Thiol carboxylic acid conversion

Compounds with an acidity constant, pK, in the range of 4 to 10, i.e. weak organic acids or bases, are present in two species forms at ambient pH. This pA a.i. range includes aromatic alcohols and thiols, carboxylic acids, aromatic amines and heterocyclic amines [15]. Conversely, alkyl-H and saturated alcohols do not undergo protonation/deprotonation in water (pA iw 14). 

The conversion of thiol carboxylic acid 54 derived from the, vj -amide, sy -64 (Fig. (31)) to 8 was then investigated. Employing Poetsch and co-workere protocol [85] using DCC in the presence of p-TsOH in pyridine gave a moderate yield (57%) (Table 10, Entry 1). 

Iranpoor, N., Firouzabadi, H., Akhlaghinia, B., and Azadi, R. (2004). Conversion of alcohols, thiols, carboxylic acids, trimethylsilyl ethers, and carboxylates to thiocyanates with triphenylphosphine/diethy-lazodicarboxylate/NH4SCN. Synthesis, 92-96. 

Ring contractions of pyran derivatives are occasionally valuable. The contraction of 3-halo-2-pyrones to 2-furoic acids under the influence of alkali has been studied and the conditions defined.58112113 The method is adaptable to the preparation of 3-furoic acid via furan-2,4-dicarboxylic acid58 and of 3,4,5-triphenylfuran-2-carboxylic acid.113 Another ring contraction involving halides is the conversion of 4-chloromethylpyrylium salts into furylmethyl ketones as indicated in Scheme 21.114 Pyridine oxides may be transformed with unexpected ease into furans through treatment with a thiol (Scheme 22).115... 

Carboxy terminal amino acid or peptide thiols are prepared from various p-amino alcohols by conversion into a thioacetate (R2NHCHR1CH2SAc) via a tosylate followed by saponification.Several methods have been used to prepare N-terminal peptide thiols, the most common procedure is the coupling of (acetylsulfanyl)- or (benzoylsulfanyl)alkanoic acids or add chlorides with a-amino esters or peptide esters, followed by deprotection of the sulfanyl and carboxy groups. 8 16 Other synthetic methods include deprotection of (trit-ylsulfanyl)alkanoyl peptides, 1718 alkaline treatment of the thiolactones from protected a-sulfanyl acids, 19 and preparation of P-sulfanylamides (HSCH2CHR1NHCOR2, retro-thior-phan derivatives) from N-protected amino acids by reaction of P-amine disulfides with carboxylic acid derivatives, followed by reduction. 20,21 In many cases, the amino acid or peptide thiols are synthesized as the disulfides and reduced to the corresponding thiols by the addition of dithiothreitol prior to use. 

Lundquist et al. (76) reported a method for the analysis of the metabolite 2-aminothiazoline-4-carboxylic acid (18) in urine using LC with fluorescence detection after conversion to N-carbamylcysteine by heating with alkali. The analyte was concentrated from urine by cation exchange resin and further processed to remove interfering thiols and disulfides. The LOD was rather high at 0.3 xM. 

Final purification by use of metal complexes was also applied in the syntheses of the ligands XS4—H4. These ligands exclusively contain thiolate donors and were prepared by Hahn et al. (23) using 2,3-dimercaptobenzoic acid as starting material (Scheme 8). Isopropyl or benzyl protection of the thiol functions, conversion into the acyl chlorides, reaction with a,oo-diamines, and deprotection of the sulfur atoms enabled the connection of two 1,2-benzene-dithiol units via carboxylic acid amide bonds. 

Other methods that can be used to prepare thiol esters from carboxylic acids include the use of aryl thiocyanates,12 thiopyridyl chloroformate,13 2-fIuoro- V-methylpyridinium tosylate,14 1-hydroxybenzotriazole, 5 and boron thiolate.16 Direct conversion of 0-esters to 5-esters can also be effected via aluminum and boron reagents.17 However, the applicability of these 1217 and other more recent methods18 to the selective thiol ester formation discussed above has not been clearly defined. 

Ty initiates melanin synthesis by the hydroxylation of L-tyrosine to 3,4-dihydroxyphenylalanine (Dopa) and the oxidation of dopa to dopaquinone. In the presence of L-cysteine, dopaquinone rapidly combines with the thiol group to form cysteinyldopas, which undergo nonen-zymatic conversion and polymerization to pheomelanin via benzothiazine intermediates. In the absence of thiol groups, dopaquinone very rapidly undergoes conversion to dopachrome, which is transformed to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) by dopachrome tautomerase. Alternatively, dopachrome is converted nonenzymatically to 5,6-dihydroxyindole (DHI). Oxidation of DHICA and DHI to the corresponding quinones and subsequent polymerization leads to eumelanins. It is still questionable if Ty is involved in this step. 

The azolides are able to participate in a wide variety of nucleophilic olysis reactions which form aldehydes, ketones, carboxylic acids, esters, amides, thiol esters, hydrazides and anhydrides (Scheme 143). In addition, 1-trifluoroacetylimidazole (252) is a convenient reagent for the conversion of aldoximes into nitriles (Scheme 144) (81601579). 

Air, the cheapest oxidant, is used only rarely without irradiation and without catalysts. Examples of oxidations by air alone are the conversion of aldehydes into carboxylic acids (autoxidation) and the oxidation of acyl-oins to a-diketones. Usually, exposure to light, irradiation with ultraviolet light, or catalysts are needed. Under such circumstances, dehydrogenative coupling in benzylic positions takes place at very mild conditions [7]. In the presence of catalysts, terminal acetylenes are coupled to give diacetylenes [2], and anthracene is oxidized to anthraquinone [3]. Alcohols are converted into aldehydes or ketones with limited amounts of air [4, 5, 6, 7], Air oxidizes esters to keto esters [3], thiols to disulfides [9], and sulfoxides to sulfones [10. In the presence of mercuric bromide and under irradiation, methylene groups in allylic and benzylic positions are oxidized to carbonyls [11]. 

Oxidations by oxygen and catalysts are used for the conversion of alkanes into alcohols, ketones, or acids [54]-, for the epoxidation of alkenes [43, for the formation of alkenyl hydroperoxides [22] for the conversion of terminal alkenes into methyl ketones [60, 65] for the coupling of terminal acetylenes [2, 59, 66] for the oxidation of aromatic compounds to quinones [3] or carboxylic acids [65] for the dehydrogenation of alcohols to aldehydes [4, 55, 56] or ketones [56, 57, 62, 70] for the conversion of alcohols [56, 69], aldehydes [5, 6, 63], and ketones [52, 67] into carboxylic acids and for the oxidation of primary amines to nitriles [64], of thiols to disulfides [9] or sulfonic acids [53], of sulfoxides to sulfones [70], and of alkyl dichloroboranes to alkyl hydroperoxides [57]. 

We introduced these guanidinium salts in a 1985 patent (Ref. 6) on the conversion of carboxylic acids to acid chlorides with phosgene. In this process, only 0.02 mol. % of HBGCI was required, two orders of magnitude less than the quantities of other catalysts typically used. Many new other applications including phosgene reactions with phenols, thiols, aldehydes, epoxides or O-demethyla-tion methods have been developed later and are discussed in this book. 

Decarboxylation of the carboxylic acid 1 can be achieved by conversion to the thiohy-droxamic ester and photolysis in the presence of tert-butyl thiol. See Scheme 4.9 and X. Liang, A. Lohse and M. Bols, J. Org. Chem., 65 (2000), 7432. 

Dithioacetals, 1,3-dithianes or 13-dithiolanes are prepared by reaction of the corresponding carbonyl compound in the presence of an acid catalyst (cone. HQ, Lewis acids such as Znh, BFs EtaO, TMS-Cl, etc.) with a thiol or dithiol. Silica gel treated with thionyl chloride was found to be an effective as well as selective catalyst for thioacetalization of aldehydes. Thioacetalization can also be achieved using a (polystyryl)diphenylphosphine-4odine complex as a catalyst Conversion of aldehydes or acetals into 1,3-dithianes is achieved with the aid of organotin thioalkoxides and organotin triflates or with 2,2-di-methyl-2-sila-l,3-dithiane. Direct conversion of carboxylic acids to 1,3-dithianes can be carried out by reaction with 1,3,2-dithiabomenane-dimethyl sulfide and tin(II) chloride or 1,3,2-dithiaborolene with trichloromethyllithium followed by basic hydrolysis. 

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