Polar morpholine

The yields ranged from 55% for the mixture of enamines formed from morpholine and methylisopropyl ketone to 94% for the enamine formed from dimethylamine and methyl t-butyl ketone. The hindered ketone 2,5-dimethylcyclopentanone could be converted to an enamine, but the more hindered ketone, 2,6-di-t-butylcyclohexanone, was inert. White and Weingarten 43) attribute the effectiveness of titanium tetrachloride in this reaction to its ability to scavenge water and to polarize the carbonyl bond. 

Nitroolefins also offer the possibilities of 1,2 cycloaddition (37,57) or simple alkylation (57-59) products when they are allowed to react with enamines. The reaction of nitroethylene with the morpholine enamine of cyclohexanone led primarily to a cyclobutane adduct in nonpolar solvents and to a simple alkylated product in polar solvents (57). These products are evidently formed from kinetically controlled reactions since they cannot be converted to the other product under the conditions in which the other... 

When the iterative maximum localization extended Hiickel (IML-EH) method is applied to the drug molsidomine 12 (Section 5.03.12), the angle widening at N2-N3-C4 observed by X-ray analysis, 115° instead of the typical 108°, is due to induced polarization <1998JMT291>. The N3 position is the most electron deficient, followed by C-5. The N+-N bond connecting N3 to the morpholine ring has no 71 character despite the electron deficiency at N3 and the distortion toward planarity. 

The influence of the substrates 1-octene and morpholine was measured by repeating the cloud titrations with addition of these substances to determine the appropriate composition of the solvent mixture for the reaction. While the addition of 1-octene has almost no effect on the TMS systems the addition of morpholine leads to a decrease of the miscibihty gap (Fig. 14). As morphoHne itself is semi-polar and can be used as a mediator a smaller amount of s3 is needed to obtain a homogeneous system. 

However, morpholine-4-carboxylic acid 2-hydroxy-1-methyl-ethyl ester is formed by the reaction of PC and the substrate morpholine in an undesired side reaction. By use of 1.4-dioxane or the pyrrolidones as mediator s3 about 30 to 45% of the morphoUne is consumed by this side reaction. The by-product is contained in the PC phase and can not be extracted to the non-polar product phase. The selectivity to the desired amines is lowered, because of the consiunption of the morphoUne. Thus, PC has to be substituted by another polar solvent (e.g. water, methanol or ethylene glycol) in future experiments. The lactates react with the morphoUne, too resulting in the corresponding amide. Overall, the hydroaminomethylation in the TMS systems PC/dodecane/lactate results in a conversion of 1-octene of about 80%, but in selectivities to the amines of only 50 to 60%. 

A more recent process for producing regenerated cellulose involves the use of V-methyl-morpholine-A-oxide, a highly polar solvent, at about 130°C to dissolve cellulose [Rosenau et al., 2001], About 5% of all regenerated cellulose is produced by this method. 

Finally, a recently reported copper catalyzed carbon-nitrogen bond forming process utilises reagents with polarity opposite to the common disconnection protocols. An electrophilic nitrogen, in most cases an (9-acyl hydroxylamine derivative, was successfully coupled with diarylzinc reagents in the presence of copper triflate or copper chloride. Di(2 -pyridyl)zinc and TV-benzoyloxy-morpholine were reacted at ambient temperature in the presence of 1% copper(I) triflate to give 2-morpholinopyridine in 71% yield (7.81.), Under these mild conditions the reaction was over in less than one hour.103... 

It has been known for a long time that maximum photosensitivity is attained with diazonium salts bearing electron-donating substituents on the benzene ring (44CKL1146). In general, the ortho isomer is the most sensitive and the substituent should be polar. Alkoxy-substituted iV-(4-diazophenyl)morpholines (105) are an important group because of their... 

Alkylation of enamines prepared from aldehydes was studied by Elkik,210 Opitz and Mildenberg,211 and Williamson 212 and alkylation of enamines prepared from ketones by Stork et al.75 These investigators demonstrated that the ease of alkylation depends on the basicity of the enamine in question. Enamines prepared from the more basic pyrrolidine are alkylated more readily than those obtained from morpholine. Better yields of the enamines (44) from pyrrolidine are obtained, in contrast to the preparations (45) from piperidine (which are bases about as strong as pyrrolidine) this may result from the stabilizing influence of the exocyclic double bond in the polarized form of the pyrrolidine derivative. 

If the amino component is used as a salt such as the hydrochloride, it has to be liberated by means of an auxiliary base which is known to further enhance the rates of racenoization.t l With bulky tertiary amines such as ethyldiisopropylanoine, W-ethylpiperidine, or W-ethyl-morpholine rather than triethylamine, this problem is partly circumvented (see Section 7.3),PI however it is advisable to avoid the use of bases whenever possible by isolating the free anoino component prior to the coupling step. Moreover, detailed investigations clearly revealed that racemization is favored at higher temperatures (rt) when the reaction is carried out in polar solvents like DMF,P l or when the polarity of the solvent is further enhanced by the presence of salts such as LiBr or triethylammonium chloride.P ... 

We have synthesised 4-(8-morpholin)capriloyl-Neu5Ac-o2Me lo [28], wishing us a long carboxylic chain with a polar end would form specific interactions with the protein, or, in alternative, to have a compound which shows resistance to the NA. 

An extension of Buchwald s catalytic amination using palladium led to amination of 2-chlorobenzoxazole [65]. The marked reactivity enhancement of the chloride is attributed to the polarization at C(2). Palladium-catalyzed amination of electron rich 2-chloroben-zoxazole with morpholine gave 2-morpholinylbenzoxazole (114) in substantial yield in the presence of Pd2(dba)3/BINAP [65], 2-Morpholinylbenzoxazole (114) also was obtained from 2-chlorobenzoxazole in 51% yield with Pd(O2CCF3)2/P(r-Bu)3 [66]. 

This requirement has been met with soluble, pre-imidized polyimides. It has been found that secondary amines react quite readily with such polyimides in polar solvents such as N-methylpyrrolidinone or dimethylacetamide The reaction was done initially with morpholine for a series of available pre-imidized polymers (see Table I). The reaction was easily followed by infra-red spectroscopy (IR) (see Figure 2), the imide carbonyl absorptions at 1780 and 1723 cm 1 being replaced by amide carbonyls at 1645 cm1. In addition, the aliphatic C-H absorptions at 2880 cm 1 were noted. 

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