1 “ morpholine

Morpholine (tetrahydro-l,4-oxazine) adopts a chair conformation. The enthalpy difference between the equatorial and axial position of the NH group (2.63 kJ moh ) is similar to that for piperidine (see p 360) and favours the equatorial conformation. 

The barrier to ring inversion of 4-methylmorpholine (48.1 kJ mol ) is comparable to the value (49.8 kJ mol ) found for 1-methylpiperidine. 

Morpholine and /-substituted morpholines 1 are obtained by cyclization of bis(2-aminoethyl) ethers or by cyclocondensation of bis(2-chloroethyl) ethers with ammonia or primary amines  

3-Disubstituted morpholines 2 are prepared from A -benzyl protected 2-aminoethanols and oxirane in the presence of 70% H2SO4 followed by catalytic debenzylation  

2-Oxomorpholine derivatives 3 are made by cyclocondensation of a-aminocarboxylic esters with oxirane or from A -substituted 2-aminoethanols with a-bromocarboxylic esters  

Methylene Blue (43) results from oxidative coupling of 4-amino-N,N-dimethyIaniline and N,N-dimethylaniHne with Na2Cr206 in the presence of Na2S203. Again, the intermediate is an indamine salt, which undergoes cyclization giving the salt of 3,7-bis(dimethylamino)phenothiazine (leuco form of Methylene Blue). Its dehydration produces the dye (Caro, 1876, Bernthsen, 1885)  

Reducing agents transform Methylene Blue into the yellow leuco form, which is reconverted to the dye by atmospheric oxygen. For this reason it is used as a redox 

Morphohne (tetrahydro-l,4-oxazine) adopts a chair conformation. The enthalpy difference 

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The mechanism of the reaction la not known with certainty. It is known from studies utilising as tracer that no change in the carbon skeleton occurs during the reaction, and also that unsaturated hydrocarbons can undergo reactions very similar to those of ketones thus both styiene and phenyl-acetylene can react with sulphur and morpholine to produce phenylaceto-thiomorphoUde, hydrolysis of which yields phenylacetic acid ... 

Cleaved with mild base such as piperidine, morpholine or dicyclohexylamine... 

The N-basicity of the commonly used amines (pyrrolidine > piperidine > morpholine) drops by 2-3 orders of magnitude as a consequence of electron pair delocalization in the corresponding enamines. This effect is most pronounced in morpholino enamines (see table below). Furthermore there is a tendency of the five-membered ring to form an energetically favorable exocyclic double bond. This causes a much higher reactivity of pyrroUdino enamines as compared to the piperidino analogues towards electrophiles (G.A. Cook, 1969). 

Another method for deallylation of ally esters is the transfer of the allyl group to reactive nucleophiles. Amines such as morpholine are used[415-417], Potassium salts of higher carboxylic acids are used as an accepter of the allyl group[418]. The method is applied to the protection and deprotection of the acid function in rather unstable /f-lactam 664[419,420]. 

The reaction of 2-mercapto-4-phenylthiazole with morpholine yields 2-morpholino-4-phenylthiazole (3) (Scheme 3) (31). 

Electrophilic reaction can account for the additions of morpholine or phosphonyl (Scheme 14), or... 

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