Sommelet oxidation

Equivalent quantities of 2,4-bis(chloromethyl)anisole and hexamethylenetetramine (small excess) in chloroform are mixed and refluxed for 2-3 h until precipitation of the salt is complete. The crystals are filtered with suction to give an essentially quantitative yield. 

A solution of 59 g (0.12 mol) of the salt in 500 mL of water is refluxed for 4 h and filtered while hot. The filtrate is cooled in an ice bath. The white needles that separate are collected and washed with cold water to give 14 g (70%) of 4-methoxyisophthalaldehyde, mp 117-118 °C. One recrystallization from 60% alcohol gives 12.6 g (63%) of the compound, mp 119-120 °C. 

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The Sommelet reaction, also known as the Sommelet oxidation, is the oxidation of benzyl halides (1) to the corresponding aldehydes (3) using hexamethylenetetramine (HMTA) followed by hydrolysis of the hexaminium salt 2.1-3 This reaction is closely related to the Delepine amine synthesis, the Duff aldehyde synthesis, and the Krtihnke reaction (see Section 7.10.3). 

Campaigne et al. have used 3-thenyl bromide obtained by benzoyl peroxide-catalyzed, side-chain bromination of 3-methylthiophene with A -bromosuccinimide, as a starting material for 3-substituted thiophenes. - 22 3-Methylthiophene is now prepared commercially from itaconic acid. The reactive halogen in 3-thenyl bromide could be directly reacted with a variety of nucleophiles, such as cyanide, or malonate, to give more complex 3-substituted compounds. 3-Thenyl bromide was converted by the Sommelet reaction to 3-thio-phenealdehyde which, with silver oxide, was oxidized to 3-thio-... 

Oxidation of the aldehyde was not used earlier because of the difficulty of obtaining the aldehyde, which is now readily available by the Sommelet synthesis from 3-thenyl bromide. Campaigne and LeSuer 7 also used alkaline permanganate as the oxidizing agent, but the yields decreased to 40-60%. The present procedure gives an over-all yield from 3-methylthiophene of about 45%. 

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 ... 

The method Is limited to activated halides which are stable to alkoxide bases and aqueous acids. According to the discoverer,the Krdhnke oxidation is inferior to the Sommelet reaction for benzyl halides, especially those bearing electron-withdrawing groups, such as nitro. Some representative examples are shown in Scheme (P and equations As can be seen, the Krdhnke oxidation is an... 

The l6bhnke oxidation often gives good results when other methods fail. In the example given (equation 13) neither the Sommelet or the Hass-Bender method gave any aldehyde. 

The Hass-Bender oxidation is often competitive with other methods in equation (16) 7 Sommelet reaction gave only 20% of the aldehyde, whereas in equation (20) DMSO and sodium hydrogen carbonate failed to furnish any of the desired product. 

Formylbenzenesulfonamide has been prepared by chromic acid oxidation of -toluenesulfonamide, the Sommelet reaction on p-chloromethylbenzenesulfonamide, and by the Stephen reduction of j -cyanobenzenesulfonamide. The present method provides a general procedure for the synthesis of substituted aromatic aldehydes as illustrated in Table I. 

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