SUBJECTS morpholine

Dithiocarbamate complexes of copper have been sythesized at a high rate. Reports of new complexes include the morpholine-4- (44), thio-morpholine, AT-methylpiperazine-4-, and piperidine- (291) dithiocarba-mates. Novel, polymeric complexes of the type Cu(pipdtc)2 (CuBr) in = 4, or 6) and Cu(pipdtc)2 (CuCl)4 have been prepared by reactions of[Cu(pipdtc)2] with the respective copper halide in CHCla-EtOH (418). The crystal structures of the polymers are known to consist of sheets of individual [Cu(pipdtc)2] molecules linked to polymeric CuBr chains via Cu-S bonds. A series of copper(I) dtc complexes have been the subject of a Cu and Cu NQR-spectral study (440). 

Lyocell A papermaking process, based on dissolving wood pulp in N-methyl morpholine. Developed by Courtaulds, but the subject of a patent dispute with Lenzing, Austria, since 1993. Courtaulds has a plant in Mobile, AL, and Lenzing has one in Heiligenkreuz, Austria. 

Azacyclic monomers containing an endocyclic nitrogen atom which are most commonly subjected to polymerisation in the presence of coordination catalysts include a-aminoacid /V-carboxyanhydrides. However, other monomers of this type, such as morpholine-2,5-dione, have also been subjected to coordination polymerisation. 

Pyrrolidine, piperidine and morpholine enamines of aldehydes and ketones have been the subject of a pioneering work by D. H. Williams and collaborators8. The most abundant fragment ion is produced by the loss of an alkyl radical R by allylic cleavage (Scheme 3). When R = H the loss of a H atom is more energy demanding and the... 

Benzodiazocine 264 was prepared through a 4-component Ugi reaction including a primary amine tethered to a BOC-protected internal amino nucleophile, followed by a postcondensation base-catalyzed cyclization. Thus, 2 equiv of aldehyde 262 were employed to promote Schiff base formation and a one-pot, double scavenging protocol with immobilized tosylhydrazine and di-isopropylethylamine removed both the excess aldehyde and any unreacted acid 261. The intermediate 263 was then subjected to treatment with TFA, followed by proton scavenging with resin bound morpholine, to promote cyclization to afford the eight-membered ring (Scheme 47) <2001TL4963>. 

The Katritzky group has developed a pyrrole synthesis based on the benzotriazole derivative 429, which was subjected to lithiation, followed by introduction of imines. The resulting intermediates 430 could thereafter be annulated to the 1,2-diarylpyrroles 431 with concomitant elimination of morpholine and benzotriazole (Scheme 54) <1995TL343>. 

Dideoxynucleosides show potent anti-retroviral activity against HIV-specific reverse transcriptase80-83. In particular, 2, 3 -dideoxy-3 -C-cyano-2 -substituted thymidine derivatives (33 A and 33 B) with a free 5 -hydroxy function (R1 = H) are potential inhibitors of the HIV-reverse transcriptase-promoted c-DNA synthesis. As these compounds have yet to be prepared by another method, the 3 -ene-nitrile 3284 was subjected to conjugate addition reactions with ammonia, primary amines, secondary amines and carbon nucleophiles. Most of these nucleophilic amine addition reactions give either the trans-isomer 33 A as the sole product (e.g., reaction with pyrrolidine, piperidine, morpholine), or as the major product along with the c/s-isomer (e.g., reaction with methylamine, benzylamine), except for the reaction with ammonia where the cts-isomer 33B is formed as the major product84. 

The plot in Fig. 12.22 further supports the conclusions. It is seen that a large amount of morpholine should be used, (Xj should be at its upper level). The amount of by-product is largely controlled by the amount of titatium tetrachloride, X2, under these conditions. The level of X2 will therefore be subject to compromise judgements. To determine a suitable level of Xjj a projection of the reduced models with x set to 2.00 is shown in Fig. 12.23. The temperature setting x = 2.00 is an extrapolation outside the explored domain and as such not strictly allowable. It corresponds to a reflux temperature (120 °C, petroleum ether) which was considered convenient and worth trying. 

Blood Sample mixed with ascorbic acid and morpholine, subjected to distillation in alkaline solution, distillate extracted with solvent and concentrated. GC-TEA 8 pg or 0.05 /tg/kg (for 20 g sample) 93% Dum et al. 1986... 

A facile and efficient synthetic route to densely substituted thiophenes based on base induced cyclization reaction between thioamides derived from morpholine and a-haloketones has been reported. Thus, the thioamides 4 were subjected to treatment with the haloketones 5 (R = H, Ar, Me) under basic conditions to provide the tetrasubstituted thiophenes 6. Likewise, the reaction was also demonstrated to give good yields of thiophenes when the haloketones were replaced with 2-bromo-3-oxobutyric acid derivatives or propargyl bromide <04T6085>. 

Various 2-oxo compounds have been subjected to a variety of reactions. Alkylation and acylation result in the formation of 1,3-disubstituted products.Similarly the Mannich reaction with morpholine gives products such as the bis compound 107. Halogenation of the 0x0 compound 108 with bromine in acetic acid," or chlorine in acetic acid, ° or with sulfuryl chloride results in formation of the monohalo derivatives 109. The chlorine atom in 109 (R = Cl) can be removed by hydrogenation over palladium on charcoal. Nitration of the chloro compound 110 with a mixture of nitric and sulfuric acids provides the nitro derivative 111, which may be catalytically reduced to the amino compound 112. If the reduction is carried out in the presence of an aldehyde, the product is a substituted amino derivative (113). Alternatively the amine 112 can be condensed with an aldehyde and the resultant Schiff base reduced to give the product 113. 

The intermediate lactol was to be subjected to a diastereoselective acetalization with (/ )-3,5-bistrifluoromethylphenyl ethanol. In order to probe this diastereoselective coupling, a variety of chiral iV-R lactols 76 was desired. In addition, since the ultimate success to aprepitant via this route depended on crystalline intermediates, numerous A -substituted lactols 76 needed to be prepared in order to investigate the crystalline properties of downstream intermediates. Accordingly, a versatile procedure to access a variety of A-substituted morpholine-2,3-diones 75 and 2-hydroxymorpholin-3-ones 76 was required. This was accomplished by the condensation of amino alcohols 74 with diethyl oxalate to afford diones 75, which could be selectively reduced to the corresponding lactols 76 (Scheme 22). A host of these substrates were synthesized however, none offered any significant advantage over the simple A-Bn lactol 69. Thus, the objective became the development of a concise synthesis for this substrate. 

The Michael addition of secondary amines to a,)S-unsaturated carbonyl compounds under MWI essentially required the presence of water to drive the amine addition to completion and the presence of at least 10 mole equivalents of the amine. Besides increasing the polarity and possibly some micellar effect, water facilitates protonation of the resulted enolate from amine addition. In a typical procedure, benzalacetophenone was mixed with morpholine (469) and water in a teflon flask and subjected to MWI for 2 min to yield 93% of the 1,4-adduct 471 (Scheme 92). The method was also extended to other morpholine derivatives 472 and 473 in 30% and 100% yields, respectively (00SC643). 

In a similar fashion, the resin-bound 5-bromo-2-aminobenzothiazole was subjected to a microwave-assisted Buchwald-Hartwig amination " with morpholine using BuONa as the base and a catalytic system comprising Pd(PPh3)4 and X-Phos in DMF at 160°C for 1 h. The product was cleaved from the resin using the previous conditions (Scheme 8.24). 

A related example disclosed recently by McNulty et al. is a one-pot Wittig reaction of aldehydes with phosphonium salts in the presence of 10 mol% of morpholine, L-proline or p-toluenesulfonamide and 2.0 equiv. of NaHCOs (Scheme 55) [227]. This reaction gives high E selectivity. A rapid and reversible condensation of the aldehyde with the amine (derivative) catalyst has been proposed to form an iminium or an imine intermediate that is subjected to olefination with the in situ generated phosphonium ylides, though a base-catalyzed pathway is not ruled out. It has been confirmed that an N-sulfonyl imine can be formed quantitatively from the corresponding aldehyde and sulfonamide under the reaction conditions. 

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