Aceto aldehyde acetals

Coumarin was first produced synthetically by Perkin. He made it by heating salicylic aldehyde, CgH (OH)i(COH), acetic anhydride, and sodium acetate. The whole solidifies to a crystalline mass, from which, on treatment with water, an oil separates containing coumarin and aceto-coumaric acid. This acid on heating is decomposed into acetic acid and coumarin, so that the product of distillation is principally coumarin. Perkin s synthesis proceeds according to the following equation —... 

Essig-. vinegar acetic, aceto-. -aal, m., -ilchen, n. vinegar eel. -aldehyd, n. acetaldehyde. 

The aldol reaction is a carbonyl condensation that occurs between two aldehyde or ketone molecules. Aldol reactions are reversible, leading first to a /3-hydroxy aldehyde or ketone and then to an cr,/6-unsaturated product. Mixed aldol condensations between two different aldehydes or ketones generally give a mixture of all four possible products. A mixed reaction can be successful, however, if one of the two partners is an unusually good donor (ethyl aceto-acetate, for instance) or if it can act only as an acceptor (formaldehyde and benzaldehyde, for instance). Intramolecular aldol condensations of 1,4- and 1,5-diketones are also successful and provide a good way to make five-and six-inembered rings. 

When the second component is an a,/i-unsaturated aldehyde, somewhat different results are reported. Thus crotonaldehyde reacts with ethyl aceto-acetate to give 4/f-pyran 65,86 whereas 3-substituted crotonaldehydes with 1,3-cyclohexadiones afford 67 to 80% of the corresponding 2//-pyrans 66. ° The reaction with 1,3-pentanedione proceeded also in the second way,110 but the former cyclization with ethyl benzoylacetate gave no pyran.8 If asymmetrically substituted 1,3-cyclohexadienone components are used, the formation of mixtures of isomeric 2//-pyrans may be expected, as shown in Eq. (2)."°... 

The synthesis of the C20—C26 fragment started with a 4-alkylation of methyl aceto-acetate The first stereocentre was introduced by enantioselecuve catalytic hydrogenation with Noyort s (S)-binap rhodium complex (cf p 102f.) Stereoselective Frater-Seebach alkylation with allyl bromide introduced the second stereocentre in 90% yield (cf p 27) Stereospecifid introduction of the stereocentres C24 and C2 was achieved by a chelation controlled addition of an allylstannane to an aldehyde (see p 66f) After some experimentation with Lewis acid catalysts and reaction conditions a single diastereomer of the desired configuration was ob-... 

Minnuni308- 367 observed that, in the presence of anhydrous zinc chloride, phenylhydrazones of aromatic aldehydes react with aceto-acetic ester and its analogs to form derivatives of jS-aminocrotonic ester, which on cyclization and dehydrogenation give the corresponding pyrazoles. 

A new series of polyhydroquinolines 64 has been prepared by Shingare and co-workers [111] using nanosized Ni as a heterogeneous catalyst in a one-pot synthesis via Hantzsch condensation by reacting an aldehyde, dimedone, ethyl aceto-acetate and ammonium acetate in a domestic microwave oven. Ni (80 0.5 nm), having a higher surface to volume ratio, has given the best results in terms of short reaction times and excellent product yields. This method has demonstrated that Ni, in the form of nanoparticles, is a potential alternative catalyst for the Hantzsch... 

From Acetic and Formic Acids.—A fourth method of synthesis from acetic and formic acid esters will be explained in detail in connection with the next acid. All of these syntheses prove the constitution of pyro-racemic acid as an a//>/fa-ketone acid as given. It may be considered as aceto formic acid which is in accord with the fourth method of synthesis. As an acid it forms all acid derivatives and as a ketone it undergoes the characteristic ketone reactions, e.g.y with phenyl hydrazine and hydroxyl amine. On heating to 150° with dilute sulphuric acid in a sealed tube it loses carbon dioxide and yields acet aldehyde. 

S3mthesis of Collidine.—The most important synthesis of pyridine homologues is that of collidine from which pyridine may be obtained by elimination of the methyl groups by oxidation and loss of carbon dioxide. When aldehyde ammonia is heated with aceto-acetic ester a derivative of a di-hydrogenated collidine is obtained, as follows ... 

The electron-rich character of keten acetals (36) means that they undergo cycloaddition with ketens with judicious choice of reactants, this results in the formation of dihydropyran-2-ones, e.g. (37), which are hydrolysed to the dioxo-derivative (38). /3-Keto-esters are cyclized by their reaction with 3-hydroxy-aldehydes and titanium(rv) chloride to form 5,6-dihydropyran-2-ones. Aroylarylacetylenes condense with either ethyl cyanoacetate or aceto-acetate in the presence of a base to form 4,6-diarylpyran-2-ones (39)." ... 

The reaction of N-aminoazonium salts with aliphatic and aromatic aldehydes in the absence of base gives the Schiff base type compounds 28.151,153-156 Some aliphatic ketones also react with N-aminoazonium salts.40,155 Hexane-2,5-dione reacts with N-aminopyridinium perchlorate to give l-(l -pyrrolyl)pyridinium cation 29 together with some of the bisper-chlorate 30.157 Certain esters such as diethyl malonate and ethyl cyano-acetate react with N-aminopyridinium salts in the presence of base to give the corresponding N-acylimines 31.48 However, the reaction of ethyl aceto-acetate and acetylacetone with N-aminoazonium salts in the presence of base gives 1,3-dipolar cycloaddition products (Section IV,C,1).36,154,158 The reaction of ethyl acetoacetate with 1-alkyl-l,2,4-triazole 4-imine affords zwitterionic triazolo[4,3-/>]pyridazines 32.139,159... 

A one-pot three-component reaction of malononitrile, ethyl aceto-acetate, and various aromatic aldehydes using a few drops of piperidine and deionized water as solvent led to 2-amino-4-aryl-3-cyano-4ff-pyrans in good-to-excellent yields (14JHC106). Similar derivatives arise from the condensation of 3-[l,4-dioxo-3,4-dihydrophthalazin-(lfi)-yl]-... 

Oxidation of ethanol to acetic acid is an important characteristic of Acetobacter and Glucombacter. Ethanol is first oxidised to acetaldehyde followed by further oxidation to acetic acid, and the reactions are catalysed by cytoplasmic membrane-bound enzymes alcohol dehydrogenase and aldehyde dehydrogenase, respectively (Figure 8.1) (Saeki et al 1997). Under acidic conditions, the alcohol dehydrogenase activity of Aceto-bacter is more stable than the activity in Glucombacter, which results in more acetic acid production by Acetobacter (Matsushita, Toyama, Adachi, 1994). 

Paterson et al. [98] in their attempt used a similar disconnection for rhizopodin as described by Menche (fragments 144 and 149) (Scheme 2.151). However, unlike, Menche, they used silyl ketene acetal 16 in an asynunetric VMAR for the addition to ( )-iodoacrolein (142) to obtain dioxinone 143 in 94% ee. Methanolysis removed the aceto-nide, and the subsequent Narasaka reduction [99] provided the syn-diol 144 in 80% yield and a 10 1 selectivity for the desired isomer. The synthesis of segment 149 started with aldehyde 145, which was ultimately derived from Roche ester. Carbon chain extension was achieved through a chelation-controlled Mukaiyama aldol reaction with silyl ketene acetal 146, which installed the new chiral center with excellent stereocontrol (20 1 dr). For the installation of the third secondary alcohol, six-membered lactone 148 was obtained by treatment with K COj in methanol. Subsequent borane reduction provided stereospecifically the desired alcohol, which was then further transformed to the desired acid (149). 

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