Ketones Perkin reaction

Aldehydes and Ketones. Pyrrole aldehydes and ketones are somewhat less reactive than the corresponding benzenoid derivatives. The aldehydes do not undergo Cannizzaro or Perkin reactions but condense with a variety of compounds that contain active methylene groups. They also react with pyrroles under acidic conditions to form dipyrryhnethenes (26). The aldehydes can be reduced to the methyl or carbinol stmctures. The ketones undergo normal carbonyl reactions. 

An important variation of the Perkin reaction is the Erlenmeyer azalactone synthesis exemplified by equation (4), involving condensation of an aldehyde and an N-acylglycine derivative in the presence of acetic anhydride and sodium acetate. Although this reaction, analogous to the classical Perkin condensation, was initially limited to the use of aromatic aldehydes, Baltazzi and Robinson reported that the use of lead acetate and THF allowed the preparation of several azalactones derived from aliphatic aldehydes (equation 15). The results for the condensation of several aldehydes and ketones with hippuric acid (28) under these conditions are shown in Table 2. The reaction proceeds through the intermediate (26) (intramolecular condensation of 25), which reacts with the aldehyde in Perkin fashion to provide the so-called azalactone product (Scheme 8). It is the formation of such oxazolones from acylamino acids which is be-... 

Simple aliphatic aldehydes and ketones cannot be used as the carbonyl component in the Perkin reaction. Knoevenagel5 reported the successful condensation of aldehydes and ketones with malonic acid in the presence of ammonia or amines. The most satisfactory method uses pyridine as a catalyst and is known as the Doebner modification.6 Thus, acetaldehyde 18 reacts with malonic acid (19) in the presence of a pyridine catalyst to afford the acid 20 in 60% yield. 

The methylene group of malonic or cyanoacetic acid is sufficiently reactive to condense under mild conditions with aliphatic or aromatic aldehydes or with ketones. Initially such reactions were carried out in the same way as the Perkin reaction, in acetic acid solution or in the presence of acetic anhydride however, use of acetic anhydride is unnecessary. 

If polyphosphoric acid is used as the dehydrating agent, then by analogy to the Perkin reaction, ben-zylidenehippuric acid 23 is formed in the intermediate step. Under these conditions, ketones can also be used in the Erlenmeyer synthesis. 

Whilst formylpyrroles behave in many ways as would be expected, some anomalous properties have attracted attention. Thus, 2-formylpyrrole gives an oxime, arylhydrazones and other typical carbonyl derivatives , and condenses with methyl ketones, hippuric acid and other reactive methylene compounds . 168, 169 It does not give the usual aldehyde reactions with Schiff s, Fehling s or Tollen s reagent ", nor does it form a cyanhydrin or take part in the Cannizzaro or Perkin reactions . ... 

Kinetic measurements were performed employii UV-vis spectroscopy (Perkin Elmer "K2, X5 or 12 spectrophotometer) using quartz cuvettes of 1 cm pathlength at 25 0.1 C. Second-order rate constants of the reaction of methyl vinyl ketone (4.8) with cyclopentadiene (4.6) were determined from the pseudo-first-order rate constants obtained by followirg the absorption of 4.6 at 253-260 nm in the presence of an excess of 4.8. Typical concentrations were [4.8] = 18 mM and [4.6] = 0.1 mM. In order to ensure rapid dissolution of 4.6, this compound was added from a stock solution of 5.0 )j1 in 2.00 g of 1-propanol. In order to prevent evaporation of the extremely volatile 4.6, the cuvettes were filled almost completely and sealed carefully. The water used for the experiments with MeReOj was degassed by purging with argon for 0.5 hours prior to the measurements. All rate constants were reproducible to within 3%. 

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 ... 

S. David and A. Thieffry, The bromiaolysia reaction of staanylene derivatives A icgiospedfic synthesis of carbohydrate-derived hydroxy-ketones, J. Chan. Soc. Perkin Trans. 3 1568 (1979). 

Lee S-H, Mendenhall GD (1988) Relative yields of excited ketones from self-reactions of alkoxyl and alkylperoxyl radical pairs. J Am Chem Soc 110 4318-4323 Leitzke A, Reisz E, Flyunt R, von Sonntag C (2001) The reaction of ozone with cinnamic acids - formation and decay of 2-hydroperoxy-2-hydroxy-acetic acid. J Chem Soc Perkin Trans 2 793-797 Lodhi ZH, Walker RW (1991) Oxidation of allyl radicals kinetic parameters for the reactions of allyl radicals with H02 and 02 between 400 and 480 °C. J Chem Soc Faraday Trans 87 2361-2365 Martini M, Termini J (1997) Peroxy radical oxidation of thymidine. Chem Res Toxicol 10 234-241... 

Baumgartner, M.T., Jimenez, L.B., Pierini, A.B. and Rossi, R.A. (2002) Reactions of o-iodohalobenzenes with carbanions of aromatic ketones. Synthesis of l-aryl-2-(o-halophenyl)ethanones. Journal of the Chemical Society, Perkin Transactions 2, 1092-1097. 

Perkins and coworkers reported on stereoselective aldol reactions with boron and titanium ketone enolates (equations 30 and 31) for the construction of a spiroacetal-dihydropyrone (108) related to natural products auripyrone A and Both are cytotoxic... 

Both imidazole-2- and -4-carbaldehydes resist the Cannizzaro, Perkin and benzoin reactions, but the 1-substituted compounds react normally. 1-Substituted 5-nitroimidazole-2-aldehydes condense readily with alkyl aryl ketones. Examples of successful condensations... 

Derivatives of Menthene.— The most important alcohols and ketones derived from the menthene unsaturated group of terpenes are terpineol, di-hydro carveol, di-hydro carvone and pulegone. The first one, the alcohol terpineol, occurs in its dextro form in cardamon oil and marjoram oil, in its leoo form in neroU oil and in its inactive form in cajeput oil. The constitution is proven by Perkin s synthesis from As-tetra-hydro para-toluic acid by means of the Grignard reaction. 

Superoxide possesses a certain basicity [265-269]. Reactions of superoxide with activated C-H functions appear to be quite general and afford the formation of alchols, ketones, or acids. In such conversions, the primary chemical reaction step appears to be the protonation of the electrogenerated base (here the superoxide) by means of the organic substrate. A Perkin Markovnikov type reaction initiated by electrogenerated superoxide as a base was pointed out [270] with malonates R R CH2 in the presence of a, w-dibromoalk-anes (see Scheme 48). However, the complexity of superoxide as reagent could be illustrated in the latter example, since ethers and epoxides were found as side products in the reaction mixture. 

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