Cyclohexyl halide

Typically, the organic substrate in these reactions is a haloalkane. Primary haloalkanes will generally give 100% substitution products, but tertiary and cyclohexyl halides usually undergo 100 % elimination, with secondary haloalkanes producing a mixture of the two. Studies of the chloride and bromide displacements of (R)-2-octyl methanesulfonate have shown that phase transfer displacements proceed with almost complete inversion of stereochemistry at the carbon centre, indicating an Sjv2-like mechanistic pathway [41],... 

Cyclohexyl halides may undergo elimination or substitution reactions. They are usually more prone to elimination, but the acetate anion MeCC>2 is not particularly basic, and nucleophiles are particularly nucleophilic in the polar aprotic solvent DMF. More cyclohexyl acetate (substitution) than cyclohexene (elimination) is likely to form. 

Although aliphatic azides can be prepared under liquidrliquid phase-transfer catalytic conditions [3-5], they are best obtained directly by the reaction of a haloalkane with sodium azide in the absence of a solvent [e.g. 6, 7]. Iodides and bromides react more readily than chlorides cyclohexyl halides tend to produce cyclohexene as a by-product. Acetonitrile and dichloromethane are the most frequently used solvents, but it should be noted that prolonged contact (>2 weeks) of the azide ion with dichloromethane can produce highly explosive products [8, 9] dibromomethane produces the explosive bisazidomethane in 60% yield after 16 days [8]. 

More evidence comes from the reactions of substituted cyclohexanes. You saw in Chapter 18 that substituents on cyclohexanes can be parallel with one another only if they are both axial. An equatorial C-X bond is anti-periplanar only to C-C bonds and cannot take part in an elimination. For unsubstituted cyclohexyl halides treated with base, this is not a problem because, although the axial conformer is less stable, there is still a significant amount present (see the table on p. 462), and elimination can take place from this conformer. 

Table 2. Barriers to ring inversion of cyclohexyl halides, and to rotation in substituted ethyl haUdest)...

Cyclohexene can be synthesized by partial hydrogenation of benzene, by partial dehydrogenation of cyclohexane, or by dehydrohalogenation of cyclohexyl halides. The hydrogenation of benzene is the most viable route in the Asahi process, cyclohexene is obtained with a 60% yield and 80% selectivity, with the remainder being converted into cyclohexane. Asahi has developed a process for the addition of water to cyclohexene to produce cyclohexanol that can then be oxidized to AA using the conventional nitric acid oxidation. 

Oxidation. Oxidation of alkyl halides by DMSO requires high temperatures (100-150°), and yields are relatively low except for primary iodides (1, 303). Epstein and Ollinger11 find that halides can be oxidized to carbonyl compounds by DMSO at room temperature (4-48 hours) in the presence of silver perchlorate as assisting agent. Chlorides are relatively unreactive, but bromides and iodides are oxidized relatively easily. Yields are higher with primary halides than with secondary halides. Cyclohexyl halides are oxidized to only a slight extent to cyclohexanone, the main product being cyclohexene, formed by elimination. 

The study of simple monosubstituted cyclohexanes is hampered by the low symmetry of the remaining 11-spin system. Reeves and Stromme (1960) and Jensen and Berlin (1960) simultaneously published results on the cyclohexyl halides. The conformational averaging at room... 

A method for synthesis of chiral cyclohexene derivatives from 4-substituted cyclohexyl halides involves derivatization to the Grignard reagent, reaction with menthyl... 

Naked cyanide ion. Alkyl halides are converted into nitriles by potassium cyanide in the presence of a catalytic amount of 18-crown-6. Acetonitrile (or benzene) is used as solvent, and the two-phase system is stirred vigorously at 25-83°. Little or no reaction occurs in the absence of the crown ether, an indication that the ether is functioning also as a phase-transfer catalyst. Primary halides are also converted quantitatively into nitriles chlorides react much faster than bromides. A few percent of elimination products are formed in the reaction of secondary halides. Cyclohexyl halides give only cyclohexene by elimination. o-Dichlorobenzene fails to react. Methacrylonitrile undergoes hydrocyanation to 1,2-dicyanopropane (92% yield). 

Lithiated (and also potassiated) allylic ethers and tertiary amines undergo mainly y-attack by primary alkyl halides. The preference for C-y is particularly strong with the metallated allylic ethers H2C=CHCH2Ot-Bu and H2C=CHCH2OSiEt3 [6,7]. Selectivities in reactions with sec-alkyl halides, allylic and cyclohexyl halides are often considerably lower than with primary alkyl halides [6,8]. Metallated allylic sulfides show mainly a-attack by primary alkyl halides [2,8,17]. 

Allen. A. Fawcett. V. Long. D.A. A Raman spectroscopic investigation of the conformation of the cyclohexyl halides CeHijX (X= chlorine, bromine, and iodine ) in thiourea clathrates. J. Raman Spectrosc. 1976, 4. 285. 

Vibrational Spectroscopy. A Raman investigation of the conformation of cyclohexyl halides trapped in thiourea clathrates has been made. The chloro- and bromo-cyclohexanes are present in the clathrate only as axial conformers whereas the iodide exists in both axial and equatorial forms. From a study of the i.r. spectra of 4-methylcyclohexanone, 4-methylcyclohex-2-enone, and several halogeno-4-methyl-cyclohexanones in the 1350-580 cm region characteristic axial and equatorial (CHj) frequencies were located. This work was subsequently extended to halo-genated 4,4-dimethylcyclohexanones and related t-butyl systems. 

The results for the cyclohexyl compounds (18b-d) parallel those reported for E2C reaction of cyclohexyl halides and tosylates with I, Br and PhS over 30 years ago it has been argued that for (18b) reaction occurs preferentially via the conformer which has the thianthrenium oxy group in the axial position, and consequently leads to a product distribution similar to that for (18c) rather than (18d). 

As expected for a bimolecular process, the reaction is faster with primary than with secondary halides. Likewise, -octyl methanesulfonate was found to undergo cyanide displacement at a greater rate than did the corresponding bromide. Moreover, elimination competes with substitution in the case of secondary halides elimination was the exclusive process observed in the reaction of cyanide ion with cyclohexyl halides. 

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