EP0000106B1 - 2-Alkyl-Nikotinoide, Verfahren zu ihrer Herstellung und ihre Verwendung - Google Patents

2-Alkyl-Nikotinoide, Verfahren zu ihrer Herstellung und ihre Verwendung Download PDF

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EP0000106B1
EP0000106B1 EP78300040A EP78300040A EP0000106B1 EP 0000106 B1 EP0000106 B1 EP 0000106B1 EP 78300040 A EP78300040 A EP 78300040A EP 78300040 A EP78300040 A EP 78300040A EP 0000106 B1 EP0000106 B1 EP 0000106B1
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methyl
compound according
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compound
lower alkyl
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EP0000106A1 (de
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Edward Barkev Sanders
Henry Valette Secor
Jeffrey Ira Seeman
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Philip Morris USA Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/57—Nitriles

Definitions

  • the present invention relates to a group of novel nicotine analogues containing alkyl substituents ortho to the pyrrolidine ring.
  • the synthetic procedures disclosed herein for the production of nicotine analogues constitute considerably shorter and more practical routes than those previously proposed.
  • the novel compounds produced by the methods of the present invention are useful as insecticides.
  • Nicotine has been used as an insecticide for many years (see, for example, D. E. H. Frear, "Chemistry of the Pesticides," 3rd Ed., D. Van Nostrand Co., New York, 1955). Although a number of natural as well as synthetic nicotinoids have been screened with regard to insecticidal activity, the vast majority are significantly less active than nicotine [see J. Yamamoto et al., Agr. Biol. Chem. 32, 1341 (1968)]. The analogues of nicotine which have been tested involve either the alteration of the pyrrolidine moiety of the molecule, or the replacement of the pyridine ring with a substituted aromatic ring.
  • the paper describes a new synthetic process for the production of 2-alkyl-3-acylpyridines and 2-alkyl-3-formylpyridines via [2,3]-sigmatropic rearrangement of 1-cyanomethyl-1-( ⁇ -alkyl-2-picolyl) pyrrolidinium salts.
  • the versatility of this procedure is evidenced by the fact that the a-cyanoamine initially obtained can be hydrolyzed to an aldehyde, reductively cleaved to an amine, or alkylated and hydrolyzed to a ketone.
  • the present invention concerns new and improved processes for the production of compounds represented by the formula: wherein R, is hydrogen, lower alkyl, phenyl, alkaryl or phenylalkyl, R 2 is lower alkyl or phenylalkyl, and R 3 is a heterocyclic group represented by the formula: wherein R 4 is hydrogen or lower alkyl, R s is lower alkyl, and n is one or two.
  • the invention also includes the resulting compounds of this formula, except that in the case of 2-methylnicotine it extends only to the isolated, substantially pure compound.
  • the present invention may make use of novel intermediate products, some of which are useful in the production of compounds of Formula I and are represented by the formula: wherein R 1 and R 2 are the same as defined in Formula I and R 6 is represented by the formula: wherein R 7 is hydrogen, lower alkyl, ⁇ -cyanoalkyl or phenylalkyl, and each R 8 is independently selected from lower alkyl or when taken together with a connecting element, a heterocyclic structure is formed.
  • R 7 is hydrogen, lower alkyl, ⁇ -cyanoalkyl or phenylalkyl
  • each R 8 is independently selected from lower alkyl or when taken together with a connecting element, a heterocyclic structure is formed.
  • the intermediates are readily prepared by the method depicted in Scheme II hereinbelow.
  • lower alkyl means straight-chain or branched alkyl groups with 1 to 6 carbon atoms, for example methyl, ethyl, propyl, isopropyl, butyl, and the like, with methyl being preferred.
  • Alkaryl means aromatic radicals containing between 7 and 10 carbon atoms such as tolyl or xylyl.
  • Phenylalkyl includes radicals such as benzyl, phenylethyl or phenylpropyl.
  • Heterocyclic structures are meant to include cyclic amines such as pyrrolidine, morpholine, pyridine or tetrahydropyridines.
  • the compounds within the scope of the Formula I have two basic nitrogen atoms and can therefore form acid addition salts with inorganic and organic acids; for example, hydrochloric acid, acetic acid, maleic acid, p-toluenesulfonic acid or ethanesulfonic acid.
  • the salts of the compounds within the scope of Formula I can also be in the form of hydrates, for example, mono, tri- or polyhydrate.
  • the compounds of Formula I may be synthesized by two different but related processes.
  • a 2-halomethyl or substituted methylpyridine represented by the formula: wherein R 1 is the same as defined in Formula I, R 2 , is hydrogen, C 1-5 alkyl, phenyl or phenylalkyl and X is halogen, such as bromine, chlorine, iodine, or fluorine, with bromine being preferred, is reacted with a 2-cyano-N-substituted heterocyclic of the formula: wherein R 4 and R 5 are lower alkyl and n is one or two, to give a 1-alkyl-1-(2-picolyl or 2-a-alkylpicolyl)-2-cyanopyrrolidinium halide or the corresponding 1,2,3,6-tetrahydropyridinium halide.
  • the 2-haloalkylpyridine starting materials are readily available or may be synthesized by known methods.
  • the 1-alkyl-2-cyanopyrrolidines are prepared by treatment of a 1-alkyl-2-pyrrolidinone with a reducing agent such as sodium aluminum hydride followed by reaction with ammonium cyanide.
  • the 2 cyano-N-substituted 1,2,3,6-tetrahydropyridines are prepared according to methods described in J. Org. Chem., 29, 1647 (1964).
  • the reaction is carried out by adding a 2-haloalkylpyridine to a 1-alkyl-2-cyanopyrrolidine dissolved in an aprotic polar solvent such as dimethylsulfoxide, acetonitrile, etc.
  • an aprotic polar solvent such as dimethylsulfoxide, acetonitrile, etc.
  • the reaction is allowed to continue until salt formation is complete as determined by, for example, thin layer chromatography.
  • the [2,3]-rearrangement (Schemes I, below) of the pyrrolidine moiety is achieved by diluting the product (VII) obtained above with an aprotic solvent such as tetrahydrofuran, dimethylsulfoxide, hexamethylphosphoric triamide, acetonitrile, and the like, with tetrahydrofuran being preferred, and then adding a strong nonnucleophilic base such as potassium-tert-butoxide, potassium hydride, sodium hydride, sodium amide, and the like. After an appropriate reaction time of about 4 to about 8 hours, the product is isolated by standard extraction techniques known in the art.
  • an aprotic solvent such as tetrahydrofuran, dimethylsulfoxide, hexamethylphosphoric triamide, acetonitrile, and the like
  • a strong nonnucleophilic base such as potassium-tert-butoxide, potassium hydride, sodium hydride, sodium amide, and the like.
  • the reaction can be carried out using a base such as sodium amide and liquid ammonia as the solvent.
  • a base such as sodium amide and liquid ammonia as the solvent.
  • the latter method minimizes formation of side products which occur in certain examples.
  • the crude 2-alkyl-2'-cyano- nicotine product (VIII) isolated by standard techniques is then treated with a reducing agent such as lithium aluminum hydride, sodium borohydride, sodium cyanohydride and the like. Heating may be required to complete the reaction and the crude product is then isolated and may be further purified by standard techniques to yield the desired 2-alkylnicotinoids of Formula IX: wherein R 1 and n are the same as defined in Formulae I and II, R 2 is hydrogen, C 1-5 alkyl, phenyl or phenylalkyl and R 4 is lower alkyl.
  • a 2-alkyl-3-(1-cyano-1-pyrrolidinylmethyl)pyridine (XIV) is generally not isolated, but its formation may be confirmed by pmr spectroscopy.
  • the compounds of Formula XIV may then be treated with one equivalent of a strong base, followed by alkylation with a haloalkylnitrile, and acid hydrolysis to give a 2-methyl-3 pyridyl cyanoalkyl ketone of Formula XV.
  • the ketone thus formed may be cyclized under reducing conditions to yield compounds of Formula (XVI).
  • the reduction can be carried out catalytically, by means of noble metal catalyst, for example, by means of platinum, or by means of Raney nickel catalyst under elevated pressure, for example, under a pressure of more than 2 atmospheres.
  • the compounds of Formula I obtained in the manner described above are unsubstituted at the nitrogen, i.e. R 4 is hydrogen.
  • the a-cyanoamine resulting from the rearrangement may be reduced to the corresponding amine or treated with an organometallic reagent to form an alkylated amine.
  • R 2 of Formula I is an alkyl group other than methyl, for example, ethyl or propyl
  • the compound may be prepared by starting with the appropriate 2-a-alkylpicoline as previously described herein above (Scheme I and Scheme II), or in an alternate approach by further alkylation of R 2 .
  • 2-methylnicotine may be readily converted to 2-ethylnicotine by treatment with phenyllithium followed by alkylation with a haloalkyl such as metholiodide.
  • 2-methylnicotine may be converted to a 2-phenylalkylnicotine by treatment with phenyllithium and alkylation with a haloalkylphenyl moiety to yield a compound of Formula I, such as, for example, 2-phenylethyInicotine.
  • the reaction mixture was cooled and the organic and aqueous phase separated.
  • the aqueous phase was washed with 100 ml of ether.
  • the ether and tetrahydrofuran phases were then combined and washed with two 100 ml portions of a saturated sodium chloride solution.
  • the organic phase was dried over sodium sulfate and filtered preparatory to removal of solvent under reduced pressure.
  • the residue was distilled to yield 10.0 g of 1-methyl-2-cyanopyrrolidine.
  • the compound had a boiling point of 57-9° at 9.5 mm of Hg.
  • the resulting oil was dissolved in 100 ml dimethylsulfoxide and 500 ml tetrahydrofuran and then cooled to -10°. To the solution was added 4.5 g (94 mmol) 50% sodium hydride dispersion. The reaction was stirred for 3.5 hours at 0° and 16 hours at room temperature. The reaction mixture was filtered and the solvent was removed under reduced pressure giving a tan oil containing some solid material. The oil was dissolved in a small amount of ether and the solution filtered to remove insolubles. The ether solution was washed three times with a basic saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to give 14.96 g of an oil.
  • the oil was dissolved in 300 ml 95% ethanol and 4.7 g (124 mmol) of sodium borohydride was added. The mixture was stirred at 0° for 1 hour and at room temperature for 2 hours. The reaction mixture was filtered and the precipitate was washed first with ethanol and then with ether. The filtrate was concentrated, taken up in ether and filtered to remove additional insolubles. The filtrate was extracted with three 20 ml portions of 20% acetic acid. The combined acid extracts were washed with ether, diluted with 11.3 ml of concentrated hydrochloric acid and concentrated to dryness. The residue was treated with 50% aqueous potassium hydroxide and extracted with three portions of ether. The ether extracts were combined and dried over sodium sulfate.
  • the solution was concentrated to about 15 ml after which 30 ml dimethyl sulfoxide was added, and the reaction mixture was stirred for 21 hours.
  • the solution was continuously extracted with ether and the ether insoluble residue was dissolved in methanol, transferred to a 500 ml three-necked flask, and evaporated in vacuo to dryness to give 7.33 g (79%) of a dark red semi-solid.
  • Two hundred fifty ml of liquid ammonia was condensed into the flask and 1.23 g (31.4 mmol) of sodium amide was added. The reaction mixture was stirred at -60° for 30 minutes and then at reflux for 2 hours.
  • the ammonia was allowed to boil off leaving a brown residue which was triturated with ether and the resulting ether solution was filtered, and concentrated to give 2.71 g of a brown oil.
  • the oil was dissolved in 125 ml of 95% ethanol and 2.0 g of sodium borohydride was added. After stirring at room temperature for 8 hours, the ethanol was removed and the residue was dissolved in ether.
  • the etheral solution was extracted with 5% hydrochloric acid, the acid solution was washed with ether, basified with aqueous potassium hydroxide, and extracted with ether. The ether extracts of the basic solution were combined, dried over magnesium sulfate, filtered, and the solvent was removed.
  • 2-methylnicotine is treated with phenyllithium as in Example 6.
  • phenyllithium is added to the resulting anion.
  • the product can be isolated by distillation.
  • 2-bromomethyl-6-methylpyridine is treated with dimethylamine to give the corresponding tertiary amine, 2-dimethylaminomethyl-6-methylpyridine.
  • the tertiary amine is treated with cyanomethyl benzenesulfonate, as in Preparation II, to give dimethylcyanomethyl-(6-methyl-2-picolyl) ammonium benzene sulfonate,
  • the quaternary ammonium salt is rearranged using sodium hydride and alkylated with benzylbromide according to the procedure described in Preparation III.
  • the alkylated cyanoamine is decyanated with sodium borohydride in ethanol to give the desired product which can be purified through its picrate.
  • a 100 mg sample of the candidate compound was dissolved in 10 ml absolute ethanol. To the solution was added 40 ml tap water containing 0.5 ml of 1% surfactant. A 5 ml sample of each solution was sprayed on to replicate ivy cuttings infested with Aphids, The results, tabulated below in Table 1 were recorded 18 hours following the application of the sprays.
  • mice LD 50 of the compounds in mice is a measure of their mammalian toxicity.
  • the second column illustrates the effectiveness of the candidate compounds as insecticides as compared to nicotine, whereas the third column is the ratio of insecticidal effectiveness to mammalian toxicity. This ratio shows that the alkylated nicotines are more effective insecticides than nicotine in that they are considerably safer with regard to mammalian response.

Claims (16)

1. Verbindung der Formel:
Figure imgb0045
in welcher R1 Wasserstoff, Niederalkyl (wie nachstehend definiert), Phenylalkyl, Phenyl oder Aralkyl (wie nachstehend definiert) bedeutet, R2 Niederalkyl (wie nachstehend definiert), oder Phenylalkyl, und R3 heterocyclisch ist und der folgenden Formel entspricht:
Figure imgb0046
in welcher bedeuten: R4 Wasserstoff oder Niederalky! (wie nachstehend definiert), R5 Niederalkyl (wie nachstehend definiert) und n eins oder zwei, jedoch ausgenommen 2-Methylnicotin; oder an Säureadditionssalz oder ein Hydrat davon; wobei "Niederalkyl" sich hier auf einen geradkettigen oder verzweigten Alkylrest mit 1 bis 6 Kohlenstoffatomen und Aralkyl auf einen aromatischen Rest, enthaltend 7 bis 10 Kohlenstoffatome, beziehen.
2. Verbindung nach Anspruch 1, in welcher R2 Methyl oder Äthyl ist.
3. Verbindung nach Anspruch 1 oder 2, in welcher R3 N-Methyl-2-pyrrolidinyl ist.
4. 2-Methylnicotin in einem isolierten und im wesentlichen reinen Zustand.
5. Verbindung nach Anspruch 1, in welcher R3 1,2,3,6-Tetrahydro-2-pyridyl ist.
6. Verbindung nach Anspruch 1, welche 2-Äthyl-3-(1-methyl-2-pyrrolidinyl)-pyridin ist.
7. Verbindung nach Anspruch 1, welche 2-Methyl- oder 2-Äthyl-3-(2-pyrrolidinyl)-pyridin ist.
8. Verbindung nach Anspruch 1, welche 2,6-Dimethyl-3-(1-methyl-2-pyrrolidinyl)-pyridin ist.
9. Verbindung nach Anspruch 1, welche 2-Methyl-3-(2-piperidinyl)-pyridin ist.
10. Verbindung nach Anspruch 1, welche 2-Methyl-3-(1-methyl-2-(1,2,3,6-tetrahydro- pyridinyl))-pyridin ist.
11. Verfahren zur Herstellung einer Verbindung nach Anspruch 1, gekennzeichnet durch:
(a) Umsetzen einer Verbindung der Formel:
Figure imgb0047
in welcher R1 wie in Anspruch 1 definiert ist, R2 Wasserstoff, Niederalkyl (ein geradkettiger oder verzweigter Alkylrest von 1-5 Kohlenstoffatomen), Phenyl oder Phenylalkyl, X Chlor, Brom, Jod oder Fluor bedeuten, mit einer 2-Cyano-N-substituierten heteroxyclischen Verbindung der Formel
Figure imgb0048
in welcher R4 Niederalkyl (wie oben definiert) ist, und R5 und n wie in Anspruch 1 definiert sind, um eine Reaktionsverbindung der Formel zu ergeben:
Figure imgb0049
(b) Behandeln des Produktes von Stufe (a) mit einer starken nicht-nucleophilen Base, um ein [2,3]-Umlagerungsprodukt der Formel zu ergeben:
Figure imgb0050
in welchen R1, R2, R4, R5 und n die gleiche Definition wie in Stufe (a) haben,
(c) Behandeln des Produktes von Stufe (b) mit einem gemischten Hydrid-Reduktionsmittel, um die Verbindung zu decyanieren, und Isolieren des Produktes.
12. Verfahren nach Anspruch 11, dadurch gekennzeichnet, daß die starke Base Kalium-tert-butoxid, Natriumhydrid, Kaliumhydrid oder Natriumamid ist.
13. Verfahren anch Anspruch 11 oder 12, in welchem das Reduktionsmittel ausgewählt ist unter. Natriumborhydrid, Lithiumaluminiumhydrid oder Natriumcyanohydrid.
14. Verfahren nach Anspruch 11, 12 oder 13, in welchem die Stufe (a) und die Stufe (b) in Gegenwart eines aprotischen Lösungsmittels durchgeführt werden.
15. Verwendung einer Verbindung nach einem der Ansprüche 1 bis 10 als Insektizid.
16. Insektizide Zusammensetzung, enthaltend als aktiven Bestandteil eine Verbindung nach einem der Ansprüche 1 bis 10 zusammen mit einem Träger oder Beförderungsmittel dafür.
EP78300040A 1977-06-13 1978-06-13 2-Alkyl-Nikotinoide, Verfahren zu ihrer Herstellung und ihre Verwendung Expired EP0000106B1 (de)

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US05/805,689 US4155909A (en) 1977-06-13 1977-06-13 2-Alkyl nicotinoids and processes for their production
US805689 1977-06-13
US05/972,161 US4220781A (en) 1977-06-13 1978-12-21 Process for preparing 2-alkyl nicotinoids

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KR100446324B1 (ko) * 1999-01-14 2004-08-30 론자 아게 1-(6-메틸피리딘-3-일)-2-[4-(메틸술포닐)페닐]에타논 및이의 제조 방법
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CN116250483B (zh) 2015-06-26 2024-01-30 奥驰亚客户服务公司 用于生产烟草植物的组合物和方法以及具有改变的生物碱含量的制品
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DE2759198A1 (de) 1978-12-21
EP0000106A1 (de) 1978-12-20
US4220781A (en) 1980-09-02
US4155909A (en) 1979-05-22

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