Replacement of carbon by nitrogen

Formation of a C-N bond with cleavage of a C-C bond occurs occasionally as undesired side reaction during nitration,166,1183 nitrosation, or azo coupling. Some examples of this have been mentioned in the respective Sections. Such reactions have preparative interest only when they form the main reaction, as in the Japp-Klingemann reaction (see page 436) and in certain oximations by nitrous acid (see page 429). 

Nitration of p-cymene by fuming nitric add leads to 2,4-dinitrotoluene.1184 Heating 1,6-dihydro-l-methyl-6-oxonicotinic acid with nitric acid (d 1.52) under reflux gives 1-methyl-3,5-dinitro-2(li/)-pyridone in good yield.1185 2,6-Dibromo-4-nitrosophenol is formed quantitatively from 3,5-dibromo-4-hydroxybenzoic acid and sodium nitrite in aqueous alcohol.166,1183 Nitrous acid replaces hydroxymethyl groups in phenols by nitro groups,1186 and diazonium salts replace them by diazo groups.1187 

An elegant method of acylation for not too weakly basic amines consists of treatment with acyl cyanides.1097a The process1188,1189 has the advantage 

Chloromycetin has been prepared analogously,1189 starting from dichloro-acetyl cyanide, which may be produced in situ from chloral and sodium cyanide.1190 

The ready cleavage of the carbon-carbon bond in chloral by strongly basic amines finds excellent application for A-formylation, particularly as the reaction usually affords very good yields under mild conditions.1191-1193 

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Further replacement of carbon by nitrogen and sulfur in 2 and 3 affords the heterocycles 9 through 16, of which all but species 10 are known. 

Replacement of carbon by nitrogen at position 8 of the pteridine ring in MTX and AMT has been accomplished by Srinivasan and Broom [36]. Starting from 6-bromomethylpyrido[3,2-rf]pyrimidine-2,4(lf/,3/f)-dione (III. 115), the xV-oxide was prepared by w-chloroperbenzoic acid oxidation and subjected to Polonovski rearrangement (AcjO-AcOH) to obtain the 6-acetoxymethyl derivative (III.116). Treatment of (III.116) with POCI3 afforded the 2,4-dichloro derivative (III.117), which on being heated at 160-170 °C in liquid ammonia in a pressure vessel was converted to the... 

Figure 17 Relaxation changes of chemiluminescence intensity for oxidized cellulose containing magnesium carbonate at 180°C during replacement of oxygen by nitrogen and vice versa.

Replacement of oxygen by nitrogen does not affect the nucleophilic character of the carbon, and acylation of macrocyclic 1,3-diiminato complexes is facile... 

A nitrogen atom at X results in a variable downfield shift of the a carbons, depending in its extent on what else is attached to the nitrogen. In piperidine (45 X = NH) the a carbon signal is shifted by about 20 p.p.m., to ca. S 47.7, while in A-methylpiperidine (45 X = Me) it appears at S 56.7. Quaternization at nitrogen produces further effects similar to replacement of NH by A-alkyl, but simple protonation has only a small effect. A-Acylpiperidines show two distinct a carbon atoms, because of restricted rotation about the amide bond. The chemical shift separation is about 6 p.p.m., and the mean shift is close to that of the unsubstituted amine (45 X=NH). The nitroso compound (45 X = N—NO) is similar, but the shift separation of the two a carbons is somewhat greater (ca. 12 p.p.m.). The (3 and y carbon atoms of piperidines. A- acylpiperidines and piperidinium salts are all upfield of the cyclohexane resonance, by 0-7 p.p.m. 

Replacement of the terminal nitrogen of the piperazine by carbon is said to enhance the antiemetic activity of the phenothiazines at the expense of the other pharmacologic effects. The simplest compound in this series, pipamazine (88), is prepared by alkylation of nipecotamide (87) with the chloropropyl phenothiazine (58). Preparation of the analogous sulfoxide begins with acetylation of the thiomethyl compound, 89 [prepared by a route... 

Diozo. A prefix denoting replacement of two ting carbons by nitrogens, and applied to names of heterocyclic compds derived from names of carbocyclic compds... 

Replacement of carbon atoms in the cyclic aliphatic side chain of proline with nitrogen leads to the azaprolines where incorporation of an additional imino group may affect molecular recognition processes via electrostatic interactions. While the proline analogues imidazoli-dine-2-carboxylic acid (3-azaproline, 15) and pyrazolidine-3-carboxylic acid (5-azaproline, 16) allow for additional side-chain modifications in peptidomimetic structures, with pyr-azolidine-2-carboxylic acid (2-azaproline, 17) (Table 2), where the a-CH is replaced by nitrogen, the peptide backbone is modified with consequently strong conformational effects. 

The photocyclizations of halogenated A-benzyl-/ -phenethylamines576 are examples of reactions in which two aryl rings are connected by a chain of four atoms, one of which is a nitrogen atom. In the cases reported, one phenyl ring has a bromine atom and the other an iodine atom at the ortho position. As expected, products were formed via initial rupture of the carbon-iodine bond and these products still contained the bromine atom. In addition, however, some unexpected cyclization products were encountered, containing iodine instead of bromine. The formation of these products was ascribed to replacement of bromine by iodine in the intermediate cyclohexadienyl radicals. 

NMR were consistent with the proposed structure (35). The UV-visible spectrum of the anionic and neutral forms of F420 are shown in Figure 5b and look very similar to the 8-hydroxyriboflavin spectra of Figure 5a except for the approximately 50-nm blue shift. This is the same shift seen on substitution of carbon for nitrogen at the 5 position in the 5-aza—> 5-deazariboflavin series (Figure 1). Thus, the spectrum is consistent with what one might anticipate by additive effects of carbon substitution at the 5 position and replacement of 8-methyl by 8-hydroxyl. 

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