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GB1598095A - Method of repelling insects from animals - Google Patents

Method of repelling insects from animals Download PDF

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Publication number
GB1598095A
GB1598095A GB51583/77A GB5158377A GB1598095A GB 1598095 A GB1598095 A GB 1598095A GB 51583/77 A GB51583/77 A GB 51583/77A GB 5158377 A GB5158377 A GB 5158377A GB 1598095 A GB1598095 A GB 1598095A
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azaspiro
alkyl
animal
urea
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Rohm and Haas Co
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/20—Spiro-condensed ring systems
    • 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
    • A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/02—Amines; Quaternary ammonium compounds
    • A01N33/08—Amines; Quaternary ammonium compounds containing oxygen or sulfur
    • 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
    • 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
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/16—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof the nitrogen atom being part of a heterocyclic ring
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/38—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the group >N—CO—N< where at least one nitrogen atom is part of a heterocyclic ring; Thio analogues thereof
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    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
    • C07C45/75—Reactions with formaldehyde
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    • C07C47/36—Saturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings containing hydroxy groups
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    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
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    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/12—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with only hydrogen atoms attached to the ring nitrogen atom
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/16—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon 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
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
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    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D317/26—Radicals substituted by doubly bound oxygen or sulfur atoms or by two such atoms singly bound to the same carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Environmental Sciences (AREA)
  • Dentistry (AREA)
  • Agronomy & Crop Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Catching Or Destruction (AREA)

Description

(54) METHOD OF REPELLING INSECTS FROM ANIMALS (71) We, ROHM AND HAAS COMPANY, a Corporation organized under the laws of the State of Delaware, United States of America, of Independence Mall West, Philadelphia, Pennsylvania 19105, United States of America, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed to be particularly described in and by the following statement:- This invention relates to a method of repelling insects from animals, other than human beings, which are subject to infestation or irritation by insects, and especially cows.
The search for insect repellents which have a combination of excellent repellency, high residual activity and essentially no toxicity is a continuing one due to recognition of the possible toxicity to animals of many known insecticides. Since long lasting repellents avoid these problems with insecticides and provide essentially the same results, compounds having these effects are in great demand.
In accordance with the present invention, is provided a method of repelling insects from animals, other than human beings, which are subject to infestation or irritation by insects, which comprises apply to the animal: (1) a compound of the formula:
wherein R1 is hydrogen, alkyl or alkenyl; R2 is hydrogen alkyl, cycloalkyl, alkoxycarbonyl, aralkyl or mononuclear aryl; or R1 and R2 are joined and form, together with the carbon atom to which they are attached, a saturated or unsaturated cycloaliphatic hydrocarbon group whose ring is optionally (a) substituted and/or (b) interrupted by a hetero oxygen atom; R3 is C1-C5 alkyl, hydroxy (C1-C5) alkyl, alkoxycarbonyl, or the group -C=Y)NR4R5 wherein Y is O or S and (a) R4 is hydrogen and R5 is alkyl, cycloalkyl other than nortricyclyl, alkenyl, alkoxycarbonyl or alkoxycarbonylalkyl or (b) R4 and R5 are joined and form, together with the nitrogen atom to which they are attached, a saturated heterocyclic group; X is alkyl, alkoxy, alkoxy-carbonylalkyl or cyano; m is 0 or an integer of 1 or 2 and n and n' are integers of 1 or 2.
(2) a compound as defined in (1) above modified in that the heterocyclic ring shown in Formula I contains a double bond but with the exclusion of compounds wherein said double bond is a carbon-nitrogen double bond, n and n' are both 1 and R' and R2 are joined to form, together with the attached carbon atom, a 5,5 dimethylcyclopentyl residue, but with the proviso that when said single double bond is a carbon-nitrogen double bond, then R3 is absent, or (3) an acid addition salt or quaternary ammonium salt of a compound as defined under (1) or (2) above.
In the case of compounds of Formula I modified in that the heterocyclic ring shown in Formula I contains a double bond, one of Rt, R2 and R3 will be absent and/or at least one of the -CH2- groups shown will lack a hydrogen atom.
The acid addition salts and quaternary ammonium salts referred to in (3) may be formed from organic or inorganic acids such as citric acid or hydrochloric acid or quaternizing agents such as alkyl halides, alkyl sulfates or aryl sulfonates, e.g. methyl chloride, ethyl iodide or p - toluene sulfonate. The above salts may be prepared by methods well known in the art.
When, in Formula I, R is alkyl it may, for example, be(C1-C9) alkyl such as methyl, ethyl, n - propyl, n - butyl, sec - butyl, tert - butyl, pentyl, hexyl, heptyl, octyl, nonyl. When R is alkenyl, it may, for example, be (C2-C5)alkenyl such as allyl.
When R2 is alkyl, it may be any of those alkyl groups listed above for R'. When R2 is cycloalkyl, this group may contain from 4 to 6 nuclear carbon atoms such as cyclobutyl, cyclopentyl and cyclohexyl. When R is alkoxycarbonyl it may contain from 2-6 carbon atoms as in ethoxycarbonyl. When R is aralkyl it may, for example, be benzyl or benzyl substituted in the ring with (C1-C5)alkyl. When R2 is mononuclear aryl, it may typically be phenyl or phenyl substituted with (C,- C5)alkyl.
When R' and R2 are joined they may, together with the carbon atom to which they are attached, form a cycloalkyl, cycloalkenyl or cyclo(alkoxyalkyl) ring, for example, a cycloalkyl, cycloalkenyl or cycloalkoxyalkyl residue of from 5 to 11 nuclear carbon atoms, the rings of these groups being optionally bridged by an alkylene group. Examples of such groups are cyclopentyl, cyclohexyl, cycloheptyl cyclooctyl, cyclononyl, cyclodecyl, cyclohexenyl, cycloheptenyl, cyclononenyl, bicyclo (2.2.l)heptyl (norbornyl), 5 - norborn - 2 - yl and tetrahydropyranyl.
When R1 and R2 are joined to form a ring which is substituted, the substituent(s) may, for example, be one or more hydroxy, (C1-C5)alkoxy or (C1-C5)alkyl groups.
When R3 is C1-C5 alkyl, it may be for example methyl, ethyl, propyl, butyl or pentyl. When R3 is alkoxycarbonyl, it may be (C2-C8)alkoxycarbonyl wherein the alkoxy moiety can be methoxy, ethoxy, propoxy, butoxy or pentoxy. When R is hydroxy (C1-C5)alkyl, it may be, for example hydroxyethyl. When R is the group -C(=Y)NR4R5 and R4 is hydrogen, R5 may, for example, be (C1-C5)alkyl, (C4 C6)cycloalkyl, (C2-C5)alkenyl or alkoxycarbonyl of up to 6 carbon atoms such as methoxycarbonyl and ethoxycarbonyl. When R4 and R5 are joined together, they may form, together with the nitrogen atom to which they are attached, a 5 to 7 membered saturated heterocyclic ring including pyrrolidinyl, piperidyl and homopiperidyl. X may, for example, be (C1-C5)alkyl such as methyl, ethyl, propyl, butyl and pentyl; (C1-C5)alkoxy atoms such as methoxy, ethoxy, propoxy, butoxy and pentoxy; or alkoxycarbonylalkyl containing up to 12 carbon atoms, for example, methoxycarbonylmethyl or butoxycarbonylethyl.
A sub-class of compounds useful in the invention is made up of compounds of Formula I above, wherein, in Formula I, R1 is hydrogen, alkyl or alkenyl; R2 is hydrogen, alkyl, cycloalkyl or mononuclear aryl; or R' and R2 are joined and form, together with the carbon atom to which they are attached, a cycloalkyl or cyclo(alkoxy alkyl) residue or a cycloalkyl residue bridged with a methylene group; R3 is C1-C5 alkyl, hydroxy (C15)alkyl, alkoxycarbonyl or the group C(=,Y)NR4R5 wherein Y is O or S and (a) R4 hydrogen and R5 is alkyl, alkenyl or alkoxycarbonyl or (b) R4 and R5 are joined and form, together with the nitrogen atom to which they are attached, a saturated heterocyclic group; X is alkyl, alkoxy, alkoxycarbonylalkyl or cyano, m is 0 or an integer of 1 or 2 and n and n' are integers of 1 or 2.
Another sub-class of compounds are those as just defined but in which the heterocyclic ring shown in Formula I contains a double bond, there being excluded from this sub-class compounds wherein, in the ring shown in Formula 1, there is a carbon-nitrogen double bond, n and n' are both 1 and R1 and R2 are joined to form, together with the attached carbon atom, a 5,5 - dimethylcyclopentyl residue. A third sub-class of compounds are those belonging to the two sub-classes just described but in which R is other than hydroxy(C1-C5)alkyl, R, is only hydrogen when R is the group -CONHalkyl and n' is 1.
For use in the method of the invention, preferred are compounds (1) having the following formula:
wherein (a) R7 is hydrogen and R8 is (C1-C5)alkyl or (C3-C11)alkoxycarbonylalkyl or (b) R7 and R8 are groups, particularly ethylene groups, which are joined to form, together with the nitrogen atom to which they are attached, a 5- or 6-membered saturated heterocyclic ring; X' is (C1-C5)alkyl or (C3-C11)alkoxycarbonylalkyl; R9, R10, R11 and R12 are either hydrogen or the two members in one of the pairs R9/R10 and R11/R12 are joined and form, together with the carbon atom to which they are attached a cycloalkyl ring of 5 to 11 nuclear atoms, n is 1 or 2 and m' is 0, 1 or 2 and (2) compounds as defined in (1) above modified in that the heterocyclic ring shown in Formula IA contains a double bond, the group C(=O)NR7R8 being absent when there is a carbon-nitrogen double bond in the ring shown in Formula IA.
When, in Formula IA, RB is (C1-C5)alkyl it may be for example methyl, ethyl, propyl, butyl and pentyl. When R8 is alkoxycarbonyl alkyl it may, for example, be methoxycarbonylmethyl, ethoxycarbonylmethyl, ethoxycarbonylethyl or butoxycarbonylethyl. When R7 and RB are joined, they can form, together with the nitrogen atom to which they are attached, a saturated heterocyclic ring such as pyrrolidyl or piperidyl. Especially preferred are those compounds wherein R7 and R8, together with the nitrogen atom to which they are attached, form a pyrrolidinyl and piperidinyl residue and n is 1. These compounds exhibit particularly good insect repellent and residual action.
Particularly preferred compounds useful in this invention are: 2 azaspiro[5.5]undec - 7 - enylcarboethoxymethyl urea (2 (ethoxycarbonylmethylcarbamoyl) - 2 azaspiro[5.5]undec - 7 - ene); 2 azaspiro[5.5]undec - 7 - enylpentamethylene urea (2 - (N,N pentamethylenecarbamoyl) - 2 - azaspiro[5.5]undec - 7 - ene); 2 azaspiro[5.5]undec - 7 - enyl - N,N - tetramethylene urea (2 - (N,N tetramethylenecarbamoyl) - 2 - azaspiro[5.5]undec - 7 - ene); 2 azaspiro[5.5]undecyltetramethylene urea (2 - (N,N - tetramethylenecarbamoyl) 2 - azaspiro[5.5]undecane); ethyl alpha(2 - methyl - 2 - azaspiro[5.5]undec - 7 ene)acetate; 2 - azaspiro[l0.5]hexadec - 1 - ene; 2 - azaspiro[5.5]undeca - 1,7 diene; 2 - azaspiro[7.5]tridec - 1 - ene; 2 - azaspiro[5.5]undec - I - ene; N - n butyl - N' - 3,3 - diethylpentamethylene urea; 2 - azasiro[5.5]undec - 7 - enylallyl urea (2 - (allylcarbamoyl) - 2 - azaspiro[5.5]undec - 7 - ene); ethyl - cg - (2 - n butyl - 2 - azaspiro[5.5]undec - 7 - ene)acetate; 2,6 - dimethylpiperidyl - N butyl urea (N - (n - butylcarbamoyl)- 2,6 - dimethylpiperidine); 2,6 dimethylpiperidyl - N- carbo - n- butoxymethyl urea (N - (n butoxycarbonylmethylcarbamoyl) - 2,6 - dimethylpiperidine; 1 - cyano - 2 - (2' hydroxyethyl) - 7 - methyl - 2 - azaspiro[5.5]undec - 8 - ene and 3 azaspiro[5.5]undecyltetramethylene urea (3 - (N,N - tetramethylene carbamoyl) 3 - azaspiro[5.5]undecane.
The compounds used in this invention are prepared in a variety of ways depending upon the size of the ring or the substituent desired. Compounds such as those having the formula:
wherein R', R2, X, m and n are as defined above are prepared by treating a compound of the formula:
with an alkali metal hydride such as lithium aluminum hydride. Any solvent which is inert or substantially inert to the reactants may be employed such as ethers including diethylether or tetrahydrofuran. The reaction may be conducted at a temperature in the range of from 0 to 100"C for a period of time of from 15 minutes to 5 hours; however, the reaction is generally initiated at room temperature and then brought to the reflux temperature of the particular solvent employed.
The preparation of compounds used in this invention and which have an R3 substituent is illustrated by the following reaction scheme.
(x) m m RW (CH2 )n R2/\( < 'H2 )n ' -- | C 5 R NNCO or 4 5 .' R R NCCi "jctl (CH,) rn R2/\( 2 )n ) N H D Raney Nickel (H2) I I (x) (x) CCH2 (CH,)n R1/.(CH2),. I R1 2/ LI C/ -CHCN (CH2)n + ) OM A E The reaction with an isocyanate (R5N=C=O) is generally conducted at a temperature in the range of from 0 to 500C in a suitably inert solvent such as benzene and the like.
The reaction with the carbamoyl halide or thiocarbamoyl halide
X X wherein R4, R5 and Y are as defined above, is generally conducted at a temperature in the range of from 0 C to room temperature in a suitably inert solvent such as benzene.
The hydrogenation of products A and E in the above reaction scheme with Raney nickel is carried out in a hydrogenator at 40 to 50 psi of hydrogen using a suitable solvent such as methanol or ethanol.
The products identified as B in the following reaction scheme can be employed in the preparation of the products identified as A in the foregoing reaction scheme. The products identified as B also have insect repellent activity and are prepared as follows:
R X /(CH2) CN (CH2)CN when n=l R2 o7 when n=2 TSC12/NaCN / B HOCH2CH20H/TSOH' R / CH20H \ C / CH2CH2CN CH2OH R1 CH2CH2CN C R2 0 2 R2 / \ CHO F G HOCH2CH2oH/TsoH' CH 2=CHCN Sodium Hydroxide Dioxane CH2OH CH2 H ( R CHO HCHO 2 R CHO Sodium Hydroxide R Methanol H 1 = Toluenesulfonic acid.
2 = Toluenesulfonyl chloride.
Product F in the immediately foregoing reaction scheme is treated with p toluenesulfonyl chloride (TSCI) at a temperature in the range of from about 0 C to room temperature with 0 C being the preferred temperature using pyridine as the solvent. The ethylene acetal radical is introduced in the molecule by treating the correspondingly substituted aldehyde product (G and H) with ethylene glycol containing p - toluenesulfonic acid (TSOH) as a catalyst. Solvents which may be employed include benzene and toluene. The reaction is generally conducted at the reflux temperature of the particular solvent employed.
The preparation of those compounds, wherein X is alkyl, alkoxycarbonyalkyl or cyano, R3 is alkyl and there is no internal ring double bond, is accomplished by methods well-known to those skilled in the art and is illustrated below.
R g (Cl2)n R2 (CH2)n' N R X ! L R2 tCH2)n, 1+ R3 I 2 n' NaO NaCN Dialkyl Alkyl malonate > / \ / (X) I m L 2 (CH2)n. N R3 The compounds used in this invention can be employed in a wide range of amounts and using a wide variety of carriers or diluents such as are conventionally used in the art. Where an insect repellent composition is used comprising the active compound and a carrier or diluent the amount of active compound employed in the can vary from 0.1 to 90 percent based on the weight of the composition and will depend upon the intended use. Usually, the compositions will contain from 0.1 to 10 weight percent of one or more of the active compounds and the latter will usually be used in intimate mixture with a carrier.
When it is desired to use the insect repellent composition directly (i.e., without further dilution), the amount of the compound present in the composition will usually be from 0.1 to 5.0 percent based on the total weight of the composition.
When it is desired to formulate a concentrated composition, i.e., one suitable for dilution prior to end use, the compounds will usually be present in the composition in an amount of from 0.5 to 90 weight percent.
In general, the repellent compositions will contain a carrier and from 0.1 to 90%, usually 0.1 to 10%, by weight of one or more of the active compounds concerned in the invention.
The carrier employed can be any of those conventionally used in insect repellent formulations, particularly those which are in no way harmful to the environment. The carrier can be any one of a variety of organic and inorganic liquid, solid, or semisolid carriers or carrier formulations conventionally used in insect repellent products and can be a mixture of such carriers.
Examples of organic liquid carriers include liquid aliphatic hydrocarbons such as pentane, hexane, heptane, nonane, decane and their analogs, as well as liquid aromatic hydrocarbons. Examples of other liquid hydrocarbons include oils produced by the distillation of coal and the distillation of various types and grades of petrochemical stocks including kerosene oils which are obtained by fractional distillation of petroleum at between 84"C and 1 300C and which usually have a flash point between 18"C and 32 C.
Other petroleum oils include those generally referred to in the art as. agricultural spray oils which are light and medium spray oils consisting of the middle fractions in the distillation of petroleum and have a viscosity in the range of from about 40 to 85 sec Saybolt at 40C and are only slightly volatile. These oils are usually highly refined and contain only minute amounts of unsaturated compounds as measured by standard sulfonation tests. The customary sulfonation range of such oils is between 90% and 94% of unsulfonatable residue. These oils are paraffin oils and can be emulsified with water and an emulsifier and diluted to lower concentrations and used as sprays. Tall oils obtained from sulfate digestion of wood pulp, like paraffin oils, also can be employed.
In addition to the above-mentioned liquid hydrocarbons, the carrier can contain conventional emulsifying agents e.g., a non-ionic surfactant such as an ethylene oxide condensate of octyl phenol or an anionic surfactant such as an alkali metal salt of an alkylbenzenesulfonic acid). Such emulsifiers are used to permit the composition to be dispersed in and diluted with water for end use application.
When paraffin oils are employed as carriers in the insect repellent compositions, they are usually used in conjunction with an emulsifier, the mixture being diluted with water immediately prior to the end-use application. Other suitable paraffin oils, particularly those used with emulsions, are referred to in the art as heavy paraffin oils and usually have a viscosity greater than 85 sec Saybolt at 40C.
Other advantageous organic liquid carriers can include liquid terpene hydrocarbons and terpene alcohols such as alpha-pinene, dipentene, and terpineol Still other liquid carriers include organic solvents such as aliphatic and aromatic alcohols, esters, aldehydes, and ketones. Aliphatic monohydric alcohols include methyl, ethyl, n - propyl, isopropyl, n - butyl, sex - butyl and t - butyl alcohols.
Suitable dihydric alcohols include glycols such as ethylene and propylene glycol and the pinacols (alcohols having the empirical formula: C6H12(OH)2. Suitable polyhydroxy alcohols include glycerol, arabitol, erythritol, and sorbitol. Suitable cyclic alcohols include cyclopentyl and cyclohexyl alcohols.
Conventional aromatic and aliphatic esters, aldehydes and ketones can be employed and are usually used in combination with the above-mentioned alcohols.
Still other liquid carriers including high-boiling petroleum products, such as mineral oil and higher alcohols, such as cetyl alcohol can also be employed.
Additionally, conventional "stabilizers" or "synergizers" such as t - butyl sulfinyl dimethyl dithiocarbamate, can be employed in conjunction with, or as a component of, the carriers used in the compositions of this invention.
Solid carriers which can be used include finely divided organic and inorganic solid materials. Suitable finely divided solid inorganic carriers include siliceous minerals such as clay, including bentonite, attapulgite, fuller's earth, diatomaceous earth, kaolin, mica, talc, and finely divided quartz, as well as synthetically prepared siliceous materials, such as silica aerogels and precipitated and fume silicas.
Examples of finely divided solid organic carrier materials include cellulose, sawdust and synthetic organic polymers.
Examples of semi-solid carriers include petroleum jelly and lanolin and mixtures of liquid and solid carriers which provide semi-solid products.
The repellent compositions can be empldyed as such or can be diluted with suitable liquids or solids to repel from animal livestock or their environments, common flying and crawling insect pests, such as roaches, moths, house and stable flies, termites, flour beetles, bean beetles, weevils, ticks, chinch bugs, lice, ants, chiggers and mosquitoes. The repellent compositions, when applied to an insect environment, effectively repel the insects.
Inspect pests can be repelled by contacting the animals on which the insects may alight or crawl with a liquid, solid or semi-solid composition. The contact can be accomplished directly (e.g., by atomizing the composition into the air as a liquid or as a dust so that the material will fall on the animal. For such uses, there are preferably used dust or spray dispensing devices such as pump-type applicators or aerosol cans charged with an insect repellent composition containing one or more of the repellent compounds concerned in this invention By way of further example, insect-infested animals, such as dogs with fleas or poultry with lice, cows with ticks may be treated with the insect repellent compositions by contacting the fur and/or feathers and the lice, fleas and ticks contained therein, thereby ending the insect infestation.
The working examples given immediately below and subsequently in this specification illustrate the preparation of compounds used in this invention.
EXAMPLE 1 2-azaspiro[5.5]undec-1-ene (Compound 1) Step A-1-(2-cyanoethyl)-1-formylcyclohexane To a stirred solution of cyclohexanecarboxaldehyde (100 g; 0.89 mole) and 50% potassium hydroxide solution (10.2 g) is added, dropwise, acrylonitrile (50.4 g: 0.95 mole) over the course of one hour, maintaining the reaction temperature between 50"d00C by occasional cooling. After all has been added, the mixture is stirred for an additional one hour until the exotherm ceases and then heated to 50 -60 C for 30 minutes. The product is acidified with dilute hydrochloric acid, taken up into ether, washed with water, dried (MgSO4) and distilled to afford 38% of colorless 1 - (2 - cyanoethyl) - I - formylcyclohexane (55.4 g), b.p. 142 146"C/5 mm.
Step B-l-(2-cyanoethyl)- 1-formylcyclohexane Ethylene Acetal A solution containing I - (2 - cyanoethyl) - 1 - formylcyclohexane (55.4 g: 0.34 mole), ethylene glycol (27.9 g; 0.45 mole) and p - toluenesulfonic acid (TSA) (100 mg) in dry benzene (250 ml) is heated under reflux with a Dean Stark tube for 12 hours. The solution is cooled, diluted with ether, washed with water and dried.
Removal of the solvent affords 98% of I - (2- cyanoethyl)- 1 - formylcyclohexane ethylene acetal (69.4 g) as a colorless mobil liquid.
Step C-2-azaspiro[5,5]undec-1-ene To a solution of lithium aluminum hydride (LAH) (12 g; 0.32 mole) in dry tetrahydrofuran (250 ml) is added, dropwise and while stirring, I - (2 cyanoethyl)- 1 - formylcyclohexane ethylene acetal (41.8 g; 0.20 mole) in tetrahydrofuran (50 ml). The mixture is heated under reflux for three hours, after which time the solvent is removed under reduced pressure and ether added (500 ml). The excess hydride is decomposed and the precipitated salts are removed by filtration. The filtrate is extracted several times with dilute hydrochloric acid and the acidic extract is allowed to stand at room temperature for one hour. The acidic extract is then made strongly alkaline with a dilute sodium hydroxide solution and extracted with ether. The ether is dried and distilled under atmospheric pressure and the residual liquid distilled to afford 53% of 2 - azaspiro[5,5]undec - 1 - ene (16 g) as a colorless mobil liquid, b.p. 65 67 C/0.70 mm.
EXAMPLE 2 2-azaspiro[5,4]dec-1-ene (Compound 2) Step A- 1 -formyl- 1 -hydroxymethylcyclohexane Methanol is added to a suspension of 37% formaldehyde solution (69 ml) and cyclohexanecarboxaldehyde (100 g; 0.89 mole) to afford a homogeneous solution.
The mixture is cooled to 0 C and a sodium hydroxide solution (IN; 67 ml) is added with stirring over the course of 15 minutes. The mixture is allowed to warm to room temperature and is stirred at 25 C overnight. The solution is then concentrated, diluted with water and extracted with ether. The ether extract is dried, evaporated in vacuo and the residual colorless liquid is distilled to afford 51 ', of I - formyl 1 - hydroxymethylcyclohexane (65 g) b.p. l200-l250C/0.90 mm.
Step B--l-formyl-l -hydroxymethylcyclohexane Cyclic Ethylene Acetal A solution containing 1 - formyl - I - hydroxymethylcyclohexane (65 g: 0.46 mole) and ethylene glycol (34.1 g; 0.55 mole) in benzene (350 ml) containing p toluenesulfonic acid (100 mg) is heated under reflux with continuous separation of water for three hours and then cooled. The benzene solution is.washed with water, dried over magnesium sulfate and concentrated to afford 90'/o' of 1 - formyl - I hydroxymethylcyclohexane cyclic ethylene acetal (77 g) as a colorless liquid.
Step C-I -formyl- 1 -p-toluenesulfonyloxymethylcyclohexane Cyclic Ethylene Acetal A solution containing 1 - formyl - I - hydroxymethylcyclohexane cyclic ethylene acetal (77 g; 0.41 mole) in anhydrous pyridine (300 ml) is cooled to 0 C and p - toluenesulfonyl chloride (TSCL) (95.5 g; 0.50 mole) is added in portions with stirring over 10 minutes. The mixture is then stored at OOC for two days, followed by dilution with water. The separated oil is extracted with ether, washed with water, dried and concentrated to afford 93 gZQ of 1 - formyl - 1 - p toluenesulfonyloxymethylcyclohexane cyclic ethylene acetal (130 g) as a colorless oil.
Step D-l-cyanomethyl-l-formylcyclohexane Cyclic Ethylene Acetal A solution of 1 - formyl - 1 -p - toluenesulfonyloxymethylcyclohexane cyclic ethylene acetal (130 g; 0.38 mole) in dimethylsulfoxide (200 ml) is added dropwise to a suspension of sodium cyanide (20.6 g; 0.42 mole) in dimethylsulfoxide (300 ml) with stirring under nitrogen at 900--950C over a period of 15 minutes. After the addition is complete, the mixture is maintained at 900C overnight. The dark solution is cooled, diluted with an equal volume of ice water and extracted with ether. The ether extract is washed with water, dried and concentrated to afford 60.0 g (81% yield) of 1 - cyanomethyl - 1 - formylcyclohexane cyclic ethylene acetal (60 g) as a dark oil.
Step E-2-azaspiro[5,4]dec-l-ene A solution containing 1 - - cyanomethyl - 1 - formylcyclohexane cyclic ethylene acetal (60 g; 0.31 mole) in dry tetrahydrofuran (50 ml) is added dropwise over 30 minutes to a suspension of lithium aluminum hydride (13.3 g; 0.35 mole) in tetrahydrofuran (200 ml) with stirring. After the addition is complete, the mixture is heated under reflux for one hour, cooled and decomposed with aqueous sodium hydroxide solution after replacing the tetrahydrofuran with ether. The resulting ether solution is extracted with a hydrochloric acid solution (2N). The aqueous extract is washed once with ether and allowed to stand at room temperature for one hour. The aqueous solution is made strongly basic and extracted with ether. The ether extract is dried and distilled to afford 14.5 g. (34% yield) of 2 - azaspiro [5,41 - dec - 1 - ene (14.5 g.) as a colorless mobile liquid, b.p
R1 o(CH2)n Preparation of compounds of the formula C R N xt X I CH CHCN - CHChO 2 C ~ C / 2 R2 / Catalyst) R2 / \ CHO He HCHq'NaOH R1N XCH2oH R2 / \ R CHO (a) H CH2CE12 Ii HOOCH2 CH2OH when (b) TSCL TSA when n=1 n=2 (c) NaCN i* X' R1 CH2CN R1 (CH2)CHCN \C/ \C/ R2/ R2/ Dy 1 (a) LAH (b) (b) acid (c) base X' ;;2) R N wherein X'=H (indicated by a hyphen in Table I) or X. TABLE 1
RtCH2)n Compound No. R1 R2 -N Compound No. R K2 n x.
3 -CCH2)7- 2 4 -CH2CH2CH=CHCH2- 2 CH2 5 -CH-CH=CH-CH-CH2 2 6 -CH(CH3)CH2CH=CHCH2- 2 7 -(CH2)6- 2 8 -(CH2)10- 2 9 -(CH2)5 - 2 4-CH3 10 -CH2CH2C(CH3)=C(CH3)CH2- 2 11 CH2CH2CH2CHCH2 2 2 OH 12 (CH2)3CH(OC2H5)CH2' 2 13 -CH2-CH2CH2-O-CH2 2 14 2 5 -C 2H5 2 15 -CH3 -CH(C2H5)(CH3) 2 16 -CH3 -CH2CH2CH3 2 17 -CH3 -( CH2)8CH3 2 18 -CH3 2 19 H < 2 TABLE I (Continued) Physical Characteristics Elemental Analysis Compound Picrate Calc. Found No. B.p./ C/mm M.p./ C C H N C H N 3 103-105/2 186-189 52.93 5.92 13.72 52.81 6.06 13.8 4 85/4.5 154-155.5 50.79 4.79 14.81 50.59 4.82 14.8 5 75-80/.85 140-144 52.31 4.65 14.35 52.03 4.63 14.7 6 74-75/.20 183-186 52.04 5.14 14.28 51.78 5.11 14.2 7 70-72/.30 177-178 51.77 5.62 14.21 51.82 5.82 14.5 8 127-130/.10 162-164.5 55.99 6.71 12.44 56.30 6.96 12.7 9 60/.05 157-158.5 51.77 5.62 14.21 51.91 5.86 14.6 10 75-77/.25 135-137 53.20 5.46 13.79 53.13 5.38 13.6 11 130-140/.30 - - - - - - 12 130-140/.55 - - - - - - TABLE I (Continued) Physical Characteristics Elemental Analysis Compound Picrate Calc. Found No. B.p./ C/mm M.pS C C H N C H N 13 85/.25 128-129.5 47.12 4.75 14.66 47.49 4.80 15.0 14 40-41/.35 180-183 48.91 5.47 15.2 49.30 5.68 15.38 15 45-47/.15 145-117 50.25 5.80 14.65 50.17 6.02 14.64 16 35-37/.15 110-112 48.91 5.47 15.21 48.73 5.53 15.52 17 105-108/.20 75-79 55.74 7.13 12.38 54.59 7.13 12.58 18 84-87/.10 147-149.5 53.73 4.51 13.93 53.81 4.56 13.83 19 72-74/.20 - - - - - - EXAMPLE 3 Ethyl &alpha;-(2-methyl-2-azaspiro[5.5]undec-7-ene) Acetate (Compound 21) Step A-2-methyl-2-azoniaspiro[5.5]undeca-1,7-diene Iodide A solution of 2 - azaspiro[5.5]undeca - 1,7 - diene (14.9 g; 0.10 mole) is dissolved in dry benzene (150 ml) and methyl iodide (21.3 g; 0.15 mole) is added.
The mixture becomes warm and a solid separates. The precipitate is filtered, washed with ether and air-dried to afford 27.0 g (93% yield) of 2 -. methyl - 2 azoniaspiro[5.5]undeca - 1,7 - diene iodide, m.p. 193-194 C.
Step B-Ethyl &alpha;-(2-methyl-2-azaspiro[5.5]undec-7-ene)acetate A solution of sodium methoxide in absolute ethanol (100 ml; 0.035 mole ) is treated with ethyl malonate (DEM) (5.61 g; 0.035 mole). The ethanol is removed under reduced pressure and the resulting sodiomalonic ester is dissolved in dry dimethyl sulfoxide (50 ml). 2 - methyl - 2 - azoniaspiro[5.5]undeca - 1,7 - diene iodide (8.73 g; 0.03 mole) is added in one portion and the mixture is stirred and heated at 90 -120 C for two hours, cooled, diluted with water and the separated oil is extracted with ether. The ether extract is washed with water, dried and concentrated. Distillation of the residual liquid yields 4.8 g (50% yield) of ethyl &alpha; (2 - methyl - 2 - azaspiro[5.5]undec - 7 - ene)acetate, b.p. 108 C/0.40 mm.
By following substantially the procedure of Example 3 and by substituting the appropriate amine and iodide for those recited in Example 3, Compounds 22-32 set forth in Table II are obtained.
TABLE II
Analysis Compound Picrate Calc. Found No. R R R B.p.( C/mm) m.p. C C H N C H N 22 -C2H5 -C2H5 CH3 90-93/.35 23 127-128 51.06 6.43 11.91 51.24 6.62 12.26 -CH2CH2CH=CHCH2- C2H5 114-115/0.15 139-141 53.43 6.12 11.33 53.63 6.38 11.54 24 -CH2CH2CH=CHCH2- C3H7 118-120/0.15 164-167 54.35 6.34 11.02 53.97 6.32 11.27 25 -CH2CH2CH=CHCH2- C4H9 126-0.15 133-135 55.163 6.56 10.72 55.25 6.74 11.26 26 -CH2CH2CH=CHCH2- C5H11 132-134/0.15 - - - - - - 27 -CH2CH2CH=CHCH2- C6H13 145-147/0.15 - - - - - - 28 -CH2CH2CH=CHCH2- C7H15 152-154/0.15 - - - - - - 29 -CH2CH2CH2CH2CH2- CH3 108-110/0.15 - - - - - - 30 -C2H5 -C2H5 C2H5- 75-77/0.07 - - - - - - 31 -C2H5 -C2H5 C3H7 101-105/0.45 - - - - - - 32 -C2H5 -C2H5 C4H9- 110/0.25 - - - - - - - EXAMPLE 4 Alternative Procedure for Preparing Ethyl e-[2-methyl-2-azaspiro- [5.5]undec-7-ene]acetate (Compound 21) To a solution containing ethyl bromoacetate (10 g; 0.06 mole) in dimethyl formamide (100 ml) is added zinc-copper couple (4.3 g). Heating and stirring are initiated and 2 - methyl - 2 - azoniaspiro[5.5]undeca - 1,7 - diene iodide (8.73 g: 0.03 mole) is added in one portion. The temperature of the resulting mixture is maintained at 1000C for 5 hours and cooled to room temperature. The solution is diluted with an equal volume of water and treated with excess concentrated ammonium hydroxide. Ether extraction, followed by drying over magnesium sulfate and subsequent distillation affords 7.0 g (73% yield) of ethyl &alpha; - [2 methyl - 2 - azaspiro[5.5]undec - 7 - ene]acetate, b.p. 108 C/.40 mm.
EXAMPLE 5 2-azaspiro[5.5]undecyltetramethyleneurea (2-(N,N-tetramethylene carbamoyl)-2-azaspiro[5.5]undecane) (Compound 35) A solution containing triethylamine (24.2 g; 0.24 mole) and pyrrolidine carbamoyl chloride (32.7 g; 0.24 mole) in benzene (200 ml) is treated dropwise, under ice cooling, with 2 - azaspiro[5.5]undecane (36.72 g; 0.24 mole). After the addition is complete, the mixture is allowed to stir at room temperature for 2 hours.
The precipitated triethylamine hydrochloride is collected by filtration and the filtrate is concentrated and the residual viscous oil is distilled to afford 53 g (88 yield) of 2 - azaspiro[5.5]undecyltetramethylene urea, b.p. 1320-I350C/.30 ml.
EXAMPLE 6 2-azaspiro[5.5]undec-7-enylpentamethylene Urea (2-(N,N-penta methylenecarbamoyl)-2-azaspiro[5.5]undec-7-ene) (Compound 36) A solution containing triethylamine (101 g; 1 mole) and piperidylcarbamoyl chloride (148 g; I mole) in toluene (1.01) is treated dropwise under ice cooling with 2 - azaspiro[5.iundec- 7 - ene (151 g; 1 mole). After the addition is complete, the mixture is allowed to stir at room temperature for 2 hours. The precipitated triethylamine hydrochloride is collected by filtration and the filtrate is concentrated and the residual oil is distilled to afford 218.5 g (83% yield) of 2 azaspiro[5.5]undec - 7 - enylpentamethylene urea, b.p. 1500-1550C/.55 mm (m.p.
370-390C).
EXAMPLE 7 2-azaspiro[5.5]undec-7-enyl Carboethoxymethyl Urea (2-(ethoxycarbonyl methylcarbamoyl)-2-azaspiro[5.5]undec-7-ene) (Compound 37) A solution containing 2 - azaspiro[5.Siundec - 7 - ene (151 g; 1 mole) in toluene (1.0 1) is treated dropwise, under ice cooling, with ethyl isocyanatoacetate (129 g; 1 mole). After the addition is complete, the mixture is kept at room temperature for 2 hours. The solvent is removed and the residual liquid distilled to afford 237 g (85% yield) of 2 - azaspiro[5.5]undec - 7 - enyl carboethoxymethyl urea, b.p. 188 190 C/.80 mm.
By following substantially the procedure of Example 9 and substituting for the ethyl isocyanatoacetate an equivalent equimolar quantity of allyl isocyanate, n propyl isocyanate and n - butyl isocyanate, there is obtained, respectively, 2 azaspiro[5.5]undec - 7 - enylallyl urea; (1 - allylcarbamoyl) - 2 azaspiro[5.5]undec - 7 - ene) (Example 7A, Compound 37A); 2 azaspiro[5.5]undec - 7 - enylpropyl urea, (1 - (n - propylcarbamoyl) - 2 azaspiro[5.5]undec - 7- ene) (Example 7B, compound 37B); and 2 azaspiro[5.5]undec - 7- enylbutyl urea, m.p. 460-490C (1 - (n butylcarbamoyl)- 2 - azaspiro[5.5]undec - 7 - ene) (Example 7C, Compound 37C).
EXAMPLE 8 2-azaspiro[5.5] undec-7-enyltetramethylene Urea (2-(N,N-tetramethylene carbamoyl)-2-azaspiro[5.5] undec-7-ene) (Compound 38) Step A-2-azaspiro[5 .5] undec-7-enecarbamoyl Chloride A solution of 2 - azaspiro[5.5]undec - 7 - ene (13 g; 0.086 mole) in benzene (25 ml) is added dropwise, under ice cooling, to a solution of phosgene (9 g: 0.09 mole) in benzene (100 ml). The solution is stirred at room temperature for 1 hour and concentrated under reduced pressure. Distillation of the residual colorless liquid affords 7.5 g (41% yield) of 2 - azaspiro[5.5]undec - 7 - enecarbamoyl chloride, b.p. l100-ll30C/.50 mm.
Step B-2-azaspiro[5.5]undec-7-enyl Tetramethylene Urea A solution containing 2 - azaspiro[5.5]undec - 7 - enecarbamoyl chloride (7.5 g; 0.035 mole) and triethylamine (3.54 g; 0.035 mole) in benzene (50 ml) is treated with pyrrolidine (2.49 g; 0.035 mole) at room temperature. After 30 minutes, the triethylamine hydrochloride is collected by filtration and the filtrate is distilled to afford 7.8 g (90% yield) of 2 - azaspiro[5.5]undec - 7 - ene tetramethylene urea, b.p. 1350-l380C/.30 mm.
By following substantially the procedure of Example 7 and by substituting for the 2 - azaspiro[5.5]undec - 7 - ene recited therein an equimolar quantity of Compound A in Table III below and by substituting for the ethyl isocyanatoacetate recited therein an equimolar quantity of Compound B in Table III, the following products are obtained: Compound B Product Compound No. Compound A Methyl isocyanate N-methyl-N'-3,3-diethylpenta39 3,3-diethylpiperidine methylene urea, m.p. 81 -83 C.
(N-(methylcarbamoyl)-3,3diethylpiperidine) n-butyl isocyanate N-n-butyl-N'-3,3-diethylpenta40 3,3-diethylpiperidine methylene urea (N-(n-butyl)carbamoyl)-3,3-diethylpiperidine Methyl isocyanate N-methyl-N'-tetrahydropyridyl 41 Tetrahydropyridine urea, b.p. 130 -135 C/1.5 mm (N-(methylcarbamoyl) tetrahydropyridine) Ethyl isocyanate N-ethyl-N'-tetrahydropyridyl 42 Tetrahydropyridine urea, b.p. 135 -138 C/1.5 mm (N-(ethylcarbamoyl)tetra hydropyridine) n-propyl isocyanate N-n-propyl-N'-tetrahydropyridyl) 43 Tetrahydropyridine urea, b.p. 125 C/0.5 mm (N-(n-propylcarbamoyl) tetrahydroxypyridine) n-butyl isocyanate N-n-butyl-N'-tetrahydropyridyl 44 Tetrahydropyridine urea. b.p. 138 C/0.75 mm (N-(n-butylcarbamoyl) tetrahydropyridine) tert-butyl isocyanate N-tert-butyl-N'-tetrahydro45 Tetrahydropyridine pyridyl urea, m.p. 130.4 C (N-(tert-butylcarbamoyl) tetrahydropyridine) Methyl isocyanate N-methyl-N'-2-methylpiperidyl 46 2-methylpiperidine urea, b.p. 127 -130 C/0.5 mm (N-(methylcarbamoyl)-2-methylpiperidine) n-propyl isocyanate N-n-propyl-N'-2-methylpiperidyl 47 2-methylpiperidine urea, b.p. 120 C/0.5 mm (N-(n-propylcarbamoyl)-2methylpiperidine) n-butyl isocyanate N-n-butyl-N'-2-methylpiperidyl 48 2-methylpiperidine urea, b.p. 140 -142 C/0.5 mm (N-(n-butylcarbamoyl)-2methylpiperidine) Allyl isocyanate 2-azaspiro[5.5]undec-749 2-azaspiro[5.5]undec7-ene enylallyl urea, b.p. 173 175 C/1.0 mm (N-(allylcarbamoyl)-2-azaspiro[5.5]undec7-ene) Compound No. Compound A Compound B Product tert-butyl isocyanate 2-methylpiperidyl-N'-tert50 2-methylpiperidine butyl urea, m.p. 125 -127 C (N-(tert-butylcarbamoyl)-2methylpiperidine) Allyl isocyanate 2-methylpiperidyl-N'-allyl urea, 51 2-methylpiperidine b.p. 140 -142 C/0.75 mm (N-(allylcarbamoyl)-2-methylpiperidine) Ethyl isocyanatoacetate 1-(2-methylpiperidyl)-3-carbo52 2-methylpiperidine ethoxymethyl urea, b.p. 155 160 C/0.5 mm (N-(ethoxycarbonylmethylcarbamoyl)-2-methylpiperidine) Ethyl isocyanate 2,6-dimethylpiperidyl-n-ethyl53 2,6-dimethylpiperidine urea, m.p. 94 -95 C (N-(ethylcarbamoyl)-2,6dimethylpiperidine) n-propyl isocyanate 2,6-dimethylpiperidyl-N-n54 2,6-dimethylpiperidine propyl urea, m.p. 77 -79 C (N-(n-propylcarbamoyl)-2,6dimethylpiperidine) n-butyl isocyanate 2,6-dimethylpiperidyl-N-n55 2,6-dimethylpiperidine butyl urea, (oil) (N-(n-butylcarbamoyl)-2,6dimethylpiperidine) Ethyl isocyanatoacetate 2',6'-dimethylpiperidyl56 2,6-dimethylpiperidine carboethoxymethyl urea, (oil) (N-(n-ethoxycarbamoylmethylcarbamoyl)-2,6-dimethylpiperidine) n-butyl isocyanatoacetate 2,6-dimethylpiperidyl-N57 2,6-dimethylpiperidine carbo n-butoxymethyl urea, (oil) (N-(n-butoxycarbonylmethylcarbamoyl)2,6-dimethylpiperidine) Methyl isocyanate 2-ethylpiperidyl-N'-methyl 58 2-ethylpiperidine urea, b.p. 155 C/3 mm (N-(methylcarbamoyl)-2ethylpiperidine) Ethyl isocyanate 2-ethylpiperidyl-N'-ethyl urea, 59 2-ethylpiperidine b.p. 153 -155 C/3 mm (N-(ethylcarbamoyl)-2-ethylpiperidine) n-propyl isocyanate 2-ethylpiperidyl-N'-n-propyl 60 2-ethylpiperidine urea, b.p. 150 C/1.75 mm (N-(n-propylcarbamoyl)-2ethylpiperidine) Compound B Product Compound No. Compound A 61 2-ethylpiperidine n-butyl isocyanate 2-ethylpiperidyl-N'-n-butyl urea, b.p. 150 -156 C/1.5 mm (N-(n-butylcarbamoyl)-2ethylpiperidine) 62 2-ethylpiperidine tert-butyl isocyanate 2-ethylpiperidyl-N'-tert-butyl urea, m.p. 113 -114 C (N-(tert-butylcarbamoyl)-2ethylpiperidine) 63 2-ethylpiperidine Allyl isocyanate 2-ethylpiperidyl-N'-allyl urea, b.p. 155 -157 C/2 mm (N-(allylcarbamoyl)-2ethylpiperidine) 64 2-ethylpiperidine Ethyl isocyanatoacetate 1-(2'-ethylpiperidyl-3-carboethoxymethylurea, b.p. 175 180 C/1.75 mm (N-(ethoxycarbonylmethylcarbamoyl)2-ethylpiperidine 65 4-ethoxycarbonyl- Methyl isocyanate 4'-carboethoxypiperidyl-N'methyl urea, b.p. 175 -180 C/2 mm (N-(methylcarbamoyl)-4ethoxycarbonylpiperidine) 66 4-ethoxycarbonyl- Ethyl isocyanate 4'-carboethoxypiperidyl-N'piperidine ethyl urea, b.p. 173 -180 C/1 mm (N-(ethylcarbamoyl)-4ethoxycarbonylpiperidine) 67 4-benzylpiperidine Methyl isocyanate 4-benzylpiperidyl-N'-methyl urea, (oil) (N-(methylcarbamoyl)-4benzylpiperidine) 68 4-benzylpiperidine Ethyl isocyanate 4'-benzylpiperidyl-N'-ethyl urea, (oil) (N-(ethylcarbamoyl)-4benzylpiperidine) 69 4-benzylpiperidine n-propyl isocyanate 4'-benzylpiperidyl-N'-npropyl urea, (oil) (N-(n-propylcarbamoyl)-4benzylpiperidine) 70 4-benzylpiperidine n-butyl isocyanate 4'-benzylpiperidyl-N'-butyl urea, (oil) (N-(n-butylcarbamoyl)-4benzylpiperidine) Compound No. Compound A Compound B Product 71 4-benzylpiperidine Ethyl isocyanatoacetate 4'-benzylpiperidyl-N-carboethoxymethyl urea, m.p. 110 -112 C (N-(ethoxycarbonylmethylcarbamoyl)4-benzylpiperidine) 72 3-azaspiro[5,5]undecane Pyrollidylcarbamoyl 3-azaspiro[5.5]undecyl-tetrachloride (tetramethylene) methylene urea, b.p. 160 -164 C carbamoylchloride) 3 mm (N-(N,N-tetramethylenecarbamoyl)-3-azaspiro[5.5]undecane) 73 3-azaspiro[5,5]undecane Allyl isocyanate 3-azaspiro[5.5]undecyl-allyl urea, m.p. 64 -67 C (N-(allylcarbamoyl)-3-azaspiro [5.5]undecane) 74 3-azaspiro[5.5]undecane Ethyl isocyanatoacetate 3-azaspiro[5.5]undecyl-carboethoxy urea, m.p. 89 -92 C (N-(ethoxycarbonylmethylcarbamoyl)3-azaspiro[5.5]undecane) 75 2-azaspiro[5,5]undec- Cyclohexyl isocyanate 2-azaspiro[5.5]undec-7-enyl)7-ene cyclohexyl-urea, m.p. 103 -106 C (N-(cyclohexylcarbamoyl)-2-azaspiro [5.5]undec-7-ene) 76 2-azaspiro[5,5]undec- Homopiperidylcarbamoyl- 2-azaspiro[5.5]undec-7-enyl-hexa7-ene chloride (hexamethylene methylene urea, b.p. 159 -162 C. 0.5 mm carbamoylchloride) (N-(N,N-hexamethylenecarbamoyl)-2azaspiro[5.5]undec-7-ene) EXAMPLE 9 2-hydroxyethyl-2-azaspiro[5.5] undec-7-ene (Compound 77) A mixture of 2 - azaspiro[5.5]undec - 7 - ene (30.2 g: 0.20 mole), 2 bromoethanol (25 g; 0.20 mole) and triethylamine (20.2 g) in toluene (250 ml) is heated under reflux for 5 hours. The solution is cooled, filtered to remove triethylamine hydrobromide and the filtrate concenttated under reduced pressure.
The residual liquid is distilled under reduced pressure to afford 28 g (72% yield) of 2 - hydroxyethyl - 2 - azaspiro[5.5]undec - 7 - ene, b.p. 900-9l0C/0.45 mm.
EXAMPLE 10 I-cyano-2-(2'-hydroxyethyl)-7-methyl-2-azaspiro[5.5]undec-8-ene (Compound 78) Step A-[2 - methyl - 1 - formyl - 1 - (2' - cyanoethyl - 3 - cyclohexene]ethylene Acetal A solution of 2 - methyl - I - formyl - 1 - (2' - cyanoethyl) - 3 - cyclohexene (122 g; 0.69 moles), ethylene glycol (62 g; 1.0 mole) and para- toluenesulfonic acid (300 m) in benzene (500 ml) is heated under reflux with a Dean Stark tube for 3 hours. The reaction mixture is cooled, washed several times with water, dried and concentrated to afford 152 g (100% yield) of [2 - methyl - I - formyl - 1 - (2' cyanoethyl) - 3 - cyclohexenelethylene acetal as a light yellow viscous liquid.
Step B-7-methyl-2-azaspiro [5.5]undeca-l ,8-diene To a solution of lithium aluminum hydride (28.5 g; 0.75 mole) in tetrahydrofuran (500 ml) is added dropwise and while stirring [2 - methyl - I formyl - 1 - (2' - cyanoethyl) - 4 - cyclohexene]ethylene acetal (15.2 g; 0.69 mole) and tetrahydrofuran (250 ml). The mixture is heated under reflux for three hours, after which the solvent is removed under reduced pressure and ether (500 ml) is added. The excess hydride is decomposed by adding successively water (28.5 ml); a 15% sodium hydroxide solution (28.5 ml) and water (85.5 ml). The precipitated salts are removed by filtration and the filtrate is extracted several times with dilute hydrochloric acid. The acidic extract is stored at room temperature overnight then made strongly basic with a concentrated sodium hydroxide solution (25%) and the solution extracted with ether. The ether extracts are dried (MgSO4) and the ether removed under atmospheric pressure and the residue distilled under vacuum to afford 52.6 g (47% yield) of 7 - methyl - 2 - azaspiro[5.5]undeca - 1,8 - diene, b.p.
740--75"C/.20 mm.
Step C-I - cyano - 2 - (2' - hydroxyethyl) - 7 - methyl - 2 azaspiro[5.5]undec - 8 - ene A solution of 7 - methyl - 2 - azaspiro[5.5]undeca - 1,8 - diene (21.2 g; 0.13 mole) and 2 - iodoethanol (22.3 g; 0.13 mole) in benzene (200 ml) is heated to reflux and allowed to cool. The benzene is removed under reduced pressure and dimethylsulfoxide (250 ml) and then sodium cyanide (9.8 g; 0.2 mole) added. The mixture is stirred at 500C for 2 hours, cooled and diluted with water (750 ml). The oil is extracted with ether and the ether solution washed with water and dried over magnesium sulfate. The ether solution is filtered and the ether removed.
Distillation of the residue under reduced pressure affords 22.5 g (74% yield) of I cyano - 2 - (2' - hydroxyethyl) - 7 - methyl - 2 - azaspiro[5.5]undec - 8 - ene, b.p. 1420-1450C/55 mm.
The following test description and results given in Table IV below show the efficacy of the compounds concerned in this invention.
Repellency Screen Male albino guinea pig (Perfection Breeders) are divided into groups of 2 each and placed into individual cages in a rodent battery equipped with an automatic watering system. Individual animal body weights ranged from 450 to 600 g. Feed and water were provided ad libitum. Guinea pigs are prepared for testing by clipping a patch of hair from the back with a size 10 clipper blade. This permits a residual amount of hair to be left on the animal.
Test compounds are formulated as 5% solutions in acetone. A 2.5 ml volume of test solution is applied with a medicine dropper pipette to an area on the animal's back measuring approximately 7 cmx5 cm. This application results in a deposit rate of 3.5 mg/cm2. Two guinea pigs are treated with each compound. The test animal is anesthetized with sodium pentobarbital administered intraperitoneally at the rate of 35 mg/kg and is placed in a cylindrical plastic cage with only the treated portion of the back exposed. The masked animal is introduced into an insect cage filled with either starved stable flies or yellow fever mosquitoes. Approximately 500-1000 insects are used as the challenge. The treated guinea pig is exposed to the test insects for a 5-10 minute period initially and at 3 hours post-treatment and then on a daily basis until the repellency activity of the compound terminates. The residual repellency activity ot a compound is regarded as terminated when three or more test insects fed on the guinea pig during the exposure period.
Protection Time Yellow Fever Compound No. Stable Fly Mosquito 1 4 days (D) 7 days (D) 2 0.5 hours (H) 0.5 hours (H) 3 2D 8D 4 3D 8D 5 3H 3H 6 3H 3H 7 3H 3H 8 4D 3H 9 3H 3H 10 2D 3H 11 3H 1D 17 1D 1D 19 3H 3H 21 3D 2D 22 1D 2D 23 2D 3H 24 3D 3H 25 4D 3H 26 ID 3H 27 3H 3H 28 3H 3H 29 2D ID 30 2D 2D 31 3D ID 32 2D 2D 35 17D 20D 36 4D 4D 37 7D 12D 38 8D 8D 39 NA (not active) 0.5H 40 3D 6D 41 NA 3H 47 0.5H 2+D 48 2D 2D 50 ID 0.5H 51 2D 0.5H 52 2D 3H 53 0.5H NA 54 NA 0.5H 55 8D 8D 56 2D NA 57 7D 7D 58 0.5H 2D 59 0.5H 2D 60 3H 3D 61 3H 2D 62 3H 3H 63 2D 3H 64 2D 3H 65 3H 3H 66 3H 3H 67 NA 0.5H 68 0.5H 0.511 Protection Time Yellow Fever Compound No. Stable Fly Mosquito 69 NA 0.5H 70 3H 3H 71 3H 3H 72 6D 7D 73 NA 2D 74 0.5H NA 75 0.5H 0.5H 76 4D 3H 77 3H 3H 78 6D 6D In conclusion reference should be made to the fact that various systems of nomenclature may be used for the compounds concerned in this invention. Thus, the compound of Example 8, Compound 38, may be named 2 azaspiro[5.5]undec - 7- enyl tetramethylene urea or 2- (N,N - tetramethylenecarbamoyl) - 2 - azaspiro[5.Slundec - 7 - ene. Compound 38 may be represented by the formula:
Also it should be noted that many of the active compounds referred to herein are novel compounds and are claimed per se in our copending Application No.
20816/80, (Serial No. 1,598,096).

Claims (20)

WHAT WE CLAIM IS:
1. A method for repelling insects from animals other than human beings which comprises applying to the animal (1) a compound of the formula:
wherein R' is hydrogen, alkyl or alkenyl; R2 is hydrogen alkyl, cycloalkyl, alkoxycarbonyl, aralkyl or mononuclear aryl; or R' and R2 are joined and form, together with the carbon atom to which they are attached, a saturated or unsaturated cycloaliphatic hydrocarbon group whose ring is optionally (a) substituted and/or (b) interrupted by a hetero oxygen atom; R3 is C1-C5 alkyl, hydroxy (C1-C5)alkyl, alkoxy carbonyl, or the group --CC-(=Y)NR4RS wherein Y is O or S and (a) R4 is hydrogen and R5 is alkyl, cycloalkyl other than nortricyclyl, alkenyl, alkoxycarbonyl or alkoxycarbonylalkyl or (b) R4 and R5 are joined and form, together with the nitrogen atom to which they are attached, a saturated heterocyclic group; X is alkyl, alkoxy, alkoxy-carbonylalkyl or cyano; m is 0 or an integer of 1 or 2 and n and n' are integers of I or 2.
(2) a compound as defined in (1) above modified in that the heterocyclic ring shown in Formula I contains a double bond but with the exclusion of compounds wherein the double bond is a carbon-nitrogen double bond and n and n' are both I and R' and R2 are joined to form, together with the attached carbon atom, a 5,5 dimethylcyclopentyl residue but with the proviso that when said single double bond is a carbon-nitrogen double bond the R3 is absent; or (3) an acid addition salt or quaternary ammonium salt of a compound as defined under (1) or (2) above.
2. A method according to Claim 1, wherein there is applied to the animal a compound as defined under (1) or (2) of Claim 1, wherein, in formula I, R' is hydrogen, alkyl or alkenyl; R2 is hydrogen, alkyl, cycloalkyl or mononuclear aryl; or R' and R2 are joined and, form together with the carbon atom to which they are attached, a cycloalkyl or cyclo(alkoxy alkyl) residue or a cycloalkyl residue bridged with a methylene group; R3 is C1-C5 alkyl, hydroxy (C1-C5)alkyl, alkoxycarbonyl or the group -C(=Y)NR4R5 wherein Y is O or S and (a) R4 is hydrogen and R5 is alkyl, alkenyl or alkoxycarbonyl or (b) R4 and R5 are joined and form, together with the nitrogen atom to which they are attached, a saturated heterocyclic group; X is alkyl, alkoxy, alkoxycarbonyl alkyl or cyano, M is 0 or an integer of 1 or 2 and n and n' are integers of 1 or 2.
3. A method according to Claim 1, wherein there is applied to the animal a compound as claimed in Claim 2, wherein R3 is other than hydroxy (C,--C,)alkyl, R2 is only hydrogen when R3 is the group -CON11- alkyl and n' is 1.
4. A method according to Claim 1, wherein there is applied to the animal (1) a compound of the formula:
wherein (a) R7 is hydrogen and R8 is (C1-C5) alkyl or (C3-C11) alkoxycarbonylalkyl or (b) R7 and R8 are alkylene groups which are joined to form, together with the nitrogen atom to which they are attached a 5- or 6-membered saturated heterocyclic ring; X' is (C,--C,)alkyl or (C3-C11)alkoxycarbonylalkyl; R9, R'O, R" and R12 are either hydrogen or the two members in one of the pairs R9/R'0 and R"/R'2 are joined and form, together with the carbon atom to which they are attached, a cycloalkyl ring of 5 to 11 nuclear atoms, n is 1 or 2 and m' is 0, 1 or 2 or (2) a compound as defined in (1) above modified in that the heterocyclic ring shown in Formula IA contains a single double bond, the group C(=O)NR7R8 being absent when said double bond is a carbon-nitrogen double bond.
5. A method according to Claim 1, wherein there is applied to the animal the compound N - butyl - N' - 3,3 - diethylpentamethylene urea.
6. A method according to Claim 1, wherein there is applied to the animal the compound 2 - azaspiro[5.5]undec - 1 - ene.
7. A method according to Claim 1, wherein there is applied to the animal the compound 2 - azaspiro[7.5]tridec - I - ene.
8. A method according to Claim 1, wherein there is applied to the animal the compound 2 - azaspiro[5.5]undeca - 1,7 - diene.
9. A method according to Claim 1, wherein there is applied to the animal the compound 2 - azaspiro[l0.5]hexadec - 1 - ene.
10. A method according to Claim 1, wherein there is applied to the animal the compound ethyl alpha(2 - methyl - 2 - azaspiro[5.5]undec - 7 - ene)acetate.
11. A method according to Claim 1, wherein there is applied to the animal the compound 3 - azaspiro[5.5]undecyltetramethylene urea.
12. A method according to Claim 1, wherein there is applied to the animal the compound 2 - azaspiro[5.5] undecyltetramethylene urea.
13. A method according to Claim 1, wherein there is applied to the animal the compound 2 - azaspiro[5.5]undec - 7 - enylpentamethylene urea.
14. A method according to Claim 1, wherein there is applied to the animal the compound 2 - azaspiro[5.5]undec - 7 - enylcarboethoxymethyl urea.
15. A method according to Claim 1, wherein there is applied to the animal the compound 2 - azaspiro[5.5]undec - 7 - enyltetramethylene urea.
16. A method according to Claim 1, wherein there is applied to the animal the compound 2 - azaspiro[5.5]undec - 7 - enylallyl urea.
17. A method according to Claim 1, wherein there is applied to the animal the compound 2,6 - dimethylpiperidyl - N - n - butyl urea.
18. A method according to Claim I, wherein there is applied to the animal the compound 2,6 - dimethylpiperidyl - N - carbo - n - butoxymethyl urea.
19. A method according to Claim 1, wherein there is applied to the animal the compound 2 - hydroxyethyl - 2 - azaspiro[5.51undec - 7 - ene.
20. A method according to Claim 1, wherein there is applied to the animal the compound 1 - cyano - 2 - (2' - hydroxyethyl) - 7 - methyl - 2 azaspiro[5.5]undec - 8 - ene.
GB51583/77A 1976-12-17 1977-12-12 Method of repelling insects from animals Expired GB1598095A (en)

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Cited By (2)

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US4515960A (en) * 1982-05-17 1985-05-07 Hoechst Aktiengesellschaft Spiro-2-aza-alkane-3-carbonitriles, their preparation and their use
WO1998013345A1 (en) * 1996-09-26 1998-04-02 Pfizer Limited Insect-repellent formulations

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US4419360A (en) * 1979-10-31 1983-12-06 Rohm And Haas Company Arthropod repellants
US5286723A (en) * 1988-08-31 1994-02-15 Daiichi Seiyaku Co., Ltd. Spiro compound
CA1336090C (en) * 1988-08-31 1995-06-27 Isao Hayakawa Spiro-substituted cyclic amines of quinolone derivatives
ATE268327T1 (en) * 1998-06-18 2004-06-15 Novartis Pharma Gmbh BENZAZOLE COMPOUNDS AND THEIR USE

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CH367171A (en) * 1958-08-12 1963-02-15 Cilag Chemie Aktiengesellschaf Process for the production of new N, N-pentamethylene ureas
US3418324A (en) * 1961-03-13 1968-12-24 Geschickter Fund Med Res Heterocyclic secondary amines
IL35988A0 (en) * 1970-01-19 1971-03-24 Du Pont Substituted pyrrolidines,their preparation and pharmaceutical compositions containing them
GB1476351A (en) * 1974-04-17 1977-06-10 Wilkinson Sword Ltd Compounds having a physiological cooling effect and compo sitions containing them
JPS5588039A (en) * 1978-12-27 1980-07-03 Olympus Optical Co Ltd One-shaft rotation type program shutter
FR2885403A1 (en) * 2005-05-03 2006-11-10 Saretco Sa GRID BAR AND GRID FOR FIREPLACE WITH SOLIDARITY GRADES

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4515960A (en) * 1982-05-17 1985-05-07 Hoechst Aktiengesellschaft Spiro-2-aza-alkane-3-carbonitriles, their preparation and their use
WO1998013345A1 (en) * 1996-09-26 1998-04-02 Pfizer Limited Insect-repellent formulations
US6130241A (en) * 1996-09-26 2000-10-10 Pfizer Inc. Insect-repellent formulations
AP1014A (en) * 1996-09-26 2001-09-28 Pfizer Insect-repellent azabicyclo [3.1] hexan-2,4-dione formulations.

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