Alloxazines and isoalloxazines. Mass spectrometric analysis of riboflavin and related compounds

The positive ion electron-impact mass spectra of a series of alloxazines, iso-alloxazines and some derivatives have been examined. The compounds employed were lumichrome (7,8-dimethylalloxazine), 1,3-dimethyllumichrome, lumiflavin (7,8,10-trimethyl-iso-alloxazine), 3-methyllumiflavin, riboflavin [7,8-dimethyl-10-(D-1′-ribityl)-iso-alloxazine], riboflavin tetraacetate, 3-methylriboflavin tetraacetate and riboflavin tetrapropionate. By using exact mass measurements, metastable ion defocusing and the mass/composition shifts occurring with derivatives, it has been possible to arrive at detailed interpretations of the mass spectra of all compounds. With lumichrome and lumiflavin, fragmentation commences by elimination of HNCO from the pyrimidine ring. With riboflavin and its derivatives the ribityl chain cleaves off first, followed by decomposition of the iso-alloxazine ring. Application of these methods and findings to the structural analysis of chemically interesting modified flavins is predicted to be rewarding.     

A reliable synthesis of 1,1-dimethylpyrazolium 5-oxides

Reliable syntheses of compounds having the novel 1,1-dimethylpyrazolium 5-oxide ring system are reported. The method involves treating the dimethylhydrazone of a β-ketoester with a small amount of concentrated sulfuric acid or other catalyst and heating under reduced pressure for 1–24 hours. In this manner two new members of the series have been prepared and characterized.     

A new regioselective synthesis and ambient light photochemistry of quinazolin-1-oxides

Quinazolin-1-oxides were prepared by the oxidation of tetrahydroquinazolines with H₂O₂-tungstate and their ambient light photochemistry was investigated. Substituent effects on their photochemical cyclization and the reactions of the products 1aH-[1,2]oxazireno[2,3-a]quinazolines under photochemical and thermal conditions are reported. The cyclization of quinazolin-1-oxides and the reactions of 1aH-[1,2]oxazireno[2,3-a]quinazolines show pronounced solvent isotope and solvent effects.     

The synthesis of 5-azaindole derivatives via mesoionic oxazolium 5-oxides

A synthesis of 5-azaindole derivatives is described. This synthetic approach involves the preparation of an appropriately substituted pyrrole derivative by a 1,3-dipolar cycloaddition reaction of dimethyl acetylenedicarboxylate with a mesoionic oxazolium 5-oxide. The pyrrole intermediate contains a protected β-aminoethyl substituent, and subsequent removal of the phthalimido protecting group results in cyclization to yield the corresponding 5-azaindole. This approach has been used for both acyclic and cyclic amino acid precursors of the 1,3-dipole which is ultimately used in the sequence.     

Syntheses of some 2-hydroxypyrazine 1-oxides

A series of 2-hydroxypyrazine 1-oxides were prepared from the corresponding chloropyrazines by two methods, including oxidation processes in satisfactory yields. The treatment of 2,3-diphenylpyrazine 1,4-dioxide ( 6 ) led to 2,3-dichloro-5,6-diphenylpyrazine ( 7 ) and 2-chloro-5,6-diphenylpyrazine 1-oxide ( 8 ), and the latter was converted to 5,6-diphenyl-2-hydroxypyrazine 1-oxide ( 9 ) by an alkaline hydrolysis.     

A new ring transformation of 3-halo-2-azidopyridine 1-oxides. A novel synthesis of 1,2-oxazin-6-ones

The course of the thermal ring-opening and recyclization of 2-azidopyridine 1-oxides is radically altered by the presence of a 3-halo substituent. Provided the 6-position is blocked, recyclization leads to a 6-cyano-6-halo-1,2-oxazine which hydrolyzes very readily to the 6H-1,2-oxazin-6-one. The structure of 4-bromo-3-methyl-6H-1,2-oxazin-6-one so obtained was confirmed by single crystal X-ray analysis. If the 6-position is not blocked, the product undergoes a further ring opening to give (Z)-β-cyanoacrylates.     

Studies in the allo- and isoalloxazine series. XII. New synthesis of 7-chloroalloxazine

A new synthesis of 7-chloroalloxazine is effected by condensing 4-chloro-O-phenylenediamine with violuric acid in 3 N HCl. The same starting materials when condensed together in 50% acetic acid give 6-chloro-2-hydroxyquinoxaline-3-carboxylic acid ureide.For Part XI see [1].     

Polycyclic N-hetero compounds. XXXVI. Syntheses and antidepressive evaluation of 11,13,15,17-tetraazasteroids and their 17-oxides

Syntheses of 11,13,15,17-tetraazasteroids, their B-homologues, and 17-oxide derivatives are described. Antidepressive evaluation of these compounds and their precursors were screened by inhibitory action of reserpine-induced hypothermia.     

A new synthesis of 5-phenylmorphans1,2

A new procedure for the synthesis of 2-azabicyclo- [3.3.1]nonanes by intramolecular cyclization of 4-acetonyl-2- piperidinecarbonitriles under acidic conditions is described. The procedure allows the preparation of the pharmacologically interesting 5-phenylmorphans and involves the initial formation of 4-acetonylidenepiperidine 4, conjugate addition of a diarylcuprate, and cyclization of the resulting 4-acetonylpiperidine by way of the corresponding 2-cyano derivative.     

A synthesis of some novel 4,5-dihydroazepines by the reaction of oxazolium 5-oxides with 1,2-dicyanocyclobutene

Heating primary or secondary α-amino acids in acetic anhydride in the presence of 1,2-dicyanocyclobutene leads to 4,5-dihydroazepines via the intermediacy of mesoionic oxazolium 5-oxides.     

A new synthesis of 2-phospholene-1-oxides. Reaction of sec-benzylphosphine oxides and related compounds with α,β-unsaturated ketones

The addition of sodium of sec-benzylphosphine oxide 1a or 1b as well as sodium O-ethyl benzylphosphonite 1c to α,β-unsaturated ketones, followed by intramolecular aldol condensation has been described. The stereochemistry of the reaction and the structure of 2-phospholene-1-oxides 6a–h thus formed is discussed.     

Syntheses of substituted 8-(aminobenzyl)dinaphthodioxaphosphocine 8-oxides

Substituted (8-aminobenzyl)dinaphthodioxaphosphocine 8-oxides were prepared in a two-step process. The first step of the reaction is one-pot synthesis of α-aminophosphonates by the reaction of aldehydes, amines, and trialkyl phosphite in the presence of ceric ammonium nitrate. The second step is cyclization of α-aminophosphonates with bis(2-hydroxy-1-naphthyl)methane in the presence of a catalytic amount of p toluenesulphonic acid under reflux conditions. Their structures were established by elemental analyses, IR, ¹H, ¹³C, ³¹P NMR, and mass spectral data. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, 1574–1580, September, 2007.     

A new synthesis of 5-hydroxy-6-methyluracil

Dehydration of 5,6-dihydro-5,6-dihydroxy-6-methyl- and 5,6-dihydro-5,6-dihydroxy-1,3,6-trimethyl-uracil in 0.4 M aqueous sulfuric acid gives 5-hydroxy-6-methyl- and 5-hydroxy-1,3,6-trimethyluracil in quantitative yields. Two possible mechanisms have been examined using the mPW1k/6-311+G(2df,2pd)//mPW1k/6-31+G(d,p) method for the transformation of methylated and non-methylated 5,6-dihydro-5,6-dihydroxy-6-methyluracils into the corresponding 5-hydroxy-6-methyluracils. The first is a hydride C5-C6 shift occurring in concert with the loss of a water molecule and formation of the corresponding protonated 5,6-dihydro-5-oxo-6-methyluracils. The second is an acid-catalyzed dehydration reaction to yield 5-hydroxy-6-methyluracils. The calculations demonstrated that the second pathway was energetically most favorable.