BENZOCYCLOHEPTENES, BENZOXEPINES AND BENZOTHIEPINES

Abstract: The subject of the invention is compounds of general formula (I), in which: X represents O or CHR; R1, R2, R3 and R4, which are identical or different, represent a hydrogen atom or a C1-C7 alkyl group, it being possible for R1 to additionally form a bond with R; R5 represents a hydrogen atom, a hydroxyl group or R5, taken together with R7, forms a bond or a <SIGN> O group; R6 represents a group of formula (a) in which R10 and R11, taken together with the carbon atom to which they are attached, form a nitrogenous heterocyclic group, and their N-oxides and pharmaceutically acceptable salts. These compounds are powerful activators of potassium channels.

Description: Benzocycloheptenes, benzoxepines and benzothiepines The subject of the present invention is new heterocyclic compounds having a pharmacological activity in the activation of potassium channels. Activators of potassium channels or potassium agonists have the property of activating the potassium channels of the cell membrane by opening these channels or prolonging their opening. This results in trans¬ membrane ionic movements and, inter alia, a decrease in free intracellular Ca ** ions which causes relaxation of smooth muscle fibres. This therapeutic potentiality makes it possible today for great hopes to be placed in potassium agonists. Among the most studied fields, arterial hypertension, angina and asthma are the most often mentioned. Large families of activators of potassium channels are already recognized for their relaxant properties. A family of benzopyran derivatives has formed the subject of many publications in this field. These compounds correspond to the following general formula A: EP-0,076,075 describes compounds of general R,-N-C-R, formula A, where I | represents a pyrrolidone. DE-3,726,261 describes compounds of general formula A, R,-N-C-R, where I n represents a pyπdone. 0 Another benzopyran family corresponds to the formula B below; it is described in EP- 0 , 298 , 452 : O-89/11477 and EP-0,360,131 relate to benzoxe¬ pines of general formula C: where X represents a nitrogenous ring connected via the nitrogen atom to the 5-position of the benzoxepines, such as a 2-oxo-l-pyrrolidinyl and 2-oxo-l-pyridyl group for the first and a 2-oxo-l-pyridyl group or a 4-fluoro- benzoyla ino group for the second. R 3 , R 4 , R s and R t represent a hydrogen atom or a lower alkyl group and R 1 and R 2 a hydrogen atom or a nitrile, arylsulfonyl or nitro group. Novel compounds possessing a benzocycloheptene or benzoxepine ring system, which show notable effects on the activation of potassium channels, have now been discovered . The subject of the invention is compounds of general formula: in which: X represents O, or CHR, R being a hydrogen atom or R, taken together with R 1# forming a bond, R x , R 3 , R 3 and R 4 , which are identical or different, represent a hydrogen atom or a C-.-C- alkyl group, it being possible for x to additionally form a bond with R; R 5 represents a hydrogen atom, a hydroxyl group or R 5 , taken together with R-, forms a bond or a ^o ; group; R 6 represents a group of formula: in which R 10 and R X1 , taken together with the carbon atom to which they are attached, form an optionally aromatic mono- or bicyclic nitrogenous heterocyclic group having from 3 to 11 members, including 1 or 2 nitrogen atoms, optionally substituted on the carbon atoms by 1 to 7 groups chosen from hydroxyl, nitro, cyano, C- ^ -C, alkyl or Cj-C, alkoxy, it being possible for at least one of the nitrogen atoms of the heterocycle to be N-oxidized; R 7 represents a hydrogen atom or a hydroxyl, C j -C, alkoxy or C^C, acyloxy group or R 5 and R 7 together form a bond or a r O group; R 8 and R 9 , which are identical or different, represent a hydrogen or halogen atom, a hydroxyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, pentafluoroethyl, C- . -C, alkyl, C^C, alkoxy, C^C, alkylthio, C^C, acylthio, C-^-C- alkylsulfonyl or (-.-_-C 7 alkylsulfinyl group, a group of formulae: 0 II -C-OR 12 ' -C-NR 12 R 13 or 1 -C-R 12 in which R 12 and R 13 , which are identical or different, represent a hydrogen atom or a C-.-C 7 alkyl group, or R 8 and R 9 represent a C 6 -C 10 aryl, (C 6 -C 10 )a- rylsulfonyl or (C 6 -C 10 )aj-ylsulfinyl group, optionally substituted by one to six substituents chosen from halo, hydroxyl, nitro, cyano, carboxyl, carbamoyl, trifluoromethyl, trifluoro ethoxy, pentafluoroethyl, Ci-C, alkyl, C^C, alkoxy, C^C- alkylthio, C^C, acylthio, C j -C, alkylsulfonyl or C^-C- alkylsulfinyl, or R 8 and R 9 , which are identical or different, represent a heterocycle having from 3 to 11 members in the ring including 1 to 4 hetereoatoms, which are identical or different, chosen from 0, S and N, optionally substituted by one to six substituents chosen from halo, hydroxyl, nitro, cyano, carboxyl, carbamoyl, trifluoromethyl, trifluoromethoxy, penta- fluoroethyl, C^C-. alkyl, C-.-C, alkoxy, Ci-C, alkyl¬ thio, Ci-C- acylthio, C^C, alkylsulfonyl or C x -C 7 alkylsulfinyl, or R 8 and R s together form a group (CΞ 2 ) n , n being a number from 1 to 6, or R, and R 9 together form a heterocycle having from 3 to 11 members including 1 to 4 heteroatoms, which are identical or different, chosen from O, S and N, optionally substituted by one to six substituents chosen from halo, hydroxyl, nitro, cyano, carboxyl, carbamoyl, trifluoromethyl, trifluoromethoxy, pentafluoroethyl, C-.-C-, alkyl, Ci-C- alkoxy, C-.-C, alkylthio, C 1 -C 7 acylthio, C j -C, alkylsulfonyl or C^C-, alkylsulfinyl, and their N-oxides and their pharmaceutically acceptable salts. "Ci-C, alkyl group" means the groups containing a linear or branched C- ^ -C, chain, especially the methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, isobutyl, pentyl, hexyl and heptyl groups. "Ci-C, alkoxy group" means the groups containing a linear or branched (.--.-C, chain, especially the methoxy, ethoxy, propoxy, butoxy, pentoxy, hexyloxy and heptyloxy groups. "C x -C 7 acyloxy group" means the alkyl groups containing a linear or branched C- ^ -Cg chain linked to a carbonyloxy functional group, especially the acetoxy and propionyloxy groups. "C j -C, alkylthio group" means the alkyl groups containing a linear or branched C- ^ -C, chain linked to a sulfur atom, especially the methylthio, ethylthio, propylthio, butylthio, pentylthio, hexylthio and heptyl- thio groups. "Ci-C, alkylsulfonyl group" means the alkyl groups containing a linear or branched C- ^ -C-, chain linked to a -SO j - sulfonyl group, especially the methylsulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, pentyl- sulfonyl, hexylsulfonyl and heptylsulfonyl groups. "Cx-C, alkylsulfinyl group" means the alkyl groups containing a linear or branched C 1 -C 7 chain linked to a -SO- sulfinyl group, especially the methylsulfinyl, ethylsulfinyl, propylsulfinyl, butylsulfinyl, pentyl- sulfinyl, hexylsulfinyl and heptylsulfinyl groups. "C 6 -C 10 aryl group" means the mono- or bicyclic carbocyclic aromatic groups, especially the phenyl, naphthyl or indenyl groups. The term "halogen" means the fluorine, chlorine, bromine or iodine atoms. The heterocycle containing from 3 to 11 atoms, - including 1 to 4 hetereoatoms chosen from O, S and N, can be aromatic or nonaromatic, monocyclic or bicyclic, and is in particular a pyridyl, imidazolyl, furyl, tetra- hydrofuryl, furazanyl, thienyl, aziridinyl, oxiranyl, azetidinyl, quinolyl, tetrahydroquinolyl and tetrazolyl group. When R 8 and R s together form a heterocycle having from 3 to 11 members, including 1 to 4 identical or different hetereoatoms chosen from 0, S and N, they represent, especially with the phenyl group to which they are attached, a quinolyl, isoquinolyl, benzimidazolyl, benzofuryl, benzothienyl and benzoxadiazolyl group. The R s group is in particular a 2-pyridyl, 2-pyridyl N-oxide, 3-pyridyl, 3-pyridyl N-oxide, 4-pyridyl, 3-hydroxy-4-pyridyl, 2-pyrimidyl, 2-pyrimidyl N-oxide, 6-pyrimidyl, 6-pyrimidyl N-oxide, 2-quinolyl, 2-quinolyl N-oxide, 1-isoquinolyl and 1-isoquinolyl N-oxide group, optionally substituted on the carbon atoms by 1 to 3 substituents chosen from hydroxyl, nitro, cyano, C^C, alkyl and C^C., alkoxy. The physiologically acceptable salts of the compounds of formula I comprise the salts formed with metals such as sodium, potassium, calcium and magnesium or salts of organic acids such as oxalic, fumaric, maleic, citric, methanesulfonic and lactic acids. The N-oxides of formula I are the compounds in which 1 or more of the nitrogen atoms of the R 6 group are oxidized. The term "trans" used for the compounds which carry asymmetric carbon atoms in the rings shows that two substituents are found on either side of a central plane of the ring, and the term "cis" is applied for two sub- stituents which are found on the same side of the same central plane of the ring. The preferred compounds of general formula I are those in which X represents an oxygen atom. Advantageously, R-_ and R 2 represent a hydrogen atom and/or R 5 represents a hydrogen atom. Advantageously, R 7 is chosen from a hydrogen atom or the hydroxyl, methoxy and acetoxy group. A first preferred family of compounds of the present invention correspond to the compounds of general formula II: in which X represents O or CH-R, and R, R 5 , R 6 , R 7 , R 8 and R 9 are as defined above. Carbon atoms 4 and 5 of the formula II can together or independently represent a chiral centre. Derivatives such as optical isomers, racemates, cis or -trans derivatives, enantiomers and diastereoisomers form part of the invention. Among the preferred compounds of formula II, it is possible in particular to mention the following compounds: 3, 3 -dimethyl-5- (2-pyridyl N-oxide) -2, 3,4, 5-tetrahydro- 1 -benzoxepin- 5 -ol ; 7 - fluoro-3 , 3 -dimethyl- 5- (2 -pyridyl N-oxide) - 2,3,4,5- tetrahydro- 1 -benzoxepin- 5 -ol ; 7-bromo-3,3-dimethyl-5- (2-pyridyl N-oxide) -2, 3,4, 5-tetra- hydro-1-benzoxepin-5-ol; β-brαmo-S^-dimethyl-S- (2-pyridyl N-oxide) -2,3,4,5-tetra- hydro-l-benzoxepin-5-ol; 7-brαmo-3,3-dimethyl-5- (3-pyridyl N-oxide) -2,3,4,5-tetra- hydro-1-benzoxepin-5-ol; 5-acetyloxy-7-bromo-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2,3,4,5-tetrahydro-1-benzoxepine; 7-bromo-4,5-epoxy-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2,3,4,5-tetrahydro-1-benzoxepine; 7-bromo-5-methoxy-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2,3,4,5-tetrahydro-l-benzoxepine; 7-ethyl-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3,4,5-tetra- hydro-1-benzoxepin-5-ol; 7 -methoxy-3 , 3 -dimethyl-5- (2 -pyridyl N-oxide) - 2,3,4,5-tetrahydro-1-benzoxepin-5-ol; 3,3-dimethyl-7- (1-methylpropyl) -5- (2-pyridyl N-oxide) - 2,3,4,5-tetrahydro-l-benzoxepin-5-ol; 3,3-dimethyl-5- (2-pyridyl N-oxide) -7-trifluoromethyl- 2,3,4,5-tetrahydro-1-benzoxepin-5-ol; 3,3-dimethyl-5- (2-pyridyl N-oxide) -7-trifluoromethoxy- 2,3,4,5-tetrahydro-1-benzoxepin-5-ol; 3 , 3 -dimethyl -7 -phenyl - 5- (2 -pyridyl N-oxide) - 2,3,4, 5- tetrahydro- 1 -benzoxepin- 5 -ol; 8-chloro-7-fluoro-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2,3,4,5-tetrahydro-l-benzoxepin-5-ol; 3, 3 -dimethyl-5- (3-pyridyl N-oxide) -7-trif luoromethyl- 2,3,4,5- tetrahydro- 1 -benzoxepin- 5 -ol ; 6, 8-dichloro-3 , 3 -dimethyl-5- (2-pyridyl N-oxide) - 2,3,4, 5- tetrahydro- 1 -benzoxepin- 5 -ol; 7 , δ-dichloro-3 , 3 -dimethyl-5- (2 -pyridyl N-oxide) - 2,3,4,5- tetrahydro- 1 -benzoxepin- 5 -ol ; 7 , 8-dichloro-3 , 3 -dimethyl-5- (3 -pyridyl N-oxide) - 2,3,4,5-tetrahydro-1-benzoxepin-5-ol; 7, 8-dimethoxy-3, 3-dimethyl-5- (2-pyridyl N-oxide) - 2,3,4,5-tetrahydro-1-benzoxepin-5-ol; 7, 9-dichloro-3, 3-dimethyl-5- (2-pyridyl N-oxide) - 2,3,4,5-tetrahydro-1-benzoxepin-5-ol. A second preferred family of compounds of the present invention correspond to the compounds of general formula III: III in which X represents 0 or CH-R, and R, R 6 , R 8 and R 9 are as defined above. Among the preferred compounds of formula III, it is possible in particular to mention the following compounds: 3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro-l-benzoxe- pine; 7-fluoro-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 7-bromo-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 7-chloro-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 8-bromo-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 7-bromo-3,3-dimethyl-5- (3-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 3 3,7-trimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 7-ethyl-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 3,3-dimethyl-7- (1-methylpropyl) -5- (2-pyridyl N-oxide) - 2,3-dihydro-1-benzoxepine; 7 -isopropyl-3 , 3 -dimethyl-5- (2-pyridyl N-oxide) - 2,3-dihydro-1-benzoxepine; 7-methoxy-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 3,3-dime hyl-5- (2-pyridyl N-oxide) -7-trifluoromethyl- 2,3-dihydro-1-benzoxepine; 3,3-dimethyl-5- (2-pyridyl N-oxide) -8-trifluoromethyl- 2,3-dihydro-1-benzoxepine; 3,3-dimethyl-5- (2-pyridyl N-oxide) -7-trifluoromethoxy- 2,3-dihydro-1-benzoxepine; 3,3-dimethyl-7-methylsulfinyl-5- (2-pyridyl) -2,3-dihydro- 1-benzoxepine; 3,3-dimethyl-7-methylsulfonyl-5- (2-pyridyl) -2,3-dihydro- 1-benzoxepine; 3,3-dimethyl-7-methylsulfonyl-5- (2-pyridyl N-oxide) - 2,3-dihydro-1-benzoxepine; 7-cyano-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 8-cyano-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 3,3-dimethyl-5- (2-pyridyl N-oxide) -7-pentafluoroethyl- 2,3-dihydro-l-benzoxepine; 3,3-dimethyl-7-phenyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1 -benzoxepine; 3,3-dimethyl-7-nitro-5- (4 -nitro- 2 -pyridyl N-oxide) - 2,3- dihydro- 1 -benzoxepine ; 7, β-dichloro-3, 3 -dimethyl-5- (3-pyridyl N-oxide) - 2,3- dihydro - 1 -benzoxepine ; 6, 8-dichloro-3 , 3 -dimethyl-5- (2 -pyridyl N-oxide) - 2,3- dihydro- 1 -benzoxepine ; 7, 9-dichloro-3 , 3 -dimethyl-5- (2-pyridyl N-oxide) - 2, 3- dihydro -1 -benzoxepine; 8, 9-dichloro-3 , 3 -dimethyl-5- (2 -pyridyl N-oxide) - 2,3- dihydro- 1 -benzoxepine ; 7, 8-dichloro-3, 3 -dimethyl-5- (2 -pyridyl N-oxide) - 2,3- dihydro - 1 -benzoxepine ; 7, 8-dif luoro-3, 3 -dimethyl-5- (2-pyridyl N-oxide) - 2,3- dihydro- 1 -benzoxepine ; • 9-ethyl-7-fluoro-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2 , 3-dihydro-l-benzoxepine; 8-cyano-3 , 3 , 7 - trimethyl-5- (2-pyridyl N-oxide) - 2, 3-dihydro-l-benzoxepine; 7 -cyano-3 , 3 , 8- trimethyl-5- (2-pyridyl N-oxide) - 2,3- dihydro - 1 -benzoxepine ; 7, 8-dimethoxy-3, 3 -dimethyl -5- (2 -pyridyl N-oxide) - 2,3-dihydro-l-benzoxepine; 8-chloro-7-fluoro-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2,3-dihydro-1-benzoxepine; 3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3,7,8,9,10-hexa- hydro-l-naphth[2,3-b] oxepine; 8-cyano-3,3-dimethyl-l- (2-pyridyl N-oxide) -4,5-dihydro- 3H-benzo [4,3-f]cycloheptene; 3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro-l-benzoxe- pine-7-carboxamide; 3,3-dimethyl-7-phenylsulfonyl-5- (2-pyridyl N-oxide) - 2,3-dihydro-1-benzoxepine; 7-chloro-8-ethyl-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2,3-dihydro-l-benzoxepine; 8-bromo-3,3-dimethyl-l- (2-pyridyl N-oxide) -3H-benzo[f] - cyclohepta- 1 , 4 -diene. The compounds of the invention can be prepared by a process comprising: a) the reaction of a ketone of general formula IV: in which X, R__. R 2 , R 3 and R 4 are as defined above, and R 5 ' , R 8 ' and R 9 ' respectively represent the optionally protected R 5 , R 8 and R 9 groups as defined above, with an organometallic compound of general formula: R 6 ' -R„ V in which R £ ' represents a group of formula: in which R 10 and R 11# taken together with the carbon atom to which they are attached, form an optionally aromatic, mono- or bicyclic nitrogenous heterocyclic group having from 3 to 11 members, including 1 or 2 nitrogen atoms, and optionally substituted on the carbon atoms by 1 to 7 groups, optionally protected if necessary, chosen from hydroxyl, nitro, cyano, C j -C, alkyl or C^C, alkoxy; and b) the deprotection of protected groups to produce a compound of general formula VI: in which X, R-_, R 2 , R 3 , R 4 , R s , R 6 , R 8 and R 9 are as defined above; and optionally either cl) the reaction of the compound of general formula VI thus obtained with a reacta t of general formula VII: R 14 -Y VII in which R 14 represents a C__-C η alkyl or C^C, acyl group and Y represents a leaving group, to produce a compound of general formula I in which R 7 represents a C-.-G- alkoxy or C j -C, acyloxy group, respectively; or c2) the dehydration of the compound of general formula VI obtained in b) in the presence of an acid or of an acid chloride to produce a compound of following general formula I: in which X, R l R 2 , R 3 , R 4 , R 5 , R 6 , R β and R 9 are as defined above; and optionally d) the reaction of the compound of formula I obtained in Stage c2) with a peroxide to produce a compound of general formula I in which R 5 and R 7 together form a 0 group; and optionally e) the reaction of the compound of general formula VI obtained in Stage b) or of the compound of general formula I obtained in Stage cl) , c2) or d) with an oxidizing agent to form a corresponding N-oxide compound; and/or optionally f) the reaction of the compound of general formula VI obtained in Stage b) or of the compound of general formula I obtained in Stage cl) , c2) or d) with a pharmaceutically acceptable inorganic or organic acid to form a corresponding salt. In the reaction of Stage a) , a compound of formula IV as defined above is advantageously reacted with an organolithium compound of formula LiR , 6 , R' 6 being as defined above. The compounds of formula LiR' 6 can be prepared in a known way by a person skilled in the art, for example by reacting a compound of the formula R' 6 Br, R' 6 being as defined above, with n-butyllithium in an organic solvent such as diethyl ether or tetrahydrofuran, optionally in the presence of hexamethylphosphoramide or of 1,3-dimethylimidazolidone at a temperature between -110°C and the reflux temperature of the solvent, or of the mixture of solvents, for a time between 4 hours and 24 hours. When the compounds of formula IV or V comprise OH groups, the latter are protected by a protective group of the hydroxyl functional group known to a person skilled in the art, for example an SiMe 3 or SiMe 3 tBu group. The reaction of Stage a) takes place in an inert organic solvent, in particular diethyl ether, THF or hexane, at a temperature between -78°C and -20°C, followed by the addition of a dilute acid to release the alcohol from the lithium alkoxide complex formed. The deprotection reaction of Stage b) is carried out by an acid treatment in aqueous medium or by the use of fluoride (for example of tetrabutylammonium fluoride) in tetrahydrofuran at a temperature between -20°C and 100°C, preferably 25°C. In Stage cl) , the leaving group Y is in particular a halogen atom or an alkyl- or arylsulfonyloxy group, in particular a mesyloxy or tosyloxy group. Preferably, an acyl halide or an alkyl halide is used in the presence of a Lewis base in a solvent such as dimethylformamide. The reaction for the removal of H 2 0 in Stage c2) is advantageously carried out in acid medium and in the presence of an organic solvent, such as benzene, toluene or xylene, the acid being in particular para-toluene- sulfonic acid or sulfuric acid. The acid can also consist of an acid chloride such as the chloride of methaneβulfonic acid, in the presence of a solvent such as chloroform, dichloromethane or dichloroethane. The reaction is advantageously carried out at the reflux temperature of the solvent. The reaction of Stage d) takes place in the presence of a peroxide, in particular a peracid, such as peracetic acid, perbenzoic acid, perphthalic acid or 3-chloroperbenzoic acid. The amount of peroxide used can vary from 1 to 4 equivalents depending on the compound to be oxidized. The solvent used is preferably water, acetic acid or chlorinated solvents such as dichloromethane, chloroform or dichloroethane. The temperature of the reaction is advantageously between -20°C and the reflux temperature of the solvent. The reaction of Stage e) takes place in the presence of an oxidizing agent, in particular a peracid such as mentioned above (for example 3-chloroperbenzoic acid) in a solvent such as dichlorome thane. The ketones prepared are in particular: 7-bromo-3, 3 -dimethyl -2 , 3, 4, 5- tetrahydro- 1 -benzoxepin - 5-one B.p. (S3 . 2 P .. 0 . 4 jIBaHg) = 117-121°C 7 - chloro -3,3 - dime thyl -2,3,4,5- tetrahydro - 1 -benzoxepin - 5-one B.p. (β6 . 5 P . „o. 5 _.__,) - 80-100°C 7 - cyano- 3 , 3 -dimethyl -2,3,4,5- tetrahydro - 1 -benzoxepin - 5-one M.p. = 114°C 7 - ethyl - 3 , 3 -dimethyl -2 , 3,4,5- tetrahydro - 1 -benzoxepin- 5-one B.p. (39 . 9 P . „ 0 . 3 lβHW = 97-104°C 7-fluoro-3, 3 -dime thyl -2, 3, 4, 5 -tetrahydro- 1 -benzoxepin - 5-one B.p. (53 . 2 p .. 0-4 ---,„,, = 102-108°C 7-isopropyl-3,3-dimethyl-2,3,4,5-tetrahydro-l-benzoxepin- 5-one B.p. (53 . 2 Pll . 04 lBBHg , = 112-122°C 7 -methoxy- 3,3- dimethyl -2,3,4,5- tetrahydro- 1 -benzoxepin - 5-one B.p. (33-25 Pa . 0-25 „ -^ = 122-126°C 3 , 3 -dime thyl -2 ,3,4, 5- tetrahydro- 1 -benzoxepin- 5 -one B.p. (103 . 4 Pa . 0 . 8 βH g) - 90°C 3,3,7- tr ime thyl -2,3,4,5- 1 e tr ahydr o - 1 - b enz oxepin - 5 - one B.p. (53 . 2 pa .0.4-Hg) = 90-104°C 7- (1-methylpropyl) -3, 3 -dimethyl -2 , 3,4, 5- tetrahydro- 1 -benzoxepin- 5 -one B.p. (532 p .. 0>4 mHg) = 115-120 °C 7-methylthio-3,3-dimethyl-2,3,4,5-tetrahydro-l-benzoxe- pin-5-one B.p. (79 . 8 p .. 06 βHg) = 125-135°C 7 -pentaf luoroethyl -3 , 3 -dimethyl- 2 , 3,4, 5- tetrahydro - 1 -benzoxepin- 5 -one 7 -phenyl -3,3- dimethyl -2,3,4,5- tetrahydro- 1 -benzoxepin - 5-one B.p. (26 . 6 P .. 0 . 2 „ w = 135-140°C 7 -phenyl thio -3 , 3-dimethyl-2,3,4, 5-tetrahydro-l-benzoxe- pin-5-one 7-trifluoromethoxy-3, 3-dimethyl-2 ,3,4, 5-tetrahydro- 1-benzoxepin-5-one B.p. (2128 Pa . 16 n ^ = 135-138°C 7-trifluoromethyl-3 , 3-dimethyl-2, 3,4, 5-1etrahydro- 1-benzoxepin-5-one B.p. (133 p .. -. „ ^ = 80-100°C 8-bromo-3,3-dimethyl-2,3,4,5-tetrahydro-lH-benzo[f]cyclo- hepten-1-one M.p. = 94°C 8-bromo-3, 3-dimethyl-2, 3,4, 5-tetrahydro-1-benzoxepin- 5-one B.p. (39 . 9 P .. 0 . 3 βEg) = 108-112°C 8- trifluoromethyl-3,3 -dimethyl-2 ,3,4,5-tetrahydro- l-benzoxepin-5-one B.p. (399 Pa . 03 m ^ = 85-110°C 9-bromo-3,3-dimethyl-2, 3,4, 5-tetrahydro-1-benzoxepin- 5-one M.p. = 86°C 7- (2-methylpropyl) -3 , 3-dimethyl-2, 3,4, 5-tetrahydro- l-benzoxepin-5-one B.p. (53-2 p , . 04 m Rg) = 128-138°C 7- (2-methylpropyl) -3 , 3-dimethyl-2 , 3,4, 5-tetrahydro- l-benzoxepin-5-one B.p. = 128-136°C 7 -bro o- 8-methyl-3 , 3 -dimethyl-2 ,3,4, 5-tetrahydro- 1-benzoxepin-5-one B.p. (53-2 Pa . 0 M ^ = 120-130°C 6, 8-dichloro-3, 3-dimethyl-2,3,4,5-tetrahydro-1-benzoxe- pin-5-one B.p. (1064 p , . 0 . 8 β Hg) = 120°C 7, 8-dichloro-3, 3-dimethyl-2,3,4,5-tetrahydro-1-benzoxe- pin-5-one M.p. = 94°C 7, 9-diehloro-3, 3-dimethyl-2,3,4,5-tetrahydro-1-benzoxe- pin-5-one B.p. (7S 8 p , . 0-6 m w = 120-130°C 8, 9-dichloro-3, 3-dimethyl-2,3,4,5-tetrahydro-1-benzoxe- pin-5-one 7-chloro- 8-ethyl-3 , 3 -dimethyl-2 ,3,4,5- tetrahydro- l-benzoxepin-5-one B.p. (S32 p , . β#4 m w = 108-112°C 7-chloro-3,3,8-trimethyl-2,3,4,5-tetrahydro- l-benzoxepin-5-one B.p. (532 Pa . 04 „, w = 115-122°C 7, 8-difluoro-3, 3-dimethyl-2,3,4,5-tetrahydro-l-benzoxe- pin-5-one M.p. = 84°C 7 -fluoro- 3,3-dimethyl-2,3,4,5-tetrahydro- 1-benzoxepin-5-one B.p. M.p. = 82°C 7-fluoro- 9-ethyl-3 , 3 -dimethyl-2 ,3,4, 5-tetrahydro- 1-benzoxepin-5-one B.p. (7S 8 p , . 0-6 m ^ = 102-106°C 7,8-dimethoxy-3,3-dimethyl-2,3,4,5-tetrahydro-l-benzoxe- pin-5-one M.p. ~ 110°C 7 - me thyl - 8 - bromo - 3 , 3 - dime thyl - 2 , 3 , 4 , 5 - t e trahydro - 1 -benzoxepin- 5 -one B .p . (66 -S p , . 0 - 5 . ^ = 125 - 130 °C 7 , 8-dichloro-3 , 3 -dime thyl -2 ,3,4, 5- tetrahydro -1-benzoxe- pin-5-one M.p. = 95°C 3, 3 -dime thyl -2, 3, 4, 5, 7, 8, 9, 10-octahydro-l-naphth [2 , 3-b] - oxepin-5-one B.p. (S3 2 p .. 0 4 m Hg) = 135-150°C. 7- ( 2-methylpropyl ) -3 , 3-dimethyl-2 ,3,4, 5-tetrahydro-l-benzoxepin-5-one B.p. = 128-136°C; 8-chloro-3, 3-dimethyl-7-trif luor omethyl-2 ,3,4,5-tetrahydro-l- benzoxepin-5-one M.p. = 80°C; 7-bromo-8-chloro-3 , 3-dimethyl-2 ,3,4, 5-tetrahydro-l-benzoxepin-5-one M.p. = 94°C; 3 , 3-dimethy l-8-phenylthio-2 ,3,4, 5-tetrahydro-lH-benzo [ f ] cyclo eptane- 1-one; 7 , 8-dichloro-3 , 3-dimethyl-2 ,3,4, 5-tetrahydro-lH-benzo [ f ] cycloheptane- 1-one M.p. = 74° 8-bromo-4, 4-cimethyl-2,3 ,4, 5-tetrahydro-lH-benzo [ f ] cycloheptane-1- one; 8-bromo-3 , 3-dimethyl-2 ,3,4, 5-tetrahydro-lH-benzo [ f ] cycloheptane-1-one M.p.= 94°C The ketones of formula IV can be obtained by cyclization of the acids of formula VIII: in which x, R 1# R 2 , R 3 , R 4 , R 5 , R 8 and R 9 are as defined above, according to the method described by Guy Fontaine (Annalen der Chemie, 1968, Volume 3, No. 3, page 180) for the preparation of benzoxepines by cyclization of phenoxybutyric acids in the presence of phosphoric acid, alone or as a mixture with an organic solvent such as xylene, toluene or benzene, or by a Friedel-Crafts reaction from aluminium chloride and the chlorides of the corresponding 4-phenoxybutanoic, 4-phenylthiobutanoic or 5-phenylpentanoic acids in a solvent such as CS 2 or nitrobenzene. Other synthetic routes can also be used, in particular the Dieckmann condensation reactions. The acids of general formula VIII can be prepared when X represents 0 by reaction of a compound of general formula IX: in which R 8 and R 9 are as defined above, with a compound of general formula X: in which R x , R 2 , R 3 , R 4 and R 5 are as defined above, according to the method of Reppe W. (Annalen der Chemie, 1955, book 596, p. 158-224) . The reaction takes place by heating in butanol in the presence of NaOH. The acids of general formula VIII can also be prepared by reacting a phenol of formula IX as defined above with a compound of general formula XI: in which x , R 2 , R 3 , R 4 and R 5 are as defined above, A represents a halogen atom and B a lower alkyl or phenyl group, in a solvent such as DMF and in the presence of K J CO J or in acetone in the presence of K^CO j and KI. When X represents CHR, the acids of general formula VIII can be prepared according to Mathur K.C. and Singh V.P. (Proc. Natl. Acad. Sci. India. Sect A, 1981, 51 (2), p. 177 and 180), or according to Klaus Michael and Mohr Peter (EP-0,315,071) by: a) reaction of a compound of formula XII: with a compound of formula XIII or XIV: in which R χ R 2 , R 3 , R 4 and R 5 are as defined above, A represents a halogen atom and B a lower alkyl or phenyl group, in the presence of A1C1 3 in a solvent like CS_ or nitrobenzene, or in the absence of solvent, to produce a compound of general formula XV: in which R-., R 2 , R 3 , R 4 , R 5 , R β , R 9 and B are as defined above; b) hydrolysis of the compound of general formula XV thus obtained either in basic medium such as NaOH, KOH, NaHC0 3 , for example in water/alcohol medium, or in acid medium: to produce a compound of general formula XVI: in which R α , R 2 , R 3 , R 4 , R 5 , R 8 and R 9 are as defined above, and c) reduction of the carbonyl functional group of the compound of formula XVI according to the Wolff- Kishner reaction in the presence of an excess of hydrazine and of strong base, for example potassium hydroxide, in diethylene glycol or polyethylene glycol at high temperature. The acids of formula VIII prepared are in parti¬ cular: 4 -phenoxy- 3 , 3 - dimethylbutanoic acid, B.p. (13 . 3 Pa . 0 . l βlHg) = 130°C; 4 - (4 -bromophenoxy) -3,3 -dimethylbutanoic acid, B.p. (53 . 2 p a -o.4».Bg) = 154-162°C; 4- (4 -chlorophenoxy) -3 , 3 -dimethylbutanoic acid, B.p. (53 . J Pa . o.4 -ag) = 130-145°C; 4 - (4-fluorophenoxy) -3 , 3 -dimethylbutanoic acid, B.p. <„.-.*..0.4..--«> = 128-134 β C; 4- (4 -methylphenoxy) -3 , 3 -dimethylbutanoic acid, B.p. ( 53 ., P ..0.4 -~-~) = 130-136*C; 4- (4 - ethylphenoxy ) - 3 , 3 -dime thylbutanoic acid, B.p., 53 . 2 p.. 0 . 4 - E ) = 132-136°C; 4 - (4-isopropylphenoxy) -3 , 3 -dimethylbutanoic acid, B.p. (53. p..0.4 »__g> = 130-142°C; 4- [4- (l-methylpropyl)phenoxy] -3, 3 -dimethylbutanoic acid, B-P-(53.a »..0.4.1.) - 155-165°C; 4 - (4-methoxyphenoxy) -3,3-dimethylbutanoic acid, M.p. = 69°C; 4- (4-trifluoromethoxyphenoxy) -3, 3 -dimethylbutanoic acid, B.p. (53 . 2 P .. 0 . 4 -. H9 ) = 100-120°C; 4 - (4 -methyl thiophenoxy) -3,3 -dimethylbutanoic acid, B.p.uoc.4 »..o.t-.Hβ) = 150-170°C; 4- (4-phenylphenoxy) -3 , 3 -dime thylbutanoic acid, M.p. = 124°C; 4 - (3 -bromophenoxy) -3 , 3 -dimethylbutanoic acid, B.p., ιoβ.4 p . o.β»Bg) = 140-160°C; 4- (3 , 5-dichlorophenoxy) -3,3 -dimethylbutanoic acid, B.p., 53.2 P..0.4 - Kg) = 130-150°C; 4- (3, -dichlorophenoxy) -3,3-dimethylbutanoic acid, M.p. ■ 66°C; 4- (2, 4-dichlorophenoxy) -3,3-dimethylbutanoic acid, B.p. (ts . 5 P ..0.5-Bg) = 150-160°C; 4- (2,3-dichlorophenoxy) -3, 3-dimethylbutanoic acid, B.p.(„.5 ..0.5 -Eg) = 130-160°C; 4- (3,4-difluorophenoxy) -3 , 3-dimethylbutanoic acid, B.p.,53. P . o.4»H 3 ) " H0-134 β C; 4- (3-chloro-4-fluorophenoxy) -3,3-dimethylbutanoic acid, B.p- (53. 2 P . - o.4.Eg) = 130-145°C; 4- (2-ethyl-4-fluorophenoxy) -3,3-dimethylbutanoic acid, B.p. (S3 . 2 P ..o. 4 - Hg ) ■ 123-136°C; 4- (3 , 4 -dime thoxyphenoxy) -3, 3 -dime thylbutanoic acid, B.p. ,53.2 P.. o. - Hg) = 150-170°C; 4- (4 -bromo- 3 -methylphenoxy) -3, 3 -dimethylbutanoic acid, B.p. (53 . 2 P , . 0 . 4 - »Hg ) ~ ~ 130-135°C; 4- (3 -bromo-4 -methylphenoxy) -3, 3 -dimethylbutanoic acid, B.P-, 53.2 P.. o.4-»Hg) » 155-160°C; 4- (5,6,7, 8-tetrahydro-2-naphthyloxy) -3, 3 -dime thylbutanoic acid, M.p. = 85°C; 4-[4-(2-methylpropyl)phenoxy]-3,3-dimethylbutanoic acid, B -P- (665 P a = S im H g)= 160-180°C; 4-(4-chloro-3-ethylphenoxy)-3,3-dimethylbutanoic acid, B -P-(53,2 Pa = 0, ™ Hg) = 160-166°C; 4-(4-chloro-3-methylphenoxy)-3,3-dimethylb tanoic acid, B -P-C53,2 Pa = 0,4 πrn Hg>= 150-158°C; 4-(4-bro o-3-chlorophenoxy)-3,3-dimethy1-butanoic acid, B -P-(53,2 Pa = 0,4 ~ι~ Hg>= 150-170°C; 5-(4-bromophenyl)-3,3-dimethylpentanoic acid, M.p. = 72°C; 5-(3,4-dichlorophenyl)-3,3-dimethylpentanoic acid; 5-(4-bromophenyl)-4,4-dimethylpentanoic acid, M.p. = 106-108°C. The compounds of the invention have excellent properties in the activation of potassium channels and have a powerful relaxant effect on smooth musculature. Consequently, they cam be used as bronchodilators in disorders of the respiratory system, and in particular against asthma and obstruction of the upper airways. They also have an advantage in the control of hypertension and in the case of disorders of the contraction of the smooth musculature of the gastrointestinal tract, of the uterus, of the urinary tract, and in incontinence phenomena. They are useful in the case of cardiovascular disorders other than hypertension, in particular cardiac insufficiency, angina pectoris, cerebral and peripheral vascular patho¬ logies and pulmonary hypertension. These compounds are additionally active in the treatment of alopecia. The "potassium channel activating" activity was measured by the rate of exit of rubidium-86 from tracheal smooth muscle cell according to the method described by Allen, S.L., Br. J. Pharmac, 1986, J37, p. 117-127 and Rate of the efflux of rubidium-86 in in vitro guinea pig trachea: Male guinea pigs weighing 250 to 600 g are stunned and exsanguinated by sectioning the jugular. The trachea is rapidly freed and cleaned in situ. The parts removed are placed on hold in an oxygenated modified Krebs-Henseleit (M.K.H.) solution. When all the tracheae are removed each is enriched in smooth muscle. The trachea is placed in a crystallizing dish containing the M.K.H. and a stream of 0 2 /C0 2 at 37°C. Two longitudinal incisions are carefully made on both sides of the muscle strip at 1 mm from the latter. The tracheae are then equilibrated in a beaker containing 30 ml of M.K.H. for 30 minutes, after which the rubidium-86 radioactive charge is added. A constant and sustained gaseous flow rate is maintained throughout the manipulation. The beaker is then replaced by another containing 25 ml of oxygenated M.K.H. and 125 microcuries of 86 Rb for 3 hours. The tracheae are washed twice in succession in a beaker containing approximately 100 ml of M.K.H. for 3 minutes. The tracheae are introduced individually into a series of 10 ml disposable tubes. The latter are filled, 30 seconds before immersion of the tracheae, with 4 ml of oxygenated M.K.H. There are then carried out an immersion of the tracheae for 5 minutes and 5 rinsings of 10 minutes and then efflux periods of 3 minutes. A first group of tubes are used for estimating the base efflux: they contain 10 μl of pure DMSO plus 4 ml of M.K.H. A second group of tubes makes it possible to bring the sample into contact with a concentration of product to be tested lasting seven periods of 3 minutes. The products are used in the form of mother solutions containing 40.1 mmol of pure DMSO, then diluted in the same solvent and introduced in the set amount of 10 μl per 4 ml. of M.K.H. The counting is carried out by the Cerenkov effect. The effective concentration of the product which increases the base efflux rate by 25 % (EC 25 % ) is deter¬ mined. The efflux rate of the tracer is expressed as percentage of release per minute with respect to the total amount of tracer at the time under consideration. The EC 25 % is calculated by linear regression from the relationship: Maximum efflux in the presence of product with respect to the base efflux as a function of the logarithm of the concentration. The results obtained with representative com- pounds of the invention are reported in Table I below. Table I Results of the activating activity of the compounds of the invention for potassium channels The bronchodilating activity was measured in vivo by the method of Konzett H. and Rossler R. (Arch. Exp. Pathol. Pharmak., 1940, 195. p. 71 to 74) and Duhault J. et al. (Arzneim. Forsch./Drug. res., 1987, 37., p. 1353 to 1362) . Measurement of the bronchodilating activity: Dukin-Hartley guinea pigs (400-500 g) are pre¬ pared according to the methodology described by Konzett and Rossler. The animals are anaesthetized by an intra- peritoneal injection of urethane (1.5 g/kg) and a tracheotomy is prepared for artificial respiration (45 cycles/min; respiratory volume 10 ml/kg) . The animal is connected to a respiratory pump, which is adjusted to deliver a volume of 1 ml per 100 g of body weight of the guinea pig. It is connected to a recorder via a pressure sensor. A catheter is placed in the jugular for the I.V. injections. An I.V. injection of gallamine and propanolol is carried out. After stabilizing the pulmonary pressure for 30 minutes, an I.V. injection of histamine is carried out every 10 minutes until reproducibility is achieved; at that point, the test product is injected 10 minutes after the last spasm. Histamine is tested 5 minutes and 15 minutes after the injection of the product and the effective dose for a 50 % inhibition is calculated. The results obtained with representative com¬ pounds of the invention are reported in Table II below. Table II Results of the bronchodilating activity of the compounds of the invention The compounds of the invention are active in man and animals, in particular in mammals, in particular in dogs, guinea pigs, rabbits, rats and mice. The compounds of the invention are non-toxic. Another subject of the invention is a pharma¬ ceutical composition comprising, as active ingredient, a compound according to the invention as defined above, in combination with a pharmaceutically acceptable vehicle. These pharmaceutical compositions are used in oral, intravenous, intraarterial, cutaneous or intestinal administration or as an aerosol. Moreover, these new products have a long-lasting action, whatever the mode of administration. The products of the general formula I will be combined in the pharmaceutical form with excipients, flavours and dyes, which are suitable for forming, for example, tablets, which can additionally be provided in the liposomal, microcapsule or nanocapsule form, or in the form of coated tablets, gelatin capsules, solutions, injectable solutions, suppositories, aerosols or creams. The excipients used can be, for example, microcrystalline cellulose, lactose, polyvidone, starch sodium glycolate, talc or magnesium stearate. The excipients for the liposomal or microcapsule forms can be poly(alkyl cyano- acrylates) or phospholipids. The coating of the tablets can be carried out with additives such as hydroxypropyl methylcellulose, various acrylic polymers, propylene glycol and titanium dioxide. The preparations for oral administration can contain artificial flavours and sweeteners such as sugar or aspartame. The injectable solution preparations will be made up with water which will contain stabilization agents, solubilization agents, such as sodium chloride, mannitol and sorbitol, and/or buffers necessary for the injectable solutions. The preparations for suppositories can use excipients such as semi-synthetic glycerides. The preparations for creams will be made, inter alia, by the addition of nonionic surface-active agents. The preparations for aerosol administration can be made from the micronized active principle, in combin¬ ation with a surface-active agent such as sorbitan trioleate, in a carrier gas such as CFC-11 and -12 or any other substituted carrier gas. The compounds of the invention can also be used in combination with any other substance of therapeutic use, for example diuretics, beta-blockers, PAF-acether antagonists, TxA j antagonists, converting enzyme inhibi¬ tors, beta-adrenergic inhibitors and anti-arrhythmics. The daily doses of active principle, administered once or a number of times, can be between 0.0001 and 100 mg/kg of body weight and preferably between 0.001 and 1 mg/kg. However, these limits can be exceeded in the event of necessity. A formulation example of a tablet and of a gelatin capsule according to the invention will be given below. Tablet formulation example : Gelatin capsule formulation example ; The following examples illustrate the invention in a non-limiting way. In the proton nuclear magnetic resonance ( H NMR) data, the following abbreviations have been used: ppm for part per million; s for singlet; d for doublet; t for triplet; q for quartet; b for broad; J for the couplings expressed in hertz; dd for double doublet. Example 1 7-Bromo-3,3-dimethyl-5- (2-pyridyl) -2,3,4,5-tetrahydro- 1-benzoxepin-5-ol C 17 H 18 BrN0 2 MM = 348 .239 Formula 1 A solution of n-butyllithium (1.6 mol/1) in hexane (93 ml, 0.15 mol) and of anhydrous diethyl ether (200 ml) is cooled to -78°C under a dry nitrogen stream. A solution of 2-bromopyridine (14.3 ml, 0.15 mol) in diethyl ether (100 ml) is added over 1 hour and the mixture is then stirred for a further 0.5 hour at -78°C. A solution of 7-bromo-3,3-dimethyl-2,3,4, 5-tetra- hydro-l-benzoxepin-5-one (13.5 g, 0.05 mol) in dry benzene (150 ml) is added over 1 hour at -78°C. Stirring is continued for 1.5 hours at -78°C and 1 hour at -15°C. Ice-cold water (100 ml) is then added via a dropping funnel and extraction is carried out with diethyl ether. The organic phase is washed with water and dried over anhydrous sodium sulfate. The solution is concentrated under reduced pressure (brown oil) . [yellow solid; 14 g; M.p. = 124-128°C; hexane; 80 %] IR in cm" 1 : 3340, 2950, 1595, 1580 'K NMR (CDC1 3 ) in ppm: 8.50 (IH, dd, J = 4.5 Hz), 7.20 (6H, m) , 5.75 (IH, s) , 4.08 (IH, d, J = 11 Hz), 3.80 (IH, d, J = 11 Hz), 2.34 (IH, d, J = 13.5 Hz), 1.66 (IH, d, J = 13.5 Hz), 1.06 (3H, s) , 0.86 (3H, s) . Elemental analysis 9.19 By using the same process, the following com¬ pounds are prepared. 7-Chloro-3,3-dimethyl-5- (2-pyridyl)-2,3,4,5-tetrahydro- 1-benzoxepin-5-ol C 17 H 18 C1N0 2 MM = 303.788 Formula 2 [flash chromatography: CH 2 C1 2 ; M.p. = 118°C; hexane; 83 %] IR in cm "1 : 3340, 2950, 1595, 1570. -H NMR (CDC1 3 ) in ppm: 8.54 (IH, dd, J = 1.5 Hz), 7.22 (6H, m) , 5.75 (IH, s) , 4.11 (IH, d, J = 11 Hz), 3.85 (IH, d, J = 11 Hz), 2.37 (IH, d, J = 13.5 Hz), 1.71 (IH, d, J = 13.5 Hz), 1.07 (3H, s) , 0.88 (3H, s) . 7 -Fluoro-3, 3 -dimethyl-5- (2-pyridyl) -2,3,4, 5-tetrahydro- 1 -benzoxepin- 5 -ol C 17 H 18 FN0 2 MM = 287.333 Formula 3 [M.p. = 110°C; hexane; 64 %] IR in cm" 1 : 3320, 2960, 1595, 1580. *H NMR (CDC1 3 ) in ppm: 8.50 (IH, dd, J = 4.5 Hz), 7.05 (6H, m) , 5.65 (IH, s) , 4.05 (IH, d, J = 12 Hz), 3.80 (IH, d, J = 12 Hz), 2.42 (IH, d, J = 14 Hz), 1.75 (IH, d, J = 14 Hz), 1.09 (3H, s) , 0.88 (3H, s) . 3, 3 -Dimethyl- 5- (2-pyridyl) -2,3,4, 5-tetrahydro-l-benzoxe- pin-5-ol C 17 H 19 N0 2 MM = 269.343 Formula 4 [chromatography with silica gel and CH 2 C1 2 ; oil; 87 %] IR in cm "1 : 3360, 2950, 1595, 1580 *H NMR (CDC1 3 ) in ppm: 8.46 (IH, dd, J = 4.5 Hz), 7.15 (6H, m), 5.75 (IH, m) , 4.15 (IH, d, J = 12 Hz), 3.85 (IH, d, J = 12 Hz), 2.37 (IH, d, J = 13.5 Hz), 1.70 (IH, d, J = 13.5 Hz), 1.10 (3H, s) , 0.92 (3H, s) . 3,3,7-Trimethyl-5- (2 -pyridyl) -2 , 3 , 4 , 5- tetrahydro- 1-benzoxepin- 5 -ol C 18 H 21 N0 2 MM = 283.369 Formula 5 [M.p. = 126°C; hexane; 66 %] IR in cm" 1 : 3310, 2960, 1595, 1575, 1500 'K NMR (CDC1 3 ) in ppm: 8.52 (IH, dd, J = 4.5 Hz), 7.05 (6H, m) , 5.63 (IH, m) , 4.07 (IH, d, J = 11 Hz), 3.85 (IH, d, J -> 11 Hz), 2.41 (IH, d, J = 13.5 Hz), 2.10 (3H, s) , 1.74 (IH, d, J = 13.5 Hz), 1.09 (3H, s) , 0.88 (3H, s) . 7-Ethyl-3,3-dimethyl-5-(2-pyridyl) -2,3,4,5-tetrahydro- 1-benzoxepin-5-ol C 19 H 23 N0 2 MM x- 297.396 Formula 6 [chromatography with silica gel and dichloromethane/ methanol: 98/2; M.p. = 84°C; hexane; 76 %] IR in cm "1 : 3350, 2970, 1595, 1565, 1500 7-lBopropyl-3,3-dimethyl-5- (2-pyridyl) -2,3,4, 5-tetra¬ hydro-1-benzoxepin-5-ol C 20 H 25 NO 2 MM -. 311.423 Formula 7 [M.p. = 72°C; crystallizes from pentane; 72 %] IR in cm '1 : 3310, 2960, 1585, 1495 *H NMR (CDC1 3 ) in ppm: 8.50 (IH, m) , 7.53 (IH, m) , 6.91 (5H, m) , 5.63 (IH, s) , 4.10 (IH, d, J = 11 Hz), 3.82 (IH, d, J = 11 Hz), 2.68 (IH, m) , 2.38 (IH, d, 13.5 Hz), 1.70 (IH, d, 13.5 Hz), 1.02 (12H, m) . 3 , 3 -Dimethyl-7 - (1 -methylpropyl) -5- (2 -pyridyl) - 2,3, ,5-tetrahydro-1-benzoxepin-5-ol C 21 H 27 N0 2 MM = 325.450 Formula 8 [chromatography with silica gel and dichloromethane/ heptane: 80/20; 33 %] IR in cm '1 : 3370, 2970, 1600, 1580, 1500 -Ε. NMR (CDC1 3 ) in ppm: 8.46 (IH, m) , 7.05 (6H, m) , 5.65 (IH, s), 4.09 (IH, d, J = 11 Hz), 3.79 (IH, d, J = 11 Hz), 2.35 (IH, d, J = 13.5 Hz), 2.22 (IH, m) , 1.65 (IH, d, J = 13.5 Hz), 1.06 (14H, m) . 7-Methoxy-3,3-d.-jnethyl-5- (2-pyridyl) -2,3,4,5-tetrahydro- 1-benzoxepin-5-ol C 18 H 21 N0 3 MM = 299.369 Formula 9 [chromatography with silica gel and dichloromethane/ methanol: 95/5; M.p. 98°C; hexane; 68 %] IR in cm" 1 : 3270, 2970, 1595, 1575, 1500 'K NMR (CDC1 3 ) in ppm: 8.50 (IH, dd, J = 4.5 Hz), 7.05 (6H, m), 5.53 (IH, s) , 3.89 (2H, s) , 3.55 (3H, s) , 2.42 (IH, d, J = 13.5 Hz), 1.76 (IH, d, J = 13.5 Hz), 1.04 (3H, s), 0.80 (3H, s) . 3,3 -Dimethyl- 5 - (2 -pyridyl) -7 - trif luoromethoxy - 2,3,4,5- etrahydro- 1 -benzoxepin- 5 -ol C 18 H 18 F 3 N0 3 MM = 353.340 Formula 10 [chromatography with silica gel and dichloromethane; M.p. = 76°C; heptane; 62 %] IR in cm "1 : 3290, 2950, 1590, 1485 *H NMR (CDC1 3 ) in ppm: 8.52 (IH, ) , 7.13 (6H, m) , 5.78 (IH, s) , 4.16 (IH, d, J = 11 Hz), 3.84 (IH, d, J = 11 Hz), 2.39 (IH, d, J = 13.5 Hz), 1.73 (IH, d, J = 13.5 Hz), 1.10 (3H, s) , 0.90 (3H, s) . 3,3-Dimethyl-7-methylthio-5- (2-pyridyl) -2,3,4,5-tetra¬ hydro-1-benzoxepin-5-ol C 18 H 21 N0 2 S MM = 315.435 Formula 11 [B.p.,.-.,,, = 180°C; 69 %] IR in cm' 1 : 3340, 2970, 1595, 1575 -S NMR (CDC1 3 ) in ppm: 8.53 (IH, m) , 7.23 (6H, m) , 5.70 (IH, s) , 4.10 (IH, d, J = 11 Hz), 3.81 (IH, d, J = 11 Hz), 2.36 (IH, d, J = 14 Hz), 2.25 (3H, s) , 1.71 (IH, d, J ■ 14 Hz), 1.09 (3H, s) , 0.89 (3H, s) . 3 , 3 -Dimethyl -7 -phenyl -5- (2-pyridyl) -2,3 , 4, 5 -tetrahydro - 1 -benzoxepin- 5 -ol C 23 H 23 N0 2 MM = 345.440 Formula 12 [chromatography with silica gel and dichloromethane; M.p. = 140-150°C; heptane; 95 %] IR in cm' 1 : 3290, 2930, 1600 X H NMR (CDC1 3 ) in ppm: 8.50 (IH, m) , 7.22 (11H, m) , 5.82 (IH, m), 4.20 (IH, d, J = 11 Hz), 3.89 (IH, d, J = 11 Hz), 2.41 (IH, d, J = 14 Hz), 1.75 (IH, d, J = 14 Hz), 1.13 (3H, s) , 0.95 (3H, s) . 8 -Bromo -3 , 3 -dimethyl-5 - (2 -pyridyl) -2,3,4,5- tetrahydro- 1 -benzoxepin- 5 -ol C 17 H 18 BrN0 2 MM = 348.239 Formula 13 [chromatography with silica gel and dichloromethane; M.p. = 110°C; crystallization from hexane; 85 %] IR in cm "1 : 3300, 2950, 1595, 1565, 1480 H NMR (CDC1 3 ) in ppm: 8.55 (IH, m) , 7.55 (IH, dd, J B 1.5 Hz, J = 7.5 Hz), 7.07 (4H, m) , 6.57 (IH, d, J = 8 Hz), 5.87 (IH, m) , 4.20 (IH, d, J = 11 Hz), 3.90 (IH, d, 11 Hz), 2.37 (IH, d, J = 13.5 Hz), 1.71 (IH, d, J = 13.5 Hz), 1.12 (3H, s) , 0.92 (3H, s) . 6,8-Dichloro-3,3-dimethyl-5- (2-pyridyl) -2,3,4, 5-tetra- hydro-1-benzoxepin-5-ol C„H-,C1,N0, MM = 338.233 Formula 14 [M.p. = 156°C; heptane; 76 %] IR in cm '1 : 3350, 3060, 2950, 1585, 1550 H NMR (CDC1 3 ) in ppm: 8.49 (IH, m) , 7.12 (5H, m) , 5.81 (IH, s), 4.16 (IH, d, J = 10.5 Hz), 3.92 (IH, d, J = 10.5 Hz), 2.12 (IH, d, J = 14 Hz), 1.52 (IH, d, J = 14 Hz), 1.19 (3H, s) , 0.98 (3H, s) . 7,8-Dichloro-3,3-dimethyl-5- (2-pyxidyl) -2,3,4,5-tetra- hydro-1-benzoxepin-5-ol C 17 H 17 C1 2 N0 2 MM = 338.233 Formula 15 [M.p. - 128°C; hexane; 73 %] IR in cm "1 : 3350, 2970, 1595, 1585, 1550 ~Α NMR (CDCl j ) in ppm: 8.51 (IH, m) , 7.35 (3H, m) , 7.08 (IH, s) , 6.83 (IH, s) , 5.77 (IH, s) , 4.12 (IH, d, J = 11 Hz), 3.83 (IH, d, J = 11 Hz), 2.34 (IH, d, J = 13.5 Hz), 1.70 (IH, d, J = 13.5 Hz), 1.06 (3H, s) , 0.88 (3H, s) . 7,9-Dichloro-3,3-dimethyl-5- (2-pyridyl) -2,3,4,5-tetra- hydro-1-benzoxepin-5-ol C 17 H 17 C1 2 N0 2 MM = 338.233 Formula 16 [chromatography with silica gel and dichloromethane; 83 %] IR in cm '1 : 3300, 2950, 1590, 1570, 1560 X H NMR (CDC1 3 ) in ppm: 8.52 (IH, m) , 7.25 (5H, m) , 5.70 (IH, s) , 4.00 (2H, s), 2.39 (IH, d, J = 14 Hz), 1.76 (IH, d, J = 14 Hz), 1.05 (3H, s) , 0.86 (3H, s) . 8, 9-Dichloro-3, 3 -dimethyl-5- (2 -pyridyl) -2, 3,4, 5 -tetra¬ hydro- 1 -benzoxepin- 5 -ol C 17 H 17 C1 2 N0 2 MM = 338.233 Formula 17 [yellow oil; 37 %] IR in cm '1 : 3300, 2960, 1595, 1585, 1560 'R NMR (CDC1 3 ) in ppm: 8.52 (IH, m) , 7.15 (5H, m) , 5.76 (IH, s) , 4.07 (2H, s) , 2.37 (IH, d, J = 13.5 Hz), 1.72 (IH, d, J = 13.5 Hz), 1.10 (3H, s) , 0.90 (3H, s) . 7,8-Difluoro-3,3-dimethyl-5- (2-pyridyl) -2,3,4, 5-tetra- hydro-1 -benzoxepin- 5 -ol C 17 H 17 F 2 N0 2 MM = 305.324 Formula 18 [M.p. = 93 °C; crystallizes from pentane; 61 %] IR in cm "1 : 3320, 2990, 1600, 1575, 1505 2 H NMR (CDC1 3 ) in ppm: 8.52 (IH, ) , 7.61 (IH, m) , 6.84 (4H, m) , 5.71 (IH, s) , 4.08 (IH, d, J = 11 Hz), 3.83 (IH, d, J = 11 Hz), 2.35 (IH, d, J = 13.5 Hz), 1.70 (IH, d, J = 13.5 Hz), 1.06 (3H, s) , 0.87 (3H, s) . 8 -Chloro-7 - fluoro-3 , 3 -dimethyl-5- (2-pyridyl) - 2 , 3 , 4 , 5- tetrahydro-l-benzoxepin-5-ol C 17 H 17 C1FN0 2 MM = 321.778 Formula 19 tM.p. = 100°C; hexane; 77 %] IR in cm" 1 : 3310, 2965, 1595, 1585, 1485 X H NMR (CDC1 3 ) in ppm: 8.55 (IH, m) , 7.61 (IH, m) , 7.10 (3H, m), 6.63 (IH, d) , 5.70 (IH, s) , 4.08 (IH, d, J = 6 Hz) , 3.83 (IH, d, J = 6 Hz) , 2.40 (IH, d, J = 13.5 Hz), 1.75 (IH, d, J = 13.5 Hz), 1.08 (3H, s) , 0.86 (3H, s) . 9 -Ethyl -7 -fluoro-3 , 3 -dimethyl- 5 - (2 -pyridyl) - 2,3,4,5-tetrahydro-l-benzoxepin-5-ol C 19 H 22 FN0 2 MM = 315.387 Formula 20 [M.p. = 100°C; crystallizes from pentane; 68 %] IR in cm "1 : 3260, 2965, 1590 'E NMR (CDC1 3 ) in ppm: 8.53 (IH, ) , 7.04 (5H, m) , 5.45 (IH, s), 3.85 (2H, s) , 2.70 (2H, q) , 2.40 (IH, d, J = 13.5 Hz), 1.75 (IH, d, J = 13.5 Hz), 1.19 (3H, t) , 1.02 (3H, s) , 0.78 (3H, s) . 7,8-Dimethoxy-3,3-dimethyl-5- (2-pyridyl) -2,3,4,5-tetra- hydro-l-benzoxepin-5 -ol C 19 H 23 N0 4 MM = 329.395 Formula 21 [chromatography with silica gel and dichloromethane/ methanol: 98/2; M.p. = 90°C; crystallization from heptane; 63 %] IR in cm' 1 : 3370, 2950, 1610, 1590, 1505 X H NMR (CDC1 3 ) in ppm: 8.52 (IH, ) , 7.56 (IH, m) , 7.06 (3H, m) , 6.54 (IH, s) , 6.31 (IH, s) , 5.50 (IH, m) , 4.08 (IH, d, J = 10 Hz), 3.81 (3H, s) , 3.80 (IH, d, J = 10 Hz), 3.55 (3H, s) , 2.38 (IH, d, J = 13 Hz), 1.73 • (IH, d, J = 13 Hz), 1.08 (3H, s) , 0.85 (3H, s) . 7-Brαmo-3,3,8-tr_bnethyl-5-(2-ρyridyl)-2,3,4,5-tetrahydro- 1-benzoxepin-5-ol C 18 H 20 BrNO 2 MM = 362.266 Formula 22 [chromatography with silica gel and dichloromethane; M.p. = 147°C; crystallizes from hexane; 63 %] IR in cm "1 : 3360, 2970, 1595, 1570, 1540 X E NMR (CDC1 3 ) in ppm: 8.54 (IH, m) , 7.60 (IH, m) , 7.05 (4H, m) , 5.70 (IH, m) , 4.10 (IH, d, J = 11 Hz), 3.81 (IH, d, 11 Hz), 2.35 (IH, d, J -> 13.5 Hz), 2.27 (3H, s) , 1.69 (IH, d, J = 13.5 Hz), 1.07 (3H, s) , 0.88 (3H, s) . 8-Bromo-3,3,7-trimethyl-5- (2-pyridyl)-2,3,4,5-tetrahydro- 1-benzoxepin-5-ol C 18 H 20 BrNO 2 MM = 362.266 Formula 23 [chromatography with silica gel and dichloromethane; m.p. = 129°C; crystallizes from hexane; 70 %] IR in cm' 1 : 3320, 2950, 1595, 1560 *H NMR (CDC1 3 ) in ppm: 8.52 (IH, m) , 7.55 (IH, ) , 7.14 (IH, s), 7.04 (2H, m) , 6.62 (IH, s) , 5.64 (IH, s) , 4.05 (IH, d, J = 11 Hz), 3.80 (IH, d, J = 11 Hz), 2.32 (IH, d, J = 13.5 Hz), 2.11 (3H, s) , 1.67 (IH, d, J = 13.5 Hz), 1.05 (3H, s), 0.66 (3H, s) . 3 , 3 -Dimethyl-5- (2 -pyridyl) -2 , 3 , 4 , 5 , 7 , 8 , 9 , 10-octahydro- 1 -naphth [2 , 3 -b] oxepin- 5 - ol C 21 H 25 N0 2 MM = 323 .434 Formula 24 [chromatography with silica gel and dichloromethane; M.p. = 134°C; 67 %] IR in cm "1 : 3330, 3060, 2930, 1620, 1595, 1570, 1500 X H NMR (CDCl j ) in ppm: 8.50 (IH, m) , 7.54 (IH, m) , 7.08 (2H, ), 6.66 (IH, s) , 6.50 (IH, s) , 5.50 (IH, s) , 4.02 (IH, d, J β 10.5 Hz), 3.77 (IH, d, J = 10.5 Hz), 2.56 (4H, m), 2.36 (IH, d, J = 13.5 Hz), 1.74 (5H, m) , 1.05 (3H, s), 0.83 (3H, s) . 3,3 -Dimethyl - 5 - (2 -pyridyl) -7 - rifluorome hyl - 2,3 , 4, 5-tetrahydro-l-benzoxepin-5-ol C -„lβ,H" 1 18 P F* 3,N' 0, MM = 337.341 Formula 25 [chromatography with silica gel and dichloromethane; M.p. = 116°C; crystallization from iβooctane; 29 %] IR in cm" 1 : 3330, 2970, 1625, 1600, 1580, 1505 α H NMR (CDCl j ) in ppm: 8.50 (IH, dd, J = 4.5 Hz), 7.25 (6H, m), 5.90 (IH, s) , 4.22 (IH, d, J -= 11 Hz), 3.90 (IH, d, J = 11 Hz), 2.35 (IH, d, J = 13.5 Hz), 1.72 (IH, d, J = 13.5 Hz), 1.10 (3H, s) , 0.92 (3H, s) . 3 , 3 -Dimethyl -5- (2 -pyridyl) - 8 - trif luorome thyl - 2,3 , 4, 5 -tetrahydro -1 -benzoxepin- 5- ol C 18 H 18 F 3 N0 2 MM = 337.341 Formula 26 [chromatography with silica gel and dichloromethane; M.p. = 78°C; 31 %] IR in cm "1 : 3330, 2970, 1595, 1575, 1500 l H NMR (CDC1 3 ) in ppm: 8.55 (IH, dd, J = 4.5 Hz), 7.25 (6H, m) , 5.94 (IH, s), 4.22 (IH, d, J = 11 Hz), 3.90 (IH, d, J = 11 Hz), 2.40 (IH, d, J = 14 Hz), 1.72 (IH, d, J = 14 Hz), 1.12 (3H, s) , 0.95 (3H, s) . 3,3 -Dimethyl-5- (2 -pyridyl) -7 -pentafluoroethyl- 2,3,4,5-tetrahydro-l-benzoxepin-5-ol C 19 H 18 F 5 N0 2 MM = 387 . 349 Formula 27 [chromatography with silica gel and dichloromethane; 42 %] IR in cm" 1 : 3330, 2950, 1620, 1595, 1575, 1500 *H NMR (CDC1 3 ) in ppm: 8.55 (IH, dd, J = 4.5 Hz), 7.28 (6H, m) , 6.00 (IH, s) , 4.33 (IH, d, J = 11 Hz), 3.94 (IH, d, J = 11 Hz), 2.38 (IH, d, J = 14 Hz), 1.75 (IH, d, J = 14 Hz ) , 1 . 15 (3H, s) , 0 .97 (3H, s) . 8-Bromo-3 , 3 -di__αethyl-l- (2-pyridyl) -2 , 3 , 4, 5-tetrahydro- lH-benzo [f ] cyclohepten-1-ol C 18 H 20 BrNO MM = 346 . 266 Formula 28 [chromatography with silica gel and dichloromethane; oil; 78 %] IR in cm "1 : 3340, 2960, 1590, 1570 'E NMR (CDC1 3 ) in ppm: 8.50 (IH, m) , 7.54 (IH, m) , 7.04 (5H, m) , 5.39 (IH, s) , 2.90 (2H, m) , 2.32 (IH, d, J = 14 Hz), 1.77 (IH, d, J = 14 Hz), 1.70 (2H, m) , 1.02 (6H, m) . 7-Bromo-3,3-dimethyl-5- (3-pyridyl) -2,3,4,5-tetrahydro- 1-benzoxepin-5-ol C 17 H 18 BrN0 2 MM = 348.234 Formula 29 By using the same process as above and the use of 3-bromopyridine replacing 2-bromopyridine. [M.p. = 170°C; ethyl acetate; 46 %] IR in cm -1 : 3120, 2950, 1585, 1475 'H NMR (CDC1 3 ) in ppm: 8.37 (2H, m) , 7.14 (4H, m) , 6.88 (IH, d, J - 9 Hz), 3.76 (2H, s) , 3.74 (IH, m) , 2.35 (IH, d, J = 13.5 Hz), 2.00 (IH, d, J -. 13.5 Hz), 1.01 (3H, s) , 0.62 (3H, s) . 7,8-Dichloro-3,3-dimethyl-5- (3-pyridyl) -2,3,4, 5-tetra- hydro-1-benz oxepin- 5 -ol C 17 H 17 C1 2 N0 2 MM = 338.233 Formula 30 [M.p. = 166°C; crystallization from heptane; 44 %] IR in cm "1 : 3100, 2930, 1595, 1585 *H NMR (CDC1 3 ) in ppm: 8.41 (2H, m) , 7.34 (4H, m) , 3.76 (3H, s) , 2.35 (IH, d, J -. 13.5 Hz); 2.00 (IH, d, J = 13.5 Hz), 1.00 (3H, s) , 0.61 (3H, s) . Example 2 7-Bromo-5-methoxy-3,3-dimethyl-5- (2-pyridyl) -1-benzoxe- pine C 18 H 20 BrNO 2 MM = 362.265 Formula 31 A solution of 7-bromo-3,3-dimethyl-5- (2-pyridyl) - l-benzoxepin-5-ol (5 g, 0.014 mol) in anhydrous DMF (50 ml) is added dropwise to a suspension of sodium hydride (50 % dispersed in oil, 0.8 g, 0.0168 mol) in anhydrous DMF (25 ml), the temperature rises to 88°C, stirring is continued for 1 hour and the reaction mixture is maintained at 80°C. A solution of methyl iodide (1.9 g, 0.014 mol) in anhydrous DMF (10 ml) is then added dropwise at 25°C. The whole mixture is stirred for 16 hours at 25°C and then hydrolysed with 600 ml of ice-cold water. The paste obtained is dissolved in dichloromethane (250 ml) . The organic phase is washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. [pasty product; 5 g; 98 %] IR in cm -1 : 2960, 1590, 1565 'X NMR (CDC1 3 ) in ppm: 8.55 (IH, dd, J = 4.5 Hz), 7.33 (6H, m) , 3.91 (IH, s) , 3.88 (IH, s) , 3.16 (3H, s) , 2.26 (2H, s), 1.11 (3H, s) , 0.43 (3H, s) . Example No. 3 7-Bromo-3,3-dimethyl-5- (2-pyridyl) -2,3,4,5-tetrahydro- 1-benzoxepin-5-yl acetate C 19 H 20 BrN0 3 MM = 390.276 Formula 32 A solution of 7-bromo-3,3-dimethyl-5- (2-pyridyl) - l-benzoxepin-5-ol (5 g, 0.014 mol) in anhydrous DMF (50 ml) is added dropwise at 60°C to a suspension of sodium hydride (50 % dispersed in oil, 0.8 g, 0.0168 mol) in anhydrous DMF (25 ml) . The suspension is stirred for 1 hour at 60°C and then cooled. Acetyl chloride (1 g, 0.014 mol) is added dropwise at 25°C and the stirring is continued at 25°C for 16 hours. The whole mixture is then hydrolysed in 600 ml of ice-cold water. The beige paste obtained is dissolved in 200 ml of dichloromethane. The organic phase is washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The oil obtained is purified by chromatography with silica gel and dichloromethane/methanol: 98/2. [M.p. = 140°C; hexane; 22 %] IR in cm' 1 : 2950, 1745, 1590, 1570, 1485 X Ε. NMR (CDC1 3 ) in ppm: 8.50 (IH, dd, J = 4.5 Hz), 7.25 (6H, m) , 3.78 (2H, s) , 2.95 (IH, d, J = 13.5 Hz), 2.38 (IH, d, J = 13.5 Hz), 2.07 (3H, s) , 1.05 (3H, s) , 0.37 (3H, s) . Example No. 4 7-Brαmo-3,3-dimethyl-5-(2-pyridyl N-oxide) -2,3,4,5-tetra¬ hydro-1-benzoxepin-5-ol C 17 H 18 BrN0 3 MM = 364.238 Formula 33 A solution of 7-bromo-3,3-dimethyl-5- (2-pyridyl) - 2,3,4,5-tetrahydro-l-benzoxepin-5-ol (3.5 g, 0.01 mol) and of 3-chloroperbenzoic acid (2.8 g, 0.016 mol) in dichloromethane (50 ml) is stirred for 16 hours at 25°C. The precipitate formed is filtered. The filtrate is washed with a 5 % sodium bisulfite solution, then with a 5% sodium bicarbonate solution and with water. The organic phase is dried over anhydrous sodium sulfate and concentrated under reduced pressure (thick yellow oil) . The product is recrystallized from hexane (2.6 g) . [M.p. = 139-140°C; hexane] IR in cm" 1 : 3240, 3050, 2950, 1480 'R NMR (CDC1 3 ) in ppm: 8.18 (IH, m) , 7.88 (IH, d) , 7.13 (5H, m) , 6.03 (IH, m) , 3.81 (IH, m) , 3.49 (IH, m) , 3.31 (IH, m) , 1.94 (IH, d, J = 13.5 Hz), 0.86 (3H, s) , 0.51 (3H, s). Elemental analysis C H Br N 0 % Found 56.07 5.02 3.73 13.42 % Calculated 56.05 4.98 21.94 3.85 13.18 By using the same process, the following com- pounds are prepared. 7-Chloro-3, 3 -dimethyl-5- (2 -pyridyl N-oxide) - 2 , 3 , 4 , 5- tetrahydro -1 -benzoxepin- 5 -ol C 17 H 18 C1N0 3 MM -. 319.787 Formula 34 [M.p. = 138-140°C; ethyl acetate; 34 %] IR in cm "1 : 3250, 3070, 2950, 1480 X H NMR (CDCl j ) in ppm: 8.23 (IH, m) , 7.77 (IH, d) , 7.11 (5H, ) , 6.05 (IH, m) , 3.82 (IH, m) , 3.50 (IH, ) , 3.32 (IH, m) , 1.93 (IH, d, J = 14 Hz), 0.85 (3H, s) , 0.56 (3H, s) . Elemental analysis C H Cl N O % Found 63.58 5.71 11.04 4.47 % Calculated 63.85 5.67 11.09 4.38 15.01 7-Fluoro-3, 3 -dimethyl-5- (2-pyridyl N-oxide) - 2,3,4,5-tetrahydro-l-benzoxepin-5-ol C 17 H 18 FN0 3 MM = 303.332 Formula 35 [M.p. = 110-112°C; hexane; 78 %] IR in cm "1 : 3390, 3110, 2950, 1485 X H NMR (CDC1 3 ) in ppm: 8.19 (IH, m) , 7.30 (7H, m) , 3.80 (IH, m) , 3.48 (IH, m) , 3.34 (IH, m) , 1.93 (IH, d, J = 14 Hz) , 0.85 (6H, s) . Elemental analysis C % Found 67 . 14 % Calculated 67 .31 15.82 3 , 3 -Dimethyl - 5 - ( 2 -py idyl N-oxide) -2,3,4,5-tetrahydro- 1 -benzoxepin- 5 -ol C 17 H 19 N0 3 MM = 285.342 Formula 36 [chromatography with silica gel and ethyl acetate/ chloroform/methanol; 60/30/10; M.p. = 127-128°C; cyclo- hexane; 41 %] IR in cm "1 : 3180, 3070, 2950, 1605, 1575, 1480 'K NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.75 (IH, ) , 7.05 (6H, m), 3.81 (IH, m) , 3.52 (IH, m) , 3.32 (IH, m) , 1.97 (IH, d, J = 14 Hz), 0.88 (3H, s) , 0.60 (3H, s) . Elemental analysis C H N 0 % Found 71.58 6.88 4.85 .% Calculated 71.56 6.71 4.91 16.82 7-Ethyl-3,3-diιaethyl-5-(2-pyridyl N-oxide)-2,3,4,5- etra¬ hydro-1-benzoxepi -5-ol C 19 H 23 N0 3 MM = 313.396 Formula 37 [chromatography with silica gel and dichloromethane/ methanol; 98/2; M.p. = 123-125°C; diisopropyl ether; 23 %] IR in cm' 1 : 3230, 3050, 2950, 1615, 1580, 1500 X H NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.60 (IH, m) , 7.11 (5H, m) , 6.50 (IH, m) , 3.80 (IH, m) , 3.50 (IH, ) , 3.30 (IH, m) , 2.64 (2H, q) , 1.93 (IH, d, J = 13.5 Hz), 1.21 (3H, t) , 0.83 (3H, s), 0.54 (3H, s) . Elemental analysis C H N 0 % Found 73.03 7.49 4.57 % Calculated 72.82 7.40 4.47 15.32 3,3-Dimethyl-7- (1-methylpropyl) -5- (2-pyridyl N-oxide) - 2 , 3 , 4, 5- tetrahydro-l-benzoxepin-5-ol C 21 H 27 N0 3 MM -. 341.449 Formula 38 [chromatography with silica gel and dichloromethane; M.p. = 131-133°C; diisopropyl ether; 39 %] IR in cm '1 : 3150, 2960, 1610, 1495 ~1 ~ NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.20 (7H, m) , 3.77 (IH, d, J - 11 Hz), 3.48 (IH, d, J = 11 Hz), 3.28 (IH, d, J -= 14 Hz), 2.58 (IH, q) , 1.92 (IH, d, J = 14 Hz), 1.10 (14H, m) . Elemental analysis C H N 0 % Found 73.66 7.97 4.39 % Calculated 73.87 7.97 4.10 14.06 7-Methoxy-3, 3 -dimethyl-5- (2-pyridyl N-oxide) - 2,3,4,5-tetrahydro-l-benzoxepin-5-ol C 18 H 21 N0 4 MM = 315.368 Formula 39 [chromatography with silica gel and dichloromethane/ methanol; 98/2; M.p. = 109-110°C; isooctane] IR in cm "1 : 3200, 3080, 2950, 1605, 1495 X H NMR (CDC1 3 ) in ppm: 8.19 (IH, m) , 7.15 (7H, m) , 3.74 (3H, s), 3.58 (3H, m) , 1.90 (IH, d, J = 13.5 Hz), 0.82 (3H, s), 0.55 (3H, s) . Elemental analysis C H N 0 % Found 68.52 6.55 4.48 % Calculated 68.55 6.71 4.44 20.29 3,3-Dimethyl-5- (2-pyridyl N-oxide) -7-trifluoromethoxy- 2,3,4,5-tetrahydro-l-benzoxepin-5-ol C 18 H 18 F 3 N0 4 MM = 370.348 Formula 40 [chromatography with silica gel and dichloromethane; M.p. = 114-116°C; heptane; 50 %] IR in cm' 1 : 3400, 3130, 3060, 2970, 1490 ~E NMR (CDC1 3 ) in ppm: 8.21 (IH, m) , 7.64 (IH, m) , 7.01 (6H, m), 3.80 (IH, d, J = 11 Hz), 3.49 (IH, d, J = 11 Hz), 3.30 (IH, d, J = 14 Hz), 1.91 (IH, d, J = 14 Hz), 0.84 (3H, s) , 0.52 (3H, s) . Elemental analysis C H F N O % Found 58.33 4.95 15.31 3.86 % Calculated 58.53 4.91 15.43 3.79 17.33 3, 3 -Dimethyl -7 -phenyl- 5- (2 -pyridyl N-oxide) - 2,3,4, 5- tetrahydro-l-benzoxepin-5-ol C 23 H 23 N0 3 MM = 361.440 Formula 41 [chromatography with silica gel and methanol; M.p. = 175 °C; diisopropyl ether/ethyl acetate; 50/50; 25 %] IR in cm "1 : 3200, 2960, 1610 X H NMR (CDC1 3 ) in ppm: 8.14 (2H, m) , 7-27 (10H, m) , 3.85 (IH, d, J = 11 Hz), 3.55 (IH, d, J = 11 Hz), 3.34 (IH, d, J = 14 Hz), 2.02 (IH, d, J = 14 Hz), 0.90 (3H, s) , 0.60 (3H, s) . Elemental analysis C H N O % Found 76.57 6.37 3.90 % Calculated 76.43 6.41 3.88 13.28 7-Brαmo-3,3-diπιethyl-5- (2-pyridyl N-oxide) -2 , 3 , 4, 5- tetra¬ hydro- 1 -benzoxepin- 5 -ol C 17 H 18 BrN0 3 MM = 364.238 [M.p. = 137-138°C; ethyl acetate; 20 %] IR in cm '1 : 3090, 2950, 1590, 1560, 1475 *H NMR (CDC1 3 ) in ppm: 8.20 (IH, ) , 7.65 (IH, m) , 7.62 (IH, d, J = 8 Hz), 7.03 (5H, m) , 3.81 (IH, d, J = 11 Hz), 3.50 (IH, d, J = 11 Hz), 3.29 (IH, d, J = 14 Hz), 1.92 (IH, d, J = 14 Hz), 0.88 (3H, s) , 0.53 (3H, s) . 6, 8 -Dichloro-3, 3 -dimethyl-5- (2-pyridyl N-oxide) - 2 , 3 , 4 , 5- etrahydro-l-benzoxepin-5-ol C 17 H 17 C1 2 N0 3 MM = 354.232 Formula 43 [M.p. = 220°C; ethyl acetate; 35 %] IR in cm "1 : 3065, 2970, 1585, 1550 X H NMR (CDC1 3 ) in ppm: 8.15 (IH, m) 6.92 (5H, m) , 4.00 (2H, s) , 2.18 (2H, s) , 1.28 (3H, s) 1.00 (3H, s) . Elemental analysis C H Cl N O % Found 57.54 4.84 20.23 4.04 % Calculated 57.64 4.84 20.02 3.95 13.55 7, 8-Dichloro-3,3-dimethyl-5- (2 -pyridyl N-oxide) - 2,3 , , 5-tetrahydro-l-benzoxepin-5-ol C 17 H 17 C1 2 N0 3 MM = 354.232 Formula 44 [M.p. = 134-136°C; diisopropyl oxide; 18 %] IR in cm "1 : 3250, 3050, 2970, 1480 -E NMR (CDC1 3 ) in ppm: 8.21 (IH, m) , 7.85 (IH, s) , 7.08 (5H, m) , 3.80 (IH, d, J = 11 Hz), 3.38 (2H, ) , 1.90 (IH, d, J = 14 Hz), 0.88 (3H, s) , 0.55 (3H, s) . Elemental analysis C H Cl N 0 % Found 57.80 4.70 19.73 4.02 % Calculated 57.64 4.84 20.02 3.95 13.55 7,9-Dichloro-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2,3,4,5-tetrahydro-l-benzoxepin-5-ol C 17 H 17 C1 2 N0 3 MM = 354.232 Formula 45 [M.p. = 150.5°C; diisopropyl ether; 33 %] IR in cm "1 : 3230, 3070, 2970, 1570 • E NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.70 (IH, m) , 7.09 (4H, m), 3.89 (IH, dd, J = 1.5 Hz, J = 11 Hz), 3.40 (IH, d, J = 11 Hz), 3.31 (IH, dd, J = 1.5 Hz, J = 13.5 Hz), 1.82 (IH, d, J = 13.5 Hz), 0.81 (3H, s) , 0.59 (3H, s) . Elemental analysis C H Cl N O % Found 57.38 4.89 20,02 3.99 % Calculated 57.64 4.84 20.02 3.95 13.55 8-Chloro-7-fluoro-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2,3,4,5-tetrahydro-1-benzoxepin-5-ol C 17 H 17 C1FN0 3 MM = 337.777 Formula 46 [M.p. = 121-123- °C; diisopropyl oxide; 24 %] IR in cm '1 : 3290, 3070, 1485 • E NMR (CDC1 3 ) in ppm: 8.23 (IH, ) , 7.87 (IH, s) , 7.60 (IH, d), 7.08 (4H, m) , 3.58 (3H, ) , 1.90 (IH, d, J = 14 Hz), 0.84 (3H, s) , 0.55 (3H, s) . Elemental analysis C H Cl F N 0 % Found 60.44 5.30 10.56 5.69 4.16 % Calculated 60.45 5.07 10.50 5.63 4.15 14.21 7, 8-Dimethoxy-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2,3,4,5-tetrahydro-l-benzoxepin-5-ol C 19 H 23 N0 5 MM = 345.394 Formula 47 [chromatography with silica gel and dichloromethane/ methanol; 98/2; M.p. = 174°C; ethyl acetate] IR in cm "1 : 3220, 3090, 2970, 1615, 1510 'E NMR (CDC1 3 ) in ppm: 8.22 (IH, m) , 7.18 (4H, m) , 6.62 (IH, s) , 3.87 (3H, s) , 3.80 (3H, s) , 3.76 (IH, d, • J = 10 Hz), 3.50 (IH, d, J = 10 Hz), 3.29 (IH, d, J = 13 Hz), 1.92 (IH, d, J = 13 Hz), 0.87 (3H, s) , 0.55 (3H, s) . Elemental analysis C H N O % Found 66.35 6.87 4.20 % Calculated 66.07 6.71 4.06 23.16 3,3-Dimethyl-5- (2-pyridyl N-oxide) -7-trifluoromethyl- 2,3,4,5- etrahydro-1-benzoxepin-5-ol C 18 H 18 F 3 N0 3 MM = 353.340 Formula 48 [M.p. = 106-107°C; hexane; 76 %] IR in cm "1 : 3400, 3110, 2950, 1615, 1590, 1500, 1480 'E NMR (CDC1 3 ) in ppm: 8.05 (2H, m) , 7.13 (6H, m) , 3.80 (IH, m) , 3.50 (IH, ) , 3.29 (IH, m) , 1.95 (IH, d, J = 13.5 Hz), 0.86 (3H, s) , 0.54 (3H, s) . Elemental analysis C H F N 0 % Found 61.40 5.08 16.01 4.01 % Calculated 61.18 5.14 16.13 3.96 13.58 3,3-Dimethyl-5- (2-pyridyl N-oxide) -8-trifluoromethyl- 2,3,4,5-tetrahydro-1-benzoxepin-5-ol C 18 H 18 F 3 N0 3 MM = 353.340 Formula 49 [chromatography with silica gel and dichloromethane/ methanol; 98/2; M.p. = 102-105°C; cyclohexane; 27 %] IR in cm' 1 : 3400, 3050, 2950, 1585, 1480 'E NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.37 (7H, m) , 3.86 (IH, m) , 3.55 (IH, m) , 3.32 (IH, m) , 1.95 (IH, d, J = 14 Hz), 0.88 (3H, s) , 0.56 (3H, s) . 7 -Broaao-5 -me thoxy-3, 3 -dimethyl-5- (2-pyridyl N-oxide) - 2,3,4,5- tetrahydro- 1 -benzoxepine C 18 H 20 BrNO 3 MM = 378.265 Formula 50 [M.p. = 178-180°C; ethyl acetate; 33 %] IR in cm '1 : 2960, 1595, 1560, 1480 X H NMR (CDC1 3 ) in ppm: 8.06 (IH, m) , 7.14 (6H, m) , 3.98 (IH, d, J = 11 Hz), 3.70 (IH, d, J = 11 Hz), 3.33 (IH, d, J = 14 Hz), 3.05 (3H, s) , 1.61 (IH, d, J = 14 Hz), 1.11 (3H, s) , 0.95 (3H, s) . Elemental analysis C H Br N 0 % Found 56.96 5.50 21.10 3.58 % Calculated 57.15 5.33 21.13 3.70 12.69 Example No. 5 7-Brαmo-3, 3 -dimethyl-5- (2-pyridyl N-oxide) -2,3,4,5-tetra- hydro -1 -benzoxepin- 5 -yl acetate C 19 H 20 BrNO 4 MM = 406.275 Formula 51 [M.p. = 145-147 °C; isooctane/ ethyl acetate: 80 - 2fJ7 IR in cm '1 : 2950, 1730, 1605, 1480 *H NMR (CDC1 3 ) in ppm: 8.05 (IH, m) , 7.17 (6H, m) , 3.58 (3H, m) , 2.19 (3H, s) , 2.07 (IH, d, J = 14 Hz), 0.93 (3H, s), 0.60 (3H, s) . Elemental analysis C H Br N 0 % Found 56.20 5.05 19.75 3.40 % Calculated 56.17 4.96 19.67 3.45 15.75 7-Brαmo-4,5-epoxy-3,3-di__αethyl-5- (2-pyridyl N-oxide) - 2,3-dihydro-1-benzoxepine C 17 H 16 BrN0 3 MM = 362.222 Formula 52 [chromatography with silica gel and ethyl acetate; M.p. = 186-187°C; ethanol; 20 %] IR in cm "1 : 3060, 2970, 1560, 1480 ~E NMR (CDC1 3 ) in ppm: 8.05 (IH, m) , 7.22 (6H, ) , 3.75 (2H, s) , 2.98 (IH, s) , 1.46 (3H, s) , 1.17 (3H, s) . Elemental analysis C H Br N O % Found 56.14 4.51 22.27 3.76 13.07 % Calculated 56.37 4.45 22.06 3.87 13.26 7-Brαmo-3,3-diπiftthyl-5- (3-pyridyl N-oxide)-2,3,4,5-tetra¬ hydro-1-benzoxepin-5-ol C 17 H 18 BrN0 3 MM - 364.233 [M.p. = 200 C C; ethanol; 38 %] IR in cm' 1 : 3180, 2950, 1595, 1560, 1485 X H NMR (DMSO) in ppm: 8.07 (2H, m) , 7.14 (5H, m) , 6.31 (IH, s) , 3.78 (2H, s) , 2.30 (IH, d, J = 13.5 Hz), 1.88 (IH, d, J = 13 Hz), 0.94 (3H, s) , 0.69 (3H, s) . Elemental analysis C H Br N 0 % Found 56.03 5.03 21.71 3.85 % Calculated 56.05 4.98 21.94 3.85 13.18 7,8-Dichloro-3,3-dimethyl-5- (3-pyridyl N-oxide) - 2,3,4,5-tetrahydro-l-benzoxepin-5-ol C 17 H 17 C1 2 N0 3 MM s 354.232 Formula 54 [M.p. = 226-228°C; isopropanol; 23 %] IR in cm '1 : 3160, 2950, 1590 • E NMR (DMSO) in ppm: 8.05 (2H, m) , 7.17 (4H, m) , 6.32 (IH, s) , 3.81 (2H, s), 2.30 (IH, d, J = 14 Hz), 1.86 (IH, d, J ■ 14 Hz), 0.96 (3H, s) , 0.71 (3H, s) . Elemental analysis C H Cl N 0 % Found 57.75 5.12 19.84 4.06 % Calculated 57.64 4.84 20.02 3.95 13.55 Example No. 6 7-Brσmo-3,3-dimethyl-5- (2-pyridyl)-2,3-dihydro-l-benzoxe- pine C 17 H 16 BrNO MM = 330 .224 Formula 55 A solution of 7 -bromo- 3 , 3 -dimethyl - 5- (2 -pyridyl) - 2 , 3 , 4 , 5- tetrahydro-l-benzoxepin-5-ol (13 . 9 g, 0 . 04 mol) and of concentrated sulfuric acid (3.3 ml of commercial solution) in benzene (170 ml) is heated for 3 hours at boiling with removal of water. The solution is washed, at 25°C, with a 1 % sodium hydroxide solution and then with water. The organic phase is dried over anhydrous sodium sulfate and concentrated Tinder reduced pressure. [13.2 g; M.p. = 113-114°C; hexane; 70 %] IR in cm "1 : 2950, 1580, 1560, 1480 'E NMR (CDC1 3 ) in ppm: 8.62 (IH, m) , 7.30 (6H, m) , 5.90 (IH, s) , 3.93 (2H, s) , 1.20 (6H, s) . Elemental analysis C H Br N 0 % Found 61.61 4.96 24.03 4.31 % Calculated 61.83 4.88 24.20 4.24 4.85 By using the same process, the following com- pounds are prepared. 7-Chloro-3,3-dimethyl-5- (2-pyridyl) -2 , 3-dihydro- 1-benzoxepine C 17 H 16 C1N0 MM = 285 .773 Formula 56 [M.p. = 100°C; hexane; 79 %] IR in cm "1 : 2960, 1585, 1565, 1490 Η NMR (CDC1 3 ) in ppm: 8.62 (IH, m) , 7.28 (6H, m) , 5.92 (IH, s), 3.91 (2H, s), 1.15 (6H, s) . 7-Fluoro-3,3-dimethyl-5- (2-pyridyl) -2,3-dihydro- 1-benzoxepine C 17 H lβ FN0 MM = 269.318 Formula 57 [thick yellow oil; 38 %] IR in cm '1 : 2970, 1590, 1565, 1495 Η NMR (CDC1 3 ) in ppm: 8.55 (IH, m) , 7.02 (6H, m) , 5.89 (IH, s) , 3.90 (2H, s), 1.16 (6H, s) . 3, 3 -Dimethyl-5- (2 -pyridyl) -2,3-dihydro-l-benzoxepine C 17 H 17 NO MM = 251.327 Formula 58 [oil; 98 %] IR in cm "1 : 2960, 1590, 1565, 1495 NMR (CDC1 3 ) in ppm: 8.56 (IH, m) , 7.20 (7H, m) , 5.83 (IH, s), 3.94 (2H, s) , 1.18 (6H, s) . 3,3,7-Trimethyl-5- (2-pyridyl) -2, 3- dihydro -1 -benzoxepine C 18 H 19 NO MM = 265.354 Formula 59 [oil; 98 %] IR in cm '1 : 2960, 1590, 1565, 1500 -E NMR (CDC1 3 ) in ppm: 8.58 (IH, m) , 7.10 (6H, m) , 5.83 (IH, s), 3.91 (2H, s), 2.10 (3H, s) , 1.18 (6H, s) . 7-Ethyl-3,3-dimethyl-5- (2-pyridyl)-2,3-dihydro-l-benzoxe- pine C 19 H 21 NO MM = 279.381 Formula 60 [yellow oil; 97 %] IR in cm" 1 : 2960, 1590, 1565, 1500 'E NMR (CDC1 3 ) in ppm: 8.58 (IH, m) , 7.14 (6H, m) , 5.84 (IH, s) , 3.91 (2H, s), 2.40 (2H, q) , 1.16 (6H, s) , 1.03 (3H, t) . 7-Isopropyl-3 , 3-dimethyl-5- (2-pyridyl) -2 , 3-dihydro- 1 -benzoxepine C 20 H 23 NO MM = 293.408 Formula 61 [yellow oil; 98 %] IR in cm" 1 : 2960, 1585, 1495 l H NMR (CDC1 3 ) in ppm: 8.59 (IH, m) , 7.64 (IH, m) , 6.90 (5H, m) , 5.84 (IH, s) , 3.91 (2H, s) , 2.68 (IH, m) , 1.10 (12H, m) . 3,3 -Dimethyl -7 - (1 -methylpropyl) - 5- (2 -pyridyl) - 2 , 3 -dihydro -1 -benzoxepine C 21 H 25 NO MM = 307.435 Formula 62 [yellow oil; 77 %] IR in cm "1 : 2965, 1585, 1565, 1500 NMR (CDC1 3 ) in ppm: 8.59 (IH, m) , 7.29 (5H, m) , 6.54 (IH, s), 5.86 (IH, s) , 3.92 (2H, s) , 2.31 (IH, m) , 1.09 (14H, m) . 7-Methoxy-3,3-dimethyl-5- (2 -pyridyl) -2 , 3 -dihydro- 1-benzoxepine C 18 H 19 N0 2 MM = 281.353 Formula 63 [M.p. = 80°C; 78 %] IR in cm '1 : 2960, 1585, 1565, 1495 NMR (CDC1 3 ) in ppm: 8.54 (IH, m) , 7.00 (6H, m) , 5.85 (IH, s) , 3.88 (2H, s) , 3.50 (3H, s) , 1.03 (6H, s) . 3,3 -Dimethyl - 5 - (2 -pyridyl) -7-trifluoromethoxy- 2,3 - dihydro- 1 -benzoxepine C 18 H 16 F 3 N0 2 MM = 335.325 Formula 64 [M.p. = 112 °C; cyclohexane; 85 %] IR in cm "1 : 3070, 3045, 2960, 1585, 1560 NMR (CDC1 3 ) in ppm: 8.59 (IH, m) , 7.66 (IH, m) , 7.13 (4H, m), 6.59 (IH, s) , 5.91 (IH, s) , 3.91 (2H, s) , 1.17 (6H, s) . 3,3-Dimethyl-7-methylthio-5- (2-pyridyl) -2, 3-dihydro- 1 -benzoxepine C 18 H 19 NOS MM = 297.420 Formula 65 [B.p.o.βMa- H g = 140-160°C; 60 %] IR in cm "1 : 2970, 2870, 1585, 1560 Η NMR (CDC1 3 ) in ppm: 8.58 (IH, m) , 7.65 (IH, m) , 6.96 (5H, ) , 5.87 (IH, s) , 3.90 (2H, s) , 2.22 (3H, s) , 1.19 (6H, s) . 3, 3-Dime hyl-7-phenyl-5- (2 -pyridyl) -2 , 3 -dihydro - 1 -benzoxepine C 23 H 21 NO MM = 327.425 Formula 66 [M.p. = 115-120°C; heptane; 42 %] IR in em "1 : 3050, 2950, 1600 NMR (CDC1 3 ) in ppm: 8.60 (IH, m) , 7.30 (11H, m) , 5.91 (IH, s) , 3.99 (2H, s) , 1.21 (6H, s) . 8-Brαmo-3,3-dimethyl-5- (2-pyxidyl) -2,3-dihydro-l-benzoxe- pine C 17 H lβ BrNO MM = 330.224 Formula 67 [yellow oil; 90 %] IR in cm "1 : 3060, 2950, 1585, 1555, 1485, 1465 NMR (CDC1 3 ) in ppm: 8.59 (IH, m) , 7.62 (IH, dd) , 7.11 (4H, m) , 6.61 (IH, d, J -= 8 Hz) , 5.90 (IH, s) , 3.95 (2H, s) , 1.18 (6H, s) . 7-Cyano-3,3-dimethyl-5- (2-pyridyl) -2,3-dihydro-l-benzoxe- pine i8 H i6 N 2 ° MM = 276.337 Formula 68 [chromatography with silica gel and cyclohexane/ chloroform/methanol; 56/33/11; M.p. = 155-157°C, ethyl acetate; 57 %] IR in cm '1 : 2960, 2220, 1590, 1570, 1495 Η NMR (CDC1 3 ) in ppm: 8.55 (IH, m) , 7.37 (6H, m) , 5.90 (IH, s) , 3.95 (2H, s) , 1.20 (6H, s) . Elemental analysis C H N 0 % Found 78.06 5.94 10.14 % Calculated 78.23 5.84 10.14 5.79 8-Cyano-3,3-dimethyl-5- (2-pyridyl) -2,3-dihydro-l-benzoxe- pine Formula 69 [chromatography with silica gel and dichloromethane; M.p. = 132°C; crystallization from heptane; 30 %] IR in cm "1 : 2950, 2210, 1585, 1565, 1540, 1500 Η NMR (CDC1 3 ) in ppm: 8.56 (IH, m) , 7.66 (IH, m) , 7.16 (4H, m) , 6.83 (IH, d, J = 8 Hz), 6.01 (IH, s) , 3.95 (2H, s), 1.19 (6H, s) . 3, 3 -Dime thyl- 5- {2-pyridyl) -7-trifluoromethyl-2,3-dihydro- 1 -benzoxepine C 18 H lβ F 3 NO MM = 319.326 Formula 70 [M.p. = 90°C; isooctane; 60 %] IR in cm "1 : 2960, 1585, 1565, 1500 3, 3 -Dime hyl-5- (2-pyridyl) - 8 - tr i f luorome thyl -2,3- dihydro - 1 -benzoxepine C 18 H 16 F 3 NO MM = 319.326 Formula 71 [oil; 85 %] IR in cm "1 : 2960, 1585, 1565, 1500 Η NMR (CDC1 3 ) in ppm: 8.60 (IH, m) , 7.34 (6H, m) , 6.00 (IH, s) , 3.98 (2H, s) , 1.19 (6H, s) . 3,3 -Dimethyl-5- (2 -pyridyl) -7 -pentaf luoroethyl - 2,3 -dihydro-1-benzoxepine C 19 H 16 F 5 NO MM = 369.334 Formula 72 [oil; 90 %] IR in cm "1 : 2960, 1590, 1565, 1500 6, 8-Dichloro-3,3-dimethyl-5- (2-pyridyl) -2, 3-dihydro- 1 -benzoxepine C 17 H 15 C1 2 N0 MM = 320.218 Formula 73 [oil] IR in cm "1 : 2960, 1585, 1545 NMR (CDC1 3 ) in ppm: 8.47 (IH, m) , 7.22 (5H, m) , 6.50 (IH, s), 4.05 (2H, s) , 1.10 (6H, s) . 7, 8-Dichloro-3,3-dimethyl-5- (2-pyridyl) -2 , 3-dihydro- 1 -benzoxepine C 17 H 15 C1 2 N0 MM = 320.218 Formula 74 [M.p. = 98°C; hexane; 81 %] IR in cm "1 : 2960, 1580, 1475 X H NMR (CDC1 3 ) in ppm: 8.58 (IH, m) , 7.40 (5H, m) , 5.88 (IH, s), 3.90 (2H, s) , 1.15 (6H, s) . 7, 9-Dichloro-3,3-dimethyl-5- (2-pyridyl) -2, 3-dihydro- 1 -benzoxepine C 17 H 15 C1 2 N0 MM = 320.218 Formula 75 [M.p. = 124°C; heptane; 66 %] IR in cm "1 : 2970, 1585, 1470 'E NMR (CDC1 3 ) in ppm: 8.59 (IH, m) , 7.45 (4H, m) , 6.62 (IH, d, J = 1.5 Hz), 5.95 (IH, s) , 4.00 (2H, s) , 1.21 (6H, s) . 8, 9-Dichloro-3,3-dimethyl-5- (2-pyridyl) -2, 3-dihydro- 1 -benzoxepine C 17 H 15 C1 2 N0 MM = 320.218 Formula 76 [M.p. = 112°C; heptane; 55 %] IR in cm" 1 : 2970, 1580, 1475 -R NMR (CDC1 3 ) in ppm: 8.62 (IH, m) , 7.67 (IH, m) , 7.15 (2H, m) , 6.92 (IH, d, J = 8 Hz) , 6.57 (IH, d, J = 8 Hz) , 5.92 (IH, s) , 4.02 (2H, s) , 1.22 (6H, s) . 7, 8-Difluoro-3,3-dimethyl-5- (2-pyridyl) -2, 3-dihydro- 1 -benzoxepine C 17 H 15 F 2 NO MM = 287.308 Formula 77 [M.p. = 86°C; crystallization from pentane; 86 %] IR in cm "1 : 3070, 2970, 1585, 1510 NMR (CDC1 3 ) in ppm: 8.58 (IH, m) , 7.68 (IH, m) , 6.85 (4H, m), 5.85 (IH, s) , 3.93 (2H, s) , 1.20 (6H, s) . 8-Cbloro-7-fluoro-3,3-di-methyl-5- (2-pyridyl) -2,3-dihydro- 1-benzoxepine C 17 H 15 C1FN0 MM = 303.763 Formula 78 [M.p.=86°C; 94 %] IR in cm "1 : 2950, 1585, 1560, 1485 'E NMR (CDC1 3 ) in ppm: 8.63 (IH, m) , 7.68 (IH, m) , 7.18 (3H, m) , 6.55 (IH, d) , 5.90 (IH, s) , 3.92 (2H, s) , 1.15 (6H, s) . 9-Ethyl-7-fluoro-3, 3 -dimethyl-5- (2-pyridyl) -2,3-dihydro- 1 -benzoxepine C 19 H 20 NFO MM = 297.372 Formula 79 [chromatography with silica gel and dichloromethane; 95 %] IR in cm '1 : 2950, 1585 l H NMR (CDC1 3 ) in ppm: 8.60 (IH, m) , 7.64 (IH, ) , 7.15 (2H, m) , 6.70 (IH, dd, J = 2 Hz, J = 8 Hz), 6.30 (IH, dd, J = 2 Hz, J = 10 Hz), 5.90 (IH, s) , 3.90 (2H, s) , 2.69 (2H, q) , 1.20 (9H, m) . 7, 8-Dimethoxy-3,3-dimethyl-5- (2-pyridyl) -2, 3 -dihydro - 1 -benzoxepine C 19 H 21 N0 3 MM = 311.380 Formula 80 [M.p. = 86°C; 57 %] IR in cm '1 : 2950, 1605, 1580, 1515 'E NMR (CDC1 3 ) in ppm: 8.61 (IH, m) 7.63 (IH, m) 7.17 (2H, m) , 6.59 (IH, s) , 6.25 (IH, s) 5.76 (IH, s) 3.92 (2H, s), 3.56 (3H, s) , 3.50 (3H, s) , 1.16 (6H, s) . 7 -Cyano- 3, 3, 8 -tr ime thyl- 5- (2 -pyridyl) -2 , 3 -dihydro - 1 -benzoxepine C 19 H 18 N 2 0 MM = 290.364 Formula 81 [chromatography with silica gel and dichloromethane; M.p. = 171°C, toluene; 32 %] IR in cm" 1 : 3060, 2970, 2220, 1610, 1585, 1560, 1495 IH NMR (CDC1 3 ) in ppm: 8.59 (IH, m) , 7.69 (IH, m) , 7.19 (2H, m) , 7.00 (IH, s) , 6.90 (IH, s) , 5.85 (IH, s) , 3.95 (2H, s), 2.41 (3H, s) , 1.19 (6H, s) . 8 -Cyano- 3, 3 , 7 - trimethyl-5- (2 -pyridyl) -2 , 3-dihydro- 1 -benzoxepine C 19 H 18 N 2 0 MM = 290.364 Formula 82 [M.p. = 136°C; hexane; 40 %] IR in cm" 1 : 3070, 2980, 2230, 1590, 1500 'E NMR (CDC1 3 ) in ppm: 8.56 (IH, m) , 7.66 (IH, m) , 7.17 (IH, s) , 7.14 (2H, m) , 6.62 (IH, s) , 5.96 (IH, s) , 3.90 (2H, s), 2.27 (3H, s) , 1.18 (6H, s) . 3 , 3 -Dimethyl - 5 - ( 2 -pyridyl) -2,3,7,8,9, 10 -hexahydro- 1-naphth [2,3 -b] oxepine C 21 H 23 NO MM = 305.419 Formula 83 [M.p. -= 75°C; crystallization from hexane; 88 %] IR in cm "1 : 2930, 1610, 1580, 1560, 1500 X H NMR (CDC1 3 ) in ppm: 8.56 (IH, m) , 7.60 (IH, m) , 7.17 (2H, m) , 6.71 (IH, s) , 6.40 (IH, s) , 5.75 (IH, s) , 3.90 (2H, s) , 2.56 (4H, ) , 1.70 (4H, m) , 1.14 (6H, s) . 8-Cyano-3,3-dimethyl-l- (2-pyridyl) -4,5-dihydro-3H-benzo- [f]cycloheptene C 1J H 18 N 2 MM = 274.365 Formula 84 [chromatography with silica gel and ethyl acetate/hexane: 25/75 mixture; M.p. = 120°C; diisopropyl ether; 31 %] IR in cm '1 : 2960, 2915, 2230, 1585, 1560 α H NMR (CDC1 3 ) in ppm: 8.55 (IH, m) , 7.62 (IH, m) , 7.20 (5H, m) , 6.30 (IH, s) , 2.80 (2H, m) , 1.88 (2H, m) , 0.95 (6Ξ, m) . 7-Brαmo-3 , 3 -dimethyl-5- (3-pyridyl) -2 , 3 -dihydro -1 -benzoxe¬ pine C 17 H 16 BrNO MM = 330 .224 Formula 85 [M.p. = 116°C; heptane; 73 %] IR in cm "1 : 2950, 1560, 1485, 1465 Η NMR (CDC1 3 ) in ppm: 8.51 (2H, m) , 7.35 (3H, m) , 6.88 (2H, ) , 5.74 (IH, s) , 3.91 (2H, s) , 1.17 (6H, s) . 7-Cyano-3,3-dimethyl-5- (3-pyridyl) -2,3-dihydro-l-benzoxe- pine C 18 H 16 N 2 0 MM = 276.237 Formula 86 [chromatography with silica gel and cyclohexane/ chloroform/methanol mixture: 56/33/11; M.p. =- 150 C C; heptane; 38 %] IR in cm "1 : 3090, 2980, 2250, 1600, 1570, 1500 NMR (CDC1 3 ) in ppm: 8.46 (2H, m) , 7.18 (5H, m) , 5.79 (IH, s) , 3.95 (2H, s) , 1.18 (6H, s) . 7, 8-Dichloro-3,3-dimethyl-5- (3-pyridyl) -2,3-dihydro- 1-benzoxepine C 17 H 15 C1 2 N0 MM = 320 .218 Formula 87 [M.p. = 112°C; diisopropyl ether; 36 %] IR in cm" 1 : 3020, 2970, 1590, 1565, 1540 Η NMR (CDC1 3 ) in ppm: 8.54 (2H, m) , 7.35 (2H, m) , 7.10 (IH, s) , 6.77 (IH, s), 5.72 (IH, s) , 3.92 (2H, s) , 1.17 (6H, s) . Example No. 7 7-Ethyl-3,3-dimethyl-5- (2-pyridyl) -2,3,4,5-tetrahydro- 1-benzoxepine C 19 H 23 NO MM = 281.386 Formula 88 A solution of 7-ethyl-3,3-dimethyl-5- (2-pyridyl) - 2,3-dihydro-1-benzoxepine (75 g, 0.26 mol) in 96 % ethanol (95 ml) is placed in a 125 ml autoclave. Palladium containing 50 % moisture is then added (0.3 g at 10 % on charcoal) . The hydrogen is introduced under pressure: 180 bar. The whole mixture is stirred for 4 hours at 80°C. The suspension is filtered and concentrated under reduced pressure, [yellow oil; 78 %] IR in cm '1 : 2960, 1590, 1570, 1495 -E NMR (CDC1 3 ) in ppm: 8.63 (IH, m) , 7.30 (5H, m) , 6.19 (IH, s) , 4.54 (IH, dd, J = 2 Hz, J = 9 Hz), 3.89 (IH, d, J -. 12 Hz), 3.48 (IH, d, J = 12 Hz), 2.42 (3H, m) , 1.67 (IH, m) , 1.20 (3H, s) , 1.03 (3H, t) , 0.85 (3H, s) . Example No. 8 3,3-Dimethyl-7-nitro-5- (4-nitro-2-pyridyl) -2,3-dihydro- 1-benzoxepine C 17 H 15 N 3 0 5 MM = 341.323 Formula 89 A mixture of 3,3-dimethyl-5- (2-pyridyl) - 1-benzoxepin-5-ol (5 g, 0.018 mol) and of a commercial concentrated sulfuric acid solution (32 ml) is cooled to 0°C. Sodium nitrate (1.8 g, 0.02 mol) is added in portions over 2 hours at 0°C with stirring. The reaction mixture is then poured into ice-cold water (100 ml) and extracted with dichloromethane. The organic phase is washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. [1.4 g; M.p. = 180°C; ethyl acetate; 25 %] IR in cm" 1 : 3100, 2970, 1545, 1530, 1480 Η NMR (CDC1 3 ) in ppm: 8.56 (IH, m) , 8.34 (IH, d, J = 2.50 Hz), 7.90 (IH, d, J = 2.50 Hz), 7.48 (3H, m) , 6.15 (IH, s) , 4.15 (2H, s) , 1.25 (6H, s) . By using the process described for Example 4, the following compounds are prepared. 7-Bromo-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine C 17 H 16 BrN0 2 MM = 346.223 Formula 90 [chromatography with silica gel and ethyl acetate; M.p. = 158-160°C; ethyl acetate; 29 %] IR in cm -1 : 3040, 2960, 1480 ~E NMR (CDC1 3 ) in ppm: 8.25 (IH, m) , 6.98 (6H, m) , 5.82 (IH, s) , 3.95 (2H, s) , 1.19 (6H, s) . Elemental analysis C H Br N % Found 59.24 4.68 23.09 3.91 % Calculated 58.97 4.66 23.08 4.05 9.24 7-Chloro-3,3-dimethyl- (2-pyridyl N-oxide) -2,3-dihydro- 1 -benzoxepine C 17 H 16 C1N0 2 MM = 301.772 Formula 91 [M.p. x- 168-170°C; acetone; 15 %] IR in cm "1 : 2960, 1480 'E NMR (CDC1 3 ) in ppm:8.25 (IH, m) , 6.93 (6H, m) , 5.84 (IH, s), 3.95 (2H, s) , 1.19 (6H, s) . Elemental analysis C H Cl N 0 % Found 67.85 5.19 11.91 4.51 % Calculated 67.66 5.34 11.75 4.64 10.60 7-Fluoro-3, 3 -dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1 -benzoxepine C 17 H 16 FN0 2 MM = 269.318 Formula 92 [M.p. = 184-185°C; ethyl acetate; 28 %] IR in cm "1 : 3050, 2950, 1490 'E NMR (CDC1 3 ) in ppm: 8.23 (IH, m) , 6.75 (6H, m) , 5.83 (IH, s) , 3.96 (2H, s) , 1.19 (6H, s) . Elemental analysis C H F N O % Found 71.62 5.57 6.91 4.81 % Calculated 71.56 5.65 6.66 4.91 11.22 3,3-Dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro-l-benzoxe- pine C 17 H 17 N0 2 MM = 265.327 Formula 93 [M.p. = 188-189°C; isopropanol; 19 %] IR in cm '1 : 3050, 3010, 2960, 2870, 1605, 1570, 1490 NMR (CDCI 3 ) in ppm: 8.20 (IH, m) , 6.91 (7H, ) , 5.80 (IH, s) , 4.00 (2H, s) , 1.21 (6H, s) . Elemental analysis C H N 0 % Found 76.53 6.45 5.05 % Calculated 76.38 6.41 5.24 11.97 3,3,7- Tr ime thyl - 5 - ( 2 -pyridyl N-oxide) -2, 3 -dihydro - 1 -benzoxepine C 18 H 19 N0 2 MM = 281.354 Formula 94 [M.p. = 146-147°C; ethyl acetate] IR in cm "1 : 3030, 2960, 2930, 2870, 1605, 1570, 1490 NMR (CDC1 3 ) in ppm: 8.23 (IH, m) , 7.21 (3H, m) 6, 89 (2H, m) , 6.34 (IH, m) , 5.75 (IH, s) , 3.95 (2H, s) 2 11 (3H, s), 2.11 (3H, s), 1.16 (6H, s) Elemental analysis C H N 0 % Found 77.04 6.75 5.07 % Calculated 76.84 6.81 4.98 11.37 7-Ethyl-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine C 19 H 21 N0 2 MM = 295.369 Formula 95 [M.p. = 126-129°C; ethyl acetate/diisopropyl ether: 2/1; 20 %] IR in cm "1 : 3030, 2960, 2930, 2870, 1610, 1575, 1500 ~E NMR (CDC1 3 ) in ppm: 8.28 (IH, m) , 7.23 (3H, m) , 6.94 (2H, ), 6.38 (IH, m) , 5.78 (IH, s) , 3.96 (2H, s) , 2.43 (2H, q) , 1.18 (6H, s) , 1.04 (3H, t) . Elemental analysis C H N 0 % Found 77.48 7.26 4.79 % Calculated 77.26 7.17 4.74 10.83 7-Isopropyl-3 , 3 -dimethyl-5- (2-pyridyl N-oxide) - 2,3 -dihydro- 1 -benzoxepine C 20 H 23 NO 2 MM = 309.407 Formula 96 [M.p. = 162-164°C; ethyl acetate] IR in cm '1 : 3025, 2950, 1500 Η NMR (CDC1 3 ) in ppm: 8.26 (IH, m) , 7.08 (5H, ) , 6.38 (IH, s) , 5.75 (IH, s) , 3.95 (2H, s) , 2.65 (IH, m) , 1.10 (12H, m) Elemental analysis C H N O % Found 77.43 7.50 4.49 % Calculated 77.64 7.49 4.53 10.34 3 , 3-Dimethyl-7- (l-methylpropyl) -5- (2-pyridyl N-oxide) - 2 , 3 -dihydro- 1 -benzoxepine C 21 H 25 N0 2 MM = 323.434 Formula 97 [chromatography with silica gel and dichloromethane/methanol: 99/1; M.p. = 110-112°C; cyclohexane] IR in cm '1 : 3030, 2950, 1605, 1500, 1480 'E NMR (CDC1 3 ) in ppm: 8.28 (IH, m) , 7.20 (3H, m) , 6.91 (2H, m) , 6.33 (IH, s) , 5.77 (IH, s) , 3.98 (2H, s) , 2.32 (IH, m) , 1.18 (6H, s) , 1.05 (8H, m) Elemental analysis C H N 0 % Found 77.93 7.81 4.24 % Calculated 77.98 7.79 4.33 9.89 7-Methoxy-3,3-dimethyl-5-(2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine C 18 H 19 N0 3 MM = 297.353 Formula 98 [M.p. = 164-166 C C; ethyl acetate] IR in cm "1 : 3050, 2960, 1615, 1580, 1510, 1495 'E NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 6.93 (5H, m) , 6.14 (IH, m), 5.79 (IH, s) , 3.93 (2H, s) , 3.56 (3H, s) , 1.15 (6H, s) Elemental analysis C H N 0 % Found 73.00 6.49 4.71 % Calculated 72.70 6.44 4.71 16.14 3, 3 -Dimethyl- 5- (2 -pyridyl N-oxide) -7-trif luoromethoxy- 2, 3 -dihydro- 1 -benzoxepine C 18 H 16 F 3 Nθ 3 MM = 351.325 Formula 99 [M.p. = 157-159°C; ethyl acetate} IR in cm "1 : 3070, 2970, 1495 Η NMR (CDC1 3 ) in ppm: 8.24 (IH, m) 7.14 (5H, m) 6.39 (IH, s), 5.85 (IH, s), 3.96 (2H, s) 1.19 (6H, s) . Elemental analysis C % Found 61.79 % Calculated 61.53 13.66 3,3-Dimethyl-5- (2-pyridyl N-oxide) -7-trifluoromethyl- 2,3-dihydro-1-benzoxepine C 19 H 16 F 3 N0 2 MM = 335.325 Formula 100 [M.p. = 152-153°C; ethyl acetate/hexane: 1/2] IR in cm "1 : 3060, 2970, 1610, 1495 X H NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.13 (6H, m) , 5.89 (IH, s) , 4.00 (2H, s) , 1.18 (6H, s) Elemental analysis C H F N 0 % Found 64.55 4.76 17.55 4.10 % Calculated 64.47 4.81 17.00 4.18 9.54 3,3-Dimethyl-7-methylsulfonyl-5- (2-pyridyl N-oxide) 2,3-dihydro-1-benzoxepine C 18 H 19 N0 4 S MM = 345.418 Formula 101 [chromatography with silica gel and acetone; M.p. = 200°C, diisopropyl ether] IR in cm "1 : 2970, 1600, 1565, 1490 'E NMR (CDC1 3 ) in ppm: 8.23 (IH, m) , 7.65 (IH, m) , 7.19 (5H, m) , 5.97 (IH, s) , 4.04 (2H, s) , 2.91 (3H, s) , 1.22 (6H, s) Elemental analysis C H % Found 62.86 5.64 % Calculated 62.59 5.54 3,3-Dimethyl-7-phenyl-5- (2-pyridyl N-oxide) -2,3-dihydxo- 1-benzoxepine C 23 H 21 N0 2 MM = 343.424 Formula 102 [chromatography with silica gel and ethyl acetate/ chloroform/methanol mixture: 60/30/10; M.p. = 165-168°C; • 35 %] IR in cm" 1 : 3050, 2960, 1605 NMR (CDC1 3 ) in ppm: 8.24 (IH, ) , 7.08 (11H, m) , 5.82 (IH, s) , 3.98 (2H, s) , 1.16 (6H, s) Elemental analysis C H N 0 % Found 80.04 6.20 4.01 % Calculated 80.44 6.16 4.08 9.32 8-Brαmo-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine C 17 H ls BrN0 2 MM = 346.223 Formula 103 [chromatography on silica gel and dichloromethane/ methanol: 98/2; M.p. = 135-137°C; diisopropyl ether/ethyl acetate: 60/40] IR in cm "1 : 3080, 2970, 1590, 1550, 1480 ~E NMR (CDCl j ) in ppm: 8.21 (IH, m) , 7.09 (5H, m) , 6.40 (IH, d, J = 8 Hz) , 5.81 (IH, s) , 3.95 (2H, s) , 1.17 (6H, s) Elemental analysis C H Br N O % Found 59.23 4.70 22.94 3.97 % Calculated 58.97 4.66 23.08 4.05 9.24 7-Cyano-3,3-dimethyl-5- (2-pyridyl N-oxide) -2, 3-dihydro- 1 -benzoxepine C 18 H lβ N 2 0 2 MM = 292.337 [M.p. = 206-207°C; ethyl acetate; 33 %] IR in cm "1 : 2985, 2220, 1595, 1560, 1490 'E NMR (CF 3 COOD) in ppm: 8.79 (IH, m) , 8.05 (4H, m) , 7.25 (IH, d, J -. 8 Hz) , 6.88 (IH, d, J = 2 Hz) , 6.22 (IH, s) , 4.15 (2H, s), 1.30 (6H, s) Elemental analysis C H N 0 % Found 74.09 5.57 9.40 % Calculated 73.95 5.52 9.58 10.95 8-Cyano-3,3-dimethyl-5-(2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine C 18 H 16 N 2 0 2 MM = 292.337 Formula 105 [chromatography with silica gel and dichloromethane/ methanol: 98/2; M.p. = 195-7°C; ethanol] IR in cm "1 : 3090, 2970, 2230, 1550 NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.18 (5H, m) , 6.64 (IH, d, J * 8 Hz), 5.95 (IH, s) , 3.96 (2H, s) , 1.20 (6H, s) . Elemental analysis C H N 0 % Found 74 .21 5 .61 9 .77 % Calculated 73 . 95 5 .52 9 . 58 10 . 95 3, 3 -Dimethyl-5- (2-pyridyl N-oxide) - 8- trifluoromethyl - 2 , 3 -dihydro- 1 -benzoxepine C 19 H ιe F 3 N0 2 MM = 335 . 325 Formula 106 [M.p . = 130 - 131 °C; hexane; 25 %] IR in cm "1 : 3060 , 2960 , 1570 , 1485 X H NMR (CDC1 3 ) in ppm: 8 .25 (IH, m) , 7 . 03 ( 6H, s) 5.95 (IH, s), 4.01 (2H, s), 1.19 (6H, s) Elemental analysis C % Found 64.74 % Calculated 64.47 9.54 3,3-Dimethyl-5- (2-pyridyl N-oxide) -7-pentafluoroethyl• 2,3-dihydro-1-benzoxepine C 1Q H 1ι: F,NO, MM = 385.333 Formula 107 [M.p. = 161-162°C; ethyl acetate] IR in cm "1 : 3070, 2970, 1610, 1585, 1600, 1590 NMR (CDC1 3 ) in ppm: 8.25 (IH, m) , 7.98 (6H, m) , 5.93 (IH, s) , 4.03 (2H, s), 1.20 (6H, s) Elemental analysis C H F N O % Found 59.52 4.31 24.27 3.62 % Calculated 59.22 4.19 24.65 3.64 8.30 • 3,3-Dimethyl-7-nitro-5- (4-nitro-2-pyridyl N-oxide) - 2,3-dihydro-1-benzoxepine C 17 H 15 N 3 0 6 MM = 357.322 Formula 108 [chromatography with silica gel and ethyl acetate/ chloroform/methanol: 60/30/10; M.p. = 228°C; methanol] IR in cm' 1 : 3100, 2970, 1545, 1530, 1480 NMR (CDC1 3 ) in ppm: 8.37 (IH, d, J = 2.70 Hz), 8.25 = 2.70 Hz) , 7.38 21 (2H, s) , 1.28 26.86 8-Cyano-3,3-dimethyl-l- (2-pyridyl N-oxide) -4,5-dihydro- 3H-benzo[f]cycloheptene C 19 H 18 N 2 0 MM = 290.364 Formula 109 [chromatography with silica gel and cyclohexane/ chloroform/methanol mixture: 70/20/10; M.p. = 189°C, toluene; 42 %] IR in cm' 1 : 2950, 2225, 1595 -E NMR (CDC1 3 ) in ppm: 8.08 (IH, m) , 7.27 (5H, m) , 6.85 (IH, s), 5.92 (IH, s) , 2.93 (2H, m) , 1.88 (2H, m) , 0.95 (6H, m) Elemental analysis C H N O % Found 78.30 5.90 9.39 % Calculated 78.59 6.25 9.65 5.51 6,8-Dichloro-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2,3 - dihydro- 1 -benzoxepine C 17 H 15 C1 2 N0 2 MM = 336.217 Formula 110 [M.p. = 163-164°C; ethyl acetate] IR in cm "1 : 3050, 2970, 1590, 1550 -E NMR (CDC1 3 ) in ppm: 8.09 (IH, m) , 7.47 (5H, m) , 6.21 (IH, s), 4.00 (2H, s), 1.15 (6H, s) Elemental analysis C H Cl N O % Found 60.75 4.70 21.26 4.12 % Calculated 60.73 4.50 21.09 4.17 9.52 7,8-Dichloro-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2 , 3 -dihydro-1-benzoxepine C 17 H 15 C1 2 N0 2 MM --- 336.217 Formula 111 [M.p. = 173-174°C; ethyl acetate; 37 %] IR in cm "1 : 3070, 2960, 1475 'E NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.20 (4H, m) , 6.60 (IH, s), 5.85 (IH, s), 3.95 (2H, s) , 1.15 (6H, s) Elemental analysis C H Cl N % Found 60.47 4.46 21.11 4.12 % Calculated 60.73 4.50 21.09 4.17 9.52 7 , 9-Dichloro-3 , 3-dimethyl-5- (2-pyridyl N-oxide) 2,3 -dihydro -1 -benzoxepine C 17 H 15 C1 2 N0 2 MM = 336.217 Formula 112 [M.p. = 155-157°C; diisopropyl ether/ethyl acetate: 70/30; 30 %] IR in cm "1 : 3035, 1470, 1419 'E NMR (CDC1 3 ) in ppm: 8.22 (IH, m) , 7.34 (4H, m) , 6.42 " (IH, d, J = 2 Hz) , 5.88 (IH, s) , 4.02 (2H, s) , 1.21 (6H, s) N 4.16 4.17 9.52 8 , 9 -Dichloro- 3 , 3 -dime thyl- 5 - ( 2 -pyridyl N-oxide) - 2 , 3 -dihydro-1-benzoxepine C 17 H 15 C1 2 N0 2 MM = 336.217 [M.p. = 168°C; ethyl acetate; 26 %] IR in cm "1 : 2960, 1470, 1422 X H NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.25 (3H, m) , 6.95 (IH, d, J = 8 Hz), 6.42 (IH, d, J = 8 Hz) , 5.85 (IH, s) , 4.07 (2H, s) , 1.24 (6H, s) Elemental analysis C H % Found 61.14 4.71 % Calculated 60.73 4.50 7, 8-Difluoro-3,3-dimethyl-5- (2 2, 3 -dihydro- 1 -benzoxepine C 17 H 15 F 2 N0 2 MM = 303.308 Formula 114 [M.p. = 163-165°C; ethyl acetate] IR in cm '1 : 3060, 2965, 1600, 1515 X E NMR (CDC1 3 ) in ppm: 8.23 (IH, m) , 7.28 (3H, m) , 6.80 (IH, dd, J = 7.0 Hz), 6.35 (IH, dd, J = 8.0 Hz), 5.80 (IH, s) , 3.95 (2H, s) , 1.18 (6H, s) Elemental analysis C H F N O % Found 67.36 4.56 12.73 4.95 % Calculated 67.32 4.99 12.53 4.62 10.55 8-Chloro-7-fluoro-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2,3 -dihydro- 1 -benzoxepine C 17 H 15 C1FN0 2 MM = 319.762 Formula 115 [M.p. = 149-151°C; ethyl acetate] IR in cm' 1 : 3050, 2970, 1485 'E NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.15 (4H, m) , 6.35 (IH, d), 5.85 (IH, s) , 3.93 (2H, s) , 1.14 (6H, s) Elemental analysis C H Cl F N O % Found 64.04 4.82 11.16 5.91 4 .41 % Calculated 63.85 4.73 11.09 5.94 4 .38 10 . 01 9-Ethyl-7-fluoro-3,3-dimethyl-5-(2-pyridyl N-oxide) - 2,3-dihydro-1-benzoxepine C 19 H 20 NFO 2 MM = 313.371 Formula 116 [chromatography with silica gel and acetone/ethyl acetate mixture: 50/50; M.p. = 120-2°C; diisopropyl ether] IR in cm '1 : 2960, 2940, 1610, 1590 NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.20 (3H, m) , 6.69 (IH, dd, J = 2 Hz, J = 8 Hz), 6.25 (IH, dd, J = 2 Hz, J = 10 Hz), 5.79 (IH, s) , 3.94 (2H, s) , 2.66 (2H, q) , 1.19 (6H, s) , 1.16 (3H, t) . Elemental analysis % Found % Calculated 2,3-dihydro-1-benzoxepine C 19 H 21 N0 4 MM = 327.379 Formula 117 [chromatography with silica gel and dichloromethane/ methanol: 98/2; M.p. = 146°C; ethyl acetate] IR in cm "1 : 3110, 2950, 1615, 1520, 1490 NMR (CDC1 3 ) in ppm: 8.26 (IH, m) , 7.25 (3H, m) , 6.57 (IH, s), 6.08 (IH, s), 5.70 (IH, s) , 3.99 (2H, s) , 3.81 (3H, s) , 3.56 (3H, s) , 1.19 (6H, s) . Elemental analysis C H N O % Found 69.86 6.70 4.12 % Calculated 69.70 6.47 4.28 19.55 7 -Cyano- 3, 3 , 8 -tr ime thyl- 5 - (2 -pyridyl N-oxide) - 2,3 -dihydro- 1 -benzoxepine C 19 H 18 N 2 0 2 MM = 306.363 Formula 118 [chromatography with silica gel and chloroform/methanol mixture: 98/2; M.p. = 230-235°C; toluene/diisopropyl ether] IR in cm "1 : 3060, 2950, 2210, 1605, 1495 Elemental analysis C H N 0 % Found 74.39 6.00 8.93 % Calculated 74.49 5.92 9.15 10.45 8-Cyano-3, 3 , 7-trimethyl-5- (2-pyridyl N-oxide) - 2,3-dihydro-1-benzoxepine C 19 H 18 N 2 0 2 MM = 306.363 Formula 119 [M.p. = 182°C; toluene; 30 %] IR in cm "1 : 3070, 2960, 2225, 1605, 1545, 1490 X H NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.22 (4H, m) , 6.44 (IH, s) , 5.90 (IH, s), 3.92 (2H, s) , 2.26 (3H, s) , 1.18 (6H, s) Elemental analysis C % Found 74.70 % Calculated 74.49 10.45 3 , 3 -Dimethyl-5 - (2 -pyridyl N-oxide) -2,3,7,8,9, 10 -hexa- hydro-1-naphth [2,3 -b] oxepine C 21 H 23 N0 2 MM = 321.418 [chromatography with silica gel and dichloromethane/ methanol: 98/2; M.p. = 184°C; toluene] IR in cm "1 : 2930, 1610, 1550, 1500 Η NMR (CDC1 3 ) in ppm: 8.22 (IH, ) , 7.22 (3H, m) , 6.72 (IH, s) , 6.24 (IH, s) , 5.69 (IH, s) , 3.95 (2H, s) , 2.58 (4H, m) , 1.70 (4H, ) , 1.16 (6H, s) . Elemental analysis C H N 0 % Found 78.30 7.39 4.48 % Calculated 78.47 7.21 4.36 9.96 7-Ethyl-3,3-dimethyl-5-(2-pyridyl N-oxide) -2,3, ,5-tetra¬ hydro-1-benzoxepine C 19 H 23 N0 2 MM = 297.385 Formula 121 [m.p. = 88-89°C; diisopropyl ether] IR in cm '1 : 3060, 3020, 2960, 2930, 2870, 1610, 1490 NMR (CDC1 3 ) in ppm: 8.28 (IH, m) , 7.16 (3H, m) , 6.96 (2H, m) , 6.45 (IH, m) , 5.20 (IH, dd, J -= 2 Hz, J = 9 Hz), 3.71 (2H, s), 2.50 (3H, m) , 1.70 (IH, dd, J = 2 Hz, J = 13.5 Hz), 1.07 (3H, s) , 1.06 (3H, t) , 0.80 (3H, s) Elemental analysis C H N 0 % Found 76.63 7.75 4.62 % Calculated 76.73 7.80 4.71 10.76 7-Bromo-3,3-dimethyl-5-(3-pyridyl N-oxide)-2,3-dihydro- 1-benzoxepine C 17 H ιe BrN0 2 MM = 346.223 Formula 122 [M.p. = 161-162°C; ethyl acetate; 50 %] IR in cm' 1 : 3090, 2950, 1580, 1540, 1460 ~E NMR (CDC1 3 ) in ppm: 8.19 (2H, m) , 7.23 (3H, m) , 6.90 (2H, m) , 5.77 (IH, s) , 3.90 (2H, s) , 1.17 (6H, s) Elemental analysis C H Br N O % Found 59.07 4.72 22.99 4.13 % Calculated 58.97 4.66 23.06 4.05 9.26 7-Cyano-3,3-dimethyl-5- (3-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine C 18 H 1S N 2 0 2 MM = 292.337 .0 " . Formula 123 [M.p. = 162-164°C; ethyl acetate; 45 %] IR in cm "1 : 3070, 2960, 2230, 1600 X H NMR (CDC1 3 ) in ppm: 8.17 (2H, m) , 7.25 (5H, m) , 5.85 (IH, s), 3.92 (2H, s) , 1.15 (6H, s) Elemental analysis C H N 0 % Found 73.89 5.52 9.68 % Calculated 73.95 5.52 9.58 10.95 7, 8-Dichloro-3,3-dimethyl-5- (3-pyridyl N-oxide) - 2,3 - dihydro -1 -benzoxepine C 17 H 15 C1 2 N0 2 MM = 336.217 Formula 124 [137-139°C; isooctane and diisopropyl ether: 50/50; 46 %] IR in cm "1 : 3120, 3030, 2950, 1590, 1540 'E NMR (CDC1 3 ) in ppm: 8.20 (2H, m) , 7.16 (3H, m) , 6.80 (IH, s) , 5.79 (IH, s), 3.90 (2H, s) , 1.19 (6H, s) Elemental analysis C H Cl N O % Found 60.70 4.54 21.24 4.05 % Calculated 60.73 4.50 21.09 4.17 9.52 3, 3 -Dime thyl- 5- (2-pyridyl N-oxide) -2,3-dihydro-l-benzoxe- pine-7 -carboxamide C 18 H 18 N 2 0 3 MM = 310.352 Formula 125 [M.p. 215-217°C; methanol; 28 %] IR in cm" 1 : 3400, 3200, 2970, 1665, 1605 'E NMR (DMSO) in ppm: 8.16 (IH, ) , 7.35 (6H, m) 5.85 (IH, s), 3.93 (2H, s) , 1.13 (6H, s) . Elemental analysis C H N 0 % Found 69.49 5.84 8.80 % Calculated 69.66 5.85 9.03 15.47 3, 3-Di-methyl-7-phenylsulfonyl-5- (2-pyridyl N-oxide) - 2,3 -dihydro-1-benzoxepine C 23 H 21 N0 4 S MM = 407.490 Formula 126 [M.p. = 167-169°C; diisopropyl ether; 19 %] IR in cm '1 : 3060, 2950, 1600, 1560, 1490 Η NMR (CDC1 3 ) in ppm: 8.20 (IH, m) , 7.38 (11H, m) , 5.93 (IH, s) , 3.99 (2H, s) , 1.19 (6H, s) Elemental analysis C H N % Found 67.84 5.34 3.42 % Calculated 67.79 5.20 3.44 7-Chloro-8-ethyl-3,3-dimethyl-5-(2-pyridy 2 , 3 -dihydro- 1 -benzoxepine C 19 H 20 ClNO 2 MM = 329.829 Formula 127 [M.p. = 144-146°C; ethyl acetate; 34 %] IR in cm' 1 : 3070, 2950, 1485 l H NMR (CDC1 3 ) in ppm: 8.23 (1H, m), 7.20 (3H, m), 6.87 (1H, s 6.50 (IH, s) , 5.78 (IH, s) , 3.95 (2H, s) , 2.62 (2H, q) , 1.18 (3H, t) , 1.15 (6H, s) Elemental analysis C H Cl N O % Found 69.25 6.01 10.89 4.26 % Calculated 69.19 6.11 10.75 4.25 9.70 8-Broano-3,3-dimethyl-1- (2-pyridyl N-oxide) -3H-benzo[f] - cyclohepta-l,4-diene C 18 H ls BrNO MM = 342.235 Formula 128 [M.p. = 167°C; diisopropyl ether; 10 %] IR in cm "1 : 3080, 2980, 1485 NMR (CDCl j ) in ppm: 8.11 (IH, m) , 7.15 (6H, m) , 6.52 (IH, d, J = 10 Hz), 5.88 (IH, s) , 5.75 (IH, d, J = 10 Hz) , 1.11 (6H, s) . Elemental analysis C H Br N O % Found 63.16 4.56 23.05 4.09 % Calculated 63.17 4.71 23.35 4.09 4.68 3,3-Dimethyl-7-(2- eUιylpropyl)-5-(2-pyridyl-N-oxide)-2,3-dihydr()-l-be-ιzoxepine FORMULA 130 [M.p. = 114-116°C; diisopropyl ether, 25%] IR in cm- 1 : 3060; 2960; 1500; 1490 -H NMR (CDCI3) in ppm:8,20(lH, m ); 7,20(3H, m); 6,86(2H, m); 6,30(1H, s); 5,76(1H, s); 3,95(2H, s); 2,22(2H, d); 1,68(1H, m); 1,16(6H, s); 0,8(3H, s); 0,58(3H, s). Elemental analysis C H N O % Found 77,92 7,55 4,42 % Calculated 77,98 7,79 4,33 9,89 7-Chloro-3 .8-trimethyl-5-(2-pyridyl-N-oxide)-2,3-dihydro-l-benzoxepine Ci8Hι 8 CIN0 2 MM = 315,803 FORMULA 131 [M.p. = 178-180°C; ethyl acetate; 20%] IR in cm" 1 : 3060; 2960; 1610; 1490 - NMR (CDCI3) in ppm: 8,19(1H, m); 7,20(3H, m); 6,85(1H, s); 6,49(1H, s); 5,75(1H, s); 3,92(2H, s); 2,22(3H, s); 1,15(6H, s). Elemental analysis C H Cl N O % Found 68,74 5,73 11,48 4,42 % Calculated 68,48 5,75 11,23 4,44 10,13 7-Bromo-8-chloro-3,3-dimethyl-5-(2-pyridyl-N-oxyde)-2,3-dihydro-l-benzoxepine CπHι 5 BιCIN0 2 MM = 380,672 FORMULA 132 [M.p. = 182-183°C; ethyl acetate; 44%] IR in cm" 1 : 3060; 2950; 1580; 1540; 1470 -U NMR (CDCI3) in ppm: 8,22(1H, m); 7,22(3H, m); 7,08(1H, s); 6,72(1H, s); 5,83(1H, s); 3,95(2H, s); l,17(6H, s). Elemental analysis C H Br Cl N O % Found 53,72 3,87 20,89 9,46 3,75 % Calculated 53,63 3,97 20,99 9,31 3,68 8,41 8-Chloro-7-cyano-3 ,3-dimethyl-5-(2-pyridyl-N-oxide)-2,3-dihydro- 1 -benzoxepine C18H15CIN2O2 MM = 326,786 FORMULA 133 [M.p. = 206-207°C; ethyl acetate; 53%] IR in cm" 1 : 3080; 2990; 2240; 1600; 1550; 1490 H NMR (CDC1 3 ) in ppm: 8,20(1H, ); 7,23(3H, m); 7,13(1H, s); 6,83(1H, s); 5,93(1H, s); 4,02(2H, s); 1,20(6H, s), Elemental analysis O 9,79 8-Chloro-3,3-dimethyl-5-(2-pyridyl-N-oxide)-7-trifluoromethyl-2,3-dihydro-l-benzoxepine C18H15CIF3NO2 MM = 369,774 FORMULA 134 [M.p. = 158-161°C] IR in cm" 1 : 3080; 2980; 1610; 1565; 1495 -H NMR (CDCI3) in ppm: 8,18(1H, ); 7.58(4H, m); 6,80(1H, s); 5,88(1H, s); 3,98(2H, s); 1,15(6H, s). Elemental analysis C H Cl F N O % Found 58,42 4,24 9,99 14,79 3,83 % Calculated 58,46 4,09 9,59 15,42 3,79 8,65 8-Bromo-3,3-dimethyl- 1 -(2-pyridyl-N-oxide)-4,5-dihydro-3H-benzo[f] -cyclohept- 1 -ene CisHigBrNO MM = 344,250 FORMULA 135 [M.p. = 173-175°C; toluene; 43%] IR in cm" 1 : 3070; 2960; 1590; 1490 -_i NMR (CDCI3) in ppm: 8,11(1H, m); 7,18(5H, m); 6,73(1H, d); 5,90(1H, s); 2,59(2H, m); l,85(2H, m); l,09(6H, s). Elemental analysis C H Br N O % Found 62,80 5,25 23,26 3,93 % Calculated 62,80 5,27 23,21 4,07 4,65 3,3-Dimethyl-8-phenylsulfonyl-l-(2-pyridyl-N-oxide)-4,5-dihydro-3H-benzo[f]cyclohept-l-ene FORMULA 136 [M.p. = 191-192°C; isopropanol; 45%] IR in cm" 1 : 3060; 2950; 1595; 1585; 1560; 1485 ~H NMR (CDCI3) in ppm: 8,08(1H, m); 7,45(1 IH, m); 5,95(1H, s); 2,92(2H, ); 1,88(2H, ); 1,10(6H, s). Elemental analysis C H N O S % Found 70,86 5,82 3,34 7,83 % Calculated 71,08 5,72 3,45 11,84 7,91 7,8-Dichloro-3,3-dimethyl-l-(2-pyridyl-N-oxide)-4^-dihydro-3H-benzo[f]cyclohept-l-ene C18H1-7CI2NO MM = 334,252 FORMULA 137 [M.p. = 195-196°C; toluene; 25%] IR in cm' 1 : 3070; 2970; 1550; 1480 l H NMR (CDCI3) in ppm: 8,12(1H, m); 7,25(4H, m); 6,68(1H, s); 5,92(1H, s); 2,61(2H, m); l,85(2H, m); l,ll(6H, s). Elemental analysis O 4,79 8-Bromo-4,4-dimethyl- 1 -(2-pyridyl-N-oxide)-3,4-dihydro-3H-benzo[f]cyclohept- 1 -ene CigHigBrNO MM = 334,250 FORMULA 138 [M.p. = 137-139°C; diisopropyl ether, 20%] IR in cm" 1 : 2960; 2930; 1610; 1590; 1550; 1490 l U NMR (CDCI3) in ppm: 8,12(1H, m); 7,12(6H, ); 6,51(1H, d); 2,58(2H, s); 1,74(2H, d); 1,05(6H, s). Elemental analysis C H Br N O % Found 62,80 5,14 23,27 4,04 % Calculated 62,80 5,27 23,21 4,07 4,65 Hemisulfate of 7-fluoro-3 -dimethyl-5(2-pyridyl-N-oxide 2,3-dihydro-l-benzoxepine Ci7Hι 7 FNθ4So,5 MM = 334,357 FORMULA 139 [M.p. = 198-199°C; ethanol; 33%] IR in cm" 1 : 3090; 2970; 1620; 1580; 1500 -U NMR (CDCI3) in ppm: 10,28(1H, s); 8 6(1H, m); 7,55(3H, m); 6,99(2H, m); 6,07(2H, m); 3,90(2H, s); l,14(6H, s). Elemental analysis Hydrochloride of 7,8^ichloro-3,3-dimethyl-5-(2-pyridyl-N-oxide)-2,3-dihydro-l-benzoxepine Cι 7 Hι 6 Cl 3 Nθ2 MM = 372,690 FORMULA 140 [M.p. = 182-186°C; acetone; 60%] IR in cm '1 : 3090; 2970; 2270; 1700; 1605; 1525 l K NMR (CDC1 3 ) in ppm: 11,78(1H, s); 8,43(1H, m); 7,63(3H, m); 7,26(1H, s); 6-55(lH, s); 6,00(1H, s); 3,95(2H, s); 1,15(6H, s). Elemental analysis C H Cl N O % Found 54,74 4,24 27,89 3,90 % Calculated 54,78 4,33 28,54 3,76 8,59 Example 9 4-(4-Fluorophenoxy)-3.3-dimethyl-butanoic acid C 12 H 15 F0 3 MM = 226.247 Formula 141 A suspension of 4-fluorophenol(21.3 g; 0.19 mol) and sodium hydroxide (7.6 g; 0.19 mol) in n-butanol under a flow of dry nitrogene is heated by an oil bath at 190°C during 10 minutes. The reactor is equipped with a distillation system for the elimination of the formed water by azeotropic removal. The heating is continued to distill all of the n-butanol. Then the 3.3-dimethylbutyrolacetone (22.8 g; 0.20 mol) is added. The reaction medium is heated 10 hours at 160°C (temperature inside the medium) , then cooled to 80°C for the addition of water (65ml). The obtained solution is washed with dichloromethane and decanted. The aqueous phase is acidified and the desired acid is extracted with dichloromethane dried over anhydrous sodium sulfate. The solution is concentrated under reduced pressure and the oily residue is distilled. (B.p.(53.2 Pa = 0.4mm Hg) = 130-134°C; 75%] IR in cm -1 : 3480; 2200; 1705; 1600; 1505 iH NMR (CDC1 3 ) in ppm: 10.75 (IH, m) ; 6.82 (4H, m) ; 3.66 (2H, S); 2.40 (2H, S); 1.11 (6H, S).

Claims: CLAIMS 1. Compounds of general formula: in which: X represents 0 or CHR, R being a hydrogen atom or R, taken together with R 1# forming a bond, R 1 R 2 , R 3 and R 4 , which are identical or different, represent a hydrogen atom or a C^-C, alkyl group, it being possible for R-. to additionally form a bond with R; R 5 represents a hydrogen atom, a hydroxyl group or R 5 , taken together with R 7 , forms a bond or a ^" ^ 0 • group; R ε represents a group of formula: ' ~ z ι y in which R 10 and R , taken together with the carbon atom to which they are attached, form an optionally aromatic mono- or bicyclic nitrogenous heterocyclic group having from 3 to 11 members, including 1 or 2 nitrogen atoms, optionally substituted on the carbon atoms by 1 to 7 groups chosen from hydroxyl, nitro, cyano, C^-C, alkyl or Cj-C, alkoxy, it being possible for at least one of the nitrogen atoms of the heterocycle to be N-oxidized; R 7 represents a hydrogen atom or a hydroxyl, Ci-C, alkoxy or Ci-C-, acyloxy group or R 5 and R 7 together form a bond or a * -~o ; group; R 8 and R 9 , which are identical or different, represent a hydrogen or halogen atom, a hydroxyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, pentafluoroethyl, Ci-C, alkyl, C^C alkoxy, C^C-, alkylthio, C^-C, acylthio, C^C-, alkylsulfonyl or C-^-C, alkylsulfinyl group, a group of formulae: 0 0 0 II II II -C-0R 12 , -C-NR 12 R 13 or -C-R 12 in which R 12 and R 13 , which are identical or dif¬ ferent, represent a hydrogen atom or a C^C- alkyl group, or R s and R 9 represent a C β -C 10 aryl, (C 6 -C 10 ) - arylsulfonyl or ( C <-C 10 )arylsulfinyl group, optionally substituted by one to six substituents chosen from halo, hydroxyl, nitro, cyano, carboxyl, carbamoyl, trifluoromethyl, trifluoromethoxy, penta- fluoroethyl, C-^-C, alkyl, C- ^ -C, alkoxy, C- ^ -C, alkyl¬ thio, C j -C- acylthio, Ci-C, alkylsulfonyl or C- ^ -C, alkylsulfinyl, or R 8 and R 9 , which are identical or different, represent a heterocycle having from 3 to 11 members in the ring including 1 to 4 hetereoatoms, which are identical or different, chosen from 0, S and N, optionally substituted by one to six substituents chosen from halo, hydroxyl, nitro, cyano, carboxyl, carbamoyl, trifluoromethyl, trifluoromethoxy, penta- fluoroethyl, C-.-C, alkyl, C^-C, alkoxy, C--C, alkyl¬ thio, C x -C 7 acylthio, ^-C, alkylsulfonyl or C-.-C, alkylsulfinyl, or R 8 and R 9 together form a group (CH 2 ) n , n being a number from 1 to 6, or R 8 and R 9 together form a heterocycle having from 3 to 11 members including 1 to 4 heteroatoms, which are identical or different, chosen from 0, S and N, optionally substituted by one to six substituents chosen from halo, hydroxyl, nitro, cyano, carboxyl, carbamoyl, trifluoromethyl, trifluoromethoxy, penta- fluoroethyl, C j -C, alkyl, C^C, alkoxy, C 1 -C 7 alkyl- thio, Ci-C-, acylthio, C^-C-, alkylsulfonyl or C- ^ -C, alkylsulfinyl, and their N-oxides and their pharmaceutically acceptable salts. 2. Compounds of general formula I according to Claim 1, characterized in that X represents an oxygen atom. 3. Compounds of general formula I according to Claim 1, characterized in that R x and R 2 represent a hydrogen atom. 4. Compounds of general formula I according to Claim 1, characterized in that R 5 represents a hydrogen atom. 5. Compounds of general formula I according to Claim 1, characterized in that R 6 is chosen from 2-pyridyl, 2-pyridyl N-oxide, 3-pyridyl, 3-pyridyl N-oxide, 4-pyridyl, 3-hydroxy-4-pyridyl, 2-pyrimidyl, 2-pyrimidyl N-oxide, 6-pyrimidyl, 6-pyrimidyl N-oxide, 2-quinolyl, 2-quinolyl N-oxide, 1-isoquinolyl and 1-isoquinolyl N-oxide, optionally substituted on the carbon atoms by 1 to 3 substituents chosen from hydroxyl, nitro, cyano, C^-C, alkyl and C^C- alkoxy. 6. Compounds of general formula I according to Claim 1, characterized in that R 7 represents a hydrogen atom or a hydroxyl, methoxy or acetoxy group. 7. Compounds according to Claim 1 of general formula: in which X represents O or CHR, and R, R 5 , R ε , R 7 , R, and R 9 are as defined in Claim 1. 8. Compounds according to Claim 1 of general formula: in which X represents 0 or or CHR, and R, R s , R 8 and R 9 are as defined in Claim 1. 9. Compounds according to Claim 1, characterized in that they are chosen from: 3,3-dimethyl-5- (2-pyridyl N-oxide) -7-trifluoromethoxy- 2,3-dihydro-1-benzoxepine; 3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro-1-benzoxe¬ pine; 7-fluoro-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 7-bromo-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 8 -bromo-3 ,3,7- trimethyl-5- (2 -pyridyl N-oxide) - 2,3-dihydro-l-benzoxepine; 7-ethyl-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 3,3-dimethyl-5- (2-pyridyl N-oxide) -7- (l-methylpropyl) - 2,3-dihydro-l-benzoxepine; 7-isopropyl-3 , 3 -dimethyl-5- (2-pyridyl N-oxide) - 2,3-dihydro-l-benzoxepine; 7-methoxy-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 3,3-dimethyl-5- (2-pyridyl N-oxide) -7-methylsulfinyl- 2,3-dihydro-l-benzoxepine; 3,3-dimethyl-5- (2-pyridyl N-oxide) -7-methylsulfonyl- 2,3-dihydro-1-benzoxepine; 3,3-dimethyl-5- (2-pyridyl N-oxide) -7-pentafluoroethyl- 2,3-dihydro-1-benzoxepine; 3,3-dimethyl-5- (2-pyridyl N-oxide) -7-trifluoromethyl- 2,3-dihydro-l-benzoxepine; 8-bromo-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 7-bromo-3,3-dimethyl-5- (3-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 3, 3-dimethyl-7-nitro-5- ( -nitro-2-pyridyl N-oxide) - 2, 3-dihydro-l-benzoxepine; 3,3-dimethyl-7-phenyl-5- (2-pyridyl N-oxide) -2, 3-dihydro- 1-benzoxepine; 8-cyano-3,3-dimethyl-5- (2-pyridyl N-oxide) -2, 3-dihydro- 1-benzoxepine; 6, 8-dichloro-3 , 3-dimethyl-5- (2-pyridyl N-oxide) - 2,3-dihydro-1-benzoxepine; 7 , 9-dichloro-3 , 3-dimethyl-5- (2-pyridyl N-oxide) - 2 ,3-dihydro-l-benzoxepine; 8 , 9-dichloro-3 , 3 -dimethyl-5- (2 -pyridyl N-oxide) - 2,3-dihydro-l-benzoxepine; 7 , 8-dimethoxy-3, 3-dimethyl-5- (2-pyridyl N-oxide) - 2,3-dihydro-1-benzoxepine; 9-ethyl-7-fluoro-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2, 3-dihydro-1-benzoxepine; 7-chloro-8-fluoro-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2, 3-dihydro-1-benzoxepine; 3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3,7, 8, 9, 10-hexa- hydro- l-naphth [2 , 3 -b] oxepine; 7 , 8 - dichloro- 3 , 3 - dimethyl - 5 - ( 2 -pyridyl N- oxide) - 2 , 3 -dihydro-l-benzoxepin-5-ol; 7-chloro-8-ethyl-3,3-dimethyl-5- (2-pyridyl N-oxide) - 2,3-dihydro-l-benzoxepine; and 8-bromo-3,3-dimethyl-1- (2-pyridyl N-oxide) -3H-benzo[f] - cyclohepta-1,4-diene* 10. Compounds of Claim 1, characterized in that they are chosen from: 7-chloro-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 3,3-dimethyl-5- (2-pyridyl N-oxide) -7- rifluoromethyl- 2,3-dihydro-l-benzoxepine; 7-cyano-3,3-dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro- 1-benzoxepine; 8-cyano-3,3-dimethyl-1- (2-pyridyl N-oxide) -4, 5-dihydro- 3H-benzo [f] cycloheptene; 7 , 8-dichloro-3 , 3 -dimethyl-5- (2 -pyridyl N-oxide) - 2, 3-dihydro-l-benzoxepine; 7 , 8-dif luoro-3, 3 -dimethyl-5- (2 -pyridyl N-oxide) - 2, 3- dihydro -1 -benzoxepine; 7 -cyano- 3 , 3 , 8 - trimethyl-5 - (2 -pyridyl N-oxide) - 2,3- dihydro- 1 -benzoxepine ; 8 -cyano -3 ,3,7- trimethyl-5- (2 -pyridyl N-oxide) - 2, 3-dihydro-l-benzoxepine; 3, 3 -dimethyl-5- (2-pyridyl N-oxide) -2,3-dihydro-l-benzoxe- pine-7-carboxamide; and 3,3-dimethyl-7-phenylsulfonyl-5- (2-pyridyl N-oxide) - 2, 3- dihydro- 1 -benzoxepine. 11. Process for the preparation of a compound of general formula I: in which: X represents O or CHR, R being a hydrogen atom or R, taken together with R 1# forming a bond, R-,, R 2 , R 3 and R 4 , which are identical or different, represent a hydrogen atom or a C x -C 7 alkyl group, it being possible for R x to additionally form a bond with R; R 5 represents a hydrogen atom, a hydroxyl group or R s , taken together w th R 7 , forms a bond or a ^" ' group; R 6 represents a group of formula: in which R 10 and R 1X , taken together with the carbon atom to which they are attached, form an optionally aromatic mono- or bicyclic nitrogenous heterocyclic group having from 3 to 11 members, including 1 or 2 nitrogen atoms, optionally substituted on the carbon atoms by 1 to 7 groups chosen from hydroxyl, nitro, cyano, C-.-C- alkyl or C- ^ -C, alkoxy, it being possible for at least one of the nitrogen atoms of the heterocycle to be N-oxidized; R 7 represents a hydrogen atom or a hydroxyl, C x -C 7 alkoxy or C x -C 7 acyloxy group or R 5 and R- together form a bond or a group; R 8 and R 9 , which are identical or different, represent a hydrogen or halogen atom, a hydroxyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, pentafluoroethyl, C x -C 7 alkyl, C^-C, alkoxy, C^C, alkylthio, C^C, acylthio, C^-C, alkylsulfonyl or C x -C 7 alkylsulfinyl group, a group of formulae: 0 0 0 II ϊ ιι -C-OR 12 , -C-NR 12 R 13 or -C-R 12 in which R 12 and R 13 , which are identical or dif¬ ferent, represent a hydrogen atom or a C- ^ -C, alkyl group, or R 8 and R 9 represent a C β -C 10 aryl, (C 6 -C 10 ) - arylsulfonyl or (C 3 -C 10 )arylsulfinyl group, optionally substituted by one to six substituents chosen from halo, hydroxyl, nitro, cyano, carboxyl, carbamoyl, trifluoromethyl, trifluoromethoxy, penta- fluoroethyl, C-.-C- alkyl, C- ^ -C, alkoxy, C- ^ -C, alkyl- thio, C α -C 7 acylthio, C^C, alkylsulfonyl or C-.-C, alkylsulfinyl, or R 8 and R 9 , which are identical or different, represent a heterocycle having from 3 to 11 members in the ring including 1 to 4 hetereoatoms, which are identical or different, chosen from 0, S and N, optionally substituted by one to six substituents chosen from halo, hydroxyl, nitro, cyano, carboxyl, carbamoyl, trifluoromethyl, trifluoromethoxy, penta- fluoroethyl, C-.-C- alkyl, C α -C 7 alkoxy, C-.-C-- alkyl- thio, Ci-C, acylthio, C^C., alkylsulfonyl or C- ^ -C, alkylsulfinyl, or R 8 and R 9 together form a group (CH 2 ) n , n being a number from 1 to 6, or R 8 and R 9 together form a heterocycle having from 3 to 11 members including 1 to 4 heteroatoms, which are identical or different, chosen from 0, S and N, optionally substituted by one to six substituents chosen from halo, hydroxyl, nitro, cyano, carboxyl, carbamoyl, trifluoromethyl, trifluoromethoxy, pentafluoroethyl, C-.-C- alkyl, Ci-C, alkoxy, C j -C, alkylthio, C^-C, acylthio, C^-C- alkylsulfonyl or C j -C, alkylsulfinyl, and of its pharmaceutically acceptable salts and N-oxides, characterized in that it comprises: either a) the reaction of a ketone of general formula IV: in which X, R x , R 2 , R 3 and R 4 are as defined above, and R 5 ' , R 8 ' and R 9 ' respectively represent the optionally protected R 5 , R 8 and R 9 groups as defined above, with an organometallic compound of general formula: R β '-Rκ V in which R 6 ' represents a group of formula: in which R 10 and R n , taken together with the carbon atom to which they are attached, form an optionally aromatic, mono- or bicyclic nitrogenous heterocyclic group having from 3 to 11 members, including 1 or 2 nitrogen atoms, and optionally substituted on the carbon atoms by 1 to 7 groups, optionally protected if necessary, chosen from hydroxyl, nitro, cyano, C-.-C-. alkyl or C- ^ -C, alkoxy; and b) the deprotection of protected groups to produce a compound of general formula VI: in which X, R 1# R 2 , R 3 , R 4 , R 5 , R β , R 8 and R 9 are as defined above; and optionally either cl) the reaction of the compound of general formula VI thus obtained with a reactant of general formula VII: R 14 -Y VII in which R 14 represents a -^-C, alkyl or C^C., acyl group and Y represents a leaving group, to produce a compound of general formula I in which R, represents a C j -C, alkoxy or C j -C, acyloxy group, respectively; or c2) the dehydration of the compound of general formula VI obtained in b) in the presence of an acid or of an acid chloride to produce a compound of following general formula I: in which X, R x , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 and R 9 are as defined above; and optionally d) the reaction of the compound of formula I obtained in Stage c2) with a peroxide to produce a compound of general formula I in which R 5 and R 7 together form a ^;0 group; and optionally e) the reaction of the compound of general formula VI obtained in Stage b) or of the compound of general formula I obtained in Stage cl) , c2) or d) with an oxidizing agent to form a corresponding N-oxide compound; and/or optionally f) the reaction of the compound of general formula VI obtained in Stage b) or of the compound of general formula I obtained in Stage cl) , c2) or d) with a pharmaceutically acceptable inorganic or organic acid to form a corresponding salt. 12. Pharmaceutical composition comprising, as active ingredient, a compound according to any one of Claims 1 to 10. 13. Compounds of the formula in which X, Rj , R2, R3, R4, Rg and Rgait as defined in Claim 1. 14. Compounds chosen from: 4-phenoxy-3,3-dimethylbutanoic acid; 4-(4-bromophenoxy)-3,3-dimethylbutanoic acid; 4-(4-chlorophenoxy)-3,3-dimethylbutanoic acid; 4-(4-fluorphenoxy)-3,3-dimethylbutanoic acid; 4-(4-methylphenoxy)-3,3-dimethylbutanoic acid; 4-(4-ethylphenoxy)-3 , 3-dimethylbutanoic acid ; 4-(4-isopropylphenoxy)-3,3-dimethylbutanoic acid; 4-[4-(l-methylpropyl)phenoxy]-3,3-dimethylbutanoic acid; 4-(4-methoxyphenoxy)-3,3-dimethylbutanoic acid; 4-(4-trifluoromethoxyphenoxy)-3,3-dimethylbutanoic acid; 4-(4-methylthiophenoxy)-3,3-dimethylbutanoic acid; 4-(4-phenylphenoxy)-3,3-dimethylbutanoic acid; 4-(3-bromophenoxy)-3,3-dimethylbutanoic acid; 4-(3,5-dichlorophenoxy)-3,3-dimethylbutanoic acid; 4-(3,4-dichlorophenoxy)-3,3-dimethylbutanoic acid; 4-(2 ,4-dichlorophenoxy)-3 , 3-dimethylbutanoic acid ; 4-(2,3-dichlorophenoxy)-3,3-dimethylbutanoic acid; 4-(3,4-difluorophenoxy)-3,3-dimethylbutanoic acid; 4-(3-chloro-4-fluorophenoxy)-3,3-dimethylbutanoic acid; 4-(2-ethyl-4-fluorophenoxy)-3 , 3-dimethylbutanoic acid ; 4-(3,4-dimethoxyphenoxy)-3,3-dimethylbutanoic acid; 4-(4-bromo-3-methylphenoxy)-3,3-dimethylbutanoic acid; 4-(3-bromo-4-methylphenoxy)-3,3-dimethylbutanoic acid; 4-(5 , 6 , 7 , 8-tetrahydronaphtyloxy)-3 , 3-dimethylbutanoic acid ; 4-[4(2-methylpropyl)phenoxy)-3,3-dimethylbutanoic acid; 4-(4-chloro-3-ethylphenoxy)-3,3-dimethylbutanoic cid; 4-(4-chloro-3-methylphenoxy)-3,3-dimethylbutanoic acid; 4-(4-bromo-3-chlorophenoxy)-3,3-dimethylbutanoic acid; 5-(4-bromophenyl)-3,3-dimethylpentanoic acid; 5 -(3 , 4-dichlorophenyl)-3 , 3-dimethylpentanoic acid ; 5-(4-bromophenyl)-4,4-dimethylpentanoic acid.

Inventors: BERTHELON JEAN-JACQUES, BRUNET MICHEL, DURBIN PHILIPPE, GUERRIER DANIEL, LUONG TRONG NGHIA, NOBLET MARC, BERTHELON, JEAN-JACQUES, BRUNET, MICHEL, DURBIN, PHILIPPE, GUERRIER, DANIEL, LUONG, TRONG, NGHIA, NOBLET, MARC
Applicants: BERTHELON JEAN JACQUES, BRUNET MICHEL, DURBIN PHILIPPE, GUERRIER DANIEL, LUONG TRONG NGHIA, MERCK PATENT GMBH, NOBLET MARC, BERTHELON, JEAN-JACQUES, BRUNET, MICHEL, DURBIN, PHILIPPE, GUERRIER, DANIEL, LUONG, TRONG, NGHIA, NOBLET, MARC
Application year: 1993
Main classification: C07D313
IPC codes: A61K31, A61P9, A61P11, A61P17, A61P21, A61P25, C07C57, C07C59, C07D213, C07D215, C07D313, C07D405, C07D409, C07D493