2- Chloro-2-methylpropane substitution

The second point to explore involves carbocation stability. 2-Methyl-propene might react with H+ to form a carbocation having three alkyl substituents (a tertiary ion, 3°), or it might react to form a carbocation having one alkyl substituent (a primary ion, 1°). Since the tertiary alkyl chloride, 2-chloro-2-methylpropane, is the only product observed, formation of the tertiary cation is evidently favored over formation of the primary cation. Thermodynamic measurements show that, indeed, the stability of carbocations increases with increasing substitution so that the stability order is tertiary > secondary > primary > methyl. 

El eliminations begin with the same uni molecular dissociation we saw in the Sfsjl reaction, but the dissociation is followed by loss of H+ from the adjacent carbon rather than by substitution. In fact, the El and SN1 reactions normally occur together whenever an alkyl halide is treated in a protic solvent with a non-basic nucleophile. Thus, the best El substrates are also the best SN1 substrates, and mixtures of substitution and elimination products are usually obtained. For example, when 2-chloro-2-methylpropane is warmed to 65 °C in 80% aqueous ethanol, a 64 36 mixture of 2-methyl-2-propanol (Sjql) and 2-methylpropene (El) results. 

Substitutions are very common synthetic reactions by their very nature they produce at least two products, one of which is commonly not wanted. As a simple example 2-chloro-2-methylpropane can be prepared in high yield by simply mixing 2-methylpropan-2-ol with concentrated hydrochloric acid (Scheme 1.10). Here the hydroxyl group on the alcohol is substituted by a chloride group in a facile SnI reaction. Whilst the byproduct in this particular reaction is only water it does reduce the atom economy to 83%. 

Formation of a symmetrical sulphide (a) (e.g. dipropyl sulphide, Expt 5.204), is conveniently effected by boiling an alkyl halide (the source of carbocations) with sodium sulphide in ethanolic solution. Mixed sulphides (b) are prepared by alkylation of a thiolate salt (a mercaptide) with an alkyl halide (cf. Williamson s ether synthesis, Section 5.6.2, p. 583). In the case of an alkyl aryl sulphide (R-S Ar) where the aromatic ring contains activating nitro groups (see Section 6.5.3, p. 900), the aryl halide is used with the alkyl thiolate salt. The alternative alkylation of a substituted thiophenol is described in Section 8.3.4, p. 1160. The former procedure is illustrated by the preparation of isobutyl 2,4-dinitrophenyl sulphide (Expt 5.205) from l-chloro-2,4-dinitrobenzene and 2-methylpropane-1-thiol. 

The order of SN2 reactivity is primary > secondary > tertiary, and branching of the chain close to the site of substitution hinders reaction. The unbranched primary halide n-butyl chloride will be the most reactive and the tertiary halide tert-butyl chloride the least. The order of reactivity will therefore be 1-chlorobutane > l-chloro-2-methylpropane > 2-chlorobutane > 2-chloro-2-methylpropane. 

Look carefully at the reactions shown in the previous section. In each case, an unsymmetrically substituted alkene has given a single addition product, rather than the mixture that might have been expected. For example, 2-methylpropene might have reacted with HCI to give l-chloro-2-methyI-propane (isobutyl chloride) in addition to 2-chloro-2-methylpropane, but it didn t. We say that such reactions are regiospecific (ree-jee-oh-specific) when only one of two possible orientations of addition occurs. 

Yet a third limitation of the Friedel-Crafts alkylation is that it s often difficult to stop the reaction after a single substitution. Once the first alkyl group is on the ring, a second substitution reaction is facilitated for reasons we ll discuss in the next section. Thus, we often observe polyalkylation. For example, reaction of benzene with 1 mol equiv of 2-chloro-2-methylpropane yields p-di-tert-butylbenzene as the major product, along with small amounts of or -butylbenzene and unreacted benzene. A high yield of monoalkylation product is obtained only when a large excess of benzo used. 

When 2-methyl-2-propanol tert-hvXyl alcohol, 65) is treated with concentrated HCl, 2-chloro-2-methylpropane (2-chloro-2-methylpropane ter -butyl chloride, 93) is isolated in 90% yield. Similarly, when 1-butanol (94) is treated with 48% HBr in the presence of sulfuric acid, a 95% yield of 1-bromobutane (96) is obtained. In both reactions, the oxygen of the alcohol reacts as a Br0nsted-Lowry base in the presence of the protonic acids, HCl, or sulfuric acid. The fact that alkyl halides are produced clearly indicates that these are substitution reactions. In previous sections, tertiary halides gave substitution reactions when a nucleophilic halide ion reacted by an Sfjl mechanism that involved ionization to a carbocation prior to reaction with the halide. Primary halides react with a nucleophilic halide ion by an 8 2 mechanism. It is reasonable to assume that tertiary alcohols and primary alcohols will react similarly, i/the OH unit is converted to a leaving group. 

A student attempted to prepare ferf-butyl ethyl ether by a substitution reaction between 2-chloro-2-methylpropane (ferf-butyl chloride) and sodium ethoxide. None of the desired ether was obtained. What product was formed and why did this route to the ether fail Suggest a different substitution reaction that should yield the desired product. 

Consider, for example, a nucleophilic substitution reaction on 2-chloro-2-methylpropane (r-butyl chloride [(CH3)3CC1], Table 7.2, example 1) in an ionizing solvent and in the presence of some nucleophile (Nu ).The starting material is going to disappear and the product is going to form. These events will occur over some measureable period of time and the object is to determine the rate at which the disappearance of starting material and/or the appearance of product occurs. This can be expressed as follows ... 

When 1-methoxy-2-methylpropene is treated with HCI, the major product is 1-chloro-1-methoxy-2-methylpropane. Although this reaction proceeds via an ionic mechanism, the Cl is ultimately positioned at the less substituted carbon. Draw a mechanism that is consistent with this outcome, and then explain why the less substituted carbocation intermediate is more stable in this case. 

The experiment described the reaction of 2-methylpropan-2-ol with concentrated hydrochloric acid, the product that we hope to obtain is 2-chloro-2-methylpropane, via a nucleophilic substitution (8 1) reaction mechanism. 

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