Aldehyde formyl fluoride

Attempts to use acetic-formic anhydride with Friedel-Crafts catalysts resulted only in acetylation. However, using anhydrous HF as a catalyst, a small amount of aldehyde is also formed in accordance with the fact that acetic—formic anhydride gives both acetyl and formyl fluoride with HF. By continuous removal of the low boiling HCOF, the reaction can be shifted to the formation of this compound (118). 

Other Formylations. Formyl fluoride, the only known stable formic acid derivative, can be used to perform Friedel-Crafts-type acylation to form aromatic aldehydes. The method was developed by Olah and Kuhn.105 Although a number of Lewis acids may be used, BF3 is the best catalyst. It is dissolved in the aromatic compound to be formylated then formyl fluoride is introduced at low temperature and the reaction mixture is allowed to warm up to room temperature. The aldehydes of benzene, methylbenzenes, and naphthalene were isolated in 56-78% yields. Selectivities are similar to those in the Gattermann synthesis ( toiuene benzene = 34.6, 53.2% para isomer). The reacting electrophile was suggested to be the activated HCOF BF3 complex and not the free formyl cation. Clearly there is close relationship with the discussed CO—HF—BF3 system. 

Acetic formic anhydride has been prepared by the reaction of formic acid with acetic anhydride2 3 and ketene,4,5 and of acetyl chloride with sodium formate.6 The present procedure is essentially that of Muramatsu.6 It is simpler than others previously described and gives better yields. It is easily adapted to the preparation of large quantities, usually with an increase in yield. Acetic formic anhydride is a useful intermediate for the formyl-ation of amines,3,7 amino acids,8,9 and alcohols,2,10 for the synthesis of aldehydes from Grignard reagents,11 and for the preparation of formyl fluoride.12... 

Formyl fluoride is useful as a reagent for the introduction of the aldehyde group in Friedet-Crafts and Schotten-Baumann type formylations. 

Acylation of both aromatic and aliphatic compounds can be carried out with relative ease using acyl halides, acid anhydrides, ketenes, nitriles, amides, acids and esters in the presence of Friedel-Craft catalysts to give ketones. Similar substitution reactions with formic acid derivatives are therefore expected to yield the appropriate aldehydes. However, since the anhydride and acyl halides of formic acid, with the exception of formyl fluoride, are either not known or are not sufficiently stable to be used in Friedel-Crafts type acylation reactions, this objective cannot be fully realized. Table 1.1 compares the main ketone syntheses (based on acylating reagents) with the corresponding aldehyde syntheses (based on formylating reagents). 

ALDEHYDE SYNTHESIS CO + HCI (Gattermann- Koch) Formyl fluoride Acetic-formic anhydride CO HCN (Gattermann) BrCN (Karrer) Formamides (Vilsmeier) Formic acid Ortho- formates... 

Recently, the [ F](luorobcnzalciehyde 5 was obtained by nucleophilic substitution of the 2-formyl-A, A, A -trimethylbenzeneammonium trifluoromethanesulfonate precursor 4 using no-carrier-added [K/222] F as the [ F]fluoride source. The ammonium trifluoromethanesulfo-natc4 is obtained by quaternization of the dimethylamino compound 3. The [ F]fluorobcnz-aldehyde 5 is used in the preparation of interesting radiopharmaceutical a-metliyl-L-amino acids for positron emission tomography, as well as potential inhibitors of enzymatic functions. 

This chiral auxiliary 3 has been employed in the diastereoselective Ugi four-component condensation using the auxiliary s amine, an aldehyde, formic acid, tert-butyl isocyanide and zinc chloride at ambient temperature. Fluoride induced cleavage from the polymer gave N-formylated, N-galactosylated amino acid derivates in 58-96% yield. The diastereomeric ratios ranged from 74 26 to 96 4 (Scheme 12.3). 

Formylation and Carboj lation. Formylatlon of aromatic compounds such as benzene, toluene, xylenes, mesltylene, Indan, tetralin, and halobenzenes Is achieved In HSOsF-SbFs under atmospheric CO pressure at 0 °C (eq 19). However, In the cases of alkylbenzenes, both formylatlon and sulfonation took place under these reaction conditions to give alkylbenzaldehydes and formylalkylbenzenesulfonyl fluorides, as well as small amounts of alkylbenzenesulfonyl fluorides and bis (alkyIphenyl) sulfones. With benzene and halobenzenes, because of their lower reactivity only aldehydes were produced. 

Yoneda N, Chen S.-Q, Hatakeyama T, Hara S, Fukuhara T (1994) Selective electrochemical formyl hydrogen-exchange fluorinaticui of aliphatic aldehydes to prepare acyl fluorides using HF-base solutions. Chem Lett 849-850... 

In order to gain a better understanding of their individual roles, hydrogen fluoride and boron trifluoride were used separately as catalysts in the formylation of toluene. The fact that no aldehyde products were obtained from BF3 as catalyst and only a minor amount from HF, accentuates the effect of their combined potential. This effect is evident when results of Run 5 and 6 in Table 2.3 are compared with Run 1 in Table 2.2. 

Chloro-aluminate ionic liquids promote the carbonylation of alkylated aromatic compounds, but fails in the case of oxygenated aromatics. Aldehyde yields of formylation in the acidified neutral ionic liquids were generally similar compared to reactions conducted in HF as solvent/catalyst (cf Table 2.2). The increase in aldehyde yields with the use of extended alkyl chain lengths of the cationic part of the melt, may be due to improved CO solubility. HF/BFs-acidified neutral ionic liquids showed both increases in para-selectivity compared to HF as solvent and catalyst. Formylation of anisole and toluene, but not of phenol in the neutral ionic liquids resulted in increased secondary product formation in comparison with hydrogen fluoride used as solvent/catalyst. This difference in behaviour is not understood at present, but suggests that phenol is a good substrate for formylation in this medium, particularly with the development of a system catalytic with respect to HF/BF3 in mind. 

Prepa ation.—Dimethylsilyl enol ethers of aldehydes and ketones may be prepared by irradiating the carbonyl compounds in the presence of dodecamethyl-cyclohexasilane (MeaSije/ Highly stereoselective formylation of (Z)-enol silyl ethers has been achieved on treatment of acyclic ketones with ethyl tri-methylsilylacetate and tetrabutylammonium fluoride on the other hand lithiation of pentan-3-one with lithium 2,2,6,6-tetramethylpiperidide followed by chloro-trimethylsilane gave mainly (84%) the ( )-enol silyl ether... 

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