+). 12791853 To a solution of 2-ethynyloxazole-4-carboxamide (0.3 g, 2.18 mmol) and Aq. NH3 (2 mL) in THF (5 mL), was added HATU (1 g, 2.62 mmol) and DIPEA (0.42 g, 3.28 mmol) at 0 °C and the reaction mixture was stirred for 16h at RT. The reaction mixture diluted with water (20 mL), was extracted with EtOAc. The organic layer was washed with ice water, brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 100 - 200 mesh) eluting with 40 - 45% EtOAc in petroleum ether to afford 0.05 g (42%) of product, a pale brown solid; M P 176 – 180 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.65 (s, 1H), 7.79 (s, 1H), 7.58 (s, 1H), 4.95 (s, 1H); ESIMS m/z 137.12 ([M+H]+). 12797705 To a stirred solution of 2-((trimethylsilyl)ethynyl)oxazole-4-carbaldehyde (0.2 g, 0.80 mmol) in MeOH (2 mL) was added K2CO3 (1 mg, cat.) at RT. The reaction mixture was stirred at RT for 5 minutes. After completion of the reaction, the reaction mixture was poured in ice water (5 mL), acidified with 1N HCl (2 mL, pH ~4) and extracted with EtOAc. Combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10 % EtOAc in petroleum ether eluent to afford the product, an off white solid (0.078 g, 43%); M P 110 - 114 °C; 1H NMR (400 MHz, CDCl3) δ 9.93 (s, 1H), 8.24 (s, 1H), 3.33 (s, 1H); ESIMS m/z 122.12 ([M+H]+). 12806755 To a stirred solution of 1-(2-((trimethylsilyl)ethynyl)oxazol-4-yl)prop-2-yn-1-ol (0.27 g, 1.14 mmol) in dichloromethane (6 mL) was added DMP (0.63 g, 1.49 mmol) at 0 °C. The reaction mixture was stirred at RT for 3h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 24 g) using 10 % EtOAc in petroleum ether eluent to afford the product, a pale brown solid (0.12 g, 42%); M P 75 - 79 °C; 1H NMR (400 MHz, CDCl3) δ 8.29 (s, 1H), 3.44 (s, 1H), 0.29 (s, 9H); ESIMS m/z 218.15 ([M+H]+). 12806763 To a stirred solution of 1-(2-((trimethylsilyl)ethynyl)oxazol-4-yl)prop-2-yn-1-one (0.2 g, 0.80 mmol) in MeOH (2 mL) was added K2CO3 (1 mg, cat.) at RT. The reaction mixture was stirred at RT for 5 minutes. After completion of the reaction, the reaction mixture was poured in ice water (5 mL), acidified with 1N HCl (2 mL, pH ~4) and extracted with EtOAc. Combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10 % EtOAc in petroleum ether eluent to afford a pale brown solid (0.024 g, 45%); M P 117 - 121 °C; 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 3.45 (s, 1H), 3.33 (s, 1H); ESIMS m/z 146.05 ([M+H]+). 12811459 1 mL MeOH was added to N-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5-carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C and the reaction was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF, the filtrate was concentrated under low temperature to get product (25 mg, 86%), a yellow solid. 12811483 1 mL MeOH was added to N-(pentan-3-yl)-2-((trimethylsilyl)ethynyl)thiazole-5-carboxamide (63 mg, 0.21 mmol), K2CO3 (58 mg, 0.42 mmol) in 3 mL of THF at 0 °C and the reaction was stirred at 0 °C for 30 min. After the reaction was completed, the mixture was filtered and washed with THF, the filtrate was concentrated under low temperature to the product, a brown solid (85%) 1H NMR (400 MHz, CDCl3) δ 7.75 (s, 1H), 6.45 (s, 1H), 4.24 (dd, J = 5.4, 2.6 Hz, 2H), 3.35 (s, 1H), 2.31 (t, J = 2.6 Hz, 1H).13C NMR (101 MHz, CDCl3) δ 155.57, 145.61, 145.06, 132.07, 81.61, 78.37, 72.49, 70.68, 29.09. ESIMS m/z 175([M+H]+). Mp, 112-113 °C. 12811491 Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidePhenyl)benzamide (150 mg, 0.54mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cul (21 mg, 0.11 mmol), NEt3 (1.5 ml) in 4.5 mL of THF. The reaction was stirred at 50 °C for 2h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 5:1) to give the product, a yellow oil. 12811493 Under N2, 2-bromo-N-(pentan-3-yl)thiazole-5-carboxamidePhenyl)benzamide (150 mg, 0.54mmol) was added to trimethylsilylacetylene (317 mg, 3.23 mmol), Pd(PPh3)4 (62 mg, 0.05 mmol), Cul (21 mg, 0.11 mmol), NEt3 (1.5 ml) in 4.5 mL of THF. The reaction was stirred at 50 °C for 2h. After the reaction was completed, the mixture was filtered and washed with THF. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 5:1) to give the product, a white solid (25%) 1H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 6.45 (s, 1H), 4.23 (dd, J = 5.4, 2.6 Hz, 2H), 2.30 (t, J = 2.5 Hz, 1H), 0.30 (s, 9H).13C NMR (101 MHz, CDCl3) δ 156.53, 147.07, 145.37, 132.91, 102.42, 91.08, 79.24, 73.24, 29.85. ESIMS m/z 247([M+H]+). Mp, 134-135 °C. 12771961 To a solution of N-(2-methylbut-3-yn-2-yl)-2-(trichloromethyl)-4-(trifluoromethyl)thiazole-5- carboxamide (273 mg, 0.719 mmol) in THF:H20 (5:1, 6 mL) was added Fe(s) in a single portion. The resulting reaction mixture was allowed to warm to 60°C. Maintained the temperature for 16h (start at 4:00 PM). The reaction was monitor by TLC (n-hexane: ethyl acetate 8:2) and LCMS. No SM was visible by TLC after 16h. The reaction mixture was concentrated (nitrogen) and adsorbed onto celite pre-column and chromatographed over silica gel. 12799175 To a solution of 5-ethynylthiazole-2-carbaldehyde ( 40 mg, 0.292 mmol) in anhydrous THF at - 78C was slowly added methylmagnesium bromide (86 µl, 0.292 mmol)as a 3.4 molar solution in THF. After the addition was complete, the reaction was allowed to slowly warm to 25 °C over 30 minutes and then quenched with sat aq NH4Cl and diluted with 50 mL ether. The layers were partitioned and the ether layer was dried over magnesium sulfate and concentrated over a stream of nitrogen to afford a brown residue (42 mg, 85%). 12816775 To a stirred solution of (5-ethynylfuran-2-yl)methanol (0.1 g, 0.82 mmol) in THF (5 mL) were added NaH (60%, 0.078 g, 1.63 mmol) and CH3I (0.12 mL, 2.04 mmol) at 0 °C. The reaction mixture was stirred at RT for 2h. After completion of the reaction (monitor by TLC), the reaction mixture was poured into water (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12g) using 5 - 10% EtOAc in petroleum ether to afford product (0.026 g, 23%) a pale brown liquid; FT IR 2111.13 cm-1 (C≡C Stretching present); 1H NMR (400 MHz, CDCl3) δ 6.60 (d, J = 3.2 Hz, 1H), 6.31 (d, J = 3.6 Hz, 1H), 4.37 (s, 2H), 3.38 (s, 3H), 3.37 (s, 1H); ESIMS m/z 135.9 ([M]+). 12816797 To a stirred solution of 1-(5-ethynylfuran-2-yl)ethan-1-ol (0.1 g, 0.60 mmol) in DMF (5 mL) was added K2CO3 (0.1 g, 0.73 mmol) and methyl iodide (0.1 mL, 1.20 mmol) at RT. The reaction mixture was stirred at RT for 16h. After completion of the reaction (monitor by TLC), the reaction mixture was poured into water (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10 - 20% EtOAc in petroleum ether to afford the product, a brown liquid (0.026 g, 26%); FT IR 3288.69 cm-1 (O-H Stretching present); 1H NMR (400 MHz, CDCl3) δ 6.59 (d, J = 3.6 Hz, 1H), 6.22 (dd, J = 0.4, 3.2 Hz, 1H), 4.86 (q, J = 4.4 Hz, 1H), 3.39 (s, 1H), 1.92 (d, J = 4.4 Hz, 1H), 1.54 (d, J = 6.8 Hz, 3H); ESIMS m/z 135.9 ([M]+). 12830209 To a stirred solution of 1-(2-ethynyloxazol-4-yl)ethan-1-ol (0.1 g, 0.72 mmol) in THF (5 mL) was added NaH (48 mg, 0.72 mmol) at 0 °C and stirred for 15 minutes at 0 °C, followed by the addition of CH3I (0.091 mL, 1.45 mmol). The reaction mixture was slowly warmed to RT and stirred for 2h. After completion of the reaction (monitor by TLC), the reaction mixture was quenched with cold water (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 24 g) using 10-20% EtOAc in petroleum ether eluent to afford Product-A8 (0.036 g, 33%) a pale yellow liquid; FT IR 2121.70 cm-1 (C≡C stretching present); 1H NMR (400 MHz, CDCl3) δ 7.54 (s, 1H), 4.36 (q, J = 6.0 Hz, 1H), 3.36 (s, 3H), 3.23 (s, 1H), 1.48 (d, J = 6.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 145.58, 143.86, 135.94, 79.91, 72.18, 71.29, 56.66, 20.13; ESIMS m/z 152.07 ([M+H]+). 12830213 To a stirred solution of 1-(2-((trimethylsilyl)ethynyl)oxazol-4-yl)ethan-1-one (0.3 g, 1.55 mmol) in THF (10 mL) was added CH3MgI [3M in Diethyl ether (0.6 mL, 1.86 mmol)] at 0 °C. The reaction mixture was stirred at RT for 3h. After completion of the reaction (monitor by TLC), the reaction mixture was quenched with saturated NH4Cl (20 mL) and extracted with EtOAc). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 24 g) using 10-20% EtOAc in petroleum ether eluent to afford Int-A-1-5 (0.2 g, 59%) a pale yellow liquid; FT IR 2175.70 cm-1 (C≡C stretching present); 1H NMR (400 MHz, CDCl3) δ 7.49 (s, 1H), 4.83 (q, J = 6.8 Hz, 1H), 2.15 (d, J = 4.8 Hz, 1H), 1.52 (d, J = 6.4 Hz, 3H), 0.27 (d, 9H); ESIMS m/z 210.18 ([M+H]+). 12853673 To a stirred solution of thiazole-2-thiol (0.3 g, 2.56 mmol) in acetone (10 mL) were added K2CO3 (0.35 g, 2.56 mmol) and propargyl bromide (0.2 mL, 2.56 mmol) at 0°C. The reaction mixture was stirred at RT for 3h. After completion (monitor by TLC) of the reaction, the reaction mixture was poured in water (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to afford product (0.15 g, 38%), a brown liquid; FT IR 2117.84 cm-1 (C≡C stretching present); 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 3.2 Hz, 1H), 7.28 (d, J = 3.2 Hz, 1H), 3.95 (d, J = 2.8 Hz, 2H), 2.28 (t, J = 5.2 Hz, 1H); ESIMS m/z 156.12 ([M+H]+). 12853681 To a stirred solution of 2-bromothiazole (0.3 g, 1.82 mmol) in 1,4-dioxane (10 mL) were added LiCl (0.23 g, 5.48 mmol) and CuI (0.1 g, 0.55 mmol) at RT. The reaction mixture was degassed with argon for 5 minutes, then added input-1 (0.66 g, 2.01 mmol) and Pd(PPh3)4 (0.1 g, 0.09 mmol) at RT. The reaction mixture was stirred at 100 °C for 16h. After completion (monitor by TLC) of the reaction, the reaction mixture was filtered through celite pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 5% - 10% EtOAc in petroleum ether to afford product (0.05 g, 22%), a brown liquid; FT IR 2235.50 cm-1 (C≡C stretching present); 1H NMR (400 MHz, DMSO-d6) δ 7.84 (d, J = 3.2 Hz, 1H), 7.77 (d, J = 3.6 Hz, 1H), 2.14 (s, 3H); ESIMS m/z 123.92 ([M+H]+). 12853683 To a stirred solution of 2-bromothiazole (1 g, 6.09 mmol) in EtOAc (20 mL) were added Et3N (3.6 mL, 26.21 mmol) and CuI (12 mg, 0.06 mmol) at RT. The reaction mixture was degassed with argon for 5 minutes, then added prop-2-yn-1-ol (input-2) (1.6 mL, 29.26 mmol) and bis(triphenylphosphine)palladium chloride (0.2 g, 0.30 mmol) at RT. The reaction mixture was stirred at 50-55 °C for 16h. After completion (monitor by TLC) of the reaction, the reaction mixture was filtered through celite pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% - 15% EtOAc in petroleum ether to afford product (0.25 g, 29%), a brown liquid; FT IR 2231.64 cm-1 (C≡C stretching present); 1H NMR (400 MHz, DMSO-d6) δ 7.91 (d, J = 3.6 Hz, 1H), 7.86 (d, J = 3.2 Hz, 1H), 5.53 (t, J = 6.2 Hz, 1H), 4.36 (d, J = 6.0 Hz, 2H); ESIMS m/z 139.94 ([M+H]+). 12853685 To a stirred solution of 2-bromothiazole (1 g, 6.09 mmol) in EtOAc (20 mL) were added Et3N (3.6 mL, 26.21 mmol) and CuI (12 mg, 0.06 mmol) at RT. The reaction mixture was degassed with argon for 5 minutes, then added the alkyne (1.6 mL, 29.26 mmol) and bis(triphenylphosphine)palladium chloride (0.2 g, 0.30 mmol) at RT. The reaction mixture was stirred at 50-55 °C for 16h. After completion (monitor by TLC) of the reaction, the reaction mixture was filtered through celite pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% - 15% EtOAc in petroleum ether to afford the desired product, a brown liquid (0.4 g, 43%); FT IR 2231.64 cm-1 (C≡C stretching present); 1H NMR (400 MHz, DMSO-d6) δ 7.84 (d, J = 3.2 Hz, 1H), 7.78 (d, J = 3.2 Hz, 1H), 4.99 (t, J = 5.6 Hz, 1H), 3.60 (q, J = 5.6 Hz, 2H), 2.64 (t, J = 6.6 Hz, 2H); ESIMS m/z 153.95 ([M+H]+). 12853687 To a stirred solution of 2-bromothiazole (1 g, 6.09 mmol) in EtOAc (20 mL) were added Et3N (3.6 mL, 26.21 mmol) and CuI (12 mg, 0.06 mmol) at RT. The reaction mixture was degassed with argon for 5 minutes, then added prop-2-yn-1-ol (input-2) (1.6 mL, 29.26 mmol) and bis(triphenylphosphine)palladium chloride (0.2 g, 0.30 mmol) at RT. The reaction mixture was stirred at 50-55 °C for 16h. After completion (monitor by TLC) of the reaction, the reaction mixture was filtered through celite pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% - 15% EtOAc in petroleum ether to afford the product, a Brown liquid (0.1 g, 21%); FT IR 2231.64 cm-1 (C≡C stretching present); 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 3.2 Hz, 1H), 7.36 (d, J = 3.6 Hz, 1H), 4.37 (s, 2H), 3.47 (s, 3H); ESIMS m/z 153.1 ([M]+). 12855341 To a stirred solution of 2 bromo thiazole (0.3 g, 2.56 mmol) in Acetone (10 mL) were added K2CO3 (0.35 g, 2.56 mmol) and propargyl alcohol (0.2 mL, 2.56 mmol) at 0°C. The reaction mixture was stirred at RT for 3h. After completion (monitor by TLC) of the reaction, the reaction mixture was poured in water (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to afford a colorless liquid (0.03 g, 17%); FT IR 2239.36 cm-1 (C≡C stretching present); 1H NMR (400 MHz, CDCl3) δ 7.13 (d, J = 3.6 Hz, 1H), 6.70 (d, J = 4.0 Hz, 1H), 5.00 (q, J = 2.4 Hz, 2H), 1.89 (t, J = 2.2 Hz, 3H); ESIMS m/z 153.83 ([M+H]+). 12855343 To a stirred solution of 2,4-dibromothiazole (0.5 g, 2.07 mmol) in 1,4-Dioxane (10 mL) were added CsF (0.47 g, 3.11 mmol) at RT. The reaction mixture was degassed with argon for 5 minutes, then added input-1 (0.82 g, 2.48 mmol) and Pd(tBu3P)2 (53 mg, 0.11 mmol) at RT. The reaction mixture was stirred at 100 °C for 16h. After completion (monitor by TLC) of the reaction, the reaction mixture was filtered through celite pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 5% - 10% EtOAc in petroleum ether to afford product (0.2 g, 41%), a yellow semi solid (0.15 g, 45%); FT IR 2235.50 cm-1 (C≡C stretching present); 1H NMR (400 MHz, CDCl3) δ 7.22 (s, 1H), 2.10 (s, 3H), 2.04 (s, 3H); ESIMS m/z 161.88 ([M+H]+). 12856621 3-ethynyl-5-methylisothiazole (1.0 equiv) was a dissolved in anhydrous methanol (0.2-0.5 mM) and charged with cesium carbonate (1.0 equiv) and cooled to 0-5 degrees C. Dimethyl (l-diazo-2- oxopropyl)phosphonate (1.0 equiv) was added dropwise after which the reaction was allowed to stir for 1-18h after which the crude mixture was concentrated onto silica gel and purified directly by flash silica gel chromatography to provide the desired alkyne 12858893 To a stirred solution of TMS acetylene (0.9 mL, 8.01 mmol) in THF (15 mL) was added n-BuLi (2.5M) (3.2 mL, 7.69 mmol) at -78 °C. The reaction mixture was stirred at -78 °C for 30 minutes. Furan-2-carbaldehyde SM-C (0.5 g, 6.41 mmol) was then added into the reaction mixture at -78 °C and stirred for 5h at RT. After completion of the reaction, the reaction mixture was quenched with aq. NH4Cl (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 40 g) using 15% - 20% EtOAc in petroleum ether eluent to afford Int-C1 (0.2 g, 16%), a yellow solid; FT IR 2177.63 cm-1 (C≡C stretching present); 1H NMR (400 MHz, CDCl3) δ 7.41 (m, 1H), 6.45 (m, 1H), 6.35 (m, 1H), 5.45 (d, J = 6.8 Hz, 1H), 2.22 (d, J = 7.2 Hz, 1H), 0.21 (s, 9H); ESIMS m/z 194.94 ([M+H]+). Synthesis of 1-(furan-2-yl)-3-(trimethylsilyl)prop-2-yn-1-one: To a stirred solution of 1-(furan-2-yl)-3-(trimethylsilyl)prop-2-yn-1-ol (0.1 g, 0.51 mmol) in DCM (5 mL) was added pyridinium chlorochromate (0.16 g, 0.77 mmol) at RT. The reaction mixture stirred at RT for 16h. After completion (monitor by TLC) of the reaction, the reaction mixture was filtered through celite pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 24 g) using 2% - 5% EtOAc in petroleum ether to afford product (0.03 g, 30%), a brown liquid; FT IR 2158.35 cm-1 (C≡C stretching present); 1H NMR (400 MHz, CDCl3) δ 7.66 (m, 1H), 7.36 (m, 1H), 6.57 (dd, J = 1.6, 3.6 Hz, 1H), 0.29 (s, 9H); ESIMS m/z 192.90 ([M+H]+). General Procedure A Under air, to a 20 mL vial, aryl halide (1 equiv.), triethylamine (3 equiv.) and copper(I) iodide (0.1 equiv.) were charged and diluted with Dioxane (0.3 M concentration of substrate). The reaction was degassed for 5 min, then ethynyltrimethylsilane (4.0 equiv.) and bis(triphenylphosphine)palladium (II) chloride (0.1 equiv.) were added under an inert atmosphere. The vial was placed in a heating block that was warmed to 80 ºC and the solution was stirred for 20 h. The reaction was cooled and passed through a pad of celite. The filtrate was concentrated, and the resulting residue was purified by flash chromatography on silica gel. General Procedure B To a 50 mL RBF charged with TMS-Alkyne (1.0 equiv.), MeOH (0.25 M concentration of substrate) and potassium carbonate (0.2 equiv.) were added. The reaction was stirred at ambient temperature for 30 min. After reaction completion, the reaction was diluted with H2O and extracted with DCM. The combined organics were passed through a phase separator and concentrated. The resulting residue was purified by flash chromatography on silica gel. General Procedure C Aldehyde (1.0 equiv.) was a dissolved in anhydrous methanol (0.2-0.5 mM) and charged with cesium carbonate (1.0 equiv.) and cooled to 0-5 degrees C. Dimethyl (l-diazo-2-oxopropyl) phosphonate (1.0 equiv.) was added dropwise after which the reaction was allowed to stir for 1- 18h after which the crude mixture was concentrated onto silica gel and purified directly by flash silica gel chromatography to provide the desired alkyne. General Procedure D To a 20 mL vial, sodium hydride (60% Wt., 1.0 Equiv.) was charged and diluted with THF (1.0 M concentration of substrate) under an inert atmosphere. Then alcohol (1.0 equiv.) was added at ambient temperature and the reaction was allowed to stir for 30 min. Then aryl halide (1.0 equiv.) in THF (0.5 M concentration of substrate) was added. The vial was placed in a heating block that was warmed to 50 ºC and the solution was stirred for 20 h. The reaction was quenched with Sat NH4Cl and extracted with Et2O. The combined organics were dried over MgSO4, filtered, and concentrated. The resulting residue was purified by flash chromatography on silica gel General Procedure E Under air, a 20 mL vial equipped with a magnetic stirring bar was charged with P(tBu)3 Pd G2 (0.03 equiv.) and the aryl halide (1 equiv. if solid). The vial was capped, and the air was purged by evacuating the vial and backfilling with nitrogen three times. Dry DMF was added (0.4 M concentration of substrate) to the vial followed by the aryl halide (1 equiv. if liquid), the TMS- protected alkyne (1.5 equiv.) and TBAF (1.5 equiv., 1 M in THF). The vial was placed in a heating block that was warmed to 80 ºC and the solution was stirred for 20 h. After the reaction time, the vial was opened to air and aqueous Na2CO3 was added (4 mL). The crude product was extracted with CH2Cl2 and purified by flash chromatography on silica gel. General Procedure F To a 20 mL vial, sodium alkoxide (1.0 equiv.) was charged. Then a solution of aryl halide (1.0 equiv.) in THF (0.2 M concentration of substrate) was added. The vial was placed in a heating block that was warmed to 50 ºC and the solution was stirred for 20 h. The reaction was quenched with saturated NH4Cl and extracted with Et2O. The combined organics were dried over MgSO4, filtered, and concentrated. The resulting residue was purified by flash chromatography on silica gel. General Procedure G A stock solution of [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.1 equiv) in dioxane (2 mL) and copper(I) iodide (0.1 equiv) in dioxane (1 mL) and triethylamine (3 equiv) were added to a vial containing a solution of Br/Cl-heterocycle (1 equiv) in dioxane (2 mL). The contents were sealed and degassed with nitrogen and the overall reaction concentration was 0.2M. With stirring, ethynyltrimethylsilane (2 equiv) was added neat and the contents were heated to 60 oC overnight for 18 hours. The reaction was quenched with AcOH (10 equiv), the product mass was observed by LCMS. The contents were diluted with EtOAc and partitioned between 2.5 M KHCO3 (2 x) and brine then dried over MgSO4. The contents were condensed by rotoary evaporation and the residue was purified by silica-gel chromatography eluting with hexanes/EtOAc 10-100% over 10 minutes to yield the product. General Procedure H To a flask containing ((trimethylsilyl)ethynyl)-heterocycle was dissolved in a solution of potassium fluoride (0.1M, 2 equiv) in methanol and stirred at ambient temperature for 18 hours. The contents were condensed by rotary evaporation and purified over silica-gel eluting with DCM/MeOH 0-10% to obtain the product. General Procedure I To a stirring solution of aldehyde (1M, 1 equiv), potassium carbonate (2 equiv) in methanol was added dimethyl (1-diazo-2-oxopropyl)phosphonate (1.1 equiv) neat. Gas evolution was observed. The contents were stirred at ambient temperature for 2 - 5 hours. The contents were diluted with water and extracted with dichloromethane. The pooled organics were dried over MgSO4 and condensed by fractional distillation. The residue was purified over a silca-gel column eluting with DCM/MeOH 0-10% over 10 minutes. The fractions containing the product were pooled and evaporated to give the product. Procedure J A nitrogen containing heterocycle posing an alkyne was dissolved in diethyl ether (1M) and treated with an equal volume of 1M acid (HCl or anhydrous H3PO4) in diethyl ether. The volatile components were removed by evaporation using a stream of nitrogen gas to give the desired salt form of the heterocycle. General Procedure K To a stirred solution of 2-bromothiazole (1 g, 6.09 mmol) in EtOAc (20 mL) were added Et3N (3.6 mL, 26.21 mmol) and CuI (12 mg, 0.06 mmol) at RT. The reaction mixture was degassed with argon for 5 minutes, then added prop-2-yn-1-ol (1.6 mL, 29.26 mmol) and bis(triphenylphosphine)palladium chloride (0.2 g, 0.30 mmol) at RT. The reaction mixture was stirred at 50-55 °C for 16 h. After completion (monitor by TLC) of the reaction, the reaction mixture was filtered through celite pad and the filtrate was concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 12 g) using 10% - 15% EtOAc in petroleum ether to afford the desired product. General Procedure L To a stirred solution of alkynyl alcohol (0.15 g, 1.07 mmol) in dichloromethane (10 mL) were added Et3N (0.2 mL, 1.60 mmol) and acetyl chloride (0.1 mL, 1.28 mmol) at 0°C. The reaction mixture was stirred at RT for 16 h. After completion (monitor by TLC) of the reaction, the reaction mixture was concentrated under reduced pressure, poured into water and extracted with DCM. The organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (Column size: 24 g) using 10% - 15% EtOAc in petroleum ether to afford the desired product. Procedure M To a stirred solution of thiazole-2-thiol (0.3 g, 2.56 mmol) in Acetone (10 mL) were added K2CO3 (0.35 g, 2.56 mmol) and methyl propargyl bromide (0.2 mL, 2.56 mmol) at 0°C. The reaction mixture was stirred at RT for 3 h. After completion (monitor by TLC) of the reaction, the reaction mixture was poured in water (10 mL) and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the desired product. Procedure N To a stirred solution of 3-bromo pyrazole (0.5 g) in TEA (5 mL) was added CuI (0.049 g). Then the reaction mixture was degassed with argon gas for 10 mins followed by addition of Pd(PPh3)4 (0.148 g) and the acetylated alkyne input (5.14 mmol) at RT. The resultant reaction mixture was stirred at 80 °C for 2 h. After completion of the reaction, the reaction mixture was concentrated under reduced pressure at 38 °C to get the crude compound, which was purified by prep-HPLC to give the desired product. Procedure O To a stirred solution of pyrazole (0.5 g) in dry THF (5V) was added NaH (2 eq) and followed by propargyl bromide (1.2 eq) at 0 °C. The resultant reaction mixture was stirred at 0 °C to RT for 3 h. After completion of the reaction, the reaction mixture was quenched with ice-cold water and extracted with ethyl acetate and washed with aqueous NaCl solution and dried over with anhydrous Na2SO4. The resultant solution was concentrated under reduced pressure at 38 °C to get the crude compound, which was purified by combi flash chromatography to afford the desired product. Analytical Methods Synthesized compounds were characterized by the following methods: melting point, ESIMS – electrospray mass spec, HRMS – high resolution mass spec, EIMS – electron ionization mass spec, GCMS – gas chromatography mass spec, SIMS – secondary ion mass spec, Fourier Transform Infrared Spectroscopy – FTIR, 1H, 13C, 19F, and 31P Nuclear Magnetic resonance spectroscopy. Chiral structures in Table 1 are indicated by “&1” adjacent to the chiral center. Table 1 Nitrification Inhibiting Compounds
Biological Testing Compound Preparation: Compounds were dissolved in DMSO at 0.1 mM concentrations. Soil Slurry Preparation: Two different soils were sourced from Kalamazoo, Michigan (loamy fine sand) and Windfall, Indiana (clay loam). After collection soils were sieved at 2 mm and stored at 4 °C for no more than 6 months. The slurry is prepared by weighing out 143 grams of field moist soil per liter of nitrification media with a chlorate block (0.8 µM K2HPO4; 0.1 µM KH2PO4; 0.5 µM(NH4)2SO4; 10 µM NaClO3) and stirring it in a Pyrex dish for 5 minutes. Experimental Approach: While stirring, 900 µL of slurry was pipetted into a 96 deep well plate. After slurry addition, 9 µL of 0.1 mM stock solution of a compound or solvent control (i.e., DMSO) was immediately added to the designated well to bring the final concentration to 0.1 µM. A sealing mat was placed on top of the plate and mixed by inverting the plates three times. Plates were incubated for 48 hours at 28°C while shaking sideways at 225 rpm. After 48 hours the plate was spun down at 3,000 rpm for 15 minutes and the supernatant was analyzed for nitrite concentrations using the colorimetric Griess assay. Nitrification rates were determined by the total amount of nitrite formed over the incubation period. Nitrification inhibition was determined by normalizing the nitrification rate by the DMSO control. The relative inhibition of tested compounds was additionally normalized to the reference nitrification inhibitor nitrapyrin. Results are shown in Table 3. Table 3 Inhibition of Soil Nitrification.

Claims

We claim: 1. A nitrification inhibiting composition comprising a carrier; and a compound selected from the group consisting of wherein R1-R4 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, and wherein at least one of R1 – R4 is C≡C or C≡C-TMS; and N R wherein R11 – R14 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3,
C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, and wherein at least one of R11 – R14 is C≡C or C≡C-TMS; and wherein R21 – R24 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, and wherein at least one of R21 – R24 is C≡C or C≡C-TMS; and wherein R31 – R34 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen,C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, and wherein at least one of R31 – R34 is C≡C or C≡C-TMS; and wherein R41 – R44 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, and wherein at least one of R41 – R44 is C≡C or C≡C-TMS; and wherein R51, R52, and R53 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, and wherein at least one of R51, R52, or R53 is C≡C or C≡C-TMS; and wherein R61, R62, and R63 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH-cyclopentyl, C(=O)NH-cyclohexyl,
C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, and wherein at least one of R61, R62, or R63 is C≡C or C≡C-TMS; and wherein R71, R72, R73, and R74 are independently H, ethynyl, trimethylsilyl-ethynyl, C1 – C6 alkoxy, C1 – C6 thioalkyl, C1 – C6 alkyl, C3 – C6 cycloalkyl, C1 – C6 alkenyl, C3 – C6 cycloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkenyl, C1 – C6 haloalkyl, C1 – C6 haloalkoxy, benzyl, CH(OH)CH3, C(=O)NH2, CO2H, CO2Me, CO2Et, C(=O)H, CH2OH, halogen, C(=O)NHCH2C≡C, C(=O)NHCH(CH3)C≡C, C(=O)NHCH(CH2CH3)C≡C, C≡N, C(=O)NHC(CH3)(CH3)C≡C, C(=O)NH-cyclopropyl, C(=O)NH-cyclobutyl, C(=O)NH- cyclopentyl, C(=O)NH-cyclohexyl, C(=O)NHCH(CH3)CH3, C(=O)NHCH(CH3)CH2CH3, C(=O)NHCH(CH2CH3)CH2CH3, C(=O)alkyl, C(=O)haloalkyl, C(=O)CH3, C(=O)Et, C(=O)C=CCH3, C(=O) C≡C, C(=O)N(CH3)CH3, and wherein at least one of R71, R72, R73, or R74 is C≡C or C≡C-TMS. 2. The composition of claim 1 wherein the compound is selected from the group consisting of , ,
3. The composition of claim 1, wherein the compound is selected from the group consisting of
4. The composition of claims 1 to 3 further comprising a source of ammonia.
5. The composition of claims 1 to 4, wherein the source of ammonia is selected from the group consisting of anhydrous ammonia, ammonium nitrate, urea ammonium nitrate, manure, and mixtures thereof.
6. The composition of claims 1 to 5 further comprising a second nitrification inhibiting compound of claim 1.
7. A method of reducing nitrification in soil comprising applying a composition of claims 1 to 6 to soil.
8. The method of claim 7, wherein the composition and source of ammonia are applied simultaneously.
9. The method of claim 7, wherein the composition and source of ammonia are applied sequentially.
EP23843911.1A 2022-07-21 2023-07-21 Nitrification inhibiting heterocycles Pending EP4558468A2 (en)

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