Containing One Nitrogen Atom

Nitration of quinoline with nitric acid or metal nitrates in acetic anhydride gives the 3-nitro derivative, together with some of the 6- and 8-isomers (40JA1640 57JCS2521) the 3-derivative (—30%) is also obtained by reaction with tetranitratotitanium(IV) [74JCS(P1) 1751 ]. These reactions almost certainly involve the free base, for which the expected positional reactivity order is 5 8 = 6 3 all of these positions are of closely similar reactivity (Section 7). Steric hindrance may reduce the amount of 

4 showing the typically higher reactivity of isoquinoline compared to quinoline [see Section l.B, paragraph (3)], the low reactivity of the 1-methylquinolinium cation here may be a solvation rather than an electronic effect [63CI(L) 1283]. 

The quinolinium ion is at least 10s times more reactive in nitration than the pyridinium ion (63JCS4204). The ratio of the reactivity of quinolinium to benzene and to naphthalene has been derived as 1.2 x 10 7 and 1 x 10 l0, respectively [63CI(L)1283 68ZC201], A detailed study of the products of nitration of quinoline by nitric acid in 80 wt% sulfuric acid at 25°C yielded the partial rate factors shown in 11.63 [71 JCS(B) 1254] so that the positional reactivity order for the quinolinium ion is 5 8 6 7 3, which is almost exactly that which applies to the free base, although the relative differences are much greater (Section 7). Likewise, partial rate factors for nitration on the isoquinolinium ion are given in 

64 (64MI2), and the differences in the i-Q/Q-rate ratios for the 5- and 8-positions (52 and 7, respectively) show the effect of conjugation between nitrogen and the 5-position in quinoline and the 8-position in isoquinoline. Nitration of isoquinoline with nitric acid in acetic anhydride almost certainly involves the free base and consequently gives the 4-derivative in 14% yield (720PP9) the 4-position is the most reactive site (see Section 7). 

Nitration of the quinoline derivatives 1,2,3,4-tetrahydroacridine (11.65) and 2,3-dihydro-l//-cyclopenta[b]quinoline (11.66) goes into the 5-and 8-positions as it does in 7,8,9,10-tetrahydrophenanthrene (11.67) (65-JPJ645). 

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In spite of the diverse nature of alkaloid structures, two structural units, i.e. fused pyrrolidine and piperidine rings in different oxidation states, appear as rather common denominators. We therefore chose to give several examples for four types of synthetic reactions which have frequently been used in alkaloid total synthesis and which provide generally useful routes to polycyclic compounds with five- or six-membered rings containing one nitrogen atom. These are ... 

Fused Heterocyclo-Quinolines Containing One Nitrogen Atom at Ring Junction Part 1. Four and Five Membered Heterocyclo-Quinolines... 

This chapter includes the recent various aspects of four and five membered heterocyclo-quinolines containing one nitrogen atom at the ring junction. They were subdivided according to the number of heteroatoms in the heterocyclic rings. The literature indicates that many of these heterocycles are of potential therapeutic value which leads to intensive research in the topic. On the other hand, there are various classes of heterocycles that fit under this heading but unreported yet. Consequently, efforts towards the synthesis of such unreported classes can be fruitful area of research. 

The preparation of five-membered rings in solid-phase organic chemistry has been reported in several publications. Versatile syntheses of these heterocycles with different numbers and kinds of heteroatoms have been described. The synthesis of five-membered rings containing one nitrogen atom (Fig. 3.6) as pyrrolidines (231) [311-316] pyrroles (232) [317-320] pyrrolidinones (233) [321-323] pyr-rolinones (234) [324—326] 2,5-pyrrolidinediones (235) [327-329] 2,4-pyrrolidine-diones (236) [330-332] 2,5-pyrrolinediones (237) [333] or heterocycles with one oxygen or one sulfur atom like tetrahydrofurans (238) [334—336] 2,5-dihydrofurans (239) [337], furans (240) [338, 339], yS-lactones (241) [340-343], 2,5-dihydrofura-nones (242) [344] (Scheme 3.35) and thiophenes (243) [345, 346] can be accomplished on solid supports. 

It turned out that only the compounds listed on the right side of the scheme, namely those containing one nitrogen atom, are reduced to the aniline base by fermenting yeast no distinct reduction of the azo derivatives was observed. Whether this would be possible by altering the experimental conditions cannot be stated offhand (see p. 100). 

Six-membered rings containing one nitrogen atom resemble cyclohexanes in their geometry, and the stereochemical dependence of substituent effects is often similar. However, there is a complication involving nitrogen inversion of neutral amines which results in different orientations of the lone pair with respect to the ring621 for such effects on chemical shifts see Section 4.1.1.1. and on /H C and 2/HH values see Section 4.1.1.2. 

Seven-membered heterocycles containing one nitrogen atom may be obtained either from 105 (see p. 376) or 6-amino-6-deoxy-D-glucose (227) by reduction122 to 228, or from 6-azido-6-deoxy-D-glucopyranose (229) by oxidation to 230 followed by reduction of 230 to 231. A... 

Fused heterocyclo-quinolines containing one nitrogen atom at ring junction, 84, 71... 

VI. Reductions of Other Heterocycles Containing One Nitrogen Atom... 

Do not confuse this calculation with the observation we made about mass spectra that the molecular weight of a com pound containing one nitrogen atom must be odd. This observation and the number of DBEs are. of course, related but they are different calculations made for different purposes. 

For covalent compounds, the chemical formula represents how many of each type of atom are in each molecule. For example, the formula NH3 signifies that a molecule of ammonia contains one nitrogen atom and three hydrogen atoms. The formula C2H6 tells you that a molecule of propane contains two atoms of carbon and six atoms of hydrogen. 

REDUCTION OF HETEROCYCLES CONTAINING ONE NITROGEN ATOM AND ONE OXYGEN ATOM... 

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