124620-30-0

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Grignard-type additions were readily achieved under the mediation of CuI (10 mol%) and samarium (2 equiv.) by employing various organohalides,e.g.benzyl, aryl, heterocyclic and aliphatic halides (Cl, Br or I), and diverse carbonyl compounds (e.g.carbonic esters, carboxylic esters, acid anhydrides, acyl chlorides, ketones, aldehydes, propylene epoxides and formamides) to afford alcohols, ketones and aldehydes, respectively, with high efficiency and chemoselectivity, in which the organosamarium intermediate might be involved.

Strecker-type reaction of nitrones using acetone cyanohydrin as a cyanide source was developed. By treating nitrones with acetone cyanohydrin in the presence of n-BuMgCl, transcyanation from the cyanohydrin to the nitrones smoothly proceeded in THF at 35 °C. The amount of n-BuMgCl could be reduced to 0.2 equiv to give the corresponding α-cyanohydroxylamines in up to 98% yields.

N-(Phenyl-substituted cycloalkyl or cycloalkylmethyl)-phenylethanolamine derivatives (I) (including benzo-heterocyclic analogs) are new. Also new are cyclopropylamine or cyclopropylmethylamine derivative intermediates (II). Phenylethanolamine derivatives of formula (I) (including optical isomers, enantiomer mixtures and racemates) and their salts, solvates and hydrates are new. n : 0 or 1; m : 1-4; X : direct bond, 2-6C alkenylene, -O-Q-, -NH-Q-, -S-Q- or -Q-; Q : 1-6C alkylene; R 1>H; and R 3>hydroxyalkyl or halo; or R 1> + R 2>OCH 2CONH, CH 2CH 2CONH, CH=CHCONH, NHCH 2CONH, SCH 2CONH, OCONH, SCONH, NHCONH or OCH 2SO 2NH (all optionally substituted (os) by 1 or 2 of alkyl, OH or halo); R 3>, R 4>H, OH, halo, 1-6C alkyl, 1-6C haloalkyl, 1-6C hydroxyalkyl, NH 2 or mono- or dialkylamino; R 5> - R 8>H, OR 9>, halo, 1-6C alkyl, 1-6C haloalkyl, 1-6C hydroxyalkyl, 3-6C cycloalkyl, 3-6C hydroxycycloalkyl, CN, NO 2, COR 9>, COOR 9>, CONR 10>R 11>, NR 10>R 11>, NR 10>COR 9>, NR 10>SO 2R 12>, SR 12>, SOR 12>, SO 2R 12>, SO 2NR 10>R 11> or halo; or two vicinal groups R 6> - R 8> together= 2-6C alkylene, 2-6C alkenylene or O-Q-O (all os by 1 or 2 of alkyl, alkoxy, OH or halo); R 9> - R 11>H, alkyl, aryl or arylalkyl; R 12>alkyl, aryl or arylalkyl; unless specified otherwise alkyl moieties have 1-4C and aryl moieties 6-10C. An independent claim is included for cycloalkylamine or cycloalkylalkylamine derivative intermediates of formula (II) as new compounds, provided that m= 1. [Image] [Image] ACTIVITY : Antiinflammatory; antiasthmatic; antiallergic; virucide; antibacterial; fungicide; protozoacide; anthelmintic; cardiant; dermatological; immunosuppressive; tocolytic; antiarrhythmic; vasotropic; antipruritic. MECHANISM OF ACTION : beta -Mimetic.

Matrix presented The viability of Ndl2 as a one-electron reducing agent in organic synthesis has been examined by studying coupling reactions between alkyl chlorides and ketones and aldehydes.

The reaction of styrene and some methyl-substituted styrenes 1 with lithium and a catalytic amount of 4,4′-di-tert-butylbiphenyl (DTBB) in the presence of several electrophiles [Me3SiCl, Me2CO, Et2CO, (CH2)5CO, Pr2CO], in THF, at temperatures ranging from -78 to 0°C, gave, after hydrolysis, products 2 resulting from addition of lithium to the olefinic double bond and successive trapping with the electrophilic reagent. When a carbonyl compound was used as electrophile, mixtures of the monoaddition-reduction compounds 3 and 4 were obtained as by-products, which could be easily separated from the diaddition products 2.

Samarium metal in the presence of catalytic amounts of iodine was found to be effective for the Barbier reaction of carbonyl compounds.

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The present invention is directed to novel cyclic nitrones and their use in the prevention of oxidation tissue damage by free radicals, their use in the treatment of a number of disease states in which radicals either damage or destroy tissues via oxidation, and pharmaceutical compositions containing these cyclic nitrones.