IL43026A - Alpha-aryloxy alkanoic acids and esters thereof and their preparation - Google Patents

Abstract

1385828 Phenoxyacetic acid and cyclopropa- [a]naphthoxyacetic acid derivatives STERLING DRUG Inc 13 Aug 1973 [29 Aug 1972] 38311/73 Heading C2C Novel compounds of the Formula I wherein R is hydrogen or C 1-6 alkyl; A and A<SP>1</SP> are C 1-3 alkyl; Q is hydrogen, halogen or C 1-3 alkyl; R<SP>1</SP> is hydrogen, C 1-3 alkyl or phenyl; R<SP>2</SP> is hydrogen or halogen; R<SP>2</SP>' is hydrogen or halogen, at least one of R<SP>2</SP> and R<SP>2</SP>' being halogen; R<SP>3</SP> is hydrogen, C 1-3 alkyl or phenyl; R<SP>3</SP>' is hydrogen or C 1-3 alkyl; n is 0 or 1 or a compound I where Q and R<SP>3</SP> together form an ethylene bridge and (CH 2 ) n is a direct bond to the benzene ring ortho to Q and salts of the free acid may be prepared by (1) reacting a compound of the Formula IV: with a mixture of chloroform, a ketone ACOA<SP>1</SP> and an alkali metal hydroxide; (2) reacting a compound IV with a compound of the formula (A)(A<SP>1</SP>)C(Br)CO 2 R, BrCH 2 CN or BrCH 2 COOR in the presence of base and when the latter two compounds are used, dialkylating the product with A-iodide in the presence of base and, if necessary, hydrolysing the cyano group to a carboxy group; (3) reacting a compound of the Formul X, Xa or Xb: with a medium generating a carbene of the formula : CR<SP>2</SP>R<SP>2</SP>' and in the case of Xa and Xb thereafter dialkylating and, if necessary, hydrolysing the product as described in (2); (4) for producing the compound Ic, reacting a compound of the formula Xc with a medium generating a carbene : CR<SP>3</SP>R<SP>3'</SP>; (5) for producing 2-[p-(2,2-dichlorocyclopropyl)- phenoxy]-2-methylpropionic acid, subjecting p-(2,2-dichlorocyclopropyl)aniline to diazotization and hydrolysis to yield p-(2,2-dichlorocyclopropyl)phenyl, treating the latter compound as in (1) or (2) using acetone or (CH 3 ) 2 C(Br)COOR respectively; followed optionally by esterifying the free acid, hydrolysing an ester to the free acid and/or forming salts of the free acid. The intermediates of the Formula IV may be prepared by ether cleavage of the corresponding anisole which in turn is prepared by reacting a corresponding alkenyl substituted anisole with a medium generating a carbene of the formula : CR<SP>2</SP>R<SP>2'</SP>. The intermediates of the Formula X in which R 1 is H may be prepared by reacting a phenol VII as in process (1) or (2) to form an intermediate VIII which on treatment with sodium borohydride yields a compound of the Formula IX in which R 1 is hydrogen, which on dehydration yields X in which R 1 is hydrogen. Alternatively the intermediate X may be prepared by reacting a phenol XI by the processes (1) or (2) above to prepare a compound XII followed by treatment with p-Isopropenylanisole may be prepared by treating p-methoxyacetophenone with methyl lithium. Pharmaceutical compositions of the compounds I show hypocholesteremic and hypoglyceridemic activity when administered orally with the usual excipients. [GB1385828A]

Description

οη33ηι D'TBORI msnn Hovel α -aryloxy alkanoic acids and esters thereof, and their preparation STERLING DRUG INCi This invention relates to novel aryloxy aliphatic acids and alkyl esters thereof and to methods for the preparation thereof. In particular the invention is concerned with halocyclopropyl-substituted phenoxyalkanoic acids and lower-alkyl esters thereof.

The compounds of the invention have the following general formula: I wherein: R is hydrogen or alkyl of 1-6 carbon atoms; A and A' are alkyl of 1-3 carbon atoms; Q is hydrogen, halogen or alkyl of 1-3 carbon atoms; R^- is- hydrogen, alkyl of 1-3 carbon atoms or phenyl; 2 R is halogen; 2 ' R is hydrogen or halogen; R3 is hydrogen, alkyl of 1-3 carbon atoms or phenyl; R3' is hydrogen or alkyl of 1-3 carbon atoms; n is 0 or 1; or a compound of the above formula where Q and R3 together form an ethylene bridge and a direct bond to the benzene ring ortho to <¾, <¾ and R^ are joined to form a six-raembered non-aromatic carbocyclic ring of a 2,3-dihydro-lH-cyclopropa a÷7naphthalene ring system. Also contem-plated are the pharmacologically acceptable basic salts of the compounds of the above formula where R is hydrogen.

In the foregoing definitions, the alkyl groups can be straight or branched, and halogen stands for any of the four halogens, fluorine, chlorine, bromine and iodine.

Preferred pharmacologically acceptable salts include the sodium, calcium, magnesium and ammonium salts, and salts of organic amines of low toxicity, for example, the diethanolamine and N-methylglueamine salts.

The compounds of Formula I can be prepared by a process which comprises treating a compound of the Formula II, X, Xa or Xb with a medium generating a carbene p P ' CR^R^ or treating a compound of the Formula Xc with a medium generating a carbene JCR3R3I wherein R in all of said starting compounds is lower-alkyl; and in the case of the reaction with the compound of Formula II hydrolyzing the compound of Formula III thus obtained and reacting the compound of Formula IV obtained with either (a) a mixture of chloroform, a ketone of the formula A-CO-A' and an alkali metal hydroxide; or (b) with a compound of the formula (A) (A' )C(Br)G02R, BrCH^CN or BrGH2G00R in the presence of a base; and in the event a compound of the Formula XVI or XVII is produced, dialkylating the product with A-iodide in the presence of a base, and, if necessary, hydrolyzing the cyano group to a carboxy group with aqueous alkali; if desired, hydrolyzing a compound obtained wherein R is lower-alkyl to provide a compound wherein R is hydrogen and, if desired, converting a compound obtained wherein R is hydrogen to a basic salt thereof. The above Formulae are given in the following descriptions showing individual reaction sequences within the above general process.

I (R is lower-alkyl) I (R is H) In Method A above an alkenyl substituted phenol lower-alkyl ether of Formula II (where R1, R3 , R3 ' and Q have the meanings given hereinabove, and lower-alkyl has from one to four carbon atoms) is caused to react .with a medium generating a carbene, :CR R^' (where R^ and R have the meanings given hereinabove).

The carbenes, :CR¾^' , can be generated from a variety of halogenated organic compounds. Particularly useful media for this purpose are haloforms in the presence of a strong base such as potassium tertiary-butoxide. The haloforms thus used include chloroform (producing :CC12) , bromoform (:CBr2), iodoform ( :σ,ΐ'2 ) , chlorodifluoromethane (:CF2), and the like. Other sources of carbenes include chlorodiazomethane (:CHCl), FG12CC0CC12F (:CFC1), ethyl trichloroacetate (:CC12), Phenyl ( trichloromethyl)mercury (:CC12), phenyl ( bromodichloromethyl)mercury (:CBr2), sodium chlorodifluoroacetate (;CF2), sodium trichloroacetate (:CC12), bis( tribromomethyl)mercury (:CBr2), bromotrifluoromethane (:CF2), methyl dichlorofluoroacetate (:CFC1), and (CH^ J^SnCF-j (:GF2)0 The reaction generally takes place und-er anhydrous conditions at ambient temperature or lower.

The second step of Method A is the cleavage of, the cyclopropyl-substituted phenol ether III, produced by the foregoing carbene reaction. The ether cleavage is carried ou in the presence of a strong acid. The strong acid can be a protonic acid, such as hydrobromic acid or hydriodic acid, or a Lewis acid such as boron tribromide. Examples of reagents for cleavage of phenol ethers include boron tribromide, boron trichloride, boron trifluoride-etherate (in presence of acetic anhydride and lithium bromide), aluminum bromide, aluminum chloride, hydriodic acid (in presence of phosphorus and acetic anhydride), hydrobromic acid, diborane and pyridine hydrochloride.

The product of the ether cleavage, the cyclopropyl substituted phenol of Formula IV, is then either treated with a bromo ester (A)( A' )C(Br )C02-lower-alkyl (where A and A' have the meanings given hereinabove, and lower-alkyl has from one to six carbon atoms) in e presence of a base; or with a mixture of chloroform, a ketone of Formula A-CO-A' (where A and A' have the meanings given hereinabove) and an alkali metal hydroxide,, The former reaction produces a compound of Formula I where R is lower-alkyl and is carried out at a temperature between about 5° and 10°G. in the presence of a basic substance such as potassium carbonate. The latter reaction, carried out at a temperature of between about O and 100°G, , conveniently at reflux temperature, produces a compound of Formula I where R is hydrogen. If desired, the compound of Formula I where R is lower-alkyl can be hydrolyzed by conventional procedures, as with mild alkali, to produce the compound where R is hydrogen.

When Q and R^ together form an ethylene bridge and (CH2)n is a direct bond to the benzene ring ortho to Q, Method A employs as a starting material the dihydronaph-thalene lower-alkyl ether of the Formula O-lower-alkyl R-*- and R3' having the meanings given hereinabove, which when treated with a medium generating a carbene :CR2R2' yields a compound of the Formula VI having the 2,3-dihydro-lH-cyclopropa/-a_7naphthalene ring system with numbering as indicated (Revised Ring Index No. 2119). The ether linkage of the latter is then cleaved and the resulting phenolic compound (Via) treated either with a bromo ester ( A) ( A' )C( Br) -CC^R , or with a mixture of chloroform, a ketone A-CO-A' and an alkali metal hydroxide to produce a compound of Formula I where Q and R3 are joined to form the six-membered non-aromatic ring of a 2 ,3-dihydro-lH-cyclopropa/a_7naphthalene ring system, viz. : R2 R2 METHOD B VII t BrG-COOR t .

R½g-halide or Rl-Li VIII (R is lower-alkyl) IX (R is lower-alkyl) Q X (R is lower-alkyl) In Method B, an alkanoyl-substituted phenol of Formula VII (R^, R^* and Q having the meanings given hereinabove) is treated either with a bromo ester ' ! ( A)( A' )C(Br )-C02R (A and A1 having the meanings given here-inabove and R being lower-alkyl of 1-6 carbon atoms) in the presence of a base; or with a mixture of chloroform, a ketone A-CO-A' and an alkali metal hydroxide, followed by esterification of the resulting compound of Formula VIII where R is hydrogen with a lower-alkanol. There is thus obtained a compound of Formula VIII where R is lower-alkyl.

The next step of Method B comprises treating the alkanoyl substituted phenoxyalkanoic ester of Formula VIII with an alkali metal borohydride, R^-magnesium halide or R-^-lithium, R1 being alkyl of 1-3 carbon atoms or phenyl, The reaction takes place in an inert solvent at ambient temperature or below. The reaction with alkali metal borohydride (MBH^, where M is alkali metal, preferably lithium or sodium) provides a carbinol of Formula IX where R1 is hydrogen and R is lower-alkyl. The reaction with R^-magnesium halide or R^-lithium provides a carbinol of Formula IX where R^" is lower-alkyl or phenyl and R is lower-alkyl.

The carbinol of Formula IX is then dehydrated to produce an alkenyl substituted phenoxyalkanoic acid ester of Formula X. The dehydration is carried out by heating the carbinol in an inert solvent with a dehydrating agent such as p-toluenesulfonic acid, p-toluenesulfonyl chloride, naphthalene-^ -sulfonic acid, methanesulfonyl chloride-sulfur dioxide, methyl chlorosulfite, boron-trifluoride etherate, or the like. The reaction is conveniently carried out at the reflux temperature of the solvent with means for removing the water produced in the reaction.

The final step is the treatment of the olefinic ester of Formula X with a medium generating a carbene of Formula :CR¾^' (R^ and ^f having the meanings given above), as described more fully in connection with Method A above, thereby producing a compound of Formula I where R is lower-alkyl. Method B is also applicable to preparing the compounds wherein Q and R^ together form an ethylene bridge and (CH2)n is a direct bond to the benzene ring ortho to Q„ -^— Alternativel , compounds of Formula VIII where Q is H and the substituents are para-oriented can be prepared by a Friedel-Crafts type reaction between reactants of the Formulas (R is lower-alkyl) The acyl group enters the position para to the ether linkage, and the reaction is carried out in the presence of a Lewis acid such as aluminum chloride.

A variant on this approach involves a Friedel-Grafts reaction between a phenoxyalkanoic ester and di-chloroacetyl chloride to afford a dichloroacetophenone derivative of the Formula Following the analogous steps of Method B above, the latter can be converted to a carbinol of Formula and an olefin of Formula Finally, the latter is treated with a medium generating 3 3' 3 31 carbene (:CR R ) , where R and R have the meanings given hereinabove. Appropriate sources of such carbenes include ethylzinc-methylene iodide, the Simmons-Smith reagent, e.g. zinc-copper couple (or zinc dust and cuprous balide) with methylene iodide or ethyl^Lodo-methy])zinc ; and ethyl-idene. iodide-diethylzinc . Phenyicarbene ( .GHC^H^) can be generated by zinc reduction of benzaldehyde in an ether solution of boron trifluoride. There is thus produced a compound of the Formula METHOD 0 XII (R is lower-alkyl) ΐ (R is lower- alkyl) X (R is lower-alkyl) In Method C, an alkanoyl-substituted phenol of Formula XI (R^ having the meaning given hereinabove) is treated either with a bromo ester ( A)( A' )C(Br)-C0 R (A and A having the meanings given hereinabove and R being lower-alkyl of 1-6 oarbon atoms) in the presence of a base; or with a mixture of chloroform, a ketone A-CO-A' and an alkali metal hydroxide, followed by esterification of the resulting compound of Formula XII where R is hydrogen with a lower-alkanol. There is thus obtained a compound of Formula XII where R is lo er-alkyl.

The next step of Method C comprises treating the alkanoyl substituted phenoxyalkanoio ester of Formula XII with a Wittig reagent, e.g., a triphenylphosphonium bromide derivative (C^H^-p-CHiR3)^' )Br (R3 and R3' having the meanings given hereinabove) in the presence of a strong base such as sodium hydride, heated between about 0 and 100°C. in an inert, anhydrous solvent. There is thereby produced an alkenyl substituted phenoxyalkanoio acid ester of Formula X, which, as described previously under Method B can be converted by carbene reaction to a compound of Formula I where R is lower-alkyl.

METHOD D Method D is a process modification for preparing a preferred species starting from commercially available p-( 2,2-dichlorocyclopropyl)aniline (XIII). The latter is subjected to diazotization and hydrolysis to produce p-( 2,2-dichlorocyclopropyl)phenol (XIV), which then is treated as described above either with a lower-alkyl 2-bromo-2-methylpropionate or with a mixture of chloroform, acetone and alkali metal hydroxide, thereby producing, respectively, lower-alkyl 2-/ -( 2 ,2-dichlorocyclo-propyl)phenoxy_7-2-methylpropionate (XV, R is lower-alkyl) or 2-^-(2,2-dichlorocyclopropyl)phenoxy_7-2-methyl-propionic acid (XV, R is hydrogen).

Alternatively, in Methods A, B, C and D, the BrG(A)(A' )COOR reactant can be replaced by BrCH2CN or BrCH2C00R, and the alpha-alkyl residues (Α=Α·) introduced subsequently by alkylation with an alkyl iodide (A-iodide) in the presence of a base. In the event a nitrile group is present, it can be hydrolyzed to a carboxyl group with aqueous alkali. For example, in the last step of Method A the substitution of BrCH2GN for BrC(A) ( A' )-lower-alkyl yields a compound of the Formula XVI which can then be alkylated with A-iodide and hydrolyzed to give a compound of Formula I. Similarly, the substitution of BrCH2C00R for BrC( A) ( A' ) -lower-alkyl yields a compound of the Formula XVII which can be alkylated with A-iodide to give a compound of Formula I. Analogous transformations can be carried out on the cyclopropa/~~a7naphthalene intermediate Via: Analogous substitutions in Methods B and C affords compounds of the Formula and The compounds of Formulas Xa and Xb then react with a carbene :CR2R2' to give compounds of Formulas XVI and XVII.

Biological evaluation of the compounds of the invention has shown that they possess hypochoiesteremic and hypotriglyceridemic activity and are therefore useful in treating atherosclerotic conditions brought about by elevated serum cholesterol and triglyceride levels.

The hypocholesteremic and hypotriglyceridemic activity was measured by oral administration to rats Turner et al. , Scando J. Clin. Lab, Investigation 210 (191+9); Arnold et al., J0 of Atherosclerosis Research J_, 111-115 (196727· Male rats are fasted for five hours, medicated via stomach tube and then fed either a normal diet or a fat diet. This regimen is continued for four days. Blood is taken by cardiac puncture on the fifth day. Serum samples are analyzed for cholesterol and triglycerides, and values are reported in mg. cholesterol or triglycerides per 100 ml. of serum. Activities of compounds are evaluated in terras of ED^ values which are the calculated doses at which a 33 per cent decrease in serum cholesterol or triglycerides occurs. The compounds of the invention were found to have ED^ hypocholesteremic values ranging from 1 mg/kg, to 250 mg./kg. and ED^ hypotriglyceridemic values ranging from 2 mg./kg. to 250 mge /kg o in rats maintained on normal dieti In rats maintained on a fat diet the ED^ values were lower.

The structures of the compounds of the invention were established by the modes of synthesis, by elementary analysis and by infrared and nuclear magnetic resonance spectral determinations.

The following Examples will further illustrate the invention without the latter being limited thereby. METHOD A EXAMPLE 1 (a) p-Isopropenylanisole.

A solution of 1 0 g. ( 1. 0 mole) of p-methoxy-acetophenone in 1 00 ml. of anhydrous ether was added drop wise over a period of 90 minutes to a solution of 22 g. ( 1 . 0 mole) of methyllithium ( 1 . 66 molar in ether) cooled in an ice bath. The reaction mixture was stirred 30 minutes at 0°C. , 30 minutes at room temperature and one hour at reflux. Two additional 0 . 1 mole portions of methyllithium were then added to the refluxing mixture at half-hour intervals. The reaction mixture was added to aqueous ammonium chloride solution, and the water layer was separated and extracted with ether. The combined ether solutions were washed with aqueous sodium bisulfite solution, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was distilled, b.p. 75-8l°C ( l o 2 mm.) to give 120 . [j. g. of p-isopropenyl-anisole. ( b ) p-( 2 , 2-Diohloro-l-methyloyolopropyl)anisole.

Potassium t-butoxide ( 228 g. , 2.OI. mole) was added portionwise over a period of two and one-half hours to a stirred solution of 120 g. of p-isopropenylanisole in 7 0 g. of chloroform and 35°0 ml. of pentane held at -l4.0°C. The reaction mixture was stirred at -rJL|.0oG . for one hour, then the cooling bath was removed and stirring was continued for three hours. The reaction mixture was quenched in ice water, the layers separated and the aqueous layer extracted with pentane. The combined pentan -- solutions were washed with water, dried over anhydrous sodium sulfate and concentrated in vacuo to give 190 g. of p-( 2 ,2- dichloro-l-methylcyclopropyl)anisole .as an oil. ( c ) p-( 2 ,2-Dichloro-l-methylcyclopropyl )phenol.

A solution of 6.1 g. ( 0.02- -2 mole) of boron tri- bromide in 25 ml. of methylene dichloride was added drop- wise to a stirred solution of 6.1 g. (O. O26I . mole) of p-( 2 ,2-dichloro-l-methylcyclopropyl)anisole in 2 ml. of methylene dichloride cooled in an ice bath. The reaction mixture was stirred at 0° for one hour, then the ice bath was removed and the mixture stirred for an additional one hour. The reaction mixture was quenched in ice water and the layers separated. The aqueous layer was extracted with methylene dichloride, and the combined methylene dichloride solutions were washed with water and with dilute sodium hydroxide solution. At this point the sodium salt of p-( 2 , 2-dichloro-l-methylcyclopropyl)phenol . out separated/and was collected by filtration. The filter cake was combined with the original aqueous layer and acidified with concentrated hydrochloric acid. The acidified solution was extracted with ether and the ether dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was recrystallized from carbon tetrachloride to give'p-( 2 ,2-dichloro-l-methylcyclopropyl)-phenal, m.p. ! 125-126°C. ( d) 2- p-( 2 ,2-Dichloro-l-methylcyclopropyl)phenoxj7-2-methylpropionic acid T A, A' and R1 are CH^, R, R3 , R3 ' 2 ? t R and R11 are CI, and ή is 0; para- orienta¬ . . ■ Chloroform (5< ge ) was added dropwise to a mixture of 9.1 g. of p-( 2,2-dichloro-l-methylcyclopropyl)-phenol and 7.2 g„ of sodium hydroxide in 200 ml. of acetone stirred at reflux. After the chloroform addition was completed, the mixture was heated at reflux for three hours and then cooled in an ice bath„ The solid sodium salt was collected by filtration, washed with cold acetone and dissolved in water0 The latter solution was acidified with concentrated hydrochloric acid, and the acidified mixture was extracted with ether, and the ether was dried over anhydrous sodium sulfate and concentrated in vacuoa The residual oil was crystallized by trituration with hexane and then reorystallized from hexane to give 8„5 g. of 2- p-( 2,2-dichloro-l~methylcyclopropyl)phenoxy_7-2' methylpropionic acid as a pale cream-colored solid, m,p. 108-lll°Ce By replacing the chloroform in the foregoing preparation by a molar equivalent amount of iodoform or chlorodiazomethane there can be obtained, respectively, 2- -( 2 ,2-diiodo°l-methylcyclopropyl)phenoxy_7-2-methyl-propionic acid JT A, A' and R1 are CH^, R, R3, R3' ar,a Q are H, ' are iodine, and n is 0; para orientation/ or 2- p~( -chloro-l-raethylcyclopropyl)phenoxi27-2-methylpropionic acid R, R2' , R3, R3! ANO Q ARE H, R2 is CI, and n is Oj para orienta- EXAMPLE 2 (a) p-( 2,2-Difluoro-l-methyleyolopropyl)anisole, A warm solution of 91.5 go of sodium chlorodi-fluoroacetate (previously dried at ?O0Ce in vacuo) in 175 ml, of diglyme was added dropwise over a period of 90 minutes to a stirred and refluxing solution of 7^ g. of p-isopropenylanisole in 00 ml0 of diglyme, containing a trace of trinitrobenzene and l|-t-butylpyrocatechol as stabilizers o The reaction mixture was stirred at reflux for five minutes, then cooled and filtered to remove sodium chloride. The sodium chloride was washed with a little diglyme and then with pentane, and the combined washings and the filtrate were mixed with 3 liters of water and extracted three times with pentanee The pentane solution was washed with 10$ aqueous potassium hydroxide, then with water, dried over anhydrous sodium sulfate and concentrated in vacuo to give 96 , g o of p-( 2 , 2-difluoro- 1-methylcyclopropyl)anisole as a straw-colored oil0 (b) p°( 2 , 2-Di luoro-l-methylcyclopropyl )phenol was prepared from 9 9 g o of p- ( 2 , 2-difluoro-l-methylcyclopropyl)anisole and 20 g„ of boron tribromide in 200 ml0 of ethylene di~ chloVide according to the procedure described above in Example 1 , part (c), affording 9 g° of pinkish oil which solidified upon standing,, (c) 2-/p° ( 8 2-Difluoro-°l-meth7loyclopropyl)phenoxy7- 2 -methylpropionic acid l; A, A» and R1 are CH^, R, R3, R-^ and Q are H, R^ and R are P, and n is Oj para orientation/ was prepared from 9 0 0 gc of p=( 2 , 2-difluoro-l=methylcyclopropyl)phenol, 10 o 9 g o of sodium hydroxide and 8 o l g0 of chloroform in 200 ml„ of acetone according to the procedure described above in Example 1, part (d)« The product was recrystallized from hexane to give 8 „ 5 g» of 2= p=( 2 , 2-difluoro -1-methyIcyclopropy 1 )phenoxv/" 2-methylpropionic acid as a pale cream-colored solid, m.p. 110-111°G.

EXAMPLE 3 (a) p-(2,2-Dibromo-l-methyloyolopropyl)anisole.

Potassium t-butoxide ( 81+. g. , 0.75 mole) was added portionwise over a period of two hours to a stirred mixture of \$ g. (0.3 mole) of p-isopropenylanisole and lj.80 g. (1.9 mole) of bromoform in 1350 ml. of pentane cooled in a dry ice bath. For the first 90 minutes the addition was carried out at -l4.0°C., then for 30 minutes at -10°C. The reaction mixture was stirred for one hour at -10°C. , then the cooling bath was removed and stirring continued for three hours. The mixture was quenched in ice water, the layers were separated and the organic layer was washed with water, dried over anhydrous sodium sulfate and con-centrated in vacuo to give 99.5 g. of p-( 2,2-dibromo-l-methylcyclopropyl)anisole as a red-brown oil. (b) p-( 2 ,2-Dibromo-rl-methyloyclopropyl )phenol was prepared from 10 g. of p-( 2,2-dibromo-l-methylcyclopropyl)anisole, 7.5 g. Of boron tribromide and 100 ml. of methylene di-chloride according to the procedure described above in Example 1, part (c). There was thus obtained 6 g. of p-( 2,2-dibromo-l-methylcyclopropyl)phenol as an off-white solid. ( c ) 2-^/ρ-( 2,2-Dibromo-l-methylcyclopropyl)phenox27-2- methylpropionic acid / ; A, A' and R1 are CH-j, R, R , R3! and Q are H, R 2 and R?' are Br, and n is 0; para orientation/ "as prepared from 11.7 g. of p-( 2,2-dibromo-l-methylcyclopropyl)phenol, 15.2 g. of sodium hydroxide, 11,3 g. of chloroform and 20 ml. of acetone according to the procedure described above in Example 1, part (d). There was thus obtained 10.2 g„ of 2- -{ 2,2-dibromo-l-methylcyclopropyl)phenoxv7~2-methylpropionic acid as a pale cream-colored solid, m.p. 130-131»5°c» when recrystal-lized from an ether-hexane mixture0 EXAMPLE ti (a) p°( 2a2-Diohloro-393"dimethyloyolopropyl )anisole was prepared from 8.3 go of p-(2,2~dimethylvinyl)anisole, 102 ge of potassium t-butoxide, l80 ml. of chloroform and l800 ml. of pentane according to the procedure described above in Example 1, part (b)„ The product was recrystallized from hexane to produce p-( 2,2-dichloro-3j3°dimethylcyclopropyl)anisole in the form of colorless needles, m.p. ^.5- 70C. (b) p-( 2 , -Dichloro~3 , 3-dimethylcyolopropyl)phenol was prepared from 65.8 g0 of p-( 2, 2-dichloro-3p3-dimethylcyclopropyl )anisole and 37.5 g. of boron tribromide according to the procedure described above in Example 1, part (c).

There was thus obtained 23.5 g. of p-( 2,2-dichloro-3,3-dimethylcyc lopropyl)phenol, m.p. 111-111.5°C. when re-crystallized from a benzene-hexane mixture. ( c ) 2-^ -( 2 ,2-Dichloro=3 ,3-dimethylcyclopropyl )phenoxyj^-2- methylpropionic acid /I; A, A', R^ and R3* are CH^, R, R1 and Q are Hp R2 and R2' are CI, and n is 0; para orienta-tion7 was prepared from 30,3 g. of p-(2,2-dichloro-3,3-dimethylcyclopropyl)phenol, 31.2 g. of sodium hydroxide, 23o2 g, of chloroform and 1000 ml. of acetone according to the procedure described above in Example 1, part (d). The product was obtained in the form of an oil.

EXAMPLE 5 (a) p-( 2 fl2-Difluoro-393-dimethylcyclopropyl)aniaole was prepared from 196c g„ of p-( 2 s2-dimethylvinyl)anisole and 100 g. of sodium chlorodifluoroacetate in 700 ml. of diglyme according to the procedure described above in Example 2 , part (a)e The product was distilled at 8l-82°C. ( 0.1 mm„ ) to give 7 .0 g„ of p»( 2 ,2-difluoro-3 , 3-dimethyl-cyclopropyl ) anisoleo (b) p°( 2 ,2-Difluoro-3 „3-dimethylcyclopropyl)phenol was prepared from 31„ 8 g0 of p-( 2 s2-difluoro-3 s>3-dimethyl-cyclopropyl)anisole and 2 g. of boron tribromide according to the procedure described above in Example lp part (c). The product was used directly in the following reaction without further purification „ (c) 2-^p-( 2 ,2=-Difluoro=3 p3»dimeth lcyclopropyl)phenox27-2-methylpropionic acid ZT. Ap A'p R- and R3 ' are OH^, R , R1 and Q are Hs R^ p and R^ ' are F, and n is Oj para orienta-tion7 was prepared from 3„ 96 g„ of -( 2 ,2-difluoro-3 , 3-dimethylcyclopropyl)phenol, Ι δΟ g0 of sodium hydroxide, 3» 59 o of chloroform and \$Q ml0 of acetone according to the procedure described above in Example 1 , part (d)e The product was obtained in the form of an oil„ EXAMPLE 6 ( a) p-( la2-Dimethylvinyl)anisole0 A mixture of 1 0 g0 of 2-(p°methoxyphenyl) -2-butanol and 360 ml0 of acetic anhydride was heated at reflux for two and one-half hours 0 The solvent was removed by distillation and the residue fractionally distilled,. The last fraction obtained above lli^C. ( 10 mm.) afforded 27<>0 g0 of p-( l,2-dimethylvinyl)anisole, chiefly the cia isomer. (b) p-(2,2-Diohloro-l t3-dimethylcyolopropyl)anisole was prepared from 61+.6 g. of p-( 1,2-dimethyl vinyl )anisole, 101 g. of potassium t-butoxide, 258 g. of chloroform and 1800 ml. of pentane according to the procedure described above in Example 1, part (b). The product was distilled at 90-98°C. (0.07-0.09 mm.) to give 79.1 g. of p-(2,2-dichloro-l,3-dimethylcyclopropyl)anisole, Q0% cis isomer, (c) p-( 2,2-Dichloro-l,3-dimethylcyclopropyl)phenol was prepared from 79.1 g. of p-( 2,2-dichloro-l,3-dimethyl-cyclopropyl)anisole, I.6.9 g. of boron tribromide and 520 ml. of methylene dichloride according to the procedure described above in Example 1, part (c). The product was recrystallized from a benzene-hexane mixture to give i 3.7 g. of p-( 2, 2-dichloro-l,3-dimethylcyclopropyl) phenol, cis isomer in the form of colorless needles, m.p. 79-82°C. (d) 2-^p-(2,2-Dichloro-l,3-dimethylcyclopropyl)phenoxy_7-2-methylpropionic acid l; A, A' , R1 and R^ are CH-j, R, R^' and Q are H, R2 and R2' are 01, and n is 0; para orientation/ was prepared from 39.1 g. of p-( ,2-dichloro-l,3- ... dimethylcyclopropyl) phenol, lj.0,6 g. of sodium hydroxide, 30.2 g. of chloroform and 1275 ml. of acetone according to the procedure described above in Example 1, part (d). The product precipitated as a sodium salt, m.p. 200-202°G., which was acidified to the free acid and recrystallized from aqueous ethanol to give 1;2. g. of 2-/p-( 2,2-di-chloro-1 ,3-dimethylcyc lopropyl acid, m.p. 133.5-13i .5°C. , cis orientation of the 1-and 3-methyl groups.

EXAMPLE 7 (a) o-( 2 t2-Diohlorooyolopropyl)anisole was prepared from 1+0.2 g. of o-vinylanisole, 81+ g. of potassium t-butoxide and 211+ g. of chloroform in 1500 ml. of pentane according to the procedure described above in Example 1 , part (b). The product was distilled at 80-85°C. ( 0.1 mm.) to give 7.91+ g. of o-( 2 ,2-dichlorocyclopropyl)anisole. (b) o-( 2 ,2-Diohlorooyolopropyl)phenol was prepared from 7.8 g. of o-( 2 ,2-dichlorocyclopropyl)anisole and 5.3 g. of boron tribromide according to the procedure described above in Example 1 , part (c), affording 7.1 g. of oil used directly in the following reaction. (c) Ethyl 2- o-( 2 ,2-dichlorocyclopropyl)phenoxy_7-2-methyl-propionate /I; A and A' are CH^, R is C2¾, R1 , R-* , R3 ' and Q are H, R and R^ are CI, and n is 0; ortho orientation/ was prepared from 6.6 g. of o-( 2 ,2-dichlorocyclo-propyljphenol, 12.7 g. of ethyl c^-bromoisobutyrate and 13.5 g. of anhydrous potassium carbonate in 30 ml. of dimethylformamide according to the procedure described below in Example 12 , part (a). The product was distilled at 98-100°C. (O.05 mm.) to give J+, 76 g. of ethyl 2- -{ 2 ,2-dichlorocyclopropyi)phenoxy_7-2-methylpropionate as a very pale yellow oil.

EXAMPLE 8 (a) p-( 2 ,2-Difluorocyclopropyl)anisole was prepared from 129 g. of p-vinylanisole and 170 g„ of sodium chlorodi-fluoroacetate in 1500 ml. of diglyme according to the procedure described above in Example 2 , part (a). There was thus obtained 122 g. of p- ( 2 ,2-difluorocyclopropyl)-anisole as a yellow oil. (b) p-( 2 ,2-Difluorooyolopropyl)phenol was prepared from 120 g. of p-( 2,2-di luorooyolopropylJanisole and 8l g. of boron tribromide according to the procedure described above in Example 1, part (c), affording 72 g. of oil used directly in the following reaction. ( c ) 2-/p-( 2,2-Difluorocyclopropyl)phenoxy_7-2-methyl- propionic acid /Ϊ: A and A' are CH^, R, R1, R , R3' and Q are H, R^ and ^ are F, and n is 0; para orientation was prepared from 25.5 g. of p-( 2,2-difluorocyclopropyl)-phenol, 36.0 g. of sodium hydroxide, 26.8 g. of chloroform and 1100 ml. of acetone according to the procedure described above in Example 1, part (d). The product was recrystal-lized from a benzene-hexane mixture to give 22 g. of 2-/p-( 2,2-difluorocyclopropyl)phenoxy_7-2-methylpropionic acid as cream-colored needles, m.p. 97-99°C EXAMPLE 9 (a) p-(2,2-Dichlorooyclopropylmethyl)anisole.

A mixture of 81. g. of p-( 2-propenyl)anisole and 80 o9 g, of phenyl dichlorobromomethylmercury (C^H^HgCC^Br) in 200 ml. of benzene was heated at reflux for five and one-half hours. The product was isolated and distilled to remove unchanged starting material and then chromatographed on 1200 g. of silica gel and eluted with pentane and with pentane containing 1-1$ ether. There was thus obtained 28 g, of p-( 2,2-dichlorocyclopropyl-raethyl)anisole as a yellow oil. (b) p-(2 >2-Dichlorocyolopropylmethyl)phenol was prepared from 28 g. of p-( 2,2-dichlorocyclopropylmethyl)anisole and 20 g. of boron tribromide according to the procedure described above in Example 1, part (c). The product was recryatallized from a benzene-cyclohexane mixture to give I7.3 g. of p-( 2,2-dichlorocyclopropylmethyl) henol as a beige solid, m.p. 57-62°C0 (c) Ethyl 2-/p-( 2 ,2-dichlorocyclopropylmethyl)phenoxy —; _7-2- , ..—*_ methylpropionate /ΐ% A and A' are OH^, R is C2H^, R1, R3, R3' and Q are H, R2 and R2' are 01, and n is 1; para orientation/ was prepared from 17.8 g. of p-( 2 ,2-dichlorocyclopropylmethyl )phenol , 56 g° of ethyl © -bromoisobutyrate and 51· 3 g. of potassium carbonate according to the procedure described below in Example 12, part (a). There was thus "'" obtained 20.6 g. of ethyl 2- p-( 2 ,2-dichlorocyclopropylmethyl )phenox_7E2-methylpropionate as a yellow oil. (d) 2- -(2,2-Dichlorocyclopropylmethyl)phenoxy_7-2-methyl- propionic acid T; A and A? are OH^, R, R1, R^, R3! and Q 2 t —r are H, R and R^ are 01, and n is 1; para orientatior .

A mixture of 19 g. of ethyl 2- p-( 2 ,2-dichloro- cyclopropylmethyl)phenoxy_7-2-methylpropionate, 25 ml. of 10 aqueous sodium hydroxide and 25 ml. of ethanol was stirred for three hours at room temperature. The reaction mixture was acidified and the resulting product collected and recrystallized twice from hexane to give 10.0 g. of 2-j p-( 2,2-dichlorocyclopropylmethyl)phenoxy_7-2-methyl- propionic acid, m.po 78-80°0E EXAMPLE 10 ^Ca^^,l-Dichloro-2,3-dihydro-5-methoxy-lH-cyclopropa^a_7- naphthalene VI; R1 and R^1 are H, R2 and R2' are 01, lower-alkyl is was prepared from I.8 g. of 6-methoxy- 3»i4--dihydro-naphthalene, 81. g. of potassium t-butoxide and 227 g. of chloroform in 1350 ml. of pentane according to the procedure described above in Example 1 , part (b), affording 76 g« of product as a red-brown oil. (b ) l,l-Dichloro- i3"dihydro-lH-cyclopropaJ ~a_7- -naphthol was prepared from 2l+. 3 g. of 1 ,l-dichloro-2 ,3-dihydro-5- \ methoxy-lH-cyclopropa -a_7naphthalene and 25.0 g. of boron tribromide according to the procedure described above in Example 1 , part (c), affording 21„i± go of a red-brown oil used directly in the following reaction. ( c ) 2-( 1 ,l-Dichloro-2 i,3-dihydrO"lH-cyclopropa/—a_7-5- χ methyl ~~~ — τ_ naphthyloxy ) °2- propionic acid I; A and A' are CH^, R, R -•"' " ■31 pi "3 "and' R-* are H, R and R are CI, Q and R-5 together are CI^CHg, and n is 0 was prepared from 21.1 - g. of 1 ,1- dichloro-2 ,3-dihydro=lH-cyclopropa ~a_7-5-naphthol, 22.14. g. of sodium hydroxide, 1601 g« of chloroform and 35° ml* of acetone according to the procedure described above in Example 1 , part (d). There was thus obtained 3« g. of 2-( 1 ,l-dichloro-2 s 3--dihydro=lH-cyclopropa >"~a__7-5-naphthyloxy ) methyl 2-7propionic acid as an olive=grey powder, m.p. lOl.-lOb.5 C. when recrystallized from cyclohexane.

METHOD B EXAMPLE 11 (a) 2-( p-Proplonylphenoxy ) °2°methylpropionic acid was prepared from 37J - go of p-hydroxypropiophenone, 600 g. of sodium hydroxide, 390 g0 of chloroform and 7 liters of acetone according to the procedure described above in Example 1 , part (d)0 There was thus obtained 321 g. of 2-( p-propionylphenoxy ) -2-methylpropionic acid, (b) Methyl 2-( -propionylphenoxy ) -2-methylpropionate.

A mixture of ll8 g. of 2-( p-propionylphenoxy ) -2-methylpropionic acid, J4.8 g.. of methanol, 3· 5 ml. of concentrated sulfuric acid and lf>0 ml. of ethylene dichlorid ^as stirred and heated at reflux for twenty-two hours. The reaction mixture was cooled, the layers separated, and the organic layer was washed successively with water, sodium bicarbonate solution and water, and dried over anhydrous sodium sulfate and concentrated jln vacuo. The residue was distilled at 122-127°G. ( 0 o 08 mm.) to give 11 .5 g* of methyl 2-( p-propionylphenoxy ) -2-methylpropionate, m,p0 I|.7-i|90C o (c) Methyl 2- -( l-hydroxypropyl)phenox^-2~methylpro-pionate.

Sodium borohydride ( 10. 6 g. , 0.279 mole) was added to a stirred solution of 111+. g. (O.I.58 mole) of methyl 2-( p-propionylphenoxy ) -2-methylpropionate in 500 ml. of methanol, held at 5°C. in an ice bath. After the exothermic reaction had slowed, the ice bath was removed and the reaction mixture stirred for one hour at room temperature. The solvent was removed In vacuo, and the residue partitioned between ether and water containing acetic acid in slight excess of that needed to make the aqueous layer acidic. The ether layer was separated, washed with sodium bicarbonate solution, dried over anhydrous sodium sulfate and concentrated _in vacuo. There was thus obtained 113 g« of methyl 2-^ -(l-hydroxypropyl)phenoxy_7-2-methylpropionate as a pale straw-colored oil. (d) Methyl 2- p-( l-propenyl)phenoxjy7-2-methylpropionate.

A solution of 113 g. of methyl 2-^p-( l-hydroxy-propyljphenox^^-methylpropionate and 1, g« of p-toluenesulfonic acid in 1000 ml. of toluene was heated at reflux under a water trap for one hour. The reaction mixture was cooled, washed with aqueous sodium bicarbonate solution, dried "over anhydrous sodium sulfate and concentrated in vacuo. The residue was distilled at 95-100°C. ( 0.05-0.08 mm.) to give 33 g. of methyl 2-/p-( 1-propenyl)- phenoxy_7-2-methylpropionate, = 1.5281. (e) Methyl 2-/p-( 2 ,2-dichloro-3-methylcyclopropyl)phenoxy_7- 2-methylpropionate /T; A, A' , R and R^ are CR3, R1, R^' and Q are H, R 2 and R ' are CI, and n is 0 ; para orientatioi -r was prepared from 37.5 g. of methyl 2- ρ-( 1-propenyl)-phenoxy_7-2-methylpropionate, \$ g. of potassium t-butoxide and 120 ml, of chloroform in 750 ml. of pentane according to the procedure described above in Example 1 , part (b).

The product was chromatographed twice on a column of 2 kg. of silica gel and the column was eluted with pentane-ether 3 : 1 to give I4.I. 3 g. of methyl 2. £$- 2 ,2-dichloro-3-methyl-cyclopropyl)phenoxy7-2-methylpropionate, n^ = 1.5 5 .

EXAMPLE 12 (a) Ethyl 2-( ij-ac etyl-2-chlorophenoxy ) -2-methylpropionate.

A solution of 2OI. g. ( 1.2 mole) of 3-chloro-l|-hydroxyacetophenone, 1+97 g. ( 3 » 6 mole) of potassium carbonate and 11-4.0 ml. of dimethylformamide was heated to 80°C. with stirring. , Ethyl 2-bromo-2-methylpropionate' ( 230 g. ) was then added over a 5 minute period, and the reaction mixture was stirred and heated for one. hour.

An additional 230 g. of ethyl 2-bromo-2-methylpropionate was then added, the mixture stirred one hour, an additional 68 g. of ethyl 2->bromo-2-methylpropionate added, and the mixture finally stirred for two and one-half hours. The reaction mixture^was filtered, the filter cake washed with ether and the combined ether washings and dimethyl-formamide solution was concentrated in_ vacuo. The residue was partitioned between dilute sodium chloride solution and ether, and the ether solution was washed with 10% sodium hydroxide solution, water and 10% sodium chloride solution, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was distilled at ll6°C. ( 0 , 02 mm.) to give 176.5 g. of ethyl 2-(i.-acetyl-2-chlorophenoxy ) -2-methylpropionate. (b) 2-(-4.-Aoetyl-2-chlorophenoxy ) -2-methylpropionio acid.

A mixture of 10 g. of ethyl 2-( l+-acetyl-2-chloro-phenoxy ) -2-methylpropionate, 1 ml. of 3$% aqueous sodium hydroxide, 25 ml. of 35% ethanol and 100 ml. of water was stirred for 15 minutes. The mixture was then acidified with hydrochloric acid, cooled, and the solid product collected and recrystallized from aqueous ethanol to give 8.35 g. of 2-(l.-acetyl-2-chlorophenoxy) -2-methylpropionic acid, m.p. 123-125°0 e (c) Ethyl 1-hydroxyethyl ) -2-chlorophenox EXAMPLE 13 Ethyl 2-^-chloro-l-( 2 s2-difluorocyclopropyl)phenox27-2- methylpropionate β. A and A» are CH^, R is C2H^, R1, R^ and RJ are H, Q is 2-01, R2 and R2' are P, and n is 0 ; para orientation/ was prepared from 1-0. 3 g. of ethyl 2-(lj.-vinyl-2-chlorophenoxy ) -2°methylpropionate and 32.9 g. of sodium chlorodifluoroacetate in 190 ml. of diglyme according to the procedure described above in Example 2 , part (a). The product was distilled at 112-lll4.°C. ( 0.01 mm.) to give 26.39 g. of ethyl 2~ 2-chloro--4.-( 2 ,2-difluoro-cyclopropyl)phenoxj/-2-methylpropionate0 EXAMPLE llj (a) Ethyl 2-( 3-acetylphenox ) -2°meth lpropionate was prepared from 177 g. of m-hydroxyacetophenone, 632 g. of ethyl 2-bromo-2-methylpropionate, 537 g. of anhydrous potassium carbonate and 1200 ml. of dimethylformamide according to the procedure described above in Example 12 , part (a). The product was distilled at 121-128.50G. ('O.OI. mm.) to give 227.3 go of ethyl 2~( 3-acetylphenoxy )-2-methyl-propionateo (b) Ethyl 2- J-( l-hydroxyethyl)phenox27-2-methylpropionate was prepared from 125 go of ethyl 2- ( 3-acetylphenoxy )-2-methylpropionate and 9.lt o of sodium borohydride according to the procedure described above in Example 11, part (c) p affording 125.6 g. of ethyl 1-hydroxyethyl ) -phenoxy_7-2-methylpropionate as an oil„ (c) Ethyl 2-( 3-vinylphenoxy )-2-methylpropionate was prepared from 125o6 g, of ethyl 2- 3-( 1-hydroxyethyl )phenoxy7-2-methylpropionate and ]+<, go of p-toluenesulfonic acid in 1 00 mlo of toluene according to the procedure described above in Example 11* part (d), affording ll5«9 go of ethyl 2-( 3-vinylphenoxy )-2-methylpropionate as an oil„ (d) 2-^ϋ""( 2j2-Dichlorocyclopropyl)phenoxy7-2-methylpropionic acid T; A and A' are CH-j, R, R1, R^, R3' and Q are Hp P P ' T R^ and R4 are CI, and n is 0; meta orientation/ was prepared from 3 ol g« of ethyl 2-( 3-vinylphenox )-2-methyl-propionate, -4.2.0 g0 of potassium t-butoxide, 107 g. of chloroform and 750 ml. of pentane according to the procedure described above in Example 1, part (b)„ The product was distilled at 123-125°C (0.08 mm.) and chroma-tographed on a column of 500 g. of silica gel. The column was eluted with pentane and with pentane-ether mixtures and the resulting purified ethyl 2-^m-( 202-dichlorocyclo-propyl )phenox27-2-methyIpropionate was hydrolyzed with 10 ml. of 35 sodium hydroxide solution in 100 ml„ of 95% ethanol. After 20 minutes at room temperature, the reaction mixture was diluted and acidified and the acidified solution extracted with ether,, The ether solution was concentrated _in vacuo and the residue crystallized from hexane to give 8„77 go of 2<~ -{ 2 ,2-dichlorocyclopropyl)- phenoxv7-2-methylpropionic acid, m.p„ 81j-860Ce (a) 2- ( -Acetylphenox ) -2-methylpropionic acid was pre pared from ¾5 g. of p-hydroxyacetophenone, 960 g. of sodium hydroxide and 715 g. of chloroform in 11 liters of acetone according to the procedure described above in Example 1 , part (d). The product was" recrystallized from carbon tetrachloride and from isopropyl acetate to give 2-( p-acetylphenoxy ) -2-methylpropionic acid as a pale cream solid, m,p, 108-110°C0 (b) Ethyl was prepared from 141 g. of ethyl 2- (p-acetylphenoxy) -2-methylpropionate [prepared by esterification of the acid of part (a) in a manner analogous to the procedure of Example 18 part (a)] and 10.7 g of sodium borohydride according to the procedure described above in Example 11, part (c) , affording 140 g. of ethyl 2- [p- (1-hydroxyethyl) phenoxy] -2-methylpropionate as a pale yellow liquid. (c) Ethyl 2- ( -vinylphenox ) -2-methy propionate - A mixture of 116 0 of ethyl 2-H-( 1-hydroxy ethyl 92 g. of p-toluene-sulfonyl chloride in $00 ml0 of pyridine was heated at reflux for three hours, kept at room temperature for about 16 hours and then heated at reflux again or six hours. The reaction "mixture was poured into ice water and ex bicarbonate, water and saturated sodium chloride solution, then dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was distilled at 10lj.-llloC.. ( 0 . 0 3-O.O8 mm.) to give 60 g„ of ethyl 2 - ( p-vinylphenoxy) - 2 -methylpropionate0 (d) Ethyl 2 , 2-dibromocyclopropyl )phenoxj£7- 2-methyl- propionate was prepared from 23° S» ° ethyl 2-(p-vinyl-phenoxy) -2-methylpropionate, 39 o 2 g„ of potassium t-butoxide and 198 g o of bromoform according to the procedure described above in Example 1 , part (b)„ The product was isolated and hydrolyzed without further purification. ( e) 2-/p-( 2 , 2-Dibromocyclopropyl)phenoxy_Z- 2=methylpropionic acid Γ; A and A« are CH^, R, R1, R^, R^ and Q are H, R^ and R^† are Br, and n is 0 | para orientation/ was hydrolyzed with sodium hydroxide in aqueous ethanol, five hours at room temperature,, The acid fraction was isolated and recrystallized from aqueous ethanol and from benzene-hexane ls2 to give l8 g0 of 2- p~( 2 , 2-dibromocyclopropy'l)- acid, m0p0 129 -131°C.

EXAMPLE 16 (a) Ethyl 2~ °( 2=chloro- 2~fluorocyclopropyl )phenoxy_7- 2-methylpropionate0 A mixture of 13 . 6 g o of ethyl 2-(l-vinylphenoxy )-2-methylpropionate and 33 g o of phenyl dichlorofluoromethyl-mercury ( in 120 ml. of benzene was refluxed for' JLj.8 hours β The reaction mixture was allowed to stand at room temperature for two hours, then filtered and the filtrate evaporated ijn vacuo„ The residue was mixed with pentane, filtered and concentrated ijn vacuo to give ethyl 2- p-( 2-chloro-2-fluorocyclopropyl )phenoxy_7-2-methyl propionate as an orange oil which was hydrolyzed as described below. (b) 2-Jp-(2-Chloro-2-fluorocyclopropyl )phenoxy_7-2-methyl-propionic acid /Γ; A and A« are CH3, R , R1 , R3, R3' and Q 2 2' -r are H, R^ is CI, R is F, and n is 0; para orientation/ was prepared by hydrolysis of the 2- p-( 2-chloro-2-fluorocyclopropyl )phenoxy_7-2-raethylpro-pionate in an aqueous ethanol solution of sodium hydroxide There was thus obtained 11+.1+ g. of 2-/p-( 2-chloro-2-fluoro cyclopropyl)phenoxy_7-2-methylpropionic acid in the form of beige needles, m.p. 97-102°C. when recrystallized from a benzene-hexane mixture.

EXAMPLE 17 (a) Ethyl 2-( -phenylac et lphenoxy ) -2-methylpropionate was prepared from 100 g. of p-phenylacetylphenol, 230 g. of ethyl 2-bromo-2-methylpropionate and 228 g. of potassium carbonate according to the procedure described above in Example 12, part (a). There was thus obtained 70 g. of ethyl 2-(p-phenylacetylphenoxy )-2-meth lpropionate, m.p. 110-113°C. (b) Ethyl 2- p-( l-hydroxy-2-phenethyl )phenoxy_7-2-methyl- propionate was prepared from 101 g. of ethyl 2-(p-phenyl-acetylphenoxy)-2-methylpropionate and 11.1 . g. of sodium borohydride, affording 97.8 g. of ethyl 2- p- ( 1-hydroxy-2-phenethyl)phenox^7-2-methylpropionate as a yellow oil. (c) Ethyl 2.- p- ( 2-phenylvinyl)phenoxy_7-2-methylpropionate was prepared from 9l .. $ g. of ethyl 2- p-( l-hydroxy-2-phenethyl)phenoxy_7-2-methylpropionate and 1.3 g. of p- toluenesulfonic acid in toluene according to the procedure described above in Example 11 , part (d)„ The product was recrystallized from 95 ethanol to give 53 <>5 g. of ethyl 2- -( 2-phenylvinyl)phenoxv7'-2-methylpropionate, mep„ 5>-65°C (d) Ethyl 2- p~( 2 i,2-dichloro-3-phenylcyclopropyl)phenoxv7- 2-methylpropionate, A mixture of 2$ g0 of ethyl 2- p-( 2-phenylvinyl)- and 39 go of phenyl dichlorobromomethylmercury in 100 ml„ of benzene was heated at gentle reflux for three hours „ An additional 5 go of phenyl dichlorobromomethylmercury was then added and the mixture heated at reflux for three hours longer,, The reaction mixture was kept at room temperature for two days, then filtered and the filtrate evaporated jLn vacuo. The residue was taken up in hexane, filtered and concentrated in vacuo to give 3^, ge of ethyl 2~ p-( 2 ,2-dichloro-3-phenylcyclo-propyl)phenoxy_7-2=methylpropionate as a brown oil which was hydrolyzed without further purificatione ( e) 2-^ °( 2 i2-Dichloro-3-=phenylcyclopropyl)phenoxy_7-2-methyl-propionio acid ϊ; A and A1 are CH^, R, R1, R3 ' and Q are H, 3 is C^H^, R2 and R2? are CI, and n is 0 ; para orientation/ was prepared by hydrolyzing ethyl 2-p-{ 2 ,2-dichloro- 3-phenylcyclopropyl)phenoxyJ7-2=methylpropionate with aqueous ethanolic sodium hydroxide,, The product was chromatographed twice on a oolumn of silica gel and eluted with pentane-ether 1.1 , and the product then recrystallized from hexane-benzene 2 ; 1 to give 1$ g. of 2-^-( 2 ,2-dichloro-3-phenylcyclopropyl )phenoxj7'-2-methylpropionic acid, m.p. 129=132°C.

METHOD C EXAMPLE 18 (a) Methyl 2-( p-aoetylphenoxy ) -2-methylpropionate was prepared by esterifioation of 222 g. of 2-(p-acetylphenoxy )-, 2-methylpropionic acid Example 1 » part (aj_7 by heating said acid with 96 g. of methanol and 7 ml» of concentrated sulfuric acid in 300 ml. of chloroform. The product was isolated and distilled at llIj.0C. ( 0.06 mm.) to give 206. 6 g. of methyl 2-( p-acetylphenoxy) -2-methylpropionate, m.p. 62-63°C. ί (b) Methyl 2- ρ-( l,2-dimethylvinyl)phenox Sodium hydride '( 15.1 g.» 0.36 mole, l in oil dispersion) was placed in a 2-liter flask and rinsed three times with pentane to remove the oil. Anhydrous dimethyl sulfoxide ( 2-4.0 ml.. ) was then added, and the flask was evacuated and flushed with nitrogen. The mixture was heated to 7i -80°C. for h minutes, then cooled in an 'ice bath.

A solution of 133 · 2 g. of ethyltriphenylphosphonium bromide in 720 ml. of dimethy^'sulfoxide was then added, he mixture stirred for 15> minutes and then treated with a solution of 70.8 g. ( 0. 30 mole) of methyl 2- ( p-acetylphenoxy ) -2-me.thyl-propionate in 120 ml. of dimethy^'sulfoxide. The reaction mixture was stirred for three hours at room temperature/ and then poured into water. The organic layer was separated washed with water and saturated sodium chloride solution and dried over anhydrous sodium sulfate to give 8l.8 g. " of methyl 2- -( l,2-dimethylvinyl)phenox27-2-methylpro-pionate as an oil (mixture of geometric isomers). ( c ) 2- p-( 2 , 2-Dichloro-l , 3-dimethylcyclopropyl )phenoxy/ -2- METHOD C EXAMPLE 18 (a) Methyl 2-( -aoetylphenox ) -2-methylproplonate was prepared by esterification of 222 g. of 2-(p-acetylphenoxy)-2-methylpropionic aoid ^Example 15, part ( aJ7 by heating said acid with 96 g. of methanol and 7 ml. of concentrated sulfuric acid in 300 ml. of chloroform. The product was isolated and distilled at lllj.0G. ( 0.06 mm.) to give 206.6 g. of methyl 2-( p-acetylphenoxy ) -2-meth lpropionate, m.p. 62-63°G. (b) Methyl 2- p-(l,2-dimethylvinyl)phenox 7-2-methylpro-pionate : Sodium hydride ( 15.1 g. , 0.36 mole, 7$ in oil dispersion) was placed in a 2-liter flask and rinsed three times with pentane to remove the oil. Anhydrous dimethyl-sulfoxide ( 2-j.O ml.) was then added, and the flask was evacuated and flushed with nitrogen. The mixture was heated to 75-80°CY'for 1+5 minutes, then cooled in an ice bath.

A solution of 133« 2 g. of ethyltriphenylphosphonium bromide in 720 ml. of dimethylsulfoxide was then added, the mixture stirred for 15 minutes and then treated with a solution of 70.8 g. (O.30 mole) of methyl 2-(p-acetylphenoxy ) -2-methyl-propionate in 120 ml. of dimethylsulfoxide. The reaction mixture was stirred for three hours at room temperature and then poured into water. The organic layer was separated, washed with water and saturated sodium chloride solution and dried over anhydrous sodium sulfate to give 81.8 g. of methyl 2-^- ( 1 ,2-dimethylvinyl )phenoxy_7-2-methylpropionate as an oil (mixture of geometric isomers). ( c ) 2-p-{ 2 ,2-Dichloro-l, 3-dimethylcyclopropyl ) phenoxjy7-2- methylpropionic acid /I A, A', R1 and R^ are CH3, R, R^1 and Q are H, R2 and R2' are 01 , and n ia 0 ; para orientation/ was prepared from 2lj..8 g. of methyl 2-^p-(l,2-di-methylvinyl)phenoxy_7-2-methylpropionate, 28 g. of potassium t-butoxide and $0 ml. of chloroform in 00 ml. of pentane according to the procedure described above in Example 1 , part (b). The methyl ester thus obtained was hydrolyzed in the usual manner with sodium hydroxide in 95$ methanol. The acid fraction thus obtained was recrystallized from a benzene-hexane mixture to give 1205 g» of 2-^p-( 2 ,2-di-chloro-1 ,3-dimethylcyclopropyl )phenoxy/-2-methylpropionic acid, m.p0 138-1-.50C. (mixture of geometric isomers).

EXAMPLE 19 2-/p-( 2 ,2-Dibromo-l,3~dimethylcyclopropyl)phenoxj£7-2-methyl- propionic acid R, R 3 * and Q are H, R2 and R2' are Br, and n is 0 j para orientation/ was prepared from 21+.8 g0 of methyl 2-^/p-( 1 ,2-diraethylvinyl) phenoxy_/-2-methylpropionate, 35 g« of potassium t-butoxide and 1 2 go of bromoform in $00 ml. of pentane according to the procedure described above in Example 1 , part (b).

The methyl ester thus obtained was hydrolyzed in the usual manner with sodium hydroxide in 95$ ethanol, and the acid product was isolated and recrystallized from a benzene-hexane mixture to give 12.9 g. of 2- p-( dimethylcyclopropylJphenoxy/^-methylpropionic acid in the form of light tan rosettes, m.p0 l-4.1-lij.2<, 5o0. (decomp.) (greater than 90% trans-isomer ).

EXAMPLE 20 (a) Ethyl 2- ( p-benzoylphenoxy ) -2°methylpropionate was prepared from 198 g0 of p-hydroxybenzophenone, 1+90 g. of ethyl 2-bromo«2~methylpropionate and l .Q½ g0 of potassium carbonate according to the procedure described above in Example 1 t part (a). The neutral fraction was isolated £ and the resulting 208 g„ of beige solid was recrystallized from a benzene-hexane mixture to give l80 g0 of ethyl 2-(p-benzoylphenoxy) - 2=methylpropionatep mep0 82=8 °Ce (b) Ethyl 2-^p-( l~phenylvinyl)phenox7- 2=methylpropionate was prepared from 31 <> 2 g„ of ethyl 2- ( p-benzoylphenoxy)-■LQ 2-methylpropionates Ij.2 o 8 g0 of methyltriphenylphosphonium bromide and » 05 g o of sodium hydride in dimethyijsulfoxide according to the procedure described above in Example 18 , part (b), affording 31 » ge of ethyl 2° p-( 1-phenylvinyl) - phenoxy_7-2-methylpropionate as a yellow liquid,, 1 (o) 2-^- ( 2 p 2-Dichloro-l~phenylcyclopropyl)phenox_7-2- methylpropionio acid R1 is G(fi$ , R, ^P R^' and Q are Hs R2 and R2' are CI, and n is 0 ; para 20 potassium t-butoxide and $0 ml0 of chloroform according to the procedure described above in Example 1 , part (b)„ The resulting ethyl ester was hydrolyzed in the usual manner with sodium hydroxide in 95$ ethanol, and the acid product was isolated and recrystallized from a 25 benzene-hexane mixture to give 20 g0 of 2- p-( 2 , 2-dichloro- 1-phenylcyclopropyl)phenox^- 2-methylpropionic acid in the form of colorless needles 9 m0p0 171-173°C0 EXAMPLE 21 2 -^ρ-( 2 p2~Dibromo-l~phenylcyclopropyl)phenoxy-7-»2-methyl- propionic acid Ϊ; A and A' are CH^, R1 is C^H^, R, R-, •31 i R and Q are H, R^ and R are Br, and n is 0; para orientation/ was prepared from 31*0 g» of ethyl 2-p-( l-phenylvinyl)phenoxy_7-2-methylpropionate ^Example 20, part (b}7* 35 g. of potassium t-butoxide and 152 g. of bromoform according to the procedure described above in Example 1, part (b). The resulting ethyl ester was hydro-lyzed in the usual manner with sodium hydroxide in 95 ethanol and the acid product was isolated and recrystallized several times from a benzene-hexane mixture to give 11.5 g» of 2- p-( 2,2-dibromo-l-phenylcyclopropyl)phenox EXAMPLE 22 2-/ -( 2,2-Difluoro-l-phenylcyclopropyl )phenox,j7-2-methyl- propionio acid /Γ: A and A' are CH-j, R1 is C^H^, R, R3, R^ and Q are H, R^ and R^ are P, and n is 0; para orienta tion7 was prepared from 62 g. of ethyl -^-( 1-phenylvinyl) phenoxy_7-2-methylpropionate ^Example 20, part (bj and 80 g, of sodium chlorodifluoroacetate in diglyme according to the procedure described above in Example 2, part (a). The resulting ethyl ester was hydrolyzed in the usual manner with sodium hydroxide in 95$ ethanol, and the resulting acid product was recrystallized from a benzene-hexane mixture to give 31.3 g, of 2- p-( 2,2-difluoro-1-phenylcyclopropyl)phenoxy_7-2-methylpr0pionio acid, m.p. 97-99°C.

EXAMPLE 23 (a) Methyl 2-^p-( l-ethylvinyl)phenoxy_7-2-methylpropionate was prepared from £2.5 g„ of methyl 2-( p-propionylphenoxy )-2-methylpropionate Example 11 , part (bj7> 107 go of methyltriphenylphosphonium bromide and 12.6 g. of sodium hydride in dimethyl^ulfoxide according to the procedure described above in Example 18, part (b)e The product was distilled at 93-95°G„ (0„1 mm0) to give 37« go of methyl 2- p-(l-ethylvinyl)phenoxv7-2-methylpropionate0 (b) Methyl 2-^-( 2,2-dichloro°l-ethyloyclopropyl)phenoxy_7-2-methylpropionate r' A, A T and R are OH^, R1 is C2H^, R-, " ' P P ' R^ and Q are H, R^ and R^ are CI, and n is 0; para orientation/ was prepared from 18„5 g» of methyl 2~p-(l-ethylvinyl)phenox7P-2-methylpropionate, 21 g, of potassium t-butoxide and £6 g„ of chloroform according to the procedure described above in Example 1, part (b), and was obtained in the form of a pale straw-colored oil, b.p. 131-133°C (0.09 mm.) (l805 g. ).

By the procedures described above, 3-methyl=l|.-hydroxyacetophenone reacts with ethyl 2-bromo-2'=methyl-propionate in the presence of potassium carbonate to form ethyl 2-( 2-methyl-i|.-acetylphenoxy) -2-methylpropionate. The latter when treated with methyltriphenylphosphonium bromide in the presence of sodium hydride produces ethyl 2-/2-methyl-l.-( l-methylvinyl)phenoxy_7-2-methylpropionate, which then can be treated with chloroform in the presence of potassium t-butoxide to afford ethyl 2-/2-methyl-Lj.-( 2,2-dichloro-l-methylcyclopropyl)phenoxy_7-2-methylpropionate A, A', R1 and Q are OH^, R is C2H^, R^ and R^' are H, R2 and R2' are 01, and n is 0; 2,ij.-orientation7.

METHOD D EXAMPLE 2k (a) p-( 2 ,2-Dichlorooyclopropyl)phenol.

A solution of $0 g. ( 0. 1+8 mole) of p-( 2 ,2-di-chlorocyclopropyl)aniline in 185 ml. of glacial acetic acid was cooled to about 10°C., and a solution of 18.9 g. ( 0.273 mole) of sodium nitrite in 185 ml. of water was added dropwise to the stirred solution. A thick slurry formed and this was added portionwise to a stirred solution of 160 ml. of concentrated sulfuric acid in 320 ml. of w ater held at 100-105°C. The reaction mixture was stir-red at 100 ; 5°C for 10 minutes, then cooled and diluted with water. The resulting product was collected by filtration, dissolved in ether and washed with sodium bicarbonate solution. The ether solution was then extracted with sodium hydroxide solution, and the sodium hydroxide solution was acidified and extracted with ether. The ether solution was dried and concentrated in, vacuo, and the residue ( 18 g.) was steam distilled affording 9 g. of a yellow gum which crystallized when triturated with ether. There was thus obtained 8 g0 of p-( 2 ,2-dichlorocyclopropyl)-phenol, m.p. 1|-. =56ο0. ( b) 2-p~( 2 ,2-Dichlorocyclopropyl)phenoxy_7-2-methylpro- pionio acid /Γ: A and A' are CH^, R, R1, 3 , R3 ' an(j Q are H, R 2 and R 2 ' are CI, and n is Oj para orientation —/r.

A mixture of 8 g0 ( 0.0356 mole) of p=( 2 ,2-di-chlorocyclopropyl)phenol, 11.2 g. (0.28 mole) of sodium hydroxide pellets, 11 g. of chloroform and 350 ml. of acetone was prepared at 0°C. The cooling bath was removed, the mixture stirred for a minute and then heated on a steam bath to reflux temperature. The reaction mixture was stirred at reflux for three hours and then concentrated in vacuo. The residual gum was partitioned between dilute hydrochloric acid and ether, and the ether layer was separated, dried and concentrated in. vacuo0 The residual oil ( II4. g, ) was partitioned between dilute aqueous sodium bicarbonate and ether. The sodium bicarbonate solution was acidified with concentrated hydrochloric acid and extracted with ether. The ether solution was dried over anhydrous sodium sulfate and concentrated. The residue (9.5 g« of yellow oil) was crystallized twice from hexane to give 6.0 g. of 2- p-(2,2-dichlorocyclopropyl)phenoxy_7- 2-methylpropionic acid in the form of a pale cream-colored solid, m.p. 11ί].-1ΐ60σ0 EXAMPLE 5 pionate T; A, A' and R are CH^, R1 R^, R3' and Q are H, 2 P ' R and R are CI, and n is 0; para orientation/.

A mixture of 10 gc (0.03^6 mole) of 2-p-(2*2- dichlorocyclopropyl)phenoxy_7-2=methylpropionic acid Example 2J+, part {b , 3„33 g. (O01038 mole) of methanol and 0.5 ml. of concentrated sulfuric acid in 100 ml. of methylene dichloride was stirred at reflux for four hours. The reaction mixture was cooled, washed with water and sodium bicarbonate solution, dried and concentrated in vacuo. The residue was distilled to give 8.5 go of methyl as a colorless oil, b.p. ll5°Ce (0.05 mm.).

Alternatively, ethyl 2-p-( 2 ,2=dichlorocyclo- propyl )phenoxv7-2-methylpropionate was prepared from 20 g« of p-( 2,2-dichlorocyclopropyl)phenol βχβχαρΐβ 2i, part (aj/, 38 g. of ethyl 2-bromo-2-methylpropionate and 12 g. of potassium carbonate in 100 mle of acetonitrile. The ethyl 2-bromo-2-methylpropionate was added in two equal portions, the second portion being added after seven hours of heating at reflux. The reaction mixture was heated at reflux for about three days and the product isolated to give 32 g. of ethyl 2,2-dichlorocyclopropyl)phenoxy_7-2-methyl-propionate. The latter was hydrolyzed in the usual-manner with ethanolic sodium hydroxide to produce -^-(2,2- acid, identical with the compound formed in Example 21+, part (b)„ By replacing the ethyl 2-bromo-2-methylpropionate in the foregoing alternative preparation by a molar equivalent amount of methyl 2-bromo-2=(n-propyl)valerate, methyl 2-bromo-2-ethylbutyrate, methyl 2-bromo-2-methylbutyrate or methyl 2-bromo-2,3°dimethylbutyrate there can be obtained, respectively, methyl 2~c/p~( 2,2~dichlorocyclopropyl)phenox_7- 2»(n-propyl) -valerate T; A and A' are CH2CH20H.j, R is CH^, R1, R , R3? and Q are H, R2 and R2' are 01, and n is 0; para orientation/i methyl 2-^p~( 2,2-dichlorocyclopropyl)-phenoxy7-2-ethylbutyrate T; A and A' are 02H^, R is CH^, R1, R^, R3' and Q are H, R2 and R2' are 01, and n is 0; para orientation/* methyl 2-^ ~( 2,2-dichlorocyclopropyl)-phenoxv7~2-methylbutyrate ^T A and R are CH^, A' is 02H^, R1, R3, R3' and Q are H, R2 and R2' a e 01, and n is 0; para orientation/; or methyl 2-p-( 2,2-dichlorocyclo-propyl)phenoxy_7-=2,3-dimethylbutyrate A and R are CH^, AF is 0H(CH3)2, R1, R3, R ' and Q are H, R2 and R2' are 01,

Claims (3)

1. 43026/2 compound of the Formula : I wherein: R is hydrogen or alkyl of 1-6 carbon atoms; A and A' are .alkyl of 1-3 carbon atoms; Q is hydrogen, halogen or alkyl of 1-3 carbon atoms; R is hydrogen, alkyl of 1-3 carbon atoms or phenyl; 2 R is halogen; R2· is hydrogen or halogen; R3 is hydrogen, alkyl of 1-3 carbon atoms or phenyl; R3' is hydrogen or alkyl of 1-3 carbon atoms; n is 0 or 1; or R3 and Q together form an ethylene bridge and (CI^^ is a direct bond to the benzene ring ortho to Q; or a basic salt thereof when R is hydrogen.

2. A compound according to claim 1, in which R^, and are both halogen, A and A' ' re methyl, Q is hydrogen and n is 0.

3. 2-/p-( 2,2-Dichlorocyclopropyl)phenoxy_7-2-methyl-propionic acid. -4.. 2-/p-( 2,2-Difluorocyclopropyl)phenoxy_7-2-methyl-propionic acid. 43026/2 5· 2-/ρ-( 2 ,2-Dichloro-l-methylcyclopropyl)phenoxy_7- 2-methylpropionic acid. 6. 2-/p-( 2 ,2-Dibromocyclopropyl )phenoxy_7-2-methyl-propionic acid, ' v 7. 2- -( 2-Chloro-2-fluorocyclopropyl)phenoxy_7-2-methylpropionic acid. 8. Ethyl 2- 2-chloro--.-( 2,2-dichloΓocyclopΓopyl)-phenox_ -2-mθth lpΓopionateβ 9. Ethyl 2- 2-chloro-lj.-(2,2-difluorocyclopropyl)-phenoxy_7-2-methylpropionate. 10. 2-( l,l-Dichloro-2,3"dihydro-lH-cyclopropaA*a_7-5 naphthyloxy) -2- methylpropionic acid. 11. 2- p-( 2,2-Dichlorocyclopropylmethyl)phenoxy7»2-methylpropionic acid. 12. A process for preparing a compound according to claim 1, which comprises treating a compound of the Formul IV (herein) with either (a) a mixture of chloroform, a ketone of the Formula A-CO-A' and an alkali metal hydroxid or (b) with a compound of the Formula ( A) ( A' )G(Br )G02R, BrCH2CN or BrGH2C00R in the presence of a base; and, in the event the reactant BrCH2CN or BrCH2G00R is used, di-alkylating the product with A-iodide in the presence of a base, and if necessary hydrolyzing the cyano group to a carboxy group with aqueous alkali; if desired, hydrolyzing a compound obtained wherein R is lower-alkyl to provide a compound wherein R hydrogen; and, if desired, converting a compound obtained wherein R is hydrogen to a basic salt thereof. 13c A process according to claim 12, in which the compound of Formula IV is reacted with a mixture of chloro form, a ketone of the Formula A-CO-A1 and an alkali metal hydroxide or with a compound of the Formula ( A)( A' )C(Br)CC>2R in the presence of a base. l^; A process for preparing a compound according to claim 1, which comprises treating a compound of the Formula X, Xa or Xb with a medium generating a carbene of the Formula :CR , and, in the event, that compounds of Formulas XVI or XVII are produced, dialkylating the product with A-iodide in the presence of a base, and if necessary, hydrolyzing the cyano group to a carboxy group with aqueous alkali; if desired, hydrolyzing a compound obtained wherein R is lower-alkyl to provide a compound wherein R is hydrogen; and, if desired, converting a compound obtained wherein R is hydrogen to a basic salt thereof. 15. A process according to claim llj., in which a compound of the Formula X in which Q is hydrogen, halogen or alkyl and R^ is hydrogen, alkyl or phenyl is reacted. 16. A process for preparing a compound of the Formula Ic (herein) wherein? R is hydrogen or alkyl of 1-6 carbon atoms; A and A1 are alkyl of 1-3 carbon atoms; R1 is hydrogen, alkyl of 1-3 carbon atoms or phenyl; R3 is hydrogen, alkyl of 1-3 carbon atoms or phenyl; R^ is hydrogen or alkyl of 1-3 carbon atoms; which comprises treating a compound of the Formula Xc with a medium generating a carbene ;CR¾^' if desired, hydrolyzing a compound obtained wherein R is lower-alkyl to provide a compound wherein R is hydrogen; and, if desired, converting a compound obtained wherein R is hydrogen to a basic salt thereof. 43026/2 17. A process for preparing 2-/_p-{ 2 ,2-dichlorocyclo- propyl)phenox_7-2~methylpropionic acid, which comprises: a) subjecting p-( 2 ,2-diehlorocyclopropyl ) aniline to diazotization and hydrolysis to produce p-( 2,2-dichloro- cyc lopropy1 ) phenolj b) treating the latter either with a mixture of chloroform, acetone and alkali metal hydroxide; or with a compound of the Formula (CH^^CtBrJCOOR, where R is lower- alkyl of 1-6 carbon atoms, in the presence of a strong base; and c) if necessary, hydrolyzing a lower-alkyl ester obtained to the free acid. 18. A process for preparing a compound according to claim 1, substantially as herein described with reference to the Examples. 19. A compound according to Claim 1 produced by the process according to any one of Claims 12 to 18. 20. A compound according to Claim 1, substantially as herein described with reference to the Examples.