Cycloalkanes substituted cyclohexanes

Substituted cyclohexanes are the most common cycloalkanes and occur widely in nature. A large number of compounds, including steroids and many pharmaceutical agents, have cyclohexane rings. The flavoring agent menthol, for instance, has three substituents on a six-membered ring. 

Name an Alkane Using the lUPAC System 122 Name a Cycloalkane Using the lUPAC System 126 Draw a Newman Projection 132 Draw the Chair Form of Cyclohexane 140 Draw the Two Conformations for a Substituted Cyclohexane 143 Draw Two Conformations for a Disubstimted Cyclohexane 146 Stereochemistry... 

Cyclopentanes, cyclohexanes, and all larger cycloalkanes exist in dynamic equilibrium between a set of puckered conformations.The lowest energy conformation of cyclopentane is an envelope conformation.The lowest energy conformations of cyclohexane are two interconvertible chair conformations. In a chair conformation, six bonds are axial and six are equatorial. Bonds axial in one chair are equatorial in the alternative chair, and vice versa. A boat conformation is higher in energy than chair conformations. The more stable conformation of a substituted cyclohexane is the one that minimizes axial-axial interactions. 

Cycloalkanes—Hydrocarbons that form ring structures are termed alicyclic. Ring strain exists in cycloalkanes containing 3,4, and 5 carbon atoms. A study of heats of combustion shows that cyclohexane is strain free. EHsubstituted cycloalkanes exhibit a form of stereoisomerism known as cis-trans isomerism. Cyclohexanes undergo rapid ring flips (Fig. 26-13). In substituted cyclohexanes, substituents compete for the equatorial positions. 

Recently, Corma et al. have patented a process of oxidizing cycloalkane with molecular oxygen to produce cycloalkanol and/or cycloalkanone in the presence of hydrotalcite-intercalated heteropoly anion [Co MnCo (H20)039] (M = W or Mo), which comprised one cobalt as a central atom and another as a substitute of a W=0 fragment in the Keggin structure [98]. At 130 °C and 0.5 MPa, 64 and 24% selectivity to cyclohexanone and cyclohexanol, respectively, was achieved at cyclohexane conversion about 5%. This catalytic system could be of practical importance provided a true heterogeneous nature of catalysis and good catalyst recyclability had been proved. Unfortunately, this information was lacking in [98]. 

Hydrogenative ring opening of cycloalkanes is also a well-studied area.16 252 253 289-292 Mainly cyclopropanes and cyclopentanes were studied, since three- and five-membered adsorbed carbocyclic species are believed to be intermediates in metal-catalyzed isomerization of alkanes (see Section 4.3.1). Ring-opening reactivity of different ring systems decreases in the order cyclopropane > cyclobutane > cyclopentane > cyclohexane.251 Cyclopropane and its substituted derivatives usually react below 100°C. 

Akhrem et al.390 have reported a unique method for the acylation of aromatics. When alkanes and cycloalkanes (propane, butane, cyclopentane, cyclohexane) are treated with CBr4-2AlBr3 in the presence of carbon monoxide, the intermediate acyl cations react with aromatic silanes to yield acylated products by desilylative acylation [Eq. (5.151)]. The ipso-substitution of trimethylsilane takes place regioselectively,... 

Several routes to cycloalkanes have been developed (Fig. 4). Bolton [29] described the synthesis of azabicyclo[4.3, 0]nonen-8-ones using an intramolecular Pauson-Khand cycliza-tion. The relative stereochemistry was controlled in this cyclization step which proceeded in good yield regardless of whether the nitrogen atom bore an allyl (shown) or propargyl (not shown) substituent. The ene reaction was employed in a route to trans-substituted cyclopentane and cyclohexanes [30], Reductive cleavage from the resin with LiBFL, provided the diol or, alternatively, cleavage with Ti(OEt)4 produced the diester. 

Step 1 Name the parent cycloalkane. In (a), the parent is cyclohexane. If the compound has an alkyl substituent with more carbons than the ring size, the compound is named as a cycloalkyl-substituted alkane. 

Remember In determining chirality in substituted cycloalkanes, always draw the rings as flat polygons. This is especially true for cyclohexane derivatives, where having two chair forms that interconvert can make analysis especially difficult. 

Little is known of the chemistry of alkyl-substituted cycloalkanes such as C6H11CH3. The presence of one tertiary C—H bond will not noticeably increase the overall rate of radical attack because of the abundance of secondary C—H bonds. Attack at a ring C—H position will tend to give a similar product distribution to that observed for cyclohexane with high yields of the various isomeric cyclohexenes at most temperatures between 600 and 1000 K. Loss of a hydrogen atom at the /3 position to the R group would induce homolysis to give cyclohexene and R radicals, particularly at temperatures above 800 K. 

Two ds—trans isomers in substituted cycloalkanes, it is adequate to draw the cycloalkane ring as a planar polygon, as is done in the following disubstituted cyclohexanes ... 

The TR MFE technique has been extensively used to measure the spin-lattice relaxation rates of radical ions in solutions, with a number of aromatic radical ions found to have a relaxation time in the order of 1 xs [ 13]. However, for cyclohexane and adamantane radical cations and their alkyl-substituted analogues [14-16] there is a surprising discrepancy in the relaxation times as shown in Table 8.2. The experimental values presented in Table 8.2 have been obtained by preparing a solution of the cycloalkane (c-RH) and hexafluorobenzene in n-hexane with typical concentrations of 0.01-0.1 and 0.01 M respectively. Upon irradiation of n-hexane with X-rays, the primary singlet correlated pairs are rapidly scavenged (within sub-nanoseconds) to produce the secondary c-RH+ and CeFg radical ion pair. 

The heterogeneous, catalytic hydrogenation of substituted aromatic rings is a powerful means for the preparation of cis-substituted cycloalkanes in a highly stereoselective fashion [16]. An elegant example has been reported by researchers at Roche in a synthesis of the anti-influenza drug oseltamivir phosphate (Tamiflu, 20, Scheme 8.4) [35]. Diester 18 was reduced at elevated pressure, exclusively affording the all-cis-substituted meso-cyclohexane 19. 

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