Sodium, reaction with esters

The reaction with sodium is by no means an infallible practical test for alcohols since, strictly speaking, it is applicable only to pure anhydrous liquids. Traces of water, present as impurities, would give an initial evolution of hydrogen, but reaction would stop after a time if an alcohol is absent furthermore, certain esters and ketones also evolve hydrogen when treated with sodium (compare Section XI,7,6). It may, however, be assumed that if no hydrogen is evolved in the test, the substance is not an alcohol. 

The condensation of aldehydes and ketones with succinic esters in the presence of sodium ethoxide is known as the Stobbe condensation. The reaction with sodium ethoxide is comparatively slow and a httlo reduction of the ketonic compound to the carbinol usually occurs a shorter reaction time and a better yield is generally obtained with the more powerful condensing agent potassium ieri.-butoxide or with sodium hydride. Thus benzophenone condenses with diethyl succinate in the presence of potassium [Pg.919]

Reactions of the Side Chain. Benzyl chloride is hydrolyzed slowly by boiling water and more rapidly at elevated temperature and pressure in the presence of alkaHes (11). Reaction with aqueous sodium cyanide, preferably in the presence of a quaternary ammonium chloride, produces phenylacetonitrile [140-29-4] in high yield (12). The presence of a lower molecular-weight alcohol gives faster rates and higher yields. In the presence of suitable catalysts benzyl chloride reacts with carbon monoxide to produce phenylacetic acid [103-82-2] (13—15). With different catalyst systems in the presence of calcium hydroxide, double carbonylation to phenylpymvic acid [156-06-9] occurs (16). Benzyl esters are formed by heating benzyl chloride with the sodium salts of acids benzyl ethers by reaction with sodium alkoxides. The ease of ether formation is improved by the use of phase-transfer catalysts (17) (see Catalysis, phase-thansfer). 

Perfluoro-2 (1 ethyl 1 methylpropyl)-3-methyl-l-pentene, the major hex-amer of tetrafluoroethylene, reacts with sodium methoxide to yield an ester, whereas a stable crowded ketene is formed by reaction with sodium hydroxide [2d] (equation 23)... 

Upon heating of a carboxylic ester 1 with sodium in an inert solvent, a condensation reaction can take place to yield a a-hydroxy ketone 2 after hydrolytic workup. " This reaction is called Acyloin condensation, named after the products thus obtained. It works well with alkanoic acid esters. For the synthesis of the corresponding products with aryl substituents (R = aryl), the Benzoin condensation of aromatic aldehydes is usually applied. 

For the mechanistic course of the reaction the diketone 5 is assumed to be an intermediate, since small amounts of 5 can sometimes be isolated as a minor product. It is likely that the sodium initially reacts with the ester 1 to give the radical anion species 3, which can dimerize to the dianion 4. By release of two alkoxides R 0 the diketone 5 is formed. Further reaction with sodium leads to the dianion 6, which yields the a-hydroxy ketone 2 upon aqueous workup ... 

The intramolecular Michael addition11 of a nucleophilic oxygen to an a,/ -unsaturated ester constitutes an attractive alternative strategy for the synthesis of the pyran nucleus, a strategy that could conceivably be applied to the brevetoxin problem (see Scheme 2). For example, treatment of hydroxy a,/ -unsaturated ester 9 with sodium hydride furnishes an alkoxide ion that induces ring formation by attacking the electrophilic //-carbon of the unsaturated ester moiety. This base-induced intramolecular Michael addition reaction is a reversible process, and it ultimately affords the thermodynamically most stable product 10 (92% yield). 

Thus, the reaction of alkyl halides and a-halo esters with sodium nitrite provides a very useful synthetic method for nitroalkanes and a-nitro esters. However, ethyl bromoacetate is exceptional in that it fails to give ethyl nitroacetate on treatment with sodium nitrite.93 This is due to the acidic hydrogen of the ethyl nitroacetate, which undergoes a further reaction with sodium nitrite to give the oxidized products (see Section 6.1, which discusses the Nef reaction). In a similar way, the reaction of benzyl bromide with sodium nitrite at 25 °C gives benzoic acid predominantly. To get phenylnitromethane, the reaction must be carried out at low temperature (-16 °C) (Eq. 2.48).93... 

The stereoselective total synthesis of (+)-epiquinamide 301 has been achieved starting from the amino acid L-allysine ethylene acetal, which was converted into piperidine 298 by standard protocols. Allylation of 297 via an. V-acyliminium ion gave 298, which underwent RCM to provide 299 and the quinolizidine 300, with the wrong stereochemistry at the C-l stereocenter. This was corrected by mesylation of the alcohol, followed by Sn2 reaction with sodium azide to give 301, which, upon saponification of the methyl ester and decarboxylation through the Barton procedure followed by reduction and N-acylation, gave the desired natural product (Scheme 66) <20050L4005>. 

Cyclization of 776 with ortho-esters gave (83JOC1628) [l,2,4]triazolo-[4,3-fc]pyrimido[5,4-< ][ 1,2,4]triazines 777, whereas reaction with sodium nitrite afforded the corresponding tetrazolopyrimidotriazine 778.3-Azido-pyrimido[4,5-e][l, 2,4]triazine 779 exists in a cyclic form as tetrazolo derivative 780, as shown by X-ray analysis (86KGS114). In solution the position of the 779 780 equilibrium depended on temperature and solvent. Higher temperatures favored 779. Azido compound 779 predominated in water, and tetrazolo compound 780 predominated in pyridine. Addition of sodium azide to the aqueous solution shifted the equilibrium toward 780. The... 

The success of the reaction with sodium triphenylmethide as a catalyst might have been due to the conversion of the keto ester into a sodio... 

The first total syntheses of these compounds were by Hibino and coworkers [91,92] and utilized palladium(0)-catalyzed coupling of 135 and 136 to produce indole-substituted imidazole 137 in 82% yield (Fig. 39). (A similar approach to closely related compounds was reported by Achab and coworkers at about the same time as the first report by Hibino) [93]. Ester 137 was hydrolyzed in near quantitative yield by reaction with sodium car-... 

The conversion of ally lie selenides into ally lie amines is illustrated for the ester 211, which forms the protected amine 212 by reaction with sodium t-butyl TV-chlorocarbamate. The reaction involves a [2,3] sigmatropic rearrangement (equation 79)209. 

For further details of this reaction, the reader is referred to Chapter 9. The catalytic allylation with nucleophiles via the formation of Ti-allyl metal intermediates has produced synthetically useful compounds, with the palladium-catalyzed reactions being known as Tsuji-Trost reactions [31]. The reactivity of Ti-allyl-iridium complexes has been widely studied [32] for example, in 1997, Takeuchi idenhfied a [lrCl(cod)]2 catalyst which, when combined with P(OPh)3, promoted the allylic alkylation of allylic esters 74 with sodium diethyl malonate 75 to give branched... 

The reaction of saccharin with sodium hydroxide results in substitution of the imide hydrogen atom of saccharin with sodium, giving a sodium salt (3.2.75). The resulting product is reacted with methyl chloroacetate, giving the saccharin-substituted acetic acid methyl ester (3.2.76). Upon reaction with sodium methoxide in dimethylsuhoxide, the product undergoes... 

Phenprocoumon Phenprocoumon, 3-(a-ethylbenzyl)-4-hydroxycoumarin (24.1.14), is synthesized by acylating sodium salts of diethyl ester (l-phenylpropyl)butyric acid with acetylsalicylic acid chloride, which forms the compound 24.1.12, which upon reaction with sodium ethoxide cyclizes to 3-(a-ethylbenzyl)-2-carboethoxy-4-hydroxycoumarin (24.1.13). Alkaline hydrolysis of this product and further decarboxylation gives phenprocoumon (24.1.14) [21-28]. 

Saponification of esters with sodium hydroxide is an important commerical reaction. In general, the reaction involves an ester reacting with sodium hydroxide to form an alcohol and sodium salt of the organic acid for example, ethyl acetate forming ethanol and sodium acetate ... 

For the synthesis of amino acids, the reaction of an a-haloalkyl boronic ester 4 with sodium azide and a phase-transfer catalyst in dichloromethane/water requires a large excess of azide in order to form the a-azidoalkyl boronic ester 5 with only 1-2% epimer34. With the exception of R1 = benzyl, where epimerization of 4 is relatively rapid, bromoalkyl boronic esters are preferred. Chloroalkyl boronic esters react so slowly that the azide and dichloromethane may generate hazardously explosive diazidomethane65,66. Chain extension of 5 to 6 proceeds normally. Sodium chlorite, which is known to oxidize aldehydes to carboxylic acids67-69, also oxidizes a-chloroalkyl boronic esters to carboxylic acids34. The azido acid is hydrogenated to the amino acid. 

In 1992, Legros and Fiaud found palladium-catalyzed benzyiic alkylation of naphthylmethyl and 1-naphthylethyl esters 103 with sodium dimethyl malonate 104 in dimethylformamide (DMF) to give the corresponding benzyiic alkylated products 105 in high yields (Equation (41)). " When trifluoroacetyl group is used as a leaving group of the ester partner, catalytic alkylation proceeds quite smoothly even at room temperature. In this reaction system, no reaction occurs with benzyiic acetates. 

The seemingly complex imidazolone (78-3) is in fact obtained in a single step by reaction of the amino-ester (78-1) with the iminoether (78-2) derived from capro-nitrile. The relatively acidic proton on the heterocyclic ring is next removed by reaction with sodium hydride. This anion is then alkylated with the same biphenyl-methyl bromide (77-2) that was used to prepare losartan to afford (78-4). The nitrile group is in this case converted to the tetrazole by means of tributyltin azide, a reagent that involves milder conditions than the traditional acidic medium used to generate hydrazoic acid. Thus, treatment of (78-4) with the tin reagent affords irbesartan (75-5) [82]. 

An efficient synthesis of ( )-quebrachamine is based on the construction of a suitable precursor via ring cleavage of an a-diketone monothioketal (810) (80JCS(P1)457). This monothioketal, available from 4-ethoxycarbonylcyclohexanone ethylene ketal, was fragmented to the dithianyl half ester (811) with sodium hydride in the presence of water. Reaction of (811) with tryptamine and DCC provided an amide which was converted to the stereoisomeric lactams (812) on hydrolysis of the dithiane function. Reduction of either the a- or /3-ethyl isomer with lithium aluminum hydride followed by conversion of the derived amino alcohol to its mesylate produced the amorphous quaternary salt (813). On reduction with sodium in liquid ammonia, the isomeric salts provided ( )-quebrachamine (814 Scheme 190). 

This reaction with sodium malonic ester is entirely in accord with what would be expected from the rela-... 

Peptide aldehydes 1 can be synthesized effectively by the oxidation of peptide alcohols 15, which are readily available without racemization by reduction of peptide esters 9 with sodium borohydride-lithium chloride (Scheme 5). The peptide alcohols 15 can be readily oxidized to afford enantiomerically pure aldehydes using Parikh-Doering or Dess-Martin reagents. This route is less popular than the previously described reductive methods due to (1) the sensitivity of the aldehydes to further oxidation, (2) racemization under the reaction conditions, and (3) instability of the products under the reaction conditions. 

One of the most important of the properties of tosyl esters is the ease of cleavage of those derived from primary alcohols. In this regard the formation of an iodo compound by reaction with sodium iodide in... 

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