Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
  • C07C49/757—Unsaturated compounds containing a keto groups being part of a ring containing —CHO groups
• • 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
  • A01N33/10—Amines; Quaternary ammonium compounds containing oxygen or sulfur having at least one oxygen or sulfur atom directly attached to an aromatic ring system
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
  • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring

Definitions

• lower-alkyl means an alkyl group containing from 1 to 8 carbon atoms, inclusive, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, and isomeric forms thereof.
• halogen is inclusive of fluorine, chlorine, and bromine.
• alkylene radical containing from 1 to 6 carbon atoms, inclusive includes methylene, ethylene, propylene, butylene, pentylene, hexylene, and isomeric forms thereof.
• a 5 to 7 ring atom saturated heterocyclic radical is inclusive of pyrrolidino, lower-alkylpyrrolidino such as 2- methylpyrrolidino, 2,2-dimethylpyrrolidino, 3-methylpyrrolidino, and the like, piperazino, lower-alkylpiperazino such as Z-methylpiperazino, 4-methylpiperazino, 2,4-dimethylpiperazino, and the like, piperidino, lower-alkylpiperidino such as Z-methylpiperidino, 3-methylpiperidino, 4,4-dimethylpiperidino, and the like, morpholino, hexamethylenimino, homopiperazino, homomorpholino, and the like.
• novel compounds of this invention as used throughout the specification embraces the acid addition and the quaternary ammonium salts of those compounds of Formula I which are tertiary amines, i.e., those compounds wherein Y represents x wherein A, R and R have the meaning hereinbefore given.
• Said acid addition salts comprise the salts of the free bases of Formula I wherein Y represents with pharmacologically acceptable acids such as sulfuric, hydrochloric, nitric, phosphoric, lactic, benzoic, methanesulfonic, p-toluenesulfonic, salicyclic, acetic, propionic, maleic, malic, tartaric, citric, cyclohexanesulfamic, succinic, nicotinic, ascorbic acids, and the like.
• pharmacologically acceptable acids such as sulfuric, hydrochloric, nitric, phosphoric, lactic, benzoic, methanesulfonic, p-toluenesulfonic, salicyclic, acetic, propionic, maleic, malic, tartaric, citric, cyclohexanesulfamic, succinic, nicotinic, ascorbic acids, and the like.
• Said quaternary ammonium salts comprise salts obtained by reacting the free bases of Formula I wherein Y represents with quaternating agents, for example, lower-alkyl halides, lower-alkenyl halides, di(lower-alky1)sulfates, aralkyl halides, lower-alkyl arylsulfonates, and the like.
• quaternating agents for example, lower-alkyl halides, lower-alkenyl halides, di(lower-alky1)sulfates, aralkyl halides, lower-alkyl arylsulfonates, and the like.
• lower-alkyl has the significance hereinbefore defined.
• lower-alkenyl means an alkenyl radical containing from 3 to 8 carbon atoms, inclusive, such as allyl, l-methylallyl, 2-methylallyl, Z-butenyl, 2-pentenyl, 2- hexenyl, 2-heptenyl, 2-octenyl, and the like.
• aralkyl means an aralkyl group containing from 7 to 13 carbon atoms, inclusive, such as benzyl, phenethyl, phenylpropyl, benzhydryl, and the like.
• loweralkyl arylsulfonates means the esters formed from lower alkanols and arylsulfonic acids such as benzenesulfonic, toluenesulfonic, xylenesulfonic, and like acids.
• Examples of quaternary salts of basic compounds of Formula I are the methobromide, methiodide, ethobromide, propyl chloride, butyl bromide, octyl bromide, methyl methosulfate, ethyl ethosulfate, allyl chloride, allyl bromide, benzyl bromide, benzhydryl chloride, methyl p-toluenesulfonate, ethyl p-toluenesulfonate, and the like.
• novel compounds of this invention possess pharmacological activity. They are active as antifertility, estrogenic, antispermatogenic, and cholesterol lowering agents.
• the compound 1,2-diphenyl-6- methoxy 1,2,3,4-tetrahydro-1,2-naphthalenediol exhibits oral antifertility activity in rats when tested by the method described by Duncan et al., Proc. Soc. Exp. Biol. Med. 112, 439-442 (1963).
• novel compounds of this invention are valuable for animal pest control.
• the compounds of this invention are formulated in combination with baits and/0r attractauts and placed in feeding stations accessible to undesirable rodents and other small animals including Canidae such as coyotes, foxes, wolves, jackals, and wild dogs and birds such as starlings, gulls, redwing blackbirds, pigeons, and the like, thus reducing hazards to aviation by eliminating their presence on runways and in the vicinity of airfields.
• the spread of disease, and destruction to property in both rural and urban areas can also be reduced.
• novel compounds of this invention can be combined with solid or liquid pharmaceutical carriers and formulated in the form of tablets, powder packets, capsules, and like solid dosage forms, using starch and like excipients, or dissolved or suspended in suitable solvents or vehicles, for oral or parenteral administration.
• the compounds of this invention are also useful as intermediates.
• the basic compounds of Formula I wherein Y represents can be reacted with fluosilicic acid to form the fluosilicate salts which in dilute aqueous solution are effective mothproofing agents as more fully disclosed in US. Patents 2,075,359 and 1,915,334.
• novel compounds of this invention can be prepared in accordance with the following reaction scheme:
• Hal represents a halogen atom, e.g., bromine or iodine
• R is an aryl radical of 6 to 10 carbon atoms, inclusive, such as naphthyl, phenyl, tolyl, chlorophenyl, fiuorophenyl, methoxyphenyl and the like.
• the acyloxy radical attached at the 2-position of Formula VI is the radical derived from the peracid used to effect the epoxidation reaction in the previous step.
• the starting material (II) is known in the art.
• the Grignard reagents (III) and (VIII) are prepared by reaction of magnesium in an anhydrous inert organic solvent such as diethyl ether, dibutyl ether, diisopropyl ether, tetrahydrofuran, and the like, with the appropriately substituted halobenzene, using procedures well known in the art for the preparation of Grignard reagents.
• an anhydrous inert organic solvent such as diethyl ether, dibutyl ether, diisopropyl ether, tetrahydrofuran, and the like
• halobenzenes from which the Grignard reagents (III) and (VIII) are prepared are, for the most part, known compounds which can be prepared by procedures conventional in the art for the preparation of halobenzenes; see, for example, Chemistry of Carbon Compounds, Volume IIIA, p. 113 et seq., 1954, Editor, E. H. Rodd 1 (Elsevier Publishing Company).
• the halobenzenes in whichYis (wherein A, R and R have the significance hereinbefore defined) can be prepared by the formation and reduction of the appropriately substituted amide of the corresponding benzoic or phenylalkanoic acid as described hereafter in Preparations 1 and 2.
• novel compounds of this invention represented by Formula I are prepared by first reacting 6-methoxy-1- tetralone (II) with the appropriate Grignard reagent (III) to obtain the corresponding 1-phenyl-6-methoxy-3,4-dihydronaphthalene (IV).
• the reaction is carried out under conditions normally employed in conducting Grignard reactions.
• the reaction is carried out under anhydrous conditions, advantageously in the presence of an inert solvent such as diethyl ether, dibutyl ether, diisopropyl ether, tetrahydrofuran, and the like.
• the reaction can be carried out at temperatures within the range of about 0 C. to about the boiling point of the solvent employed, and preferably is carried out within the range of about 15 C.
• the l-phenyl-6-methoxy-3,4-dihydronaphthalene (IV) thus obtained can be isolated from the reaction mixture by conventional procedures.
• the reaction mixture is decomposed by the addition of water, ammonium chloride, and the like, followed by separation of the organic layer and removal of the solvent therefrom.
• the residue is purified, if desired, by conventional procedures, for example, by chromatography, recrystallization, and the like.
• the 3,4-dihydronaphthaiene (IV) thus obtained is oxidized with an organic peracid to give the corresponding 1,2-epoxide (V), which is treated with boron trifluoride etherate without isolating the epoxide from the reaction mixture to give the enol acylate, namely, the corresponding 1-phenyl-2-acyloxy-6-methoxy-3,4-dihydronaphthalene (VI), wherein the acyl radical is that of the peracid used above for the epoxidation reaction.
• the enol acylate thus obtained can be isolated from the reaction mixture by conventional methods, for example, chromatography and/ or crystallization from a suitable organic solvent, such as methanol, ethanol, isopropanol, acetone, ethyl acetate, chlorinated hydrocarbons and the like.
• a suitable organic solvent such as methanol, ethanol, isopropanol, acetone, ethyl acetate, chlorinated hydrocarbons and the like.
• Peracids which can be used to obtain the desired 1,2- epoxide are for example, m-chloroperbenzoic, perbenzoic, pernaphthoic, p-methylperbenzoic, p-fluoroperbenzoic, pmethoxyperbenzoic, and the like.
• the epoxidation is carried out in accordance with methods known in the art, for example, Zaugg et al., J. Org. Chem. 15, 1197 (1950).
• the boron trifiuoride etherate reaction is carried out by treating the intermediate epoxide (V) with boron trifluoride etherate in accordance with methods known in the art, for example, Mills et al., J. Chem. Soc. 4213 (1956).
• the epoxidation and boron trifiuoride etherate reactions are carried out within a tempearture range of about 0 C. to about 40 C.
• the reactions are preferably conducted at about 5 C. to about 30 C. for a period of time sufficient to complete the reactions.
• the enol acylate (VI) thus obtained is then treated with an aqueous alkali metal hydroxide in an alkanol and in the presence of oxygen to obtain the corresponding l-phenyl 1 hydroxy-6-methoxy-3,4-dihydro-2(1H)- naphthalenone (VII).
• Bases which can be used are, for example, sodium hydroxide, potassium hydroxide, and the like.
• Alkanols which can be used include for example, methanol, ethanol, isopropanol, tertbutanol and the like.
• the reaction is carried out in the presence of air or oxygen at a temperature within the range of about 25 C. to the reflux temperature of the reaction mixture.
• reaction is preferably carried out using aqueous potassium or sodium hydroxide and tert.butanol at about 15 C. to about 30 C. until the reaction is complete. A period of from about 2 to 4 hours is generally sufficient.
• the product (VII) can be recovered from the reaction mixture and purified by conventional methods such as chromatography and/or crystallization from a suitable organic solvent, for example, ligroin, Skellysolve B hexanes (hereinafter referred to as Skellysolve B) and the like.
• the compounds of Formula VII can be prepared by treating the 1,2-epoxide (V), with an aqueous acid, such as hydrochloric acid, sulfuric acid, phosphoric acid, and the like. In carrying out this reaction it is not necessary to isolate the epoxide from the reaction mixture in which it is produced.
• the epoxide is formed by treating the selected compound (IV) with perphthalic acid within a temperature range of about C. to 40 C. until the reaction is complete. Room temperature, about 25 C., is preferred.
• the acid addition salts of those compounds of the invention having Formula I which contain a tertiary amino group can be prepared by methods Well known in the art.
• the acid addition salts of the invention can be prepared by reacting the free base with a pharmacologically acceptable acid as hereinbefore defined, in the presence of an inert solvent such as water, ether, and lower alkanols such as methanol, ethanol, and the like.
• the quaternary ammonium salts of those compounds of the invention (I) which contain a tertiary amino group can be prepared by reacting the free base of the Formula I with a quaternating agent, for example, an alkyl halide such as methyl iodide, ethyl iodide, isopropyl bromide, and the like, an alkenyl halide such as allyl chloride, allyl bromide, Z-butenyl bromide, and the like, a dialkyl sulfate such as dimethyl sulfate, diethyl sulfate, and the like, an aralkyl halide such as benzhydryl chloride, benzyl chloride, phenethyl bromide, and the like, or an alkyl arylsulfonate such as methyl p-toluenesulfonate, and the like.
• a quaternating agent for example,
• the reaction is effected by heating the reactants together in the presence of an inert solvent such as acetonitrile, acetone, methanol, ethanol, and the like.
• an inert solvent such as acetonitrile, acetone, methanol, ethanol, and the like.
• the desired quaternary salt separates from solution upon cooling the reaction mixture and can be isolated by filtration. Purification of the quaternary salt can be effected by conventional methods, for example, by recrystallizatiton.
• the anion of the quaternary ammonium salt obtained as described above can be exchanged for any other desired anion, e.g., the anions of the various acids enumerated previously, by conventional procedures.
• any of the quarternary ammonium salts of the invention can be converted to the corresponding quaternary ammonium hydroxide, illustratively by treatment with silver oxide, and the hydroxide so obtained is reacted with the appropriate acid to obtain the desired quaternary ammonium salt.
• a solution of the acid so obtained in a mixture of 50 ml. of thionyl chloride and 500 ml. of benzene was heated under reflux for 5 hours. The resulting mixture was allowed to stand for 17 hours at room temperature before removing the solvent by distillation under reduced pressure.
• the crude acid chloride so obtained was dissolved in 200 ml. of benzene and added slowly with stirring over a period of 15 minutes to a. solution of 82 ml. of pyrrolidine in 200 ml. of benzene. The resulting mixture was stirred for 3 hours at room temperature before evaporating to dryness under reduced pressure. The residue was dissolved in diethyl ether and water and the organic layer was separated.
• the organic layer was Washed successively with water, 2.5 N hydrochloric acid, and saturated aqueous sodium chloride solution before being evaporated to dryness.
• the residue was recrystallized from cyclohexane to give 37.91 g. of 1-(p-bromohydrocinnamoyl) pyrrolidine in the form of a crystalline solid having a melting point of 59 to 65 C.
• An analytical sample was prepared by recrystallization from ligroin.
• EXAMPLE l.-l-phenyl-6-methoxy-3,4-dihydronaphthalene (IV) A solution of 18.6 g. of 6-methoxy-l-tetralone (II) in 200 ml. of diethyl ether was added to an ice-cooled solution of 0.3 mole of phenylmagnesium bromide (III) in 300 ml. of diethyl ether. The reaction mixture was stirred for about 18 hours at room temperature, 50 ml. of water was then added, followed by 200 ml. of saturated aqueous ammonium chloride solution. The organic layer was separated, washed with water and brine and taken to dryness.
• p-tolylmagnesium bromide p-ethylphenylmagnesium bromide, p-fluorophenylmagnesium bromide, p-chlorophenylmagnesium bromide, o-propylphenylmagnesium bromide, o-bromophenylmagnesium bromide, m-tolylmagnesium bromide, m-isopropylphenylmagnesium bromide, and m-trifiuoromethylphenylmagnesium bromide there are respectively obtained:
• EXAMPLE 4.1-phenyl-1-hy'droxy-6-methoxy-34 dihydro-2( 1H) -naphthalenone (VII) A solution of 1.86 g. of 1-phenyl-6-methoxy-3,4-dihydronaphthalene (IV) in 25 ml. of diethyl ether was allowed to stand overnight in the refrigerator with 11.5 ml. of 0.88 N perphthalic acid in diethyl ether. The reaction mixture was filtered to remove the precipitated acid and the filtrate taken to dryness. The residue thus obtained was dissolved in diethyl ether and shaken with 50 ml. of 1.25 N hydrochloric acid for 3 hours.
• peracids such as those named hereinabove can be used in place of perphthalic acid.
• the resulting mixture is allowed to stand for 17 hours at room temperature beforebeing decomposed by the careful addition of water.
• the mixture so obtained is filtered and the organic filtrate is washed with water and saturated aqueous sodium chloride solution before being evaporated to dryness.
• the residue thus obtained is disolved in diethyl ether and the ether solution is extracted with three ZOO-ml. portions of 2.5 N hydrochloric acid. The acid extracts are then thoroughly extracted with methylene chloride and chloroform.
• the hydrochloride so obtained is dissolved in methylene chloride and washed with aqueous sodium bicarbonate solution.
• the washed methylene chloride solution is evaporated to drynes to yield l-phenyl-Z-[p-(pyrrolidinopropyl)phenyl] 6-methoxy 1,2,3,4-tetrahydro 1,2- naphthalenediol.
• the latter is dissolved in methylene chloride and chromatographed on a column of magnesium silicate (Florisil).
• the column is eluted with petroleum ether containing increasing proportions of acetone and those fractions which, on the basis of paper chromatographic analysis, are found to contain the desired material are combined and evaporated to dryness.
• EXAMPLE 7 .1-phenyl-2- p- (3-dimethyllaminopropyl) phenyl]-6-methoxy-1,2,3,4-tetrahydro-1,2-naphthalenediol (I) and the hydrochloride and hydriodide thereof Using the procedure described in Example 6, but replacing the Grignard reagent from p-(3-pyrrolidinopropyl) bromobenzene by that from p-(3-dimethylaminopropyl) bromobenzene, there are obtained 1-phenyl-2-[p-(3 dimethylaminopropyl)phenyl] 6-rnethoxy 1,2,3,4-tetra hydro-l,2-naphthalenediol and the hydrochloride and hydriodide thereof.
• EXAMPLE 8.1 phenyl-2-[p-(3-dimethylaminopropyl) phenyl] 6 methoxy-l,2,3,4-tetrahydro-1,2-naphthalenediol methiodide
• a solution of 1 g. of 1-phenyl-2-[p-(3-dimethylaminopropyl)phenyl] 6 methoxy-1,2,3,4-tetrahydro-1,Z-naphthalenediol in 12 ml. of acetonitrile is cooled in ice. To the cooled solution is added 1.4 m1. of methyl iodide and the mixture is allowed to stand overnight before being poured into ml. of diethyl ether.
• a solution of 1 g. of 1-phenyl-2-[p-(3-dimethylaminopropyl)phenyl] 6 methoxy-l,2,3,4-tetrahydro-1,2-naphthalenediol methiodide in dimethylformamide is shaken with a suspension of silver oxide until the precipitation of silver iodide is complete.
• the resulting mixture is filtered and the filtrate containing the corresponding quaternary ammonium hydroxide is neutralized by the addition of aqueous hydrochloric acid.
• the resulting mixture is evaporated to dryness to obtain l-phenyl-Z-[p-(3-dimethylaminopropyl)phenyl] 6 methoxy-1,2,3,4-tetrahydro-1,2 naphthalenediol methochloride.
• the anion of any of the quaternary salts of the invention can be exchanged by any other desired anion by forming the corresponding quaternary ammonium hydroxide and reacting the latter with the appropriate acid.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Life Sciences & Earth Sciences (AREA)
• Health & Medical Sciences (AREA)
• Pest Control & Pesticides (AREA)
• Plant Pathology (AREA)
• Agronomy & Crop Science (AREA)
• Engineering & Computer Science (AREA)
• Dentistry (AREA)
• General Health & Medical Sciences (AREA)
• Wood Science & Technology (AREA)
• Zoology (AREA)
• Environmental Sciences (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (1)

Publications (1)

Family

ID=24289785

Family Applications (1)

Country Status (6)

Cited By (4)

Citations (2)

• 1966
  • 1966-08-17 US US572889A patent/US3452102A/en not_active Expired - Lifetime
• 1967
  • 1967-07-12 GB GB32145/67A patent/GB1181295A/en not_active Expired
  • 1967-07-25 DE DE19671668763 patent/DE1668763A1/de active Pending
  • 1967-07-28 CH CH1073867A patent/CH490299A/de unknown
  • 1967-08-14 NL NL6711142A patent/NL6711142A/xx unknown
  • 1967-08-17 BE BE702767D patent/BE702767A/xx unknown

Patent Citations (2)

Also Published As

Similar Documents