Morpholines 2-hydroxy

Morpholin 2-Hydroxy-4-(2-hydroxy-ethyl)-2,3,3-trimethyl- VI/4, 598 Nonan 1-Nitrooxy- EI6c, 29 (Br - 0-N02)... 

The intermediacy of dipolar species such as 186 has been demonstrated by reaction of enamines with 2-hydroxy-1-aldehydes of the aromatic series (129). The enamine (113) reacts in benzene solution at room temperature with 2-hydroxy-1-naphthaldehyde to give the crystalline adduct (188) in 91 % yield. Oxidation with chromium trioxide-pyridine of 188 gave 189 with p elimination of the morpholine moiety. Palladium on charcoal dehydrogenation of 189 gave the known 1,2-benzoxanthone (129). 

The side chain hydroxy group of 3-(2-hydroxyethyl)-2-methyl-9-methoxy-4//-pyrido[l,2-u]pyrimidin-4-one, and that of its 6,7,8,9-tetrahydro derivative was acylated with MeS02Cl in the presence of NEts in CH2CI2 at room temperature (95MIP4, 96MIP2). The hydroxy group of 2-[4-(4-hydro-xybenzoyl)benzyloxy]-3-methyl-4//-pyrido[l, 2-u]-pyrimidin-4-one, its 6-methyl derivative and 2-[4-(4-hydroxybenzoyl)benzylthio]-3-methyl-4//-pyrido[l, 2-u]pyrimidin-4-one was alkylated with 4-(2-chloroethyl)morpholine hydrochloride and 4-picolyl chloride hydrochloride (96EUP733633). 

Irradiation of 4-(3-benzoylpropionyl)-1,4-morpholine (267) yielded an epimeric mixture of 9-hydroxy-9-phenylperhydropyrido[2,l-c][l,4]oxazin-6-ones 268 and 269 via hydrogen abstraction from the position 3 of the morpholine moiety of 267 (98T2529). It was assumed that the steric hinderance between the phenyl group and the hydrogen atoms of 5-methylene group of 267 in the biradicals contributed to the observed selectivity. 

In a scheme intended to produce a more highly substituted oxazolidone, epichlorohydrin is condensed with morpholine in the presence of strong base to give the aminoepoxide, 27. Ring opening of the oxirane by means of hydrazine gives the hydroxy-hydrazine (28). Ring closure with diethyl carbonate leads to the substituted oxazolidone (29). Condensation with 18 affords furaltadone (30). ... 

Although the morpholine ring is often used as a modified version of a tertiary nitrogen, the ring system finds only rare use as a nucleus for medicinal agents. Both compounds below, in fact, may be regarded as more properly related to cyclized forms of hydroxy-phenethylamines. 

Hydroxy-4-benzyl-5,6-diphenyl-2,3-dihydro-1,4-oxazin wird durch Lithiumalanat iiber das Enol-Salz zu 2-Hyclroxy-4-benzyl-2,3-diphenyl-morpholin reduziert6. Durch Ringoffnung und Schliefiung wird die Hydr-oxy-Gruppe verschoben. 

Stem nuclei. Morpholine, 5. Hydroxy compounds Scopolamine, 99. Carbonyl compoimds, 135 Saccharin, 169. Carboxylic acids, 313. Sulphonio acids, 355. Amines, 361 Meldola s blue, 383. 

Moreover, Kim and coworkers have shown that a-amino-butyrolactones can be synthesized by a related process employing the amino acid homoserine with an unprotected hydroxy functionality [31]. In a more recent publication by the same research group, morpholin-2-one derivatives of type 9-37 have been prepared (Scheme 9.6) [32]. Herein, glycolaldehyde dimer 9-32 acts as a bifunctional compound, which first reacts with the a-amino acids 9-33 to give the iminium ions 9-34,... 

The hexahydro-2-methyl-477-[l,4]oxazino[3,4-3][l,3]oxazin 4-one 393 was prepared in excellent yield by electrochemical oxidation and cyclization of the 3-hydroxy-l-(morpholin 4-yl)butanone 392 (Equation 44). The oxazino[3,4+][l,3]oxazin-4-one 393 is one of a series of compounds obtained by utilization of electrochemistry in parallel and combinatorial syntheses <2000JC0545>. 

Initially PDPs were synthesized by stepwise polycondensation of linear activated depsipeptide [93]. In 1985, Helder, Feijen and coworkers reported the synthesis of PDPs by ROP of a morpholine-2,5-dione derivative (cyclic dimer of ot-hydroxy- and a-amino acid cyclodepsipeptide, cDP) [94, 95]. The ROP method gives an alternative type of PDP by homopolymerization and also allows the copolymerization with other monomers (lactones and cyclic diesters) including LA, GA, and CL to give a wide variety of functional biodegradable materials. The synthesis of PDPs as functional biomaterials has been recently reviewed [17]. 

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%. 

Photolytic. Mathew and Khan (1996) studied the photolysis of metolachlor in water in the presence of kaolinite, montmorillonite, and goethite and fulvic acid under neutral and acidic conditions at 22 °C. Metolachlor degraded in all the treatments at both pH conditions. The rate of photolysis and degradation products formed was dependent on the duration of UV exposure, the initial pH of the solution, and the composition of the suspended/dissolved material. The following photoproducts identified included 2-hydroxy-A-(2-ethyl-6-methylphenyl)-A-(2-methoxy-l-meth-ylethyl)acetamide, 4-(2-ethyl-6-methylphenyl)-5-methyl-3-morpholine (major product forming at 74-84% yield), 8-ethyl-3-hydroxy-A-(2-methoxy-l-methylethyl)-2-oxo-l,2,3,4-tetrahydroquino-line, 2-chloro-A -(2-(l-hydroxyethyl)-6-methylphenyl)-7V-(2-hydroxy-l-methylethyl)acetamide, and 2-chloro-A -(2-ethyl-6-hydroxymethylphenyl)-A-(2-methoxy-l-methylethyl)acetamide. 

The 6//-l,3-thiazin-6-iminium hydroperchlorate salts 78-81 give interesting products when treated with nucleophiles <2003H(60)2273>. Hydrolysis of 6-imino-6//-l,3-thiazine hydroperchlorate 78 affords (2Z,4Z)-2-cyano-5-hydroxy-5-phenyM-azapenta-2,4-dienethioamide 82 in excellent yield, while treatment with morpholine gives 2-(morpholinomethylene)malononitrile 83 and thiobenzamide. The 5-(ethoxycarbonyl) -(methylthio)-2-aryl-6/7-l,3-thiazin-6-iminium salts 79 and 80 react with hydroxide or morpholine to afford ethyl 4-(methylthio)-2-aryl-6-thioxo-l,6-dihydropyrimidine-5-carboxylates 84 and 85. In the case of the 4-chloro analogue 80, the (Z)-ethyl 2-(5-(4-chlorophenyl)-37/-l,2,4-dithiazol-3-ylidene)-2-cyanoacetate 87 is also formed for the reaction with sodium hydroxide. The 1,2,4-dithiazoles 86 and 87 can be obtained as the sole product when 79 and 80 are treated with sodium acetate in DMSO. Benzoxazine 88 is isolated when the iminium salt 81 is treated with morpholine or triethylamine. Nitrile 89 is formed as a ( /Z)-mixture when 6-imino-67/-l,3-thiazine hydroperchlorate 79 is reacted with triethylamine and iodomethane in methanol <2003H(60)2273>. 

Hydrogen peroxide converts morpholine into its 4-hydroxy derivative (50JA2280), but TV-alkyl morpholines yield 3-oxo compounds if ruthenium(VIII) oxide or sodium metaperiodate are used as oxidants (76S598). Chlorine at -70 °C oxidizes the thiomorpholine (116) to the dihydro-1,4-thiazine (117) (73JCS(Pl)l32l), but more vigorous conditions result in the formation of S-oxides. 

Morpholine-2,5-diones have been prepared by intramolecular, nucleophilic cleavage of polystyrene-bound amino acids acylated with a-hydroxy acids (Entry 2, Table... 

Enamines. In the presence of alumina (Woelm 200 neutral) cw-a,p-epoxy-silanes can be opened by pyrrolidine or morpholine to give a-amino-p-hydroxy-silanes, from which the pure as-enamine can be obtained by KH-induced syn p-elimination (equation I). The isomeric trans-a,p-epoxysilane is inert to this ring... 

When amino alcohols are used as the amine components along with glyoxal or a-keto-aldehydes, this process generates 2-hydroxy-morpholines 128 (Scheme 7.17) [62, 63], According to Carboni [63], this reaction proceeds with variable diastereo-selectivities (e.g. 129-131), and we have found that certain chiral amino alcohols give modest asymmetric induction (e.g. 132) [62]. 

Compendial reviews state that rocuronium bromide had been identified as having eight different impurities, which are labeled as impurities A, B, C, D, E, F, G, and H. Impurity A (i.e., related compound A) is 3a-hydroxy-2/i (morpholin-4-yl)-16/ -(pyrrolidin-l-yl)-5a-androstan-17/ -yl acetate impurity B (i.e., related compound B) is l-[3a,17/i-bis(acetyloxy)-2/i-(morpholin-4-yl)-5a-androstan-16/i-yl]-l-(prop-2-enyl)pyrrolidinium impurity C (i.e., related compound C) is l-[3a,17/i-dihydroxy-2/i-(morpholin-4-yl)-5a-androstan-16/ -yl]-l-(prop-2-enyl)pyrrolidinium and impurity D (i.e., related compound D) is l-[3a-(acetoxy)-17/J-hydroxy-2/J-(morpholin-4-yl)-5x-androstan-16/j-yl]-l-(prop-2-enyl)pyrrolidinium impurity E (i.e., related compound E) is l-[17/ -(acetoxy)-3a-hydroxy-2/ -(pyrrolidin-l-yl)-5a-androstan-16/)-yl]-l-(prop-2-enyl)pyrrolidinium impurity F (i.e., related compound F) is l-[3a,17/ -bis(acetiloxy)-2/ -(pyrrolidin-l-yl)-5a-androstan-16/i-yl]-l-(prop-2-enyl)pyrrolidinium impurity G (i.e., related compound G) is 2/)-(morpholin-4-yl)-16/i-(pyrrolidin-l-yl)-5a-androstane-3a,17/i-diol and impurity H (i.e., related compound H) is l-[17/i-(acetyloxy)-2-(morpho-lin-4-yl)-3-oxo-57-androst-l-en-16/i-yl]-l-(prop-2-enyl)pyrrolidinium [5-7], The molecular structure of rocuronium bromide is shown in Fig. 6.1, while the structures of the known impurities are illustrated in Fig. 6.2. 

---