Carboxylic acids and Grignard reagents

KETONES FROM CARBOXYLIC ACIDS AND GRIGNARD REAGENTS METHYL 6-OXODECANOATE (Oecanolc acid, 6-oxo-, nethyl ester]... 

KETONES FROM CARBOXYLIC ACIDS AND GRIGNARD REAGENTS ... 

Ketones from Carboxylic Acids and Grignard Reagents Methyl 6-Oxodecanoate... 

Conductivity measurements have revealed that DMF and carboxylic acid chlorides form salt-like adducts (22) in an equilibrium reaction (equation 12). Such adducts can be prepared either from DMF and acid halides (chlorides and bromides) or from chloromethyleneiminium salts and salts of carboxylic acids. Acyloxyiminium salts (23) can be prepared in the pure state by reacting acid amides with carboxylic acid chlorides in the presence of silver trifluoromethanesulfonate (equation 13). Salts of type (24 equation 14) are regarded as being intermediates in the synthesis of ketones from carboxylic acids and Grignard reagents in the presence of a-chloroenamines as well as in the preparation of acyl halides (F, Cl, Br, I) by action of a-haloenamines on carboxylic acids. ... 

Synthesis of Keto-esters.—Keto-esters are produced, in good yield, by the reaction between carboxylic acids and Grignard reagents if it is mediated by the iminium chloride (100) (Scheme 56). P-Keto-esters are prepared by acylation of un-... 

Among the methods for preparing carboxylic acids carboxylation of a Grignard reagent and preparation and hydrolysis of a nitrile convert RBr to RCO2H The malonic ester synthesis converts RBr to RCH2CO2H... 

Grignard reagents can be successfully prepared from 4-iodoisoxazoles and these react with CO2 and ketones to give carboxylic acids and methanols, respectively. 3-Bromo- or... 

On the other hand, following the same sequences from the differently protected serine-derived nitrone 168, through the formation of hydroxylamines 169, C2 epimers of carboxylic acid and aldehydes are obtained, i.e., (2S,3R)-170 and (2S,3R)-171. Moreover, the syn adducts 164 were exclusively obtained in the addition of Grignard reagents to the nitrone 163, whereas the same reactions on nitrone 168 occurred with a partial loss of diastereoselectivity [80]. Q, j6-Diamino acids (2R,3S)- and (2R,3R)-167 can also be prepared from the a-amino hydroxylamines 164 and 169 by reduction, deprotection and oxidation steps. The diastereoselective addition of acetylide anion to N,N-dibenzyl L-serine phenyhmine has been also described [81]. 

If the carboxyl group is attached to a tertiary, or even a secondary carbon atom, the Sn2 reaction with cyanide will not be so good and the carboxylation of a Grignard reagent is probably better. Pivalic acid 44 is available but can be made from r-BuCl in good yield.13 A detailed... 

Under forcing conditions, alkyl aryl ethers are cleaved by Grignard reagents by displacement of aryloxide [A]. Such reactions are not generally useful in synthesis, but the displacement of methoxide from positions ortho to alkoxycarbonyl [2] and oxazolinyl groups [3] has been applied to the synthesis of orffco-substituted carboxylic acids, and displacement ortho to diphenylphosphino groups has also been reported [4], The following example describes the key step in a synthesis of anthraquinones. Recently, asymmetric induction by a chiral oxazolinyl substituent has been reported [5] ... 

Meyers Al, Temple DL et al (1974) Oxazolines. XL Synthesis of functionalized aromatic and aliphatic acids. Useful protecting group for carboxylic acids against Grignard and hydride reagents. J Org Chem 39 2787-2793... 

Aromatic carboxylic acids can be prepared by oxidation of the corresponding benzyl alcohols and benzaldehydes. An aromatic methyl group is also sufficiently activated by the aromatic ring for it to be oxidized to the acid under vigorous conditions, such as heating with chromium(VI) oxide. Other conventional methods include the hydrolysis of aromatic nitriles and the carboxylation of aromatic Grignard reagents with carbon dioxide. 

The reaction of carbon dioxide and Grignard reagents initially gives a salt of a carboxylic acid that is able to react further with the reagent [Eq. (18)] ... 

Kende has demonstrated that the mixed anhydride from carboxylic acids and diphenylphosphinic chloride would acylate Grignard reagents to afford ketones in moderate to good yield. Tertiary carbinols were not observed unless excess Grignard reagent was added. The intermediate anhydrides were generally isolated and made free of triethylamine hydrochloride before addition of the nucleophile. The reaction shown in equation (52) gave improved yields over the simple addition of methyllithium to the carboxylic acid. ... 

Because alcohols are much less acidic than carboxylic acids or mineral acids, they don t react with weak bases such as amines or bicarbonate ion, and they react to only a limited extent with metal hydroxides such as NaOH. Alcohols do, however, react with alkali metals and with strong bases such as sodium hydride (NaH), sodium amide (NaNH-2), and Grignard reagents (RMgX). Alkoxides are themselves bases that are frequently used as reagents in organic chemistry. 

---