Carboxylic acids and derivs synthesis

Nitrilases convert nitriles to the corresponding carboxylic acids and NH3 through a cysteine residue in the active site [50]. Because of their high enantio- and regio-selectivity, nitrilases are attractive as green catalysts for the synthesis of a variety of carboxylic acids and derivatives (Figure 1.10) [51,52]. Recently, a number of recombinant nitrilases have been cloned and characterized heterologously for synthetic applications [50,53,54]. 

The photolysis of carboxylic acids and derivatives as lactones, esters and anhydrides can yield decarboxylated products 253>. This reaction has been utilized in the synthesis of a-lactones from cyclic diacyl peroxides 254) (2.34) and in the synthesis of [2,2]paracyclophane by bis-decarboxylation of a lactone precursor (2.35) 255). This latter product was also obtained by photoinduced desulfurization of the analogous cyclic sulfide in the presence of triethyl phosphite 256). 

Reactions of 1,2-diaminoalkenes with alcohols, aldehydes, or carboxylic acids and derivatives at high temperatures in the presence of a dehydrogenating agent are common approaches to the synthesis of 2-substituted imidazoles (89KFZ1246). In the absence of the dehydrogenating agent the products are imidazolines. 

Hi) Carboxylic acids and derivatives. The haloform reaction on thienyl methyl ketones leads to thiophenecarboxylic acids, which can be treated with Raney nickel to produce the open-chain acids. This method has been used for the five-carbon homologation of carboxylic acids and to produce dicarboxylic acids (Scheme 51). Long-chain carboxylic acids may also be prepared by using dicarboxylic acid derivatives for the acylation of thiophenes (Scheme 52). In the synthesis of Queen substance, the precursor (213) has been generated by Raney nickel desulfurization of the appropriate thiophene-2-acetic acid derivative (79T329). 

See also page 403, Section 6, for the synthesis of a,/3-unsaturated nitriles, carboxylic acids and derivatives, and page 1711, Section 4, for the homologation of carbonyl compounds. 

In this development, both amino moieties are differentially protected and thus, incorporation of these amino acids into peptide chains either at the a- or p-position is possible. This procedure has also been applied to the synthesis of piperazine-2-carboxylic acids and derived peptides [135], Scheme 51. For example, the bicyclic a-hydroxy (S-lactam 161, upon ring expansion and subsequent coupling of the resulting NCA 162 with a-amino esters, affords 163 in good yield. 

Table 21 Synthesis of phosphole carboxylic acids and derivatives...

Synthesis from thioamides. Compounds prepared using thioamides include 4-(4-chlorophenyl)-2-[4-(hydroxy or acyl)phenyl] thiazol-5-ylacetic acids,2-(hydroxyphenyl)thiazole-4-carboxylic acids and derivatives, and substituted... 

Thallium(m) acetate effects a one-step synthesis of aliphatic a-acyloxy-carboxylic acids (Scheme 28) the transition state (92) is proposed. a-Aminoesters are readily oxidized to the corresponding a-diazoesters by isoamyl nitrite in the presence of acetic acid. A review has been published on the radical addition of carboxylic acids and derivatives to unsaturated linkages. ... 

The fluorocarbon chlorosulfonates represent a new class of compound and are useful intermediates in the synthesis of fluorocarbon carboxylic acids and derivatives. ... 

Carboxylic Acids and Derivatives.—A convenient synthesis of o-alkyl-, o-alkenyl-, and o-aryl-benzoic acids utilises nucleophilic aromatic substitution of o-methoxyaryl-oxazolines (Scheme 11). The oxazolines (92) are converted into the acids (93) by organometallic replacement of the methoxy-group, and... 

These formulae explain the scission products of the two alkaloids and the conversion of evodiamine into rutaecarpine, and were accepted by Asahina. A partial synthesis of rutaecarpine was effected by Asahina, Irie and Ohta, who prepared the o-nitrobenzoyl derivative of 3-)3-amino-ethylindole-2-carboxylic acid, and reduced this to the corresponding amine (partial formula I), which on warming with phosphorus oxychloride in carbon tetrachloride solution furnished rutaecarpine. This synthesis was completed in 1928 by the same authors by the preparation of 3-)S-amino-ethylindole-2-carboxylic acid by the action of alcoholic potassium hydroxide on 2-keto-2 3 4 5-tetrahydro-3-carboline. An equally simple synthesis was effected almost simultaneously by Asahina, Manske and Robinson, who condensed methyl anthranilate with 2-keto-2 3 4 5-tetrahydro-3-carboline (for notation, see p. 492) by the use of phosphorus trichloride (see partial formulae II). Ohta has also synthesised rutaecarpine by heating a mixture of 2-keto-2 3 4 5-tetrahydrocarboline with isatoic anhydride at 195° for 20 minutes. 

The recent discovery of a convenient synthesis of sulfur tetrafluoride from sulfur dichloride and sodium fluoride in acetonitrile invited the application of this reagent in fluorination reactions. Hasek, Smith and Engelhardt showed that carboxylic acids and their derivatives can be converted into trifluoromethyl derivatives and that aldehydes and ketones are converted into 5 em-difluoro compounds. They also observed that the reaction was acid... 

Carboxylic acids and their anhydrides acy late a variety of benzene derivatives, fused ring systems, and heterocyclic compounds. An improved procedure for the preparation of l,4-difluoroanthracene-9,10-dione involves reacting phthalic anhydride and 1,4-difluorobenzene to prepare an intermediate carboxylic acid [35] Intramolecular acylation in polyphosphonc acid completes the synthesis (equahon 24). 

The smooth conversion of the enol acetate (151) into an A -acyl derivative (152) under extremely mild conditions points to the high acylating capacity of these esters. This cleavage of isoxazolium salts is also caused by other anions of carboxylic acids, and thus they can be readily converted to reactive enol esters. A very convenient and specific synthesis of peptides due to Woodward et is based on... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Figure 29 (a) Synthesis route of the molecule (b) (i) S8, NaOH, tetraethyleneglycol dimethyl ether, heat, (28%). (b) Adamantane upper rim derivative based on the thiacalix[4]arene platform. (c,d) The carboxylic acid and ester derivative of adamantane can also be used as substituents. Taken from Ref. [109] with permission. 

Esters of [1-(diethoxyphosphinyloxy)perfluoro-l-alkene]-phosphonic acid appear to be effective reagents for the synthesis of perfluoro-a,B-unsaturated carboxylic acids and their derivatives presumably an initially-generated perfluoroketene (166 ) is acted upon by a nucleophile (NuH=RNH2, I NH, or ROH). The ( E) / (Z) ratio of the product components increases with increasing length of R. 2 ... 

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