Condensations of ketones

They are colourless liquids with characteristic odours, and are prepared by the condensation of ketones with alkyl orthoformates in the presence of alcohols, or by the reaction of acetylenes with alcohols in presence of HgO and BF3. In some cases trichloroethanoic acid is used as the catalyst. They lose alcohol when heated and form vinyl ethers. Exchange of alcohol groups occurs when the ketals of the lower alcohols are boiled with alcohols of greater molecular weight. See acetals. 

The situation is similar for other ketones Special procedures for aldol addition and self condensation of ketones have been developed but are rarely used... 

An important biological process is the basis for a general coupling method of aldehydes into symmetncal acyloins, such as BETYROIN. The key catalyst is 5-(2-hydroxyethyl)-4-methyl-l,3-thiazole, an analog of thiamin. Condensation of ketones and aldehydes with excess acetonitrile can be accomplished in a simple way to produce a,p-unsaturated nitriles Cyclohexanone leads to CY-CLOHEXYLIDENEACETONITRILE while benzaldehyde gives CINNA-MONITRILE. 

The condensation of ketones with 3-aminonitriles or S-aminoesters ai cyclization to 4-pyridone derivatives was expanded (717-719). 

Formation of pyrroles by condensation of ketones with a-aminoketones... 

Antidepressant agents show almost the same degree of tolerance as to the nature of the tricyclic moiety as do the antipsychotic agents. Thus the dehydration product(s) from the condensation of ketone 9 with the Grignard reagent from 3-chloroethyl-N, J -dimethylamine affords the antidepressant diothiepin (98). ... 

Base-promoted condensation of ketones with 3-nitroaniline results in the formadon of indoles. The reacdon proceeds in one pot via a NASH-type reacdon and subsequent cyclizadon fEq. 9.55. ... 

Substitution effects have been observed for both the homogeneously and heterogeneously base-catalyzed Claisen-Schmidt condensation of ketones and aldehydes with functional groups substituted in the para-position [5 -12], In this... 

The final step to 46 is cyclocondensation of 3,7-diazabicyclo[3.3.1]nonane (51), bispidine70, with formaldehyde. There are two different approaches to 51 (i) a pyridine is converted to a piperidine and (ii) the double Mannich or Robinson-Schopf condensation of ketone 52 with formaldehyde and primary amines affords 1,5-disubstituted 3,7-dazabicyclo[3.3.1]nonan-9-one (53), bispidone, from which 5,7-disubstituted l,3-diazaadamantan-6-one (61) is derived. Route (i) is adopted by Galinovsky and Langer,71 Stetter and... 

Acid-catalyzed condensation of ketones with furans gives 2,2 -methylene-bisfurans and eventually, if both 2(5)-positions are free, the quaterenes mentioned in Section XI,A.163... 

Similarly, imines can be formed by the condensation of ketones and suitable primary amines under microwave conditions (Scheme 6.148). Since the formation of imines is an equilibrium process, these transformations are best carried out under... 

Reaction of 2-aminobenzophenone with acetyl acetone in the presence of Bi(OTf)3 (5 mol%) results in the formation of 3-acetyl-2-methyl-4-phenylquinoline [117]. Various 1,3-diketones, acyclic ketones and cyclic ketone undergo the condensation with 2-aminoaryl ketones. The scope and generality of this process is illustrated with respect to various 2-aminoaryl ketones and a wide array of a-methylene ketones, and the results are summarized in Table 6. This method is free from side reactions such as the self-condensation of ketones, which is normally observed under basic conditions. Unlike reported methods, the present protocol does not require high temperature or drastic conditions to produce quinoline derivatives. 

The possibility of an attack by the drying agent on the compound to be dried must always be considered carefully and if necessary examined by small-scale tests, as has been mentioned before. Most notable for such unwanted aggression amongst the popular drying agents is the molecular sieve. Various grades of molecular sieve have different activities and specialist publications should be consulted for details. The main reactions which must be kept in mind are that they can catalyse the dehydrochlorination of alkyl chlorides and the condensation of ketones, they can dehydrate alcohols and can form exposive compounds from nitroalkanes (see Section 4.6.3.). 

Aldol condensations are reversible, and with ketones the equilibrium is unfavorable for the ondensation product. To effect condensations of ketones, the product is continuously removed from he basic catalyst. )3-Hydroxycarbonyl compounds are readily dehydrated to give a,j3-unsaturated arbonyl compounds. With Ar on the carbon, only the dehydrated product is isolated. 

Aldol condensation. Anhydrous lithium iodide (ca. 5 equivalents) promotes aldol condensation of ketones with enolizable or nonenolizable aldehydes. The intermediate aldol is usually not isolable, but can be intercepted by addition of ClSi(CH3)3 and N(C2H5)3. In this case Lil can be used in a catalytic amount. The salt cannot be replaced by LiBror LiCl or Nal. 

Sequential aldol condensation and hydrogenation. Since the aldol condensation of ketones is an equilibrium reaction, there are some advantages in hydrogenation of the a,/i-unsaturated ketone as formed to shift the equilibrium. Thus it is possible to convert acetone into methyl isobutyl ketone in one step using two different heterogeneous catalysts (equation I). 

Base catalysis is one of the less-well developed areas of heterogeneous catalysis. We have developed novel bases derived from amines via the one-step process outlined above. A range of supported amines have been prepared and evaluated in a series of reactions We have also investigated the nature of the amine groups attached to the surface in comparison with those formed by grafting onto pre-formed silica. While many workers have studied the use of basic catalysts for the Knoevenagel condensation of aldehydes, with three articles on the use of MCM derivatives[ 12], little has been done on the more demanding condensation of ketones. 

Dimethylaminonitroethylene is prepared from the anion of nitromethane and the salt prepaffed from dimethylformamide and dimethyl sulfate. The condensation step is general for other types of active methylene compounds, indicating further potential for pyrrole synthesis. A related process involves the condensation of ketones with the moao-N,N-dimethylhydrazone of glyoxal base-catalyzed condensation affords the hydrazones of a conjugated 1,4-dicarbonyl system, and sodium thiosulfate reduction then affords 2,3-disubstituted pyrroles (equation 85) (77CB491). 

An important variation on the Claisen condensation is to use a ketone as the anionic reagent. This often works well because ketones usually are more acidic than simple esters and the base-induced self-condensation of ketones (aldol addition) is thermodynamically unfavorable (Section 17-3C). A typical example is the condensation of cyclohexanone with diethyl ethanedioate (diethyl oxalate) ... 

There are two main methods for the synthesis of monothio-/i-diketones, both affording yields in excess of 50%. The first method involves the passage of H,S through a dilute solution of the /5-diketone in ethanol, followed by the rapid passage of HC1 at — 70 °C the conditions are critical.184,183 The second method involves the Claisen-type condensation of ketones with thionic esters, RC(S)OMe, or dithionic esters, RC(S)SMe, in ether in the presence of sodamide.186-188 This method has the advantage that both isomers (46) and (47) can be prepared, whereas the first method yields only isomer (46) when R has a greater electron-withdrawing power than R. 

A microwave-assisted synthesis of various 1,5-benzodiazepines was also investigated by condensation of ketones with o-phenylenediamines under dry media conditions (i.e., no solvent/solid support)68. The reactions were carried out by first simply mixing the o-phenylenediamine with the ketone (2.1 equiv) in the presence of a catalytic amount of acetic acid. The reactions mixtures were then irradiated in a domestic microwave oven (Scheme 3.43). The resulting benzodiazepine derivatives were obtained in almost quantitative yields. 

For conversion of ketones into a,/3-unsaturated aldehydes containing two additional carbon atoms, several multistep processes via ethynyl or vinyl carbinol intermediates have been reported.4-10 Although the overall yields obtained by these routes for the conversion of cyclohexanone into cyclohexylideneacetaldehyde have never exceeded 50%, they were the only useful methods for this type of conversion until the excellent process of Wittig11 appeared. This process consists of normal aldol condensations of ketones with the lithium salt of ethylidenecyclohexylamine and subsequent dehydration and hydrolysis. 

The third step is a Horne r-Wodsworth-Dnnu>ns reaction in which a C-C double bond is created by condensation of ketone 44 with the lithium salt of the p-thia/olephosphoric acid dialkyl ester 12. The desired compound 13 is obtained selectively with Irons geometry The precise mechanism of the Ho me r-Wuds orth Emmons reaction is not yet known, so the source of the irons selectivity remains uncertain. It is assumed that analogous to the Wit tig reaction. an oxaphosphetane forms as an intermediate (see also Chapter 91... 

An open-transition-state model is proposed for the Darzens condensation of ketones with (—)-8-phenyhnenthyl a-chloroacetate the diastereoselectivity observed is explained in terms of a 71-aryI interaction between the enolate and phenyl moieties.78... 

Some other catalytic events prompted by rhodium or ruthenium porphyrins are the following 1. Activation and catalytic aldol condensation of ketones with Rh(OEP)C104 under neutral and mild conditions [372], 2. Anti-Markovnikov hydration of olefins with NaBH4 and 02 in THF, a catalytic modification of hydroboration-oxidation of olefins, as exemplified by the one-pot conversion of 1-methylcyclohexene to ( )-2-methylcycIohexanol with 100% regioselectivity and up to 90% stereoselectivity [373]. 3. Photocatalytic liquid-phase dehydrogenation of cyclohexanol in the presence of RhCl(TPP) [374]. 4. Catalysis of the water gas shift reaction in water at 100 °C and 1 atm CO by [RuCO(TPPS4)H20]4 [375]. 5. Oxygen reduction catalyzed by carbon supported iridium chelates [376]. - Certainly these notes can only be hints of what can be expected from new noble metal porphyrin catalysts in the near future. 

A cationic rhodium complex, [(Me5Cp)Rh(j/6-benzene)]2+, catalyses direct aldol condensation of ketones.153... 

Condensation. Although aluminum alkoxides are effective in bringing about the mesityl oxide type condensation of ketones, as, for example, in the formation of dypnoue (XXVII) from acetophenone (XXVI),26 aluminum isopropoxide rarely induces this reaction to any significant degree in the reduction of ketones. 

Multi-component condensation of ketones (or aldehydes), a-aclivc methylene nitriles and elementary sulfur (the Gewald reaction) is an efficient methodol-... 

Ketones are less reactive electrophiles than aldehydes. Therefore, the aldol condensation of ketones is not often used because the equilibrium is unfavorable. However, the intramolecular condensation of diketones is useful if the size of the resulting ring is fa-... 

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