Morpholine, 4-methyl preparation

Morpholine enamine of methyl isopropyl ketone prepared by this method was found to be a 3 7 mixture of di- and tetrasubstituted isomers (126 and 127). 

The piperidine, pyrrolidine, and morpholine enamines of cyclohexanone substituted in the 3-position by methyl, phenyl, and l-butyl have been prepared (49). The complexity of the NMR spectra in the ethylenic hydrogen region indicated a mixture of isomeric enamines. Estimation of the per cent of each isomer by examination of the NMR spectra was not possible, nor were the isomeric enamines separable by vapor-phase chromatography. 

Enamines of several methyl ketones have been prepared and their isomer content estimated by NMR spectroscopy (13,39,43). The reaction of Ti[N(CH3)2l4 as the amine source and 3-methyl-2-butanone gave only 26 (Ri = Rj = CH3), which could be isomerized by prolonged heating to a 1 1 mixture ofthatenamine and enamine 27 (R, = Rj = CH3)(39). The reaction of morpholine and 3-methyl-2-butanone in benzene with a trace of acetic... 

E) Preparation of 2-( 1-Succinyloxyethyl)-3-Methyl-5-(2-Oxo-2,5-Dihydro-4-Furyl)Bemo[b] -Furan (409 CBj 8.65 grams of compound 3574 CB in 43 ml of pyridine are warmed for 30 minutes, on a water bath, with succinic anhydride. At the end of this, the pyridine is stripped off in vacuo. The mixture is treated with dilute sulfuric acid and with ether, the crystalline product filtered off, washed with water and with ether, and recrystallized from ethyl acetate (9.35 grams). MPq = 144°C (measured after drying at 90°C and 0.1 mm). Yield 77%. The product yields an equimolecular compound with morpholine. MPc= 136°C (from ethyl acetate). 

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>. 

Methylthiopyrido[2,3-e][ 1,2,4]triazine 41 was prepared (76KGSI140) by cyclization of 2-amino-3-hydrazinopyridine 40 with carbon disulfide followed by methylation. Oxidation of 41 with chlorine afforded the 3-methylsulfonopyridotriazine 42. Heating 41 with morpholine or pyrrolidine gave 43, whereas the reaction at 20°C gave 44. 

S)-AlaOMe] [(S)-AlaOMe HC1] = 1.0 N 2.0) showed 3H incorporations to decrease from 12.2 to 0.7% in roughly a 1/N2 dependence this was independent of whether the (S)-AlaOMe was added directly or was prepared by titration of (S)-AlaOMe HC1 with NEt3. iV-Methyl-morpholine was shown to be not as effective a deprotonating base, even though in this case all the reagents remained in solution. 

S-Methyl-A-(2-pyridyl)methylenedithiocarbazate (nns) can be prepared by the condensation of S-methyldithiocarbazate and pyridine-2-aldehyde. The low-spin complexes [Fe(nns)2].X (X = CIO or FeCl ) have both been isolated.2,1.3-Benzothiodiazole. 2,1,3-benzoselenodiazole, and their derivatives (L) form the octahedral complexes FeL2Cl3. and morpholine-4-carbodithioate (mdtc) forms the complex [Felmdtclj]. Mossbauer and magnetic data for a series of monothio- -diketonate-iron(iii) complexes have been interpreted in terms of a thermal equilibrium between the sextet and doublet states. 

Transformation of both the ester and nitrile derivatives 726 or 727 into pyrano[2,3-t7 pyridazines 728 or 729, respectively, by treatment with dilute HCl at room temperature involved nucleophilic displacement of the morpholine group by the hydroxyl group with an acidic hydrolysis followed by intramolecular iminolactonization and then hydrolysis of the formed imino group to a carbonyl group. Compounds 726 and 727 were prepared by Vilsmeier-Haack formylation of 2-methyl-5-morpholino-3(2/7)-pyridazinone 724 followed by condensation of the resulting product 725 with either ethyl a-cyanoacetate or malononitrile in EtOH (Scheme 34) <1994H(37)171>. 

The prototype for this class of compounds is ibufenac (42-3), developed by a group at Boots in the UK. This drug was to be quickly superseded by its a-methylated congener, ibuprofen, from the same laboratory [43]. The mechanistically very complex Wilgerodt reaction constitutes the key to the preparation of ibufenac. Thus, reaction of the acetylation product (42-1) from isobutyl benzene and acetyl chloride with sulfur and morpholine leads to the transposition of the oxidized function to the terminal carbon and formation of thiomorpholide (42-2). Hydrolysis of the thioamide... 

A milestone in the routine employment of perruthenate in the oxidation of alcohols was established with the publication by Griffith, Ley et al. in 1987 on the catalytic use of tetra- -propylammonium perruthenate (TPAP).11 The presence of the tetra- -propylammonium cation renders this compound soluble in apolar media and allows the existence of a high concentration of perruthenate ion in organic solvents. The tetra- -propylammonium perruthenate is easily prepared and can be employed catalytically in CH2CI2 solution in the oxidation of alcohols to ketones and aldehydes, using /V-methyl morpholine A-oxide (NMO) as the secondary oxidant. 

Reactions of 5f/-2-methyl-l,2,4-triazepino[2,3- ]benzimidazol-4-one 71, prepared by reaction of 1,2-diaminobenz-imidazole 72 with acetoacetic ester 73, with different reagents was described, in the search of new heterocycles with biological activity <2002CHE598>. When lactam 71 was treated with aromatic aldehydes in boiling 1-BuOH with addition of piperidine 74, 577-3-arylidene-2-methyl-l,2,4-triazepino[2,3- ]benzimidazol-4-ones 75a-c were obtained (Scheme 7). Coupling lactam 71 with phenyldiazonium chloride 76 in dioxane afforded the 3-phenylazo-substituted tricycle 77. When 71 was treated with phosphorus pentasulfide 78 in boiling dioxane or pyridine, its thio analog 79 was obtained. The reaction proceeded most efficiently when lactam 71 was refluxed with twofold excess of 78 in dry dioxane. These thiones 79 react with ammonia and amines by nucleophilic substitution. When 79 was refluxed with ammonia, benzylamine, piperidine, or morpholine, the 4-amino-substituted tricycles 80a-d were obtained. All the described compounds were identified by NMR, mass spectrometry, and IR spectroscopy. 

The Upjohn Dihydroxylation allows the sy/i-selective preparation of 1,2-diols from alkenes by the use of 0s04 as a catalyst and a stoichiometric amount of an oxidant such as NMO (N-methyl morpholine- JV-Oxide). 

Cyclic ketone with exo cyclic methylenes can be prepared in just the same way and used in situ. Morpholine is often used as a convenient secondary amine for the Mannich reaction and the resulting amino-ketones can be methylated and undergo elimination-addition reactions with stabilized enoUtes such as that derived from ethyl acetoacetate. This starting material wias prepared from natural menthone and the mixture of diastereoisomers produced is unimportant because the product is to be used in a Robinson annelation (see below). 

A wide range of other nitrogenous, heterocyclic solvents has been used as solvents for the preparation of sucrose surfactants by ester exchange. These include N-methyl- and various N-acyl-morpholines, 272,328-330 jV-formyl- and N-acetyl-piperdine,272 N-formyl- and N-acetyl-... 

Preparation of A-(3-methyl-benzylidene)-A - 6-morpholin-4-yl-2-[2-(l-oxy-pyridin-2-yl)-ethoxy]-pyrimidin-4-yl -hydrazine... 

Zong eta/, reported a new method for preparing A -acyloxaziridines 359 via the tandem 0,N-addition of hydroxamic acids 357 to methyl propiolate 358 (Equation 14) <1998TL6227>. The reaction was carried out in the presence of a catalytic amount of A -methyl morpholine. The desired A -acyl oxaziridines were obtained in good to excellent yields (Table 32). 

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