3-Morpholino

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). 

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

Variously trisubstituted thiazoles were prepared by Ried and Kaiser by condensing PhNHCPh=NCSR with BrCH R, (Scheme 149), R = OEt, morpholino and Ri = 4-NO2C6H4, Ac, Bz, COjEt, CN, 4-PhCsH4CO, NO2, 4-NO2C6H4CO, 4-BrCgH4CO, COCHaBr yields ranged from 45 to 92% (811). 

Also, piperidino- and morpholino- are preferred to 1-piperidyl- and 4-morpholinyl-, respectively. 

AACC Method32-07for TDF, SDF, and IDF. This approved method is a modification of the Prosky method. The phosphate buffer is replaced by a buffer of 2(A[-morpholino)ethanesulfonic acid (MES) [4432-31-9] and tris(hydroxymethyl)aminomethane (TRIS) [77-86-1]. Precision is improved and analysis time is reduced. I DE may be determined on a separate sample or calculated by summing the SDE and IDE values. The MES /TRIS-modified method has received final approval by AACC and official first action by AO AC (5). 

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