Carbonyl compound , acidity alkylation

Still another possibility in the base-catalyzed reactions of carbonyl compounds is alkylation or similar reaction at the oxygen atom. This is the predominant reaction of phenoxide ion, of course, but for enolates with less resonance stabilization it is exceptional and requires special conditions. Even phenolates react at carbon when the reagent is carbon dioxide, but this may be due merely to the instability of the alternative carbonic half ester. The association of enolate ions with a proton is evidently not very different from the association with metallic cations. Although the equilibrium mixture is about 92 % ketone, the sodium derivative of acetoacetic ester reacts with acetic acid in cold petroleum ether to give the enol. The Perkin ring closure reaction, which depends on C-alkylation, gives the alternative O-alkylation only when it is applied to the synthesis of a four membered ring ... 

All the above-mentioned initiators are very sensitive towards substances with active hydrogen. Care must therefore be taken to exclude acids, water, thiols, amines, and acetylene derivatives. Oxygen, carbon dioxide, carbon monoxide, carbonyl compounds, and alkyl halides which can react with the initiator, also interfere with the reaction. Careful purification and drying of the starting materials and apparatus is, therefore, absolutely essential, especially when dealing with living polymers (see Example 3-19). 

Primary and secondary alkyl peroxyesters thermally decompose by a nonradical process, giving almost quantitative yields of carboxylic acids and carbonyl compounds. Art-Alkyl peroxyesters are much less sensitive to radical-induced decompositions than diacyl peroxides. Induced decomposition is only significant in peroxyesters containing nonhindered a-hydrogens or a, /(-unsaturation. 

Carbonyls. Several papers have appeared this year from Issleib s group describing the synthesis of heterocyclic phosphorus compounds by acid-catalysed condensations of phosphines with carbonyl compounds. (Mercapto-alkyl)phenylphosphines (31) react with aldehydes or ketones to form 1,3-thiaphospholans or 1,3-thiaphosphorinans. The intermediate compound (32) can be isolated from a similar reaction with phenylisothiocyanate and is converted into a thiaphospholan by intramolecular loss of hydrogen sulphide. 

Review. Seebach and Corey have published a general paper on the preparation and metalation of 1,3-dithianes and examples of the reaction of 2-lithio-l,3-dithianes with electrophilic reagents (alkyl halides, carbonyl compounds, acids, and oxides). The value of these sulfur-stabilized anionic reagents is that they are equivalent to acyl anions (a), in which the normal polarity of the carbonyl group is reversed (reversible umpolung). 

Arsenic.—Carbanions of the type Ph2As(0)CHR and Ph2AsCHCH2R are obtainable by deprotonation of the conjugate acids with LiNPr and by addition of RLi to Ph2AsCH=CH2 respectively. They react with electrophiles such as carbonyl compounds or alkyl halides to give the expected products, e.g. Ph2As(0)CHRE (E = group derived from electrophile), and the arsenic moiety can subsequently be replaced by Br or by a nucleophilic moiety. In the case of products obtained from carbonyl compounds as electrophiles, the products derived from brominolysis are bromoalkenes. ° ... 

Since from the beginning two electrophiles (carbonyl compound and alkyl chloroformate) and two nucleophiles (HMDS and allyltrimethylsilane) are present in the media, the challenge of this reaction is to drive it for the previously described pathway. Side reactions such as allylation of the carbonyl compound and reaction between electrophihc alkyl chloroformate and nucleophilic allyltrimethylsilane were efficiently avoided using the proper Lewis acid as catalyst, being in this case the inexpensive FeSO -TH O. 

Probably unjustly these have been somewhat neglected as protective groups, except perhaps in the carbohydrate field. They are prepared by acid-catalyzed reaction of carbonyl compounds with alkyl thiols or with dithiols. The conditions which have been used include ethanedithiol in acetic acid-boron trifluoride [73], ethane-thiol or -dithiol in the presence of hydrogen chloride [81, 82, 83], or in dioxan in the presence of zinc chloride [84]. An interesting alternative is offered by the reaction of carbonyl compounds with ortho-thioboric esters at room temperature without catalyst [85]. 

Reactions.—A variety of interesting and useful syntheses have been published involving the reaction of dimsyl anion [MeS(0)CHa ] with esters and lactones,with disulphides, with chlorosilanes, with sulphinate esters, with organoboranes, and with stilbenes. Simple and functionalized a-sulphinyl carbanions can be condensed with carbonyl compounds or alkylated, often in a stereocontrolled manner, as in a nicely conceived synthesis of biotin. Considerable attention has been given to methods for the removal of the sulphoxide function following carbon-carbon bond formation. Among the methods used are reduction by aluminium amalgam (with j3-keto-sulphoxides), reduction with Raney nickel, pyrolytic elimination of sulphenic acid, elimination of sulphur dioxide from sultines, e.g. (64), and sulphoxide-... 

The alkyl derivatives of thiazoles can be catalytically oxidized in the vapor phase at 250 to 400°C to afford the corresponding formyl derivatives (21). Molybdenum oxide, V2O5, and tin vanadate are used as catalysts either alone or with a support. The resulting carbonyl compounds can be selectively oxidized to the acids. 

Two aldehydes two ketones or one aldehyde and one ketone may be formed Let s recall the classes of carbonyl compounds from Table 4 1 Aldehydes have at least one hydrogen on the carbonyl group ketones have two carbon substituents—alkyl groups for example—on the carbonyl Carboxylic acids have a hydroxyl substituent attached to the carbonyl group... 

Such copolymers of oxygen have been prepared from styrene, a-methylstyrene, indene, ketenes, butadiene, isoprene, l,l-diphen5iethylene, methyl methacrjiate, methyl acrylate, acrylonitrile, and vinyl chloride (44,66,109). 1,3-Dienes, such as butadiene, yield randomly distributed 1,2- and 1,4-copolymers. Oxygen pressure and olefin stmcture are important factors in these reactions for example, other products, eg, carbonyl compounds, epoxides, etc, can form at low oxygen pressures. Polymers possessing dialkyl peroxide moieties in the polymer backbone have also been prepared by base-catalyzed condensations of di(hydroxy-/ f2 -alkyl) peroxides with dibasic acid chlorides or bis(chloroformates) (110). 

Most ozonolysis reaction products are postulated to form by the reaction of the 1,3-zwitterion with the extmded carbonyl compound in a 1,3-dipolar cycloaddition reaction to produce stable 1,2,4-trioxanes (ozonides) (17) as shown with itself (dimerization) to form cycHc diperoxides (4) or with protic solvents, such as alcohols, carboxyUc acids, etc, to form a-substituted alkyl hydroperoxides. The latter can form other peroxidic products, depending on reactants, reaction conditions, and solvent. 

Piimaiy and secondary alkyl peroxyesters thermally decompose by a nonradical process, giving almost quantitative yields of carboxylic acids and carbonyl compounds (213,241) ... 

Induction of Asymmetry by Amino Acids. No fewer than sis types of reactions can be carried out with yields of 75—100% usiag amino acid catalysts, ie, catalytic hydrogenation, iatramolecular aldol cyclizations, cyanhydrin synthesis, alkylation of carbonyl compounds, hydrosdylation, and epoxidations (91). 

In the oxaziridines (1) ring positions 1, 2 and 3 are attributed to oxygen, nitrogen and carbon respectively. The latter almost always is in the oxidation state of a carbonyl compound and only in rare cases that of a carboxylic acid. Oxaziridinones are not known. The nitrogen can be substituted by aryl, alkyl, H or acyl the substituent causes large differences in chemical behavior. Fused derivatives (4), accessible from cyclic starting materials (Section 5.08.4.1), do not differ from monocyclic oxaziridines. 

In the diaziridine field many compounds are known bearing N-YL, A/-alkyl and A-acyl groups, but here no dramatic changes in reactivity are caused by A-substituents. N-Aryldiaziridines are underrepresented. The ring carbon is in the oxidation state of a carbonyl compound or, in the diaziridinones (5) and the diaziridinimines (6) that of carbonic acid. In single cases, diaziridine carbon bears chlorine or fluorine. 

Oxaziridines are powerful oxidizing agents. Free halogen is formed from hydrobromic acid (B-67MI50800). Reduction by iodide in acidic media generally yields a carbonyl compound, an amine and two equivalents of iodine from an oxaziridine (1). With 2-alkyl-, 2-acyl and with N-unsubstituted oxaziridines the reaction proceeds practically quantitatively and has been used in characterization. Owing to fast competing reactions, iodide reduction of 2-aryloxaziridines does not proceed quantitatively but may serve as a hint to their presence. 

Two substituents on two N atoms increase the number of diaziridine structures as compared with oxaziridines, while some limitations as to the nature of substituents on N and C decrease it. Favored starting materials are formaldehyde, aliphatic aldehydes and ketones, together with ammonia and simple aliphatic amines. Aromatic amines do not react. Suitable aminating agents are chloramine, N-chloroalkylamines, hydroxylamine-O-sulfonic acid and their simple alkyl derivatives, but also oxaziridines unsubstituted at nitrogen. Combination of a carbonyl compound, an amine and an aminating agent leads to the standard procedures of diaziridine synthesis. 

Titanium(IV) is a powerful but selective Lewis acid which can promote the coupling of allylsilanes with carbonyl compounds and derivatives In the presence of titanium tetrachlonde, benzalacetone reacts with allyltnmethylsilane by 1,4-addition to give 4-PHENYL-6-HEPTEN-2-ONE. Similarly, the enol silyl ether of cyclopentanone is coupled with f-pentyl chloride using titanium tetrachlonde to give 2-(tert-PENTYL)CYCLOPENTANONE, an example of a-tert-alkylation of ketones. 

Stereoselectivity in the condensation reaction of 2-arylethylamines with carbonyl compounds to give 1,2,3,4-tetrahydroisoquinoline derivatives was somewhat dependent on whether acid catalysis or superacid catalysis was invoked. Particularly in the cases of 2-alkyl-N-benzylidene-2-phenethylamines, an enhanced stereoselectivity was observed with trifluorosulfonic acid (TFSA) as compared with the weaker acid, trifluoroacetic acid (TFA). Compound 43 was cyclized in the presence of TFA to give modest to good transicis product ratios. The analogous compound 44 was cyclized in the presence of TFSA to give slightly improved transicis product ratios. 

However, the 0-alkyl derivatives are potentially unstable with respect to thermal elimination of a carbonyl compound and consequent reduction to the corresponding lactam. A combination of steric and electronic factors may permit this decomposition, i.e., 133 -a- 134, to occur at quite moderate temperatures. The 0-methyl derivative of the benzalphthalimidine (132) undergoes slow loss of formaldehyde at 177° (Ti/a in dimethyl sulfoxide 40 minutes), but this elimination is much faster in certain thiohydroxamic acid derivatives, e.g., 135, which lose benzaldehyde readily at 139° in dimethyl sulfoxide (T1/2 6 minutes). The outstanding example of this decomposition, however,... 

Thus the structure of the oxazirane must formally involve elimination of water from one molecule each of the carbonyl compound and of an alkyl hydroxylamine. (In the synthesis of oxazirane from N-methylhydroxylamine-O-sulfonic acid and benzaldehyde, this method... 

The A-phthalimidomalonic ester 8 can be further alkylated at the malonic carbon center with most alkyl halides, or with an o ,/3-unsaturated carbonyl compound thus offering a general route to a-amino acids 9. 

By application of the Leuckart-Wallach reaction,amines 2 can be alkylated with a carbonyl compound 1 formic acid is used as reductive agent, and is in turn oxidized to give carbon dioxide. 

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