Nitrogen scheme

Amino-5-methylthiazole does not react with diazotized p-nitroaniline in solutions acidified with acetic or hydrochloric acid (391). 2-Amino-4,5-dimethylthiazole with the diazonium salts of para-substituted anilines, however, gives product 193, involving reactivity of the exocyclic nitrogen (Scheme 122) (399). 

Alkylation of bis(4-methyl-2-thiazolyl)urea (257) with dimethyl sulfate gives product 258 dimethylated on the ring nitrogens (Scheme 154) (488). Alkylation of l-alkyl-3-(2-thiazolyl)urea from its derived anion formed by NaH gives 259 (Scheme 155). 

The 2-azo derivative (322), when heated with butyl glycidyl ether in acetic acid, reacts through the ring nitrogen (Scheme 186) (585). 

Complex tautomerism for azoles with heteroatoms in the 1,2-positions occurs for pyrazoles which are not substituted on nitrogen. Scheme 10 shows the four important tautomeric structures (148)-(151) for 3-methylpyrazolin-5-one, and (152) and (153) as examples of other possible structures. A detailed investigation of this system disclosed that in aqueous solution (polar medium) the importance of the tautomers is (149) > (151) (150) or (148), whereas in cyclohexane solution (non-polar medium) (151) > (148) (149) or (150). 

Special attention has been given to the study of tautomeric equilibria in solutions of histidine 22 because the key functional role of such equilibria in proteins is recognized. In aqueous solutions the tautomers of histidine rapidly interconvert and only a single averaged signal is observed for each ring nitrogen (Scheme 10). 

Tliree-bond formation through consecutive (3 + 1 + 1) atoms heterocy-clization of 4(6)-aminopyrimidines with one carbon followed by one nitrogen (Scheme 1). 

Two-bond formation through (4+1) atoms heterocyclization of pyrimidines having an -N-C-N appendage at C4(6) with one nitrogen (Scheme 3). 

More than 90 years ago Bamberger (1897) discovered that iV-nitrosoacetanilide decomposes easily in benzene to give biphenyl, acetic acid, and molecular nitrogen (Scheme 2-24). 

The reaction of 1,4-disubstituted tetrazoliums (149) with aliphatic tertiary amines such as triethylamine leads via deprotonation to 150 followed by ring opening to form a carbodiimide (74) with the loss of nitrogen (Scheme 20).237,238 Under the same conditions, 1,4,5-trisubstituted... 

Unlike others, the 5-isopropyl tetrazoliums (155) undergo photode-protonation to 156 which then yields the aziridimine (157) with the elimination of nitrogen (Scheme 22).254... 

Perhydropyrazino[l,2-c]pyrimidincs were all synthesized by formation of the pyrimidine ring. The antifilarial agent, Centperazine, 166, was built from [6+0] fragments by bond formation a to the ring junction nitrogen (Scheme 21). Compound 165 was prepared in two steps from 2-vinylpyrazine and the yield over five steps was 23% < 1998IJB1149>. 

Diethyl azidomethanephosphonate 228 reacts with norbornadiene at room temperature to give triazoline 229 in 86% yield. When heated at 60°C, derivative 229 decomposes with elimination of cyclopentadiene to provide (1,2,3-triazol-l-yl)methanephosphonate 230 in 74% yield. However, when it is left at room temperature for an extended period of time, triazoline 229 undergoes slow conversion to aziridine 231 with elimination of nitrogen (Scheme 30)... 

The JV-benzyl aziridines 69, 92-95 which differ only in the nature of the norbomane bridge (CH2, spirocyclopropyl, isopropylidene, oxygen, substituted nitrogen) (Scheme 14), have been prepared and reacted with each of the corresponding benzonorbomadienes 36-40 from which they were derived. All 25 reactions were conducted to produce 14 of the possible 15 different... 

Moustafa and Ahmed reported the synthesis of isoxazoles [92,93]. These compounds are related to pyrazoles except that an oxygen replaces the amine nitrogen. Scheme 49 shows the synthesis of 182 from the corresponding chal-cone 183 by reaction with hydroxylamine. Although these compounds were not tested for cytotoxicity as tubulin binders, they were found to possess antibacterial and anti-fungal activity. 

A series of substituted 177- and (mesoionic) 277-pyrrolotetrazoles were prepared by Moderhack et al. by cyclization of tetrazolium salts 66 and 69 bearing acylmethyl functions both at the ring carbon and the adjacent nitrogen (Scheme 7)... 

An alternative substrate design, in which the alkene radical cation is substituted only at the internal position, forces the nucleophilic cyclization into the endocyclic mode, leading overall to bicyclic systems with a bridgehead nitrogen (Scheme 31) [139,140]. 

The replacement of the -carbon atom by oxygen or nitrogen (Scheme 34)... 

Anodic amide oxidations have also proven useful for selectively converting amides into enamides that have in turn been used to functionalize the carbon beta to nitrogen. For example, the four-electron oxidation of carbamates was used to introduce a carbonyl beta to a nitrogen (Scheme 21) [50]. In this example, the starting carbamate was oxidized at a carbon... 

Amines and amides undergo oxidation at or adjacent to nitrogen (Scheme 27). A neutral amine, for example, can be oxidized to afford a cation radical (117 to 116). Similarly, electrooxidation of the anion produced via deprotonation of a secondary amine leads to an aminyl radical (119) that is capable of participating in carbon-nitrogen bond-forming reactions with remotely tethered alkenes. 

Increases 1n X N agree well with the amount calculated for a crossUnklng mechanism Involving two crosslinker units linked by a nitrogen (Scheme 7). Inefficient formation of more sterically congested structures containing three crosslinker units per nitrogen Is also consistent with the data. 

Electrophilic substitutions of rings with a single N-nucleophilic site proceed smoothly. Thus, indolo benzazepine 36a, protected on the indole ring, and benzoxepine 36c are easily methylated on the benzazepine nitrogen (Scheme 79 (1991JHC379)). 

In addition to the protected pyrroles mentioned above, the 1-azafulvene dimer formed by Mannich reaction of pyrrole-2-carboxaldehyde with di-methylamine has also been successfully lithiated adjacent to both pyrrole nitrogens (Scheme 10). Reaction with electrophiles and subsequent hydrolysis leads to 5-substituted pyrrole-2-carboxaldehydes in good yield [88TL777 92JOM(423)173]. 

Scheme 3 shows the conceivable reaction sites of alkenylbismuthonium salts, alkynylbismuthonium salts, bismuth ylides, and bismuth imides in carbon-carbon and carbon-heteroatom bond forming reactions. In the initial step, nucleophiles (Nu) attack the positively charged bismuth(V) center, a-proton or (3-carbon (Scheme 3a, b) whereas electrophiles (El) attack the negatively charged a-carbon or a-nitrogen (Scheme 3c, d). Usually, the resulting bismuth(V) intermediates... 

In 1972 Cava and Sprecker reported the formation of analogs of 149, in which one of the two sulfur atoms is replaced by oxygen or nitrogen (Scheme 9). Reactions of tetrabenzoylethane (146) with HCl or methylamine in acetic acid afforded 3,4-dibenzoyl-2,S-diphenylfuran (152) or 3,4-dibenzoyl-l-methyl-2,5-diphenyl pyrrole (153), respectively. 

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