Oxazine, Dihydro

Acidic hydrolysis of 2-trichloromethyl-5,6-dihydro //-oxazine derivatives gave the corresponding amino alcohols in high yields <1996GC355, 1997TL607, 1998CC761>. 

Aube et al. [105] employed an interesting variant during their preparation of the oxazolines 259 and the dihydro oxazines 261 based upon the use of an azide function as the nucleophile instead of an allylsilane. 

On the other hand, sublimation of iV-isobutyroylcycloxobuxidine-F, under high vacuum, leads to the ring-opened product (171). A dihydro-oxazine (172) is obtained when sublimation is carried out in the presence of a base (tetramethyl-ammonium hydroxide). 

In the reactions of metallated methylpyridines, imines, thiazolines, and dihydro-oxazines, quaternization reactions with the acylating reagent may form an additional problem. 

Nitroso compounds react with 1,3-dienes to form oxazine derivatives. Aromatic nitroso compounds, Ar—N=0, undergo cycloaddition with most dienes. Thus, butadiene and nitrosobenzene react readily at 0°C to give A-phenyl-3, 6-dihydro-oxazine in high yield (3.29). With unsymmetrical 1,3-dienes, cycloaddition is often highly regioselective. 

Intramolecular cycloaddition reactions with nitroso dienophiles have been used in a number of syntheses of alkaloids. For example, cycloaddition of the acyl nitroso compound formed from the hydroxamic acid 31 gave the dihydro-oxazine 32, which was converted to the alkaloid gephyrotoxin 223AB (3.31). ... 

Another type of nitroso dienophile that has found use in organic synthesis bears an a-chloro substituent. Such a-chloronitroso compounds react with dienes to give the usual dihydro-oxazine product, however, in the presence of an alcoholic solvent, this cycloadduct reacts further and the product actually isolated is the A-unsubstituted dihydro-oxazine (3.32). Hence the use of a-chloronitroso dienophiles gives the product formed, in effect, by addition of HN=0 to the diene. This has been exploited by a number of research groups, an example of which, towards the natural compound conduramine FI, is illustrated in Scheme 3.33. 

Another example of [4 + 2] cycloaddition is offered by the reaction of Qo with nitroso alkenes 86 formed in situ by reaction of a-bromo oximes with a base. The reaction occurs at room temperature and affords C Q-fused dihydro-oxazines 87 in moderate yields (conversions in parenthesis) (09TL7337). 

A large number of 1-oxa-l-dethiacephalosporins have been prepared from a readily available penicillin-derived azetidinone. The central feature of the synthesis is the use of an intramolecular Wittig reaction, as shown in Scheme 140, to form the dihydro-oxazine ring. ... 

Cycloaddition of the D-mannose-derived chloronitrosocompound (106) with mejo-5,6-diacetoxy-l,3-cyclohexadiene gave rise to the chiral dihydro-oxazine (107), which could be converted to various aminocyclitols. Use of the ribose-derived chloronitroso species (108) gave products in the enantiomeric series. 

As one would expect, oximes and nitroso-compounds are frequently encountered starting materials throughout the chemistry of this group of heterocycles. Further examples of their reactions have appeared. Reaction with enol ethers produces dihydro-oxazines (260), which may be converted to pyridine N-oxides upon treatment with HCl. Dihydro-oxazines are also obtained upon treatment of 7,6-unsaturated dicarbonyl compounds with nitrous acid. Thermolysis of these products leads to nitrones (261). 

Oxazines. The synthetic utility of dihydro-1,3-oxazines ° has been considerably extended by Meyers. The reactivity of the double bond in dihydro-oxazines is enhanced on quaternization with methyl iodide the resulting salt readily adds a range of organometallic reagents, affording the versatile ketone synthesis summarized in Scheme 62. 

The potential of dihydro-oxazines is displayed to advantage in a high-yield synthesis of the male bollworm moth pheromone, tra/w-l-acetoxy-10-n-propyltrideca-5,9-diene. Alkylation of anions from dihydro-oxazines with a,o)-dihalogenoalkanes and subsequent elaboration of the terminal halide provides a route to variously functionalized aldehydes (Scheme 63). 

The failure of all but 2-methyl- or 2-benzyl-dihydro-l, 3-oxazine anions to alkylate has been turned to ingenious advantage. Meyers has reported that the above two anions are stable at the generation temperature, —78 °C, but, on warming to room temperature, they rapidly rearrange to the keteni-mines (140) higher alkyl dihydro-oxazine anions form the ketenimine spontaneously at —78°C. Thus, dihydro-oxazine anions can function as nucleophiles or electrophiles, depending on the temperature employed. This has been used for the assembly of ketones with a-quaternary carbon atoms of varied structure, but specifically alkylated in one of two available sites (Scheme 64). 

The Kouklovsky/Vincent and co-workers formal synthesis of ( )-porantheridine 197 (discovered from the Australian bush Poranthera corymbosa) is complementary to the work of Kibayashi (Scheme 41.41). ° The treatment of hydroxamic acid 192 with sodium periodate in the presence of cyclopentadiene 33 in methanol and water at 0°C delivered the bicyclic 3,6-dihydro-oxazine 193 in 61% yield. Ring-rearrangement metathesis (ring opening/ring... 

Dibenz[h,e]azepine-6,11-diones ent-Morphinan nomenclature, 1, 29 Morphinan, 1,2,3,4-tetrahydro-nomenclature, 1, 29 14-a-Morphinan, N-methyl-synthesis, 1, 480 Morphinans nomenclature, 1, 29 as pharmaceuticals, 1, 148 synthesis, 2, 377 Morphine, 2, 512 as analgesic, 1, 167 as metabolite of normorphine, 1, 235 as pharmaceutical, 1, 146, 147, 148 synthesis, 1, 480 Morphine alkaloids structure, 4, 534 Morphin-7-en nomenclature, 1, 29 Morphinone, dihydro-as pharmaceutical, 1, 147 Morpholine — see also 1,4-Oxazine, tetrahydrocarcinogenicity, 1, 229 corrosion inhibitor, 1, 409 metabolism, 1, 226 nomenclature, 3, 996 structure, 2, 5 synthesis, 2, 89 Morpholine, 4-aciyloyl-polymers, 1, 291 Morpholine, alkenyl-polymers, 1, 291... 

H-1,2-Oxazine, 3,6-dihydro-6-(2-pyridyl)-mass spectra, 2, 529 2H-1,2-Oxazine, tetrahydro-synthesis, 2, 92 4H-l,2-Oxazine, 5,6-dihydro-pyrolysis, 3, 999 synthesis, 3, 1017 tautomerism, 3, 999 4H-1,2-Oxazine, 5,6-dihydro-3-methyl-metallation, 1, 484 4H-l,2-Oxazine, 5,6-dihydro-3-nitro-reactions, 3, 1000 6H-l,2-Oxazine, 3,5-diphenyl-stability, 3, 997 synthesis, 3, 1014... 

H-l,2-Oxazine-3-carboxylic acid, 5,6-dihydro-synthesis, 1, 484 Oxazine-4,6-dione, 2-methylene-synthesis, 3, 1031... 

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