Carboxylic acid esters acetals

Thioanalogs of ketones, acetals, carboxylic acids, esters, amides, ° isocyanates, " urethanes, and ureas are often prepared by reactions similar to those used for... 

Dimethylformamide dineopentyl acetal Carboxylic acid esters from carboxylic acids... 

Notice in the list of Lewis bases just given that some compounds, such as carboxylic acids, esters, and amides, have more than one atom ivith a lone pair of electrons and can therefore react at more than one site. Acetic acid, for example, can be protonated either on the doubly bonded oxygen atom or on the singly bonded oxygen atom. Reaction normally occurs only once in such instances, and the more stable of the two possible protonation products is formed. For acetic add, protonation by reaction with sulfuric acid occurs on... 

The reaction of alcohols with CO was catalyzed by Pd compounds, iodides and/or bromides, and amides (or thioamides). Thus, MeOH was carbonylated in the presence of Pd acetate, NiCl2, tV-methylpyrrolidone, Mel, and Lil to give HOAc. AcOH is prepared by the reaction of MeOH with CO in the presence of a catalyst system comprising a Pd compound, an ionic Br or I compound other than HBr or HI, a sulfone or sulfoxide, and, in some cases, a Ni compound and a phosphine oxide or a phosphinic acid.60 Palladium(II) salts catalyze the carbonylation of methyl iodide in methanol to methyl acetate in the presence of an excess of iodide, even without amine or phosphine co-ligands platinum(II) salts are less effective.61 A novel Pd11 complex (13) is a highly efficient catalyst for the carbonylation of organic alcohols and alkenes to carboxylic acids/esters.62... 

This drug can be used as a carboxylic acid ester, in particular, as an acetate. It causes the mucous membranes of the uterus to move into the secretory phase, which facilitates development of impregnated oocytes. It reduces the excitability and contractility of uterine musculature. It is used for amenorrhea, uterine bleeding, infertility, miscarriage, myoma, mastopathy, endometrial cancer, and other pathologies. Synonyms of this drug are conce-plan, norfor, brevinor, and many others. 

In terms of A -substitution, Hartwig reported improved conditions for the Pd(0) catalyzed N-arylation of indoles and pyrrole <99JOC5575>. It was found that when commercially available P(<-Bu)3 was employed as ligand and cesium carbonate as base, the reaction between indoles 95 and unhindered aryl bromides 96 or chlorides occurred under milder conditions than the Pd(OAc)2/DPPF system previously reported yielding the A/-arylated products 97. Alternatively, it has been found that pyrrole- and indole-2-carboxylic acid esters can be selectively 7V-arylated with phenylboronic acids in the presence of cupric acetate and either tiiethylamine or pyridine <99T12757>. 

The principal method for preparation of pyrazino[2,3- [l,3]oxazines, as reported in CHEC-II(1996) <1996CHEC-II(7)737> involves cyclization of a 2-aminopyrazine-3-carboxylic acid ester with an aromatic acid chloride. Further applications of this three-step approach have been reported <19948405, 2000BMC2803>, but a one-pot approach has also been developed (Equation 157). This cyclization has also been carried out using acetic anhydride in place of an acid chloride <2005JMT(741)67>. 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives.134 The acids or their chlorides or anhydrides can be a chlorinated by treatment with CuCl in polar inert solvents (e.g., sulfolane).135 Acyl halides can be a brominated or chlorinated by use of N-bromo- or N-chlorosuccinimide and HBr or HC1.136 The latter is an ionic, not a free-radical halogenation (see 4-2). Direct iodination of carboxylic acids has been achieved with L-Cu(II) acetate in HO Ac.137 Acyl chlorides can be a iodinated with L and a trace of HI.138 Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium N-isopropylcyclohexylamide in THF and treatment of this solution at - 78° with I2138 or with a carbon tetrahalide.139 Carboxylic acids, esters, and amides have been a fluorinated at -78°C with F2 diluted in Ni.,4°... 

Solid esters are easily crystallisable materials. It is important to note that esters of alcohols must be recrystallised either from non-hydroxylic solvents (e.g. toluene) or from the alcohol from which the ester is derived. Thus methyl esters should be crystallised from methanol or methanol/toluene, but not from ethanol, n-butanol or other alcohols, in order to avoid alcohol exchange and contamination of the ester with a second ester. Useful solvents for crystallisation are the corresponding alcohols or aqueous alcohols, toluene, toluene/petroleum ether, and chloroform (ethanol-free)/toluene. Carboxylic acid esters derived from phenols are more difficult to hydrolyse and exchange, hence any alcoholic solvent can be used freely. Sulphonic acid esters of phenols are even more resistant to hydrolysis they can safely be crystallised not only from the above solvents but also from acetic acid, aqueous acetic acid or boiling n-butanol. 

Thus, at standard conditions (pH 0, all species at 1 M concentration), reaction 5 occurs in the opposite direction. In fact, carboxylic acid esters such as ethyl acetate may be synthesized under acidic conditions in water/alcohol mixtures. However,... 

The trialkoxy benzhydrol linker, developed by Rink in 1987 [46] ( Rink acid resin , Figure 3.4) is a further acid-labile linker for carboxylic acids. Esters of this linker can, like trityl esters, be cleaved with acids as weak as acetic acid or HOBt [47], and care must be taken to avoid loss of the product during synthetic operations. 

Generally, there is no limitation in the 1,3-dicarbonyl compound used. However, several types of these substances are not stable, such as malone dialdehydes or formyl acetic acid. In such cases, l,l,l-trichloro-4-oxo-butanone 96 is an appropriate substitute, since the trichloromethylcarbonyl moiety can easily be transformed into a carboxylic acid ester after the reaction by treatment with an alcohol and a... 

Efforts have also been made to utilize ketone acetals bearing a trichlorosilyl group as an enolate donor (Scheme 6.12) [63a]. This reaction led to optically active / -hydroxy carboxylic acid esters (S)-23 in good yields, although enantioselectivity remained modest only (ee values up to 50% ee when phosphoramide is used in... 

Method E, which assumes the N(7)-C(7a) bond formation in the cyclization step, is also rarely used in the synthesis of thienopyridines. For example, the method (1997H255, 1998JMC(E)33, 1998PS21) for the preparation of 4-oxo-4,7-di-hydrothieno[2,3-Z>]pyridine-5-carboxylic acid esters 54 is based on intramolecular /V-nucleophilic substitution of (E/Z)-aminomethylene derivatives of (2,5-dichloro-3-thenoyl)acetic acid esters 52 in the presence of a strong base. Esters 52 and products of their alkaline hydrolysis 56 have an antibacterial action the influence of the substituents on the biological activity of the resulting compounds was studied. 

By increasing the temperature over > 300°C, the phenyl glycidic acid esters are converted to phenyl acid esters. That occurs in a consecutive decarbonylation of a-ketone carboxylic acid esters as intermediate. In the case of p-tert-butyl glycidic acid ester in the presence of a boron-pentasil zeolite at 350 °C the ratio between a-ketone carboxylic acid ester and the phenyl acetic acid ester is 65 35. 

At a first glance it may appear eccentric to show interest in the basicities of carboxylic acids. However, this is not as curious as it seems, since protonated carboxylic acids and their derivatives play the role as important intermediates during acid-catalysed reactions of these compounds. As a matter of fact, Scheele showed as early as in 1782 that addition of sulphuric acid to a mixture of acetic acid and ethanol accelerated esterification [192]. In this respect it is a key point that carboxylic acids, esters and anhydrides possess two oxygens which are po-... 

Various terminal alkenes with fbnctional groups are oxidized to the corresponding methyl ketones. Since the oxidation proceeds under mild conditions, various functional groups, such as an aldehyde, carboxylic acid, ester, " alcohol, " MOM ether, acetal, bromide, selenide, sulfonyl ester and amines, which are located at suitable positions, remain intact. Though it is known that alcohols are oxidized to aldehydes or ketones with PdCb, " the oxidation of terminal alkenes is faster than that of alcohols under these conditions. 

Protodesilylation, A new preparation of -unsaturated carboxylic acids involves the amide acetal Claisen rearrangement of a 3-(trimethylsilyl)allyl alcohol such as 1 to allylsilanes (2). Desilylation of 2 by usual methods results in formation of stereoisomers. However, use of liquid HF at low temperatures results only in (E)-3 in 88% yield. The HF-pyridine complex is not so stereoselective. Amides such as 3 can be converted into carboxylic acid esters by Meerwein s trialkyloxonium salts (—70% yield). 

Further adaptations of the boranes has led to reagents which reduce carboxylic acids but afford thio-acetals rather than the aldehyde itself.Thus, with the thioborane (3 equation 1), aliphatic acids give 80-87% yields of thioacetals but aromatic acids respond less well in giving significant quantities of sulfides as well. Carboxylic acid esters are inert to this reagent but give sulfides if a Lewis acid is included. Similarly, the 1,3,2-dithiaborinane-dimethyl sulfide adduct (4 equation 2) affords cyclic dithioacetals in 70-90% isolated yields in the presence of SnCb. Aliphatic acids react in about 6 h at room temperature but aromatic acids need about 20 h and yields are somewhat poorer. This area has been reviewed.From a practical viewpoint, it should be noted that the dithiaborinane (4) requires a week for its preparation. 

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