Cycloheptanone synthesis

Thus, the condensation product of cyclohexanone and ethyl cyanoacetate (125) affords the intermediate (126) for the synthesis of cyclobarbital (112) on alkylation with ethyl bromide. The condensation product of cycloheptanone (127) affords the starting... 

This reaction is nicely applied to total synthesis of Claviilarin A" " as shown in Scheme 7.3. The key reactions involve a high enandoselecdve adchdon-eliminadon process" and stereose-lecdve synthesis of cii -2,3-chsubsdmted cycloheptanones." ... 

The first synthesis of tropinone (124), which was presented by Willstatter and consisted of a route of 16 steps from cycloheptanone to tropinone (124) (Scheme 1), has been thoroughly discussed by Holmes (1) and will not be further noted. 

The retentive power of graphite towards adipic acid and the catalytic effect of the magnetite, especially present in A, are obvious. TEM examinations of a graphite A sample before and after reaction showed that crystallites of Fe304 appeared to be smaller after the reaction. However, the same graphite sample was reused for three successive reactions without significant loss in yield. When applied to the synthesis of other cyclic ketones (Scheme 7.14), less volatile than 74, it was observed that pressure had an effect on the recovery of product (Tab. 7.9, entries 3 and 4). A slightly reduced pressure (300 mm Hg) was necessary to obtain 3-methylcyclopentanone (75) or cyclohexanone (76) in convenient yield (Tab. 7.9, entries 4 and 5). For the cycliza-tion of suberic acid (73), a less favorable structure, the yield in cycloheptanone (77) remained low (Tab. 7.9, entry 6). 

In the particular case of natural products, once all the possibilities that the "logic-centred methodology" offers have been explored, it is pertinent to consider the biogenetic pathways by which they are synthesised in Nature since these can be a source of inspiration and may introduce an intrinsic element of elegance into the synthetic plans. In this context, tropine (131 offers a unique example in the history of organic synthesis. In 1902 this rather simple alkaloid was synthesised by Willstatter from cycloheptanone [8] through a sequence of about twenty steps, as shown in Scheme 3.4. 

TABLE 15. Synthesis of 2-methyl-2-(substituted)cycloheptanones (199) from cyclohexanone derivative 195,1-chloroethyl /j-tolyl sulfoxide, and electrophiles... 

The synthesis of aza-2-cycloheptanone (e-caprolactam) by the Beckmann rearrangement of the oxime of cyclohexanone is of commercial importance because the lactam is an intermediate in the synthesis of a type of nylon (a polyamide called nylon-6 2) ... 

Hexahydroazocines. The synthesis of stable ketene aminal diphenylphosphates 46 was accomplished departing from the eight-membered iV-BOC or iV-COOPh protected lactams 45 via their potassium enolates (Scheme 13 <1998CC1757>). Azocane-2-one 45 was easily obtained from cycloheptanone 44 by Beckmann rearrangement of its cycloheptanone-oxime and subsequent protection of the amino moiety. 

Two examples that show selectivity in synthetic applications are the synthesis of cycloheptanone (19),7 which involves ring expansion via a [1,5] hydrogen shift, and the synthesis of sarkomycin (20 Scheme 5). 7 In both of these protocols, the intermediate cyclopropyl ketone or vinylcyclopropane system could be rearranged to dihydrofurans or cyclopentenes respectively by the appropriate adjustments in the experimental conditions. ... 

The above conditions allow the synthesis of a large variety of a,a-dialkyl substituted ketones including spiro derivatives and cyclopentanones, cyclohexanones, cycloheptanones and cyclododecanones bearing two alkyl groups at die a-posidon (Scheme 162, e Scheme 165, c Scheme 166, e Scheme 186, a and b Scheme 187 Scheme 188, a Scheme 189, a and The reactions are less selective when the dichlorocarbene is generated from bromodichloromethane and lead to gem-dichlorocyclopropanes if the dichlorocarbene is produced from chloroform and potassium r-butoxide (Scheme 162, f Scheme 188, b Scheme 189, c). ... 

Epoxides may be cleaved by amines. This reaction is used in the synthesis of aminoalcohols (53) studied as potential adrenergic drugs (Scheme 21). The amine cleavage of the epoxide and the subsequent nitrous acid deamination of the aminoalcohol are used for the ring enlargement of alicyclic ketones (TiffeneauDemjanov reaction). By this sequence of reactions, for example, cycloheptanone (54) may be converted to cydooctanone (55) (Scheme 21). 

Perhaps the commonest ring expansion method of azocine synthesis is by Beckmann or Beckmann-type rearrangements of cycloheptanone... 

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