In six-membered rings

Azetidines under analogous reaction conditions to those above result in six-membered ring formation. However, diketene (472), an oxetan-2-one, offers considerable promise for five-membered heterocycle formation. With hydroxylamine the 3-methylisoxazolin-5-one (473) was formed. Phenylhydrazine gave the corresponding 3-methyl-l-phenylpyrazolin-5-one. 

These steric factors are also indicated by the relative basicity of enamines derived from five-, six-, and seven-membered ketones. The five- and seven-membered enamines are considerably stronger bases, indicating better conjugation between the amine lone pair and the double bond. The reduced basicity of the cyclohexanone enamines is related to the preference for exo and endo double bonds in six-membered rings (see Section 3.10). 

In six-membered rings containing heteroatoms, the basic principles are the same that is, there are chair, twist, and boat forms, axial and equatorial groups, and so on. The conformational equilibrium for tetrahydropyridines, for example has been studied. In certain compounds, a number of new factors enter the picture. We deal with only two of these. ... 

The reaction fails if the proton to be removed is sterically hindered - either tertiary as in 21 or neopentyl-like as in 2263). In six membered rings, the ds, syn hydrogen must be axial for elimination. In the parent cyclohexyl system 23, a mixture of 24 and 25 results29) whereas, in a eonformationally rigid cyclohexane... 

The process of assessing the preferred conformation has become of importance of cyclic compounds, at least in six-membered rings because in their formation, almost all the strains are involved. We have seen that cyclohexane exists mostly in the chair conformation and the boat form occurs in negligible proportion because of higher energy which is of the order of >6 K cals/mole. 

The approximately 2 1 preference for the p anomer is consistent with our knowledge of conformations in six-membered rings (see Section 3.3.2) this anomer has the variable hydroxyl in a more favourable equatorial position. Note that the difference in thermodynamic stability is not sufficient to force the equilibrium completely in favour of the P anomer, and it is perhaps unexpected that there is quite so much of the a anomer present at equilibrium. We shall return to this topic, the anomeric effect, in Section 12.4. 

In addition to the characteristic CH stretching VCD, a number of molecules that are strocturally similar to 3-methylcyclohexanone exhibit characteristic ROA features in the skeletal region below 700 cm. Figure 6 (11). In particular, a bisignate couplet near 500 cm is observed in six-membered ring compounds with a carbonyl substituent [(-F)-pulegone(73), (-F)-camphor (74), (-t-)-3-brom-ocamphor (74), (+)-nopinone (75)] and a broad low frequency couplet is observed in ketones with a 3-methyl substituent (75). The ROA of 3-methylcyclohexanone exhibits a third characteristic couplet near 400 cm. In all cases the sense of the observed couplets correlates with the absolute configuration of the most stable chair conformation. 

Metalation can also occur adjacent to the bridgehead 5p -nitrogen in six-membered rings, and examples include the lithio derivatives of 3-ethylthioimidazo[l,5-fl]pyridine 67 (80TL2I95, 80TL4193), 1,2,3-triaz-... 

Stereochemical Dependence of H- and I3C-Chemical Shifts in Six-Membered Ring Systems... 

Conformation in Six-Membered Rings Containing Hetero Atoms... 

Alkyl groups adjacent to the reactive annular nitrogen atom of a five-membered ring inhibit quaternization, but the magnitude of this steric effect is considerably less than in six-membered rings.75 Thus, the rate constant for the methylation of 2-fer/-butylthiazole by Mel is only 4.2 (acetone)124 and 41 (nitrobenzene)67 times less than that for the... 

The amino group is more nucleophilic than the hydroxyl group, and has, therefore, a greater tendency to react with the anomeric center. In solution, 5-amino-5-deoxyhexoses and 6-amino-6-deoxyhexuloses are present completely in six-membered ring-forms, containing the nitrogen atom in the ring 4-amino-4-deoxyaldoses are, to a considerable extent,... 

In six-membered rings containing three or more heteroatoms, any substituent must necessarily be close to, or on, a heteroatom. In this respect the reactivity of substituents in these systems is controlled by the adjacent heteroatoms. For example, halogens on carbon atoms or to a heteroatom are readily displaced. For the most part, the reactivity of substituents is fairly easy to predict on the basis of the chemistry of the functional groups of which they are part, and of the generalizations outlined in Chapter 2.02. 

Conformations in Six-Membered Rings. The nonplanar ring compound. cyclohexane, which contains six contiguous —CH — units, may exist in chair or boat forms (hydrogens are not shown) ... 

The methyl group in the y-position of the side-chain interferes with cyclization. The rate of C5-cyclization of n-butylbenzene at 371°C over platinum-on-silica gel is 3.5 times higher than that of 2-phenylpentane (Table IV) (14). The difference in C6-cyclization is even larger. Now, the side-chain carbon atoms involved in the cyclizations of n-butylbenzene and 2-phenylpentane have identical natures (i.e., secondary in five-membered ring closure and primary in six-membered ring closure). The difference between the two molecules (the extra methyl group) is far removed from the two carbon atoms involved in the formation of the new bond ... 

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