Primary alkyl halides, oxidation

As will be discussed later in this chapter, although the alkylation reaction is in almost all cases reasonably successful with methyl iodide and primary alkyl halides, ethylene oxide and terminal epoxides, it is... 

In the Kornblum oxidation, a primary alkyl halide is oxidized to the aldehyde with DMSO and NaHC03, typically with microwave heating ... 

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

Grignard reagents react with ethylene oxide to yield primary alcohols containing two more carbon atoms than the alkyl halide from which the organometallic compound was prepared... 

Thiols, the sulfur analogs of alcohols, are usually prepared by Sjv 2 reaction of an alkyl halide with thiourea. Mild oxidation of a thiol yields a disulfide, and mild reduction of a disulfide gives back the thiol. Sulfides, the sulfur analogs of ethers, are prepared by an Sk2 reaction between a thiolate anion and a primary or secondary alkyl halide. Sulfides are much more nucleophilic than ethers and can be oxidized to sulfoxides and to sulfones. Sulfides can also be alkylated by reaction with a primary alkyl halide to yield sulfonium ions. 

Primary alkyl halides (chlorides, bromides, and iodides) can be oxidized to... 

Several examples have been reported of the use of palladium-mediated oxidation reactions of alcohols and alkyl halides. Palladium(II) acetate in the presence of iodobenzene converts primary and secondary alcohols into carbonyl compounds under solid-liquid two-phase conditions [20], However, other than there being no further oxidation to carboxylic acids, the procedure has little to commend it over other methods. It is relatively slow with reaction times in the order of 2 days needed to achieve yields of 55-100%. 

The reaction of a -halocarboxylic acids with sodium nitrite has been used to synthesize ni-tromethane, nitroethane and nitropropane, although the reaction fails for higher nitroalkanes. " A number of other reactions have been reported which use nitrite anion as a nucleophile, including (1) reaction of alkyl halides with potassium nitrite in the presence of 18-crown-6, (2) reaction of alkyl halides with nitrite anion bound to amberlite resins, (3) synthesis of 2-nitroethanol from the acid-catalyzed ring opening of ethylene oxide with sodium nitrite, and (4) reaction of primary alkyl chlorides with sodium nitrite in the presence of sodium iodide. ... 

Organoborane intermediates can also be used to synthesize alkyl halides. Replacement of boron by iodine is rapid in the presence of base.150 The best yields are obtained with sodium methoxide in methanol.151 If less basic conditions are desirable, the use of iodine monochloride and sodium acetate gives good yields.152 As is the case in hydroboration-oxidation, the regioselectivity of hydroboration-halogenation is opposite to that observed for direct ionic addition of hydrogen halides to alkenes. Terminal alkenes give primary halides. 

The solutions of alkali pentaphospholides MP5 are gold-orange to red in color and are extremely sensitive to oxidation. The pentaphospholide ion P5 reacts with alkyl halides RBr and RI. The alkyl pentaphospholes RP5 which are to be assumed as the primary products are non-aromatic and unstable, however, and rearrange to alkyl polyphosphines such as R3P7 and R3P9 <88AG288>. The trimethylsilyl pentaphosphole is known as a complex ligand (see Section 4.22.12.1.2). 

The catalytic system tranx-[Ru(0)2 (105(0H) 3] /K(I0 )/aq. KOH or aq. Aliquat converted primary alcohols [554, 555] and primary activated alkyl halides [555] to carboxylic acids, while secondary alcohols [554, 555], and secondary alkyl halides were oxidised to ketones [555]. As with catalytic oxidations by aqueous [RuO ] double bond cleavage occurs [555]. 

This can be used for oxidations in aqneons base of primary alcohols, aldehydes, activated alkyl halides, ctT-diols and nitroalkanes to carboxylic acids, and of secondary alcohols and secondary halides to ketones. 

Primary alkyl halides (chlorides, bromides, and iodides) can be oxidized to aldehydes easily and in good yields with dimethyl sulfoxide.311 Tosyl esters of primary alcohols can be similarly converted to aldehydes,312 and epoxides313 give a-hydroxy ketones or aldehydes.314 The reaction with tosyl esters is an indirect way of oxidizing primary alcohols to aldehydes (9-3). This type of oxidation can also be carried out without isolation of an intermediate ester The alcohol is treated with dimethyl sulfoxide, dicyclohexylcarbodiimide (DCC),315 and anhydrous phosphoric acid.316 In this way a primary alcohol can be converted to the aldehyde with no carboxylic acid being produced. 

Another way to oxidize primary alkyl halides to aldehydes is by the use of hexamethylenetetramine followed by water. However, this reaction, called the Sommelet reaction. is limited to benzylic halides. The reaction is seldom useful when the R in RCH2CI is alkyl. The first part of the reaction is conversion to the amine ArCH2NH2 (0-44), which can be isolated. Reaction of the amine with excess hexamethylenetetramine gives the aldehyde. It is this last step that is the actual Sommelet reaction, though the entire process can be conducted without isolation of intermediates. Once the amine is formed, it is converted to an imine (ArCH2N=CH2) with formaldehyde liberated from the reagent. The key step then follows transfer of hydrogen from another mole of the arylamine to the imine ... 

Phenols attached to insoluble supports can be etherified either by treatment with alkyl halides and a base (Williamson ether synthesis) or by treatment with primary or secondary aliphatic alcohols, a phosphine, and an oxidant (typically DEAD Mitsu-nobu reaction). The second methodology is generally preferred, because more alcohols than alkyl halides are commercially available, and because Mitsunobu etherifications proceed quickly at room temperature with high chemoselectivity, as illustrated by Entry 3 in Table 7.11. Thus, neither amines nor C,H-acidic compounds are usually alkylated under Mitsunobu conditions as efficiently as phenols. The reaction proceeds smoothly with both electron-rich and electron-poor phenols. Both primary and secondary aliphatic alcohols can be used to O-alkylate phenols, but variable results have been reported with 2-(Boc-amino)ethanols [146,147]. 

It may be mentioned that the Grignard reaction can also be applied to the production of primary alcohols by the interaction of ethylene oxide and magnesium alkyl halide. 

The photocatalytic reactions in acetonitrile were observed to have fewer primary products and a higher chemical yield of the desired sulfoxide (Fox et al., 1990). The photocatalytic oxidation of 2-chloroethyl methyl sulfide was found to be faster than the degradation of 2-chloroethyl ethyl. UV/ Ti02, in the presence of oxygen, yields the greatest amount of removal for the alkyl halides. The rate of alkyl halide removal was found to increase with increased concentrations of TiOz. 

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