Morpholine chemistry

L. Hough and A. C. Richardson, From sugars to morpholines, spiro-acetals and alkaloids, in H. Ogura, A. Hasegawa, and T. Suami, (Eds.), Carbohydrates Synthetic Methods and Applications in Medicinal Chemistry, Kodansha, Tokyo, 1992, pp. 108-119. 

Organometallic compounds in the chemistry of morpholine alkaloids 91MI42. 

Chemistry of compounds with a morpholine ring 91MI13. 

Subtle reactivity differences are also found in the reaction of 6-bromo[l,2,5]thia- (or selena) diazolo[3,4-/)]pyridines (92) with morpholine and cuprous cyanide which afford the C(7)-amine (94) and C(6)-nitrile (95), respectively (Scheme 15). Under identical reaction conditions, 6-bromo-benzo[l,2,5]thiadiazole affords exclusive C(6)-amination and C(6)-cyanation. The anomalous regio-chemistry in the formation of (94) is attributed to initial formation of a hetaryne intermediate (93), which adds morpholine at the more electron-deficient C-7 position <79IJC(B)13,86IJC(B)500>. 

In the nineties a new compound class, the strobilurins, was introduced into the market. In Europe azoxystrobin and kresoxim-methyl were heavily used in cereals and the established product concepts and treatment systems had to be adjusted. Namely the importance of anti-resistance management (ARM) was recognized as a key factor in managing crop treatments and product portfolios. Therefore, contrary to first assumptions, product classes like the morpholines were not substituted directly by this new chemistry, but added as a complement to new product combinations to suppress resistance build vp. 

Removal of the iV-a-protective group (r-Boc or Fmoc). In r-Boc chemistry, TFA is used in Fmoc chemistry, piperidine or morpholine is used. 

As an extension of this chemistry, the [3+2] cycloaddition reaction of new atropisomeric 4-dialkylamino-5-chloro-l,2-dithiole-3-thiones 130 and DMAD or its diethyl analogue has been utilized to give thioacid chlorides 131 (Scheme 13) <20030L929>. These have been converted into thioamides 132 with 2 equiv of pyrrolidine (or morpholine) by substitution of the 5-chloro substituent and phthalimide ring opening. Similar reactivity toward 1 or 2 equiv of pyrrolidine was noted for 130, which was obtained according to the general method described. 

A key feature of this molecule is the cis vicinally-substituted morpholine core. This skeleton also contains a mixed acetal juncture and a third stereocenter that is adjacent to the oxygen ether linkage. The route that the medicinal chemistry group designed contained many attractive features that were initially envisioned to be the cornerstone of a longer... 

The two nonpolar solvents most commonly used for the determination of dipole moments by the dielectric constant method are benzene and dioxane, however, numerous other solvents have been used for this purpose. The use of other solvents often becomes a necessity in heterocyclic chemistry where many heterocycles with polar groups are not soluble in solvents of low polarity. For example, we have successfully used ethyl acetate, acetic acid, and n-butyl ether. In some cases, the use of mixed solvents was necessary (dioxane-morpholine, dioxane-... 

Chemistry Piperazines, pyridines, pyrimidines, imidazoles, triazoles Morpholines, piperidines, spiroketalamines Hydroxyanilides Thiocarbamates, allylamines... 

Figure 9 Comparison of RP-LC (A) and CZE (B) separations of tryptic peptides of hGH. Peak assignments and correlations for selected fragments are noted. CZE background electrolyte 0.01 mol I Tricine, 0.045 mol I morpholine, 0.02 mol I NaCI, pH 8.0, detection at 200 nm, 316 V cm, 20 pA. LC column Aquapore RP-300 (4.6 x 250 mm), flow rate 1 ml min, detection 214 nm. Solvents A, 0.1% trifluoroacetic acid (TEA) in water B, 0.1% in acetonitrile gradient 0-20% B in 20 min, 20-25%B in 25 min. (Reprinted with permission from Grossman PD, Colburn JC, Lauer HH, et al. (1989) Application of free-solution capillary electrophoresis to the analytical scale separation of proteins and peptides. Analytical Chemistry 61(11) 1186-1194 American Chemical Society.)...

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