By the Sommelet reaction

P-Naphthaldehyde. This preparation illustrates the use of -bromo-succinimide (Section VI.26) in the conversion of the readily available P-methylnaphthalene into 2-bromomethylnaphthalene and of the latter into p-naphthaldehyde by the Sommelet reaction. 

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-... 

The procedure described is a modification of the general procedure of Angyal2 for the preparation of aldehydes from benzylamines by the Sommelet reaction. Isophthalaldehyde has been prepared from w-xylene by preparation of the tetrachloro derivative and hydrolysis,3 from isophthaloyl chloride by the Rosenmund reaction,4 from a,a -dibromo-m-xylene by the Sommelet reaction,5 and from isophthaloyl chloride by reduction with lithium tri-Cbutoxyaluminumhydride.6... 

The formyl group is generally introduced via the Vilsmeier reaction by dimethylformamide in the presence of phosphorus oxychloride, by the Sommelet reaction via the corresponding chloromethyl derivative, or by treating the lithio compound with dimethylformamide.87... 

Selenophene-3-aldehyde has been obtained by the Sommelet reaction of 3-bromomethylselenophene (obtained from 3-methyl-selenophene and A-bromosuccinimide), by reaction of dimethyl-formamide with 3-lithioselenophene (obtained by lithium-iodine exchange at — 60°C),74 and by reduction and subsequent hydrolysis of selenophene-3-carbonitrile.75... 

Dimethyl-3-formylselenophene was obtained by the Sommelet reaction on 2,5-dimethyl-3-chloromethylselenophene.60 2,5-Diformyl-selenophene has been prepared in two ways reaction of dimethyl-formamide with 2-lithio-5-formylselenophene (obtained from 2-formylselenophene and butyllithium) and hydrolysis of the nitrone from the reaction of p-nitrosodimethylaniline with the pyridinium salt obtained from 2,5-bischloromethylselenophene.76... 

The synthesis of aldehydes by the Sommelet reaction, the Rosenmund reduction and the Stephens reaction all involve the conversion of a group already present in the molecule. The Rosenmund reduction (Scheme 6.7) is the catalytic hydrogenation of a benzoyl chloride in the presence of a catalyst poison, quinoline/sulfur, which prevents over-reduction to the alcohol. In the Stephens reaction (Scheme 6.7), a nitrile group is reduced by tin(II) chloride and hydrochloric acid to an imine salt, which is then hydrolysed. 

The Sommelet reaction has been widely extended to heterocycles, which are important to medicinal chemists. With yields ranging from 50% to 57%, aldehydes of pyridine, isoquinoline, and thiazole were prepared from the corresponding heteroarylmethyl bromides.27 5-Benzyloxy-3-bromomethyl-benzo[i]thiophene (30) was converted to 3-carboxaldehyde 31 in 40% yield.28 Thiazole 32 was the core structure in another Sommelet reaction to give 33 although in poor yield.29 In contrast, a different thiazole substrate 34 gave aldehyde 35 in 49% yield.30 Benzopyrans are also tolerated by the Sommelet reaction conditions.31,32 For example, substrate 36 was converted to aldehyde 37 in 58% yield.32... 

The preparation of 2-thiophenecarbaldehyde from the corresponding chloro-methyl compound,542 and of 4-stilbenecarbaldehyde from 4-methylstilbene by way of 4-(bromomethyl)stilbene,543 may also be noted, m- and / -Dialdehydes, but not a-dialdehydes, can also be obtained by the Sommelet reaction. 

The given compound has a -C-H group attached to thiophene at position 2. One method of achieving this is by chloromethylation via electrophilic substitution, followed by the Sommelet reaction ... 

The process whereby aldehydes are produced from arylmethyl (also alkyl and other) halides by the action of hexamine is known as the Sommelet reaction. The reaction is essentially the conversion of an amine into an aldehyde the hexamine serves the dual role of converting the halide into the amine and the amine into the aldehyde, but its function is different in the two steps. When starting from a halide, the reaction proceeds in three stages —... 

It has been suggested that the Sommelet reaction proceeds by a hydride ion transfer, the acceptor being the conjugate acid of a Schiff base ... 

The Sommelet reaction failed with 5-nitro-2-thenyl bromide. 5-Nitro-2-thiophenealdehyde is, therefore, best obtained by nitration of 2-thiophenealdehyde diacetate and separation of the 5-isomer. ... 

Evidently this is a hydrogenation and the source of the hydrogen is benzylamine as indicated by the production of benzaldehyde and ammonia in equivalent amounts presumably the benzylamine is dehydrogenated to the imine C,HjCH =NH, which is then hydrolysed. In the absence of hexamine, the maximum yield of benzaldehyde is 50 per cent. When hexamine is added to the reaction mixture, the yield of aldehyde is increased and that of methylbenzylamine is decreased, and methyl-amine is present at the end of the reaction. Hexamine reacts as the methylene derivative of ammonia, CH2=NH, which is hydrogenated to methylamine. The fundamental stage of the Sommelet reaction may be written as ... 

Naphthaldehyde has been made from a-naphthonitrile by reduction with stannous chloride, and from naphthalene by the action of aluminum chloride, hydrogen cyanide, and hydrochloric acid. The best preparation is the Sommelet reaction from a-chloro- or a-bromomethylnaphthalene and hexamethylenetetramine in aqueous alcohol is.is. .is.w or glacial acetic acid. This method has been improved in the present procedure by the use of 50% acetic acid as solvent. 

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 ... 

Thenaldehyde (thiophene-2-carbaldehyde) is readily available via the Vilsmeier-Haack reaction of DMF with thiophene catalyzed by phosphorus oxychloride. The Sommelet reaction with 2-chloromethylthiophene also gives reasonable yields (63AHC(l)l). Likewise, thiophene is readily acylated with acyl anhydrides or acid chlorides (equation 14), using mild Friedel-Crafts catalysts, such as tin(IV) chloride, zinc chloride, boron trifluoride, titanium tetrachloride, mercury(II) chloride, iodine and even silica-alumina gels or low-calcium-content montmorillonite clays (52HC(3)l). 

Aromatic and heteroaromatic aldehydes can alternatively be prepared from the corresponding methyl compound by subjecting the chloromethyl or bromomethyl derivative to the Sommelet reaction. This procedure involves an initial reaction between the halomethyl compound and hexamethylenetetramine (hexamine), and hydrolysing the resulting quaternary hexamine salt (4) with hot aqueous acetic acid. 

Cognate preparations. p-Nitrobenzaldehyde. This preparation is an example of the Sommelet reaction in which the hexaminium salt is isolated. Dissolve llg (0.13mol) of hexamethylenetetramine in 70ml of chloroform (CAUTION) and add 11.4 g (0.067 mol) of p-nitrobenzyl chloride or 14.4 g of p-nitrobenzyl bromide (Expt 6.28). Heat the mixture under reflux on a steam bath for 4 hours a precipitate gradually separates. Replace the reflux condenser by a condenser set for distillation and distil off about 35 ml of solvent. Add 35 ml of acetone, cool in ice, collect the precipitate by suction filtration and dry it in the air. Heat the hexaminium salt thus obtained under reflux for 1 hour with 100 ml of 50 per cent acetic acid then add 100 ml of water and 25 ml of concentrated hydrochloric acid and continue the refluxing for 5-10 minutes. Cool the solution in ice, collect the crystals of p-nitrobenzaldehyde and dry them in a vacuum desiccator. The yield is 6.4 g (63%), m.p. 106 °C. The p.m.r. spectrum is noted in Expt 6.117. 

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