Carbocyclic ring

The irans form, b.p. 143 "C, m.p. — 6 "C is of stereochemical interest since it is the smallest carbocyclic ring capable of accommodating a trans double bond. 

Hetero)cyclic hydrocarbons Ln.J T.n.J L beginning of a carbocyclic ring T beginning of a heterocydic ring n number of atoms of the ring system f termination of the ring system... 

Benzimidazole (viii) and indazole (ix) differ from the azanaphthalenes in being nitrated at the / -position [C(g)] of the carbocyclic ring. ... 

As is broadly true for aromatic compounds, the a- or benzylic position of alkyl substituents exhibits special reactivity. This includes susceptibility to radical reactions, because of the. stabilization provided the radical intermediates. In indole derivatives, the reactivity of a-substituents towards nucleophilic substitution is greatly enhanced by participation of the indole nitrogen. This effect is strongest at C3, but is also present at C2 and to some extent in the carbocyclic ring. The effect is enhanced by N-deprotonation. 

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

This category corresponds to the construction of the carbocyclic ring by 2 + 4 cycloaddition with pyrrole-2,3-quinodimethane intermediates. Such reactions can be particularly useful in the synthesis of 5,6-disubstituted indoles. Although there are a few cases where a pyrrolequinodimethane intermediate is generated, the most useful procedures involve more stable surrogates. Both 1,5-di-hydropyrano[3,4-b]pyrrol-5(lf/)-ones[l] and l,6-dihyropyrano[4,3-b]pyrrol-6-(in)-ones[2] can serve as pyrrole-2,3-quinodimethane equivalents. The adducts undergo elimination of CO2. 

Introduction of substituents on the carbocyclic ring relies primarily on electrophilic substitution and on organometallic reactions. The former reactions are not under strong regiochcmical control. The nitrogen atom can stabilize any of the C-nng o-complexes and both pyrrole and benzo ring substituents can influence the substitution pattern, so that the position of substitution tends to be dependent on the specific substitution pattern (Scheme 14.1). 

The presence of activating substituent on the carbocyclic ring can, of course, affect the position of substitution. For example, Entries 4 and 5 in Table 14.1 reflect such orientational effects. Entry 6 involves using the ipso-directing effect of a trimethylsilyl substituent to achieve 4-acetylation. 

Upon nitration of phthalazines a nitro group is introduced only into the carbocyclic ring. Side reactions occur frequently. For example, nitration of phthalazine or its 1-methyl analog with potassium nitrate in concentrated sulfuric acid gives the 5-nitro derivative (100) as the main product together with 5-nitrophthalazin-l(2H)-one (101) as a by-producf (Scheme 27). 

SECTION 3.4. CARBOCYCLIC RINGS OTHER THAN SK-MEMBERED... 

Of the two carbocyclic rings in 272 or in simpler precursors such as 275, ring A, which has no independent stereocenters, is more strategic for disconnection. Indeed, ring B and the carbon stereocenter bearing the /-butyl (C-8) qualify for preservation as initial or origin structural units for the synthesis. The stereocenter at C(8) with its bulky... 

Among the most logical disconnections of the carbocyclic rings of 272 (or the other precursors shown extending to 278) is that involving the strategic C(4)-C(5), C(6)-0 bond pair in 272 - 278. 

The effectiveness of various sources of fluoride ion in the displacement of the trifluoromethanesulfonic group has been demonstrated while introducing a fluorine atom into the five-membered carbocyclic ring of a prostaglandin precursor Treat tnent of the corresponding triflyl derivative with potassium fluoride in acetonitrile or with cesium fluonde in refluxing diinethylformamide or hexamethylphosphoric... 

The reaction of cyanogen azide with enamines of cyclic ketones to yield a cyanoamidine with one less member in the carbocyclic ring represents a potentially valuable method of ring contraction under mild conditions (199a). The reaction probably proceeds first by 1,3 cycloaddition of the azide to the enamine followed by rearrangement and elimination of a molecule of nitrogen. 

Alkoxyisoindoles bearing substituents at the carbocyclic ring exist exclusively in the benzenoid structure the o-quinoid form could not be detected spectroscopically (88CB243). 3-(Methylthio)isoindoles are far more reactive than the corresponding alkoxy-isoindoles. These compounds prefer the benzenoid strueture, too (88CB243). 

These results show that inverse Diels-Alder reactions of pyrimidines open an easy access to a number of differently substituted pyridines and especially to compounds, in which the carbocyclic ring and the heterocyclic rings are annelated on the b position of pyridine. An interesting illustrating example... 

The original Demjanov reaction is the conversion of an aminomethyl-cycloalkane into a cycloalkanol consisting of a carbocyclic ring that is expanded by one carbon center e.g. the reaction of aminomethylcyclohexane 8 with nitrous acid leads to formation of cycloheptanol 9 ... 

Incorporation of the phenethyl moiety into a carbocyclic ring was at first sight compatible with amphetamine-like activity. Clinical experience with one of these agents, tranylcypromine (79), revealed the interesting fact that this drug in fact possessed considerable activity as a monamine oxidase inhibitor and as such was useful in the treatment of depression. Decomposition of ethyl diazoacetate in the presence of styrene affords a mixture of cyclopropanes in which the trans isomer predominates. Saponification gives acid 77. Conversion to the acid chloride followed by treatment with sodium azide leads to the isocyanate, 78, via Curtius rearrangement. Saponification of 78 affords tranylcypromine (79). 

It is of note that hypoglycemic activity is maintained even when the aromatic ring is fused onto a carbocyclic ring. Chlor-sulfonation of hydrindan gives chloride, 206. Reaction of the sulfonamide (207) obtained from that intermediate with cyclohexyl isocyanate leads to glyhexamide (208). ... 

In a continuation of the theme of simplification of the morphine ring, it was found that one of the carbocyclic rings (that which contained the allyl alcohol in morphine proper) can be dispensed with as well, to give compounds that show the full activity of the natural prototype. These agents, the benzomorphans, are of... 

Pyrroles are hydrogenated with more difficulty than are carbocyclic aromatics. In compounds containing both rings, hydrogenation will proceed nonselectively or with preference for the carbocyclic ring (/9), unless reduction of the carbocyclic ring is impeded by substituents. Acidic solvents are frequently used but are not necessary. 

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