Formylation and Carboxylation

The electrophilic formylation of arenes with CO in the presence of acids (Gatterman-Koch conditions) is an efficient method for preparing aromatic aldehydes. HF-SbFs-SO2CIF is the most active system for this reaction [82]. It has been demonstrated that even diformylation can be achieved on polymeric aromatics such as biphenyl with the use of fluoroantimonic acid (Eq. 36) [83]. 

Hydrolysis of the resulting acyl cations yields the corresponding carboxylic acids (Eq. 37) (Koch reaction) [84]. With excess alkane present, ketones can be obtained (Eq. 38). 

An interesting method has been developed for the carboxylation of bicyclic enones in HF-SbFs [85]. It has been demonstrated that diprotonated a,/3-unsaturated ketones react with CO to form acylium ions. Quenching of these acylium ions with methanol leads to the corresponding carboxylic esters in good yields (Eq. 39). 

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For formyl and carboxyl groups, 3,6-diformylpyridazine, prepared by an improved synthesis, was condensed with 1,3-diaminopropane with formation of a 44-membered macrocyclic ring with four pyridazine units [94JCS(CC)487 96JCS(CC)2579, 96JCS(D)2117], The 3- and 4-pyridazinecarbaldehydes were reacted with a variety of compounds with a reactive methylene group under the conditions of Knoevenagel-,... 

The lithio derivative (97) can be used as both a formyl and carboxyl acyl anion equivalent, and this species undergoes conjugate addition to a,6-unsaturated carbonyl groups to give 1,4-adducts in good yield. This versatile reagent has also been used to prepare a-hydroxy aldehydes and ketones. 

After the formation of the hydroxyl group, the oxidation proceeds with the formation of formyl and carboxyl groups. 

Agaritine may be enzymatically oxidised at the C-4 hydroxymethyl group to the corresponding formyl and carboxyl derivatives, P-JV-[y-L-glutamyl]-4-(formyl)phenylhydrazine and -N-[y-L-glutamyl]-4-(carboxy)phenylhydrazine (10-226), repectively. The presence of P-JV-[y-L-glutamyl]-4-(carboxy)phenylhydrazine,... 

In general, the methylene and methyne groups must be activated by two carbonyl groups. The carbonyl, formyl and carboxyl group form highly... 

In readily available (see p. 22f.) cyclic imidoesters (e.g. 2-oxazolines) the ot-carbon atom, is metallated by LDA or butyllithium. The heterocycle may be regarded as a masked formyl or carboxyl group (see p. 22f.), and the alkyl substituent represents the carbon chain. The lithium ion is mainly localized on the nitrogen. Suitable chiral oxazolines form chiral chelates with the lithium ion, which are stable at —78°C (A.I. Meyers, 1976 see p. 22f.). 

Schemes based on the acid-catalyzed condensation of a bipyrrole with a dipyrrylmethane are in general unsuccessful for the synthesis of corroles. Thus, the bipyrroles 1 fail to give corroles when reacted with the appropriate dipyrrylmethane 2.10,11 However, cobalt(III) corrole 3 can be prepared in moderate yield by a [2 + 2] approach involving bipyrrole T and dipyrrylmethane 2 bearing formyl groups and carboxylic groups, respectively, and heating initial condensation products, presumably norbilenes, with cobalt(II) acetate and triphenylphosphane in methanol.12...

The main application of the enzymatic hydrolysis of the amide bond is the en-antioselective synthesis of amino acids [4,97]. Acylases (EC 3.5.1.n) catalyze the hydrolysis of the N-acyl groups of a broad range of amino acid derivatives. They accept several acyl groups (acetyl, chloroacetyl, formyl, and carbamoyl) but they require a free a-carboxyl group. In general, acylases are selective for i-amino acids, but d-selective acylase have been reported. The kinetic resolution of amino acids by acylase-catalyzed hydrolysis is a well-established process [4]. The in situ racemization of the substrate in the presence of a racemase converts the process into a DKR. Alternatively, the remaining enantiomer of the N-acyl amino acid can be isolated and racemized via the formation of an oxazolone, as shown in Figure 6.34. 

Chemical/Physical. Ozonation in water at 60 °C produced 7-formyl-1-indanone, 1-indanone, 7-hydroxy-l-indanone, l-indanone-7-carboxylic acid, indane-l,7-dicarboxylic acid, and indane-1-formyl-7-carboxylic acid (Chen et al, 1979). Wet oxidation of acenaphthene at 320 °C yielded formic and acetic acids (Randall and Knopp, 1980). The measured rate constant for the gas-phase reaction of acenaphthene with OH radicals is 8.0 x 10 " cmVmolecule-sec (Reisen and Arey, 2002). 

The transformation of lithio derivatives of dibenzothiophene into alkyl, alkenyl, hydroxyalkyl, formyl, acetyl, carboxylic acid, alkyl and arylsilyl, boronic acid, aryl and carbinol derivatives of dibenzothiophene is dealt with in the appropriate sections. In addition, the four mono-tritio derivatives of dibenzothiophene have been prepared from the corresponding lithio derivatives via hydrolysis with tritiated water (Section III, 0,2). ... 

Wynberg and Feijen studied thieno[3,4-6]thiophene (3) formylation and found that both positions 4 and 6 are attacked. This is in accordance with theoretical predictions. The reaction produces a mixture (7 3) of 4-formyl- (194) and 6-formylthieno[3,4-6]thiophene (195) in 56% total yield after separation and purification. The formyl derivatives obtained were oxidized to the corresponding carboxylic acids 196 and 197, which were converted into 3-ethylpentanoic 198 and 4-methylhexanoic (199) acids by desulfurization with Raney nickel [Scheme 15]. 

In each table, substituted azoles are ordered in the following way alkyl, substituted alkyl, aryl, formyl, acetyl, carboxylic acid, alkoxycarbonyl, cyano, amino, azido, diazonium salt, nitroso, nitro, hydroxy, alkoxy, fluoro, chloro, bromo, and iodo. 

Amino-Terminal and Carboxyl-Terminal Modifications The first residue inserted in all polypeptides is Al-formylmethio-nine (in bacteria) or methionine (in eukaryotes). However, the formyl group, the amino-terminal Met residue, and often additional amino-terminal (and, in some cases, carboxyl-terminal) residues may be removed enzymatically in formation of the final functional protein. In as many as 50% of eukaryotic proteins, the amino group of the amino-terminal residue is Al-acetylated after translation. Carboxyl-terminal residues are also sometimes modified. 

Only blastmycinone (36), valienamine (39), 40, 41, and 44 have no substituent at the branching carbon atom (Type B). A diversity (such as formyl, hydroxymethyl, methyl, 1-hydroxyethyl, acetyl, 2-hydroxyace-tyl, 1,2-dihydroxyethyl, higher alkyl, and carboxyl groups) is observed in the branchings, but, some of them are chemically interconvertible, and also can be derived from a common intermediate (see Scheme 1). 

Formylation and Acylation of Organic Compounds with Substituted Amides of Carboxylic Acids V. I. Minkin and G. N. Dorofeenko, Russ. Chem. Rev. (Engl. Transl.), 1960, 29,599-618. 

Numerous derivatives of (1) have been thus prepared, notably 2,3-dimethyl (or dialkyl)benzofurans Bz-substituted by alkyl radicals,36,213-218 methoxyl groups,101,219-221 halogen atoms,217,222-224 aryl groups,225 acetyl groups,215,218,226 formyl groups,222,226 and carboxyl groups.226,227 The method is especially valuable in the case of formyl derivatives, which are difficult to obtain otherwise. 

The 7-formyl- and 7-acetyl- pyrrolizines are formed by an iminium carboxylate intermediate followed by decarboxylation to the cyclic iminium ion which underwent nucleophilic addition followed by aldol ring closure. This pathway accounts for the 7-formyl-5-methyl [vi] and 7-acetyl-5-methyl [vii] depending if the iminium addition is by OHCCH2OH or CH3COCH2O. 

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