Dehydration sequences

The irreversible elimination drives the reversible aldol reaction and gives a favourable conjugated ketone in a favourable six-membered ring. On paper, one could also draw an acceptable mechanism in which the order of events was reversed. This is not so neat, and would require generating an enolate anion y to the a,P-unsaturated ketone formed by the first aldol-dehydration sequence. 

More recently, a catalyst-free aqueous version of this strategy was proposed with simple acyclic 1,3-dicarbonyls, formaldehyde, and styrene or anilines derivatives (Scheme 40) [131], In the first case (Scheme 40), the very reactive 2-methylene-1,3-dicarbonyl intermediate reacts smoothly at 80°C with a variety of substituted styrenes to give the corresponding dihydropyrans in moderate to good yields. Remarkably, when styrenes were replaced by A-ethylaniline, a novel five-component reaction involving twofold excess of both formaldehyde and 1,3-dicarbonyl selectively occurred (Scheme 41). The result is the formation of complex fused pyranoquinolines following a Friedel-Craft alkylation - dehydration sequence to furnish the quinoline nucleus, which suffers the Hetero-Diels-Alder cyclization in synthetically useful yields. 

A series of the regioisomeric benzofuran derivatives are produced from a base-catalyzed cyclization/dehydration sequence of dihydroxydibenzoylbenzenes (Equation 89) <2002HC0179, 2005T545>. The cyclization of the related derivatives containing benzyl or bromoalkyl substituents (R = benzyl or Br(CH2) -i, where = 8 or 12) has been reported to occur in benzene under photochemical conditions <1995JOC1303, 2002J(P1)310>. 

Cyclohydrocarbonylation of 1-allylpyrroles 74a-d catalyzed by Rh4(CO)i2 gave the corresponding 5,6-dihydro-indolizines 77a-d in good yield and excellent regioselectivity (Scheme 12)." This reaction proceeded through a cascade hydroformylation-cyclization-dehydration sequence (Scheme 12). Exclusive introduction of a formyl group... 

An aldol condensation-dehydration sequence can be used to construct the carbon skeleton. 

JOC3904>. Pyrazole thioamides 22 were transformed into pyrazolothiazoles 23 via a cyclization/dehydration sequence <02S1079>. l-Acetyl-2-methoxyazulene (24) reacted with arylhydrazines in refluxing ethanol to give 1 -aryl-3-methylazuleno[ 1,2-r/]pyrazoles 25 in moderate to high yields <02H(56)497>. 

An investigation of alkylation of 1,1-enediamines with a,/ -unsaturated aldehydes and ketones has been recently conducted by Jones and Hirst36. The reaction of 1,1-enediamine 93 and a,/ -enals affords the fused 1,4-dihydropyridines 133, via a nucleophilic addition and intramolecular dehydration sequence (equation 49). 93 reacts with propenal, however, to give the cyclohexene carboxaldehyde 134 in almost quantitative yield (equation 50). The formation of 134 is most probably due to addition of 93 to two... 

The structural and textural changes involved in the thermal decomposition of the three trihydroxides have been studied in considerable detail (Aldcroft et al., 1968 Lippens and Steggerda, 1970 de Boer, 1972 Rouquerol etal., 1975,1979a Ramsay and Avery, 1979 Stacey, 1987). It is now clear that the dehydration sequence is dependent not only on the crystalline structure of the trihydroxide, but also on its texture and the conditions of heat treatment. 

Mercurioferrocenes (290) and (291) are separable by Soxhlet extraction and these may be used to prepare bromoferrocene or dibromoferrocene or the iodo analogs. Alternatively, these halogenated ferrocenes are prepared from the ferrocene boronic acids or from anions (322) or (323). Bromoferrocene is the starting material for cyanoferrocene, azidoferrocene, or aminoferrocenes, generally in the presence of a copper salt. Amtnoferrocene can be acylated to produce an amide, or converted to isocyanoferrocene by a formylation/dehydration sequence (Scheme 96). The 1,T-diisocyanoferrocene is available from the bis(acyl)azide, itself derived from ferrocene dicarboxylic acid. ... 

The change in the structure of aluminas through the dehydration sequence from either gibbsite or boehmite to, ultimately, a-Al203, is perhaps where Al NMR spectroscopy has been most frequently appUed. The results of a selection these... 

Sautet also used the calculated energies for the trihydroxides, monohydroxides and a-Al203 structures to estimate the relative stability of these materials based on the dehydration sequence ... 

Not surprisingly, if the ketone in the starting material is flanked by an unsaturated functional group i.e. C02Me or NO ), dehydration gives exclusively the a,P-unsaturated product (the p,y-unsaturated regioisomer is available via other methods, discussed below). While the methods described above involve direct dehydration of the alcohol, a number of reduction-dehydration sequences have been conducted by initial reduction of the ketone and subsequent derivatization of the resultant alcohol (as the phenyl methanesulfonate, methyl p-toluenesulfonate, xanthate, acetate, methyl ether, etc.). This type of reduction-dehydration sequence is discussed in detail in Volume 6, Chapter 5.1. 

The nucleophilic addition of a carbanion to an aldehyde or a ketone having a conjugated double bond and the subsequent dehydration sequence (Knoevenagei reaction) is a popular method for generating dienes and polyenes (equation 37). This reaction takes place efficiently and stereoselectively, when LDA is used as a base in the presence of chlorotrimethylsilane (equation 38). Knoevenagei condensation was a key reaction during many classical carotenoid syntheses. Recently, Seltzer and coworkers used the dimefiiyl acetal of acetylacetaldehyde for aldol condensation with a Cis-aldehyde, to generate the tetraenyl ketone acetal (equation 39). ... 

Alkenes are converted to epoxides by oxidation with peroxy acids, and thereby they are protected with regard to certain chemical transformations. Alkaline hydrogen peroxide selectively attacks enone double bonds in the presence of other alkenes. The epoxides can be transformed back to alkenes by reduction-dehydration sequences or using triphenylphosphine, chromous salts, zinc, or sodium iodide and acetic acid. A more advantageous and fairly general method consists, however, of the treatment of epoxides with dimethyl diazomalonate in the presence of catalytic amounts of binuclear rhodium(II) car-boxylate salts. This deoxygenation proceeds under neutral conditions and without isomerization or cy-clopropanation of the liberated alkene (Scheme 97). Furthermore, epoxides can be converted to alkenes with the aid of various metal carbonyl complexes. Thus, they may be nucleophilically opened with... 

The following examples illustrate the bioprecursor-prodrug approach, although the intentional use of bioprecursor design is relatively recent and, in some cases, there are some doubts about the prospective or the retrospective character of the design. The hrst examples relate to oxidative bioactivations they are followed by examples of reductive bioactivations and dually by non-redox reactions. Often, however, the active species results from a cascade of metabolic reactions involving oxidative as well as reductive processes, complicated by hydrolytic reactions or hydration-dehydration sequences. 

In this manner the crystallographic siting of all Cu + species in hydrated and dehydrated zeolites Na-A and K-A were determined(5). The two following dehydration sequences were determined in which the subscript on Cu denotes the number of coordinated waters. Note the cocation effect. The distances in brackets indicate the displacement from site S2 into the 8-cage. 

The more general routes from phthalimidines to isoindoles require an addition-dehydration sequence this is a useful approach to 2-substituted and 1,2-disubstituted systems.5,27 In a variant of the hydride reduction,... 

This information was used to design bucloxic acid, fenbufene and furobufene, which are all bioprecursor forms of anti-inflammatory arylacetic acids (Fig. 33.36). For all these compounds the bioactivation takes place through a multistep process implying reductive, oxidative and hydration-dehydration sequences. 

It is difficult to understand the structures of chromia-alumina catalysts without being familiar with the various types of aluminas. Excellent reviews of this subject may be found in Lippens Ph.D. thesis (3) and the Alcoa Technical Paper No. 10 Alumina Properties (36). The dehydration sequence from aluminum hydroxide to corundum (36,37) is shown in Fig. 4, although a variation in experimental conditions pro-... 

Fig. 4. The dehydration sequences from the aluminum hydroxides to corundum (37).

The symbols A-D have the same significance as in footnote d. These parameters only apply to the hydration itage, and not to the concomitant dehydration sequence. The original references (290-294) should also be con-iulted. 

Scheme 7.16 Synthesis of cyclohexenones by cascade Michael/aldol/dehydration sequence.

The salts FeH2P30io and CrH2P30io are formed in similar dehydration sequences, and the acid salts of all three metals exist in various isomorphous and polymorphic forms. Both CrH2P30io 2H2O and AIH2P3O10 2H2O find use in anti-corrosive pigment formulations. Both salts can form intercalation compounds (Chapter 12). 

An elegant synthesis of the sesquiterpenoid natural product ( )-modhephene ° started fScheme 9.181 with the conversion, via a Grignard methylation/dehydration sequence, of the readily available bicyclic enone 124 into the cyclopentannulated cyclohexa-1,3-diene 125 (86% yield of an admixture with double-bond isomers). Diene 125 engaged in a Diels-Alder... 

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