4- -1,4-morpholine irradiation

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. 

Microwave irradiation of 2-(morpholin-4-yl)benzaldehyde on AI2O3-KF gave the expected 1,2,4/hz-tetrahydro-6//-[l,4]oxazino[4,3-tf][3,l [bcnzoxazine only in low yield (6%), whereas the pyrrolidino and piperidino analogues gave the respective tricyclic compounds in good yields <2005T9052>. 

A solvent-free synthesis of substituted spiroindolinonaphth[2,l-fo][l,4]oxazines through condensation of 2-methylene-l,3,3-trimethylindoline derivatives with 1-nitroso-2-naphthol under microwave irradiation has been described by Fedorova and colleagues (Scheme 6.263) [453], In a typical reaction, an equimolar mixture of the two starting materials was irradiated at 65-110 °C for 15 min to produce the desired spiroindolinonaphth[2,l-fo][l,4]oxazines, which are useful as photochromic compounds. In a related procedure, addition of morpholine to the reaction mixture led to the formation of the corresponding 6 -amino-functionalized spiroindolino-naphth[2,l-fo][l,4]oxazines, which exhibit a strong hypsochromic color shift (not shown) [453]. 

Thiomorpholides have been obtained by the reaction of nitriles or ketones and elemental sulfur with morpholine under microwave irradiation (Scheme 5).21,22... 

The addition of morpholine to 2,3-dihydrofuran in the presence of palladium(II) thiocyanate-bis(triphenylphosphine) yields 2-(morpholin-4-yl)tetrahydrofuran (276)303. Irradiation of mixtures of 2-(2-methylpropenyl)phenol (277) and alkylamines yields adducts, e.g. 278 with isopropylamine304. 

It is known that irradiation of perfluorophenyl azide in the presence of diethylamine results in the formation of hydrazine along with some other products. LFP of azides 16f, 16g demonstrates that in the presence of amines (piperidine and morpholine) the decay of the aryinitrene absorption (Figure 17, Spectrum 1) is accompanied by formation of the transient absorption with maximum at 320 nm (Figure 17, Spectrum 2). Unlike the adduct of singlet aryinitrene with pyridine (ylide 22e), this intermediate is unstable and its lifetime is about 2.5 ps. The product of its transformations absorbs slightly in the near-UV region (Figure 17, Spectrum 3), which is typical of hydrazines (24). 

The reaction of - -t with diethylamine to yield both t-1-amine adducts (68) and t-1 reduction products (64 and 65) was initially reported by Kawanisi and Matsunaga (131). Analogous products are obtained upon irradiation of 1,2-diphenylcyclobutene (7) with diethylamine or morpholine (118). 

A mixture of phenyl acetaldehyde 1 (0.6 g, 5 mmol) and morpholine 2a (0.48 g, 5.5 mmol) was placed in a small beaker and irradiated in an unmodified household microwave oven at its full power (900 W) for 2 min. Salicylaldehyde 4a (0.61 g, 5 mmol) and ammonium acetate (0.02 g, 0.25 mmol) were then added to the same reaction vessel, and the reaction mixture was further irradiated in the microwave oven at its 50% power for 5 min using a pulse technique. Upon completion of the reaction, followed by TLC, the reaction mixture was passed through a bed of basic alumina using hexane-ether (9 1, v/v) as an eluent to afford pure 2-aminomorpholinoisoflav-3-enes 6a (yield 80%, mp 103-105 °C). 

Keywords aromatic/heteroaromatic chloride, piperidine, morpholine, basic alumina, nucleophilic aromatic substitution, microwave irradiation... 

The photochromic spiroindolinonaphth[2,l-fc][l,4]oxazines conjugated with aza-15(18)-crown-5(6) ether moieties or morpholine in the presence of Pb2+ or Eu3+ give highly coloured betaine merocyanine, the open form of the compound, which can return to the initially closed non-coloured form by irradiation with light (Scheme 125).188 When the merocyanine complexes are kept in the dark, the corresponding oxazole derivatives are formed irreversibly and regioselectively. 

Great effort should be taken to stabilize a formulation in such a way that the shelf life becomes independent of the storage conditions. The photostability of drugs and excipients should be evaluated at the formulation development stage in order to assess the effects of packaging on the stability of the final product. Molsidomine tablet preparations in inadequate primary containers (blister) without secondary containers when exposed to irradiation may produce morpholine. These results illustrate the importance of packaging for the stability of molsidomine [19]. 

Ss, morpholine, AI2O3 MW irradiation no solvent r3 = esters, amides... 

A detailed study of the photochemical behaviour of the benzoquinone (354) with arenes has been reported. Photoreaction of the quinone (355) with morpholine affords the amine substituted quinone (356). This reaction was found to occur with several amines. Sunlight irradiation of an ethereal solution of the diquinone (357) is reported to afford the light stable intramolecular cyclized product (358). - ... 

Amino-3-cyano-thiophenes or 2-amino-thiophene-3-esters result from this route, generally conducted as a one-pot process, involving a ketone that has an a-methylene, ethyl cyanoacetate or malononitrile, sulfur, and morpholine. Various improvements to the original procedure include using microwave irradiation on solid snpport, or with potassium fluoride on alumina as the base, or solvent-free,and using morpho-lininm acetate in excess morpholine for aryl alkyl ketones. 

Piperidine, morpholine, pyrrolidine, N-alkylpiperazines, and anilines have been converted to N-aryl derivatives by use of aryl triflates under the action of microwave irradiation in NMP [58]. The amination reaction proceeded efEciently in the absence of base and catalyst, and was not affected by traces of water (Scheme 10.23). 

Recently, the group of Boruah achieved the synthesis of annelated pyridines from yfi-formyl enamides via a Henry reaction in a one-pot process [186]. Under the action of microwave irradiation, in the presence of a base, for example pyrrolidine, morpholine or piperidine, yields from 80 to 90% were obtained after 8 to 10 min (Scheme 10.96). 

The reality of the excitation exchange between 5 and fi is demonstrated by the fact that a polymerization can be initiated under laser irradiation at 440 nm (a wavelen h which is only absorbed by S in the presence of S fi but not in presence of S atone. The relative quantum yield of polymerization obtained is similar to that of the system S+morpholine (at =363 nm under CW At laser) but considerably less than that of at the same irradiation wavelength [26]. This observation is in good agreement with the assumption of an electron transfer process predominating in non-polar media. 

Initial experiments were undertaken with morpholine, dicyclohexylamine and dibutylamine terminated GPTA systems as well as the diethylamine sample which has already been investigated in previous work (14,15). The effect of Microscal irradiation on the increase in hydroxyl index of these amine acrylates is illustrated by the data in Table I. This shows that the nature of the terminal amine functionality has a marked effect on the hydroxyl index profile during irradiation. The following order of increasing hydroxyl index was observed relative to amine functionality ... 

Figure 1. Change in intensity of the second derivative uv absorption band at 275 nm during Microscal irradiation for uv cured (5% w/w benzophenone) (4 m thick) GPT after reaction with ( ) diethylamine, (O) morpholine, ( ) dicyclohexylamine and (0) di-n butylamine.

The rates of loss do not correlate with the rates of increase in the hydroxyl index for these systems or with the photoyellowing and uv phenomena. This indicates that the mechanism of oxidation of the amine functionality is complex. An additional feature of interest is the profile of this band loss as related to terminal amine structure. In the simple alkyl substituted systems namely diethyl, dimethyl and dibutyl there is an initial rapid loss followed by a slowing down of the rate of decrease on prolonged irradiation. However, with the oxygen containing systems namely morpholine, N-ethyl ethanolamine and N-methyl ethanolamine the rate of decrease is linear with irradiation time. Evidently, there must be two different mechanisms in operation here. The loss of these infra-red absorption bands may be due to a process of dealkylation via oxidation (see reactions later). The band situated at 2978 cm"l exhibited similar behaviour although the extent of the loss was less than that observed with the previous band and the order of rate loss was marginally different. 

The synthesis of W-arylamines 474 by amination of aryl halides with morpholine (469) was carried out in the presence of basic alumina under MWI. This required 4-5 min of irradiation to give 88-89% yields (Scheme 92). Conventional heating at 120 °C required 8h for completion to give 65-69% yields (00MI3). 

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