Isomerism alkyl halides

It is a type of structural isomerism exhibited by isomeric alkyl halides, that differ in the number of carbon atoms forming the parent chain. Alkyl halides that have same molecular formula but differ in the length of the parent chain, are called chain isomers and the phenomenon of their existence is known as chain isomerism. For example, n-butyl chloride and isobutyl chloride are chain isomers. 

As shown in the following examples, hydrogen halide addition to alkenes can be highly regioselective, even regiospecific. In both cases, two constitutionally isomeric alkyl halides can be formed by addition to the double bond, but one is formed in preference to the other. 

Aliphatic nitro compounds. These are isomeric with the alkyl nitrites and may be prepared from the alkyl halide and silver nitrite, for example C,H,aBr + AgNOj — C Hj NO + AgBr... 

Rearrangement can occur and the desired alkyl halide is sometimes accompanied by an isomeric halide An example is seen m the case of the secondary alcohol 2 octanol which yields a mixture of 2 and 3 bromooctane... 

Pyrazoles, isoxazoles and isothiazoles with a hydroxyl group in the 3-position (491 Z = NR, O, S) could isomerize to 3-azolinones (492). However, these compounds behave as true hydroxy derivatives and show phenolic properties. They give an intense violet color with iron(III) chloride and form a salt (493) with sodium hydroxide which can be O-alkylated by alkyl halides (to give 494 R = alkyl) and acylated by acid chlorides (to give 494 R = acyl). 

Electrophilic attack on the sulfur atom of thiiranes by alkyl halides does not give thiiranium salts but rather products derived from attack of the halide ion on the intermediate cyclic salt (B-81MI50602). Treatment of a s-2,3-dimethylthiirane with methyl iodide yields cis-2-butene by two possible mechanisms (Scheme 31). A stereoselective isomerization of alkenes is accomplished by conversion to a thiirane of opposite stereochemistry followed by desulfurization by methyl iodide (75TL2709). Treatment of thiiranes with alkyl chlorides and bromides gives 2-chloro- or 2-bromo-ethyl sulfides (Scheme 32). Intramolecular alkylation of the sulfur atom of a thiirane may occur if the geometry is favorable the intermediate sulfonium ions are unstable to nucleophilic attack and rearrangement may occur (Scheme 33). 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Although the tin hydride reductions of alkyl halides seem simple, one must be careful because these reactions occur by a free radical mechanism. This is important, because the carbon radical produced in the reaction can isomerize68,78 and one often obtains two different stereoisomers from the synthesis. Another problem is that chiral centres can be lost in tin hydride reductions when an optically active halide is reduced. One example of this is the reduction of benzyl-6-isocyanopenicillanate with tributyltin deuteride78 (Scheme 14). The amount of isomerization depends on the temperature, the concentration of the tin hydride and the presence of and /-substituents78-82. However, some authors have reported tin hydride reductions where no racemization was observed78. 

Acceptor-substituted allenes can be prepared from the corresponding propargyl precursors by prototropic isomerization (see Section 7.2.2). Conversely, such allenes can also be used to synthesize propargyl compounds. For example, treatment of the sulfoxides 417 with 1 equivalent of a lithiation reagent leads to the intermediates 418, which furnish propargyl sulfoxides 419 by hydrolysis (Scheme 7.55) [101]. If the electrophiles used are not protons but primary alkyl halides or carbonyl compounds, the products 420 or 421, respectively, are formed by C,C linkage. 

A solution of 1 equiv of (S)- or (/ )-2-methoxymetliyl-1-[(2,2-dimethyl-l,3-dioxan-5-ylidene)amino]pyrro-lidine in THF (4 mL/mmol) is cooled to — 78 °C. 1.1 Equiv of tert-butyllithium in hexane (1.7 M) are added dropwise and the mixture is stirred for 2 h at — 78 °C. The solution of the metalated hydrazone is cooled to — 100 CC, 1.2 equiv of the alkyl halide (neat or as a solution in anhyd THF) are added dropwise, and the mixture is stirred for 1 h at —100 °C and then warmed slowly to r.t. (about 15 h). Finally, diethyl ether (30 mL/mmol) is added and the mixture is washed with pH 7 buffer (3 mL/mmol) and two 3-mL portions of brine, dried over MgSO and evaporated under reduced pressure. The Crude product is heated to 50 C for a short time if necessary (about 15 min for isomerization from the Z- to the L-isotiler monitored by TLC) and purified by silica gel column chromatography (diethyl ether/ pentane, 1 1 -2 5 Rf - > RfZ-iso-mer) to give a colorless or pale yellow product. See Table 2 for physical data. 

A recent development in the synthesis of 3//-3-benzazepin-2-ones has been the photocyc-lization of A-(chloroacetyl)phenethylamines (Scheme 25). Ring closure is by homolysis of the alkyl halide followed by intramolecular coupling of the alkyl radical with an aromatic radical cation. Yields are good, especially with a stabilizing electron-donating group (MeO, NMe2) at the position meta to the ethylamino function (i.e. ortho or para to the site of cyclization). Isomeric benzazepinones are normally obtained (Scheme 25) with meta-substituted phenethylamines (80H(14)ll). 

Nitro compounds. Aliphatic nitro compounds are acidic. They are freed from alcohols or alkyl halides by standing for a day with concentrated sulphuric acid, then washed with water, dried with magnesium sulphate followed by calcium sulphate and distilled. The principal impurities are isomeric or homologous nitro compounds. In cases where the nitro compound was originally prepared by vapour phase nitration of the aliphatic hydrocarbon, fractional distillation should separate the nitro compound from the corresponding hydrocarbon. Fractional crystallisation is more effective than fractional distillation if the melting point of the compound is not too low. 

Castro, C. E., and E. W. Bartnicki, Conformational isomerism and effective redox geometry in the oxidation of heme proteins by alkyl halides, cytochrome C, and cytochrome oxidase , Biochem., 14,498-503 (1975). 

Studies of Lewis acid-catalyzed isomerization of alkylnaphthalenes were carried out by Olah and Olah in connection with alkylation of naphthalene with alkyl halides.88 Methyl-, ethyl-, isopropyl- and ferf-butylnaphthalene readily undergo isomerization with A1C13 in CS2 solution. The rate of isomerization and the equilibrium concentration of the p isomer were found to increase with increasing branching of the alkyl substituent (Table 4.3). 

As was already mentioned, isomerizations (rearrangement of the reactant alkyl halide, as well as positional isomerization in the aromatic ring, or disproportiona-tive transalkylation) may occur during alkylation. The ease of rearrangement of alkylating agents follows the order primary < secondary < tertiary. As a rule,... 

Positional isomerization occurs similarly as during alkylation with alkyl halides. HF and H2S04, which are weaker catalysts than the conjugate Friedel-Crafts acids, however, do not bring about ready positional isomerization of the alkylated products. Rearrangement in the side chain always takes place before the attachment of the substituent to the aromatic ring when these catalysts are used. 

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