Thiomorpholines

Dichlorophenyl)-2-[2-(perhydropyrido[l,2-u]pyrazin-2-yl)benzyli-dene]thiomorpholin-3-one was claimed as a psychotherapeutic agent (98MIP6). Inhibitory concentration and proportion of high and low affinity... 

Recently, Preti and co-workers (291) prepared Co(II) complexes with piperidine (pipdtc), thiomorpholine (Timdtc), and iV-methylpiperazine-4-carbodithioate (Me-Pzdtc) (XX). 

Figure L Calibration plot for nitrosation potential showing amount of t -nitroso-thiomorpholine formed vs, the square of the nitrogen dioxide concentration. Standard conditions of 50%relative humidity, 25°C, and 1 L/min flow rate for 30 min...

Hydroamination of activated alkenes has been reported with complexes 91-93 (Fig. 2.15). For example, 91 catalyses the hydroamination of methacrylonitrile (X = CN in Scheme 2.13) by a range of secondary amines (morpholine, thiomorpholine, piperidine, iV-methylpiperazine or aniline) in good to excellent conversions (67-99%) and anfi-Markovnikov regioselectivity (5 mol%, -80°C or rt, 24-72 h). Low enantioselectivies were induced ee 30-50%) depending on the amine used and the reaction temperature [79]. 

Diaryl-octahydropyrazino[2,l -dl l, 4]thiazincs were prepared from 2-aryl-6-(arylaminomethyl)thiomorpholine and 1,2-dibromoethane in the presence of Et3N <2002W02002/094799>. 

In the cycloaddition reactions of diaminooxindoles 215 (cf. Scheme 60), the piperidine can be replaced by morpholine, thiomorpholine, or iV-methylpiperazine to give the corresponding tricycles with two heteroatoms in the six-membered ring <1990T6433> (Equation 43). 

The syntheses of these three compounds share a common route as described by Brickner et al. [53] and Barbachyn et al. [54]. Namely, the coupling reaction of 3,4-difluoronitrobenzene (82) with piperazine, morpholine, or thiomorpholine to yield the corresponding 4-substituted 3-fluoro-nitrobenzene (83), which upon reduction gives rise to the aniline derivative (84). Carbobenzoxy protection of the active nitrogen of 84 using benzyloxy-carbonyl chloride (CbzCl) results in the formation of carbamates 85a and 85b. Treatment of 85a,b with n-BuLi and (i -glycidyl butyrate yields a 5-(R)-... 

An orchestrated six-step reaction sequence using seven different supported reagents has been described for the synthesis of a piperidino-thiomorpholine Hbrary... 

Protonated thiomorpholine loses ethylene in chemical ionization giving the cation CzH NS as main peak (ot/z 76). Methylated and ethylated derivatives lose ethylene in a similar manner (Scheme 3) <19840MS539>. 

The carbon-sulfur bond of thiazines can be reductively cleaved (Sections 7.06.5.7 and 7.06.6.7) and 2//-thiazines, being imines, can be hydrolyzed (Section 7.06.5.5). Saturated thiazines (thiomorpholines) are stable toward alkaline hydrolysis <1981CPB1554> and Lewis-acidic boron trifluoride <1980JHC449>. 

Hydrogenated derivatives of the monocyclic and bicyclic oxazines and thiazines are also very well established compounds and a number are so familiar that they too have trivial names. Tetrahydro-l,4-oxazine, for example, is better known as morpholine, a name first allocated to it because of a supposed, but erroneous, relationship to the alkaloid morphine. By analogy the corresponding thiazine is called thiomorpholine or sometimes thiazane. 

Both tetrahydro-l,4-oxazine (morpholine) and its thia analogue (thiomorpholine) find application as solvents and bases, morpholine having particular value in synthesis as it is often used to prepare enamines from ketones with a free a-hydrogen atom. TV-Acylation and -alkylation are readily accomplished and a great diversity of TV-substituted morpholines and thiomorpholines are encountered in the patent literature, some having biological activity. 

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. 

The reactions of zinc and cadmium with thiomorpholin-3-one (L) and thiazolidine-2-thione (L1) result in the complexes ML4(N03)2, ML2SCL, ML4(N03)2, Znl4s04 and CdL4S04 except in the last case, IR evidence indicates coordinated sulfate, while nitrate is ionic in all cases. L is coordinated via oxygen and L1 via nitrogen.716... 

The structure of the bromo analogue also was determined and was found to be very similar to that of the chloro complex (Fe-Br, 2.42 A) (114). The XFe(R2Dtc)2 complexes were rediscovered in 1975 (527) and a series of these molecules were obtained with the piperidine, thiomorpholine, and morpholine dithiocarbamates. 

An improved stability toward oxidation is found for the Co(R2Dtc)2 complexes with large R groups (426). The green paramagnetic complexes with R2 = piperidine, thiomorpholine-4-, and n-methylpiperazine-4- (/Lieff = 2.00, 2.03, and 1.60 BM, respectively) have been obtained and are thought to contain four-coordinate planar Co(ll) (426). 

Hydroxymethylthio)-4-oxo-4//-pyrido[l,2-a]pyrimidine-3-carboxy-late 522, prepared from 9-mercaptopyridopyrimidine-3-carboxylate 513 (R1 = COOEt, R2 = H) and 27% formaldehyde at 100°C, was reacted with thiomorpholine in the presence of magnesium sulfate in tetrahydrofuran under ice-cooling for 1 hour to afford 9-(4-thiomorpholinomethylthio)-pyridopyrimidine-3-carboxylate 523 (89EUP329126). 

Verwendet man Reagentien, die zwei nucleophile Zentren besitzen, so entstehen cyclische Verbindungen. Knunjanz u. Mitarb. 113> stellten auf diese Weise die mit Penicillin nahe verwandte Verbindung 77 dar. Kon-densation von 4-Brommethyl-2-benzyliden-A3-oxazolinon-(5) mit Peni-cillamin-methylester ergab zunachst das Thiomorpholin-Derivat 76, das sich durch Erhitzen oder Behandeln mit Basen in 77 umwandeln lieB. 

BM, with an N2C12 donor set.120 The effect of pressure on the electronic spectrum of this complex has been examined.121 Thiomorpholine-3-thione, S=CNHCH2CH2S< H2, and thiazolidine-2-selenone, Se=CNHCH2CH2, form tetrahedral CoL2X2 (X = Cl, Br, or I) complexes spectral evidence suggests that co-ordination is via the N rather than the S or Se atoms.122... 

The complexes of thiomorpholin-3-one, (CuLI) and [Cu2L4C12] are diamagnetic compounds probably containing Cu—S co-ordination.602 Chlorobis(2-thiouracil)-copper(i),DMF, formed from copper(n) chloride and thiouracil, contains almost trigonal-planar Cu1 with S2C1 co-ordination.653... 

Thiomorpholin-3-one forms Cu(tm)2X2 (X = Cl, Br, or I), Cu2(tm)2(S04)2 and [Cu(tm)4](N03)2 which are probably S-bonded in contrast to the O-bonding found in the nickel(n) complexes.602 Diethanol dithiocarbamic acid forms Cu[(HOC2H4)2-NCS2]2 which is a monomeric planar CuS4 chromophore in solution, but Cu - S interaction probably occurs between neighbouring molecules in the solid state.603... 

Reaction of the zinc halides with morpholine, thiomorpholine, and thioxan gives... 

Diarylpyrrole derivatives Catalyst pharmacophore Had difficulty predicting N-methyl piperazine and thiomorpholine derivatives. No numerical prediction data were presented Biava et al. (47)... 

Dieckmann cyclization of ethyl 4-[2-(ethoxycarbonyl)ethyl]-3-thiomor-pholine-3-acetate and ethyl 4-(3-ethoxycarbonylpropyl)thiomorpholine-3-carboxylate on the action of fert-BuOK in Et20, with subsequent acidic hydrolysis and decarboxylation, afforded octahydropyrido[2,l-c][l,4]-thiazin-8-one and -9-one, respectively (82EUP57536 92BMC1293). 

---