Formyl chloride synthesis

Aldehyde Synthesis. Formylation would be expected to take place when formyl chloride or formic anhydride reacts with an aromatic compound ia the presence of aluminum chloride or other Friedel-Crafts catalysts. However, the acid chloride and anhydride of formic acid are both too unstable to be of preparative iaterest. 

The range of the reaction was extended by the elegant aldehyde synthesis of Gattermann and Koch. If a mixture of carbon monoxide and hydrogen chloride is allowed to act in the presence of aluminium chloride (and cuprous chloride) on toluene (benzene is less suitable), the reaction occurs which might he expected with formyl chloride if this substance were capable of existence. 

The Gatterman-Koch synthesis is a variant of the Friedel-Crafts acylation in which carbon monoxide and HC1 generate an intermediate that reacts like formyl chloride. Like Friedel-Crafts reactions, the Gatterman-Koch formylation succeeds only with benzene and activated benzene derivatives. 

Staab introduced azolides as versatile reagents in organic synthesis. The reaction of carbonyldiimid-azolide with carboxylic acids produces imidazolides under mild conditions which can be converted by the action of hydrogen halides to acid halides in high yield (equation 20). The method does not even require the isolation of the imidazolides, but can be carried out as a one-pot synthesis. The possibility of carrying out this reaction at low temperatures allows the preparation of temperature sensitive compounds. Formyl chloride, which decomposes at -40 °C, has been prepared in this way. 

A direct synthesis of the aromatic aldehydes by means of the Friedel-Crafts reaction could not be brought about until recently, because of the instability of formyl chloride, which, if formed, decomposes immediately into carbon monoxide and hydrochloric add ... 

The synthesis of benzaldehyde from benzene poses a problem because formyl chloride, the acyl halide required for the reaction, is unstable and cannot be purchased. Formyl chloride can be prepared, however, by means of the Gatterman-Koch formyla-tion reaction. This reaction uses a high-pressure mixture of carbon monoxide and HCl to generate formyl chloride, along with an aluminum chloride-cuprous chloride catalyst to carry out the acylation reaction. 

Problem 16.47. Amides can also be synthesized by using the acid chloride or acid anhydride instead of the carboxylic acid. Give equations for the synthesis of formamide from formyl chloride and formic anhydride. 

Aldehydes cannot be synthesized by the Friedel-Crafts reaction using methanoyl chloride (formyl chloride) because it is an unstable compound. However, a gaseous mixture of carbon monoxide and hydrogen chloride reacts like formyl chloride. The formylation of an aromatic compound using this gaseous mixture and aluminum trichloride is called the Gatterman—Koch synthesis. Like the Friedel-Crafts reaction, this method is limited to activated aromatic compounds. 

The most important method for the synthesis of aromatic ketones 3 is the Friedel-Crafts acylation. An aromatic substrate 1 is treated with an acyl chloride 2 in the presence of a Lewis-acid catalyst, to yield an acylated aromatic compound. Closely related reactions are methods for the formylation, as well as an alkylation procedure for aromatic compounds, which is also named after Friedel and Crafts. 

The preparation of a formyl-substituted aromatic derivative 3 from an aromatic substrate 1 by reaction with hydrogen cyanide and gaseous hydrogen chloride in the presence of a catalyst is called the Gattermann synthesis This reaction can be viewed as a special variant of the Friedel-Crafts acylation reaction. 

Synthesis of the remaining half of the molecule starts with the formation of the monomethyl ether (9) from orcinol (8). The carbon atom that is to serve as the bridge is introduced as an aldehyde by formylation with zinc cyanide and hydrochloric acid (10). The phenol is then protected as the acetate. Successive oxidation and treatment with thionyl chloride affords the protected acid chloride (11). Acylation of the free phenol group in 7 by means of 11 affords the ester, 12. The ester is then rearranged by an ortho-Fries reaction (catalyzed by either titanium... 

Mesitaldehyde may be prepared from mesitylmagnesium bromide by the reaction with orthoformate esters3 or ethoxy-methyleneaniline 3 from acetylmesitylene by oxidation with potassium permanganate,4 from mesitoyl chloride by reduction,5 from mesityllithium by the reaction with iron pentacarbonyl and from mesitylene by treatment with formyl fluoride and boron trifluoride,7 by treatment with carbon monoxide, hydrogen chloride, and aluminum chloride,8 or by various applications of the Gatterman synthesis.9-11... 

An alternative approach towards the PASP synthesis of isocyanides was developed by Bradley [100,101]. It involved the use of a polymer-supported sul-fonyl chloride in the presence of base to afford the dehydration of formamides (Scheme 21). The formamides required could be easily prepared by reaction of the corresponding amines with a formylated benzotriazole resin. Opti-... 

The strategies used in the synthesis of polymethine dyes are illustrated for a series of indoline derivatives in Scheme 6.1. There is an even wider range of synthetic routes to polymethine dyes than is described here, but they are based for the most part on a similar set of principles. The starting material for the synthesis of this group of polymethine dyes is invariably 2-methylene-1,3,3-trimethylindolenine (121), known universally as Fischer s base. As illustrated in the scheme, compound 121 may be converted by formylation using phosphoryl chloride and dimethylformamide into compound 122, referred to as Fischer s aldehyde, which is also a useful starting material for this series of polymethine dyes. When compound 121 (2 mol) is heated with triethylorthoformate (1 mol) in the presence of a base such as pyridine, the symmetrical cyanine dye, C. I. Basic Red 12 109 is formed. The synthesis of some hemicyanines may be achieved by... 

For the synthesis of the natural blue pigment trichotomine dimethyl ester, L-Trp-OMe was used as a starting material. The first step of this synthesis was conversion into methyl l-methyl-3,4-dihydro-/8-carboline-3-carboxylate with acetyl chloride in TFA (85JOC3322). An improved method starts from the corresponding thioamides via thioiminium salts which cyclize spontaneously in refluxing solvent (82CPB4226). A-Formyl-tryptophan also cyclized readily with no side reactions (68CJC3404). 

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