Epoxide with morpholine

The formation of the amine (496) when 3)5-toluene-p-sulphonates are treated with 2-dimethylaminoethanol involves both inversion at C-3 and demethyla-tion. The reaction of androstane-16,17-ketols and 17 -acetoxy-16a,Ha-epoxide with morpholine to give a-morpholino-ketones has been thoroughly investigated and rationalised. H/5-Aminoandrosta-3,5-diene, prepared by reduction of the H-oxime, possesses some antimicrobial activity which is not enhanced by substitution of the amino-groups with 2-chloroethyl, 2-hydroxy-ethyl, or 3-aminopropyl groups similar 2-chloroethyl substituted H)5-amines have been cyclised by treatment with base to give H -aziridines. All four... 

Condensation of that intermediate with epichlorohydrin in the presence of a catalytic amount of piperidine affords the chlorohydrin 213, admixed with some epoxide. Reaction with tertiary butylamine completes construction of the propanolamine side chain. Displacement of the remaining halogen atom of 214 with morpholine under more strenuous conditions affords timolol (215). ... 

The racemic polyzonimine (19) is prepared as shown in Scheme 33. The expoxide (314) is rearranged to the aldehyde (315) by refluxing with LiBr-HMPA in benzene. Morpholine enamine (316) derived from 315 is condensed with nitroethylene, generated in situ from 2-acetoxynitroethane, to afford the nitroaldehyde (317). Ethylene acetalization, reduction over Raney nickel, and subsequent deacetalization give ( )-polyzonimine (19) in 22% overall yield from the epoxide (314) 113). 

In the presence of oxygen the hydroamination products can not be obtained. Instead - especially with secondary amines or diamines - dehydrogenated di- and polyadducts are formed [79]. By reaction of morpholine or piperidine in air-saturated benzene solution the bisadduct, tetraadduct epoxide and the dimer shown in Figure 3.8 could be isolated and characterized. A defined 1,4-addition pattern is found in all these products. 

The morpholine derivative 75 has an obvious amide disconnection to 76 and a less obvious 1,2-diX disconnection at the ether to 77. This is obviously an epoxide 78 adduct with ammonia. 

Moxnidazole is,an antiparasitic drug, and our next target molecule is an important intermediate in its synthesis, The obvious first disconnection is of the carbamate group, revealing two 1,2 relationships. A 1,2-diX disconnection gives an epoxide that can be made by alkylation of morpholine with epiehlorohydrin,... 

Morpholine reacts with the 17j3-acetoxy-16oc,17a-epoxide (86) to give the 16 -morpholino-17-ketone (87) in presence of water, or the 17)8-morpholino-16-... 

Most interest in biological activity has been centered on 4,5,6,7-tetra-hydrothieno 2,3-c, - or - 3,2-c pyridines. A considerable number of derivatives of these systems have been prepared by the sodium borohy-dride reduction of quaternary ammonium salts,90,91 or by reaction of the 4,5,6,7-tetrahydro base with a suitable halide,9,I°4 tosyl derivative,105 epoxide,106 or activated alkene.107 An alternative, and very convenient, synthesis of 2-amino-3,6-substituted 4,5,6,7-tetrahydrothieno[2,3-c[-pyridincs (89), used mostly by Nakanishi and his co-workers, involves reaction of an N-substituted 4-piperidone, a compound of the type 88 and sulfur, in the presence of morpholine. The group X can be CN,... 

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