Base-catalysed

The term Knoevenagel Condensation was originally applied to the base-catalysed condensation of the carbonyl ( CO) group of aldehydes and ketones with the reactive methylene group of malonic acid, with loss of w ater ... 

The mecluLnism of this base-catalysed reaction probably involves the intermediate formation of an aldol ... 

A probable mechanism of these base-catalysed aldol reactions may be written in gena-al terms as follows ... 

The mechanism, of the base-catalysed acylation of ketones by esters probably involves several steps (compare acetoacetlc ester condensation see discussion prloi to Section 111,151) —... 

Which giyes formaldehyde as one of the starting materials. Base-catalysed reactions with this yery reacfiye aldehyde often giye poor yields because of polymerisation and other side reactions. The Marmich reaction is used instead ... 

Analysis This is the substitution pattern for a base-catalysed epoxide opening PhCHjO-J- OH... 

Ojj 1.5068, was obtained in a yield of 82%. The equilibrium mixture obtained in the isomerization under the influence of KO-tert.-61,89 in DHSO consisted of about 70% of allene and 30% of yneamine. Base-catalysed isomerization is therefore not a suitable method to prepare the yneamCne. 

The resulting oligonucleotide is often of surprising purity as judged by analytic HPLC or electrophoresis, and up to 30 mg of a deoxyeicosanucleotide (20-base DNA) can be routinely obtained. Nevertheless small amounts of short sequences, resulting from capping and from base-catalysed hydrolysis, must always be removed by quick gel filtration, repeated ethanol precipitation from water (desalting), reverse-phase HPLC, gel electrophoresis, and other standard methods. 

The main example of a category I indole synthesis is the Hemetsberger procedure for preparation of indole-2-carboxylate esters from ot-azidocinna-mates[l]. The procedure involves condensation of an aromatic aldehyde with an azidoacetate ester, followed by thermolysis of the resulting a-azidocinna-mate. The conditions used for the base-catalysed condensation are critical since the azidoacetate enolate can decompose by elimination of nitrogen. Conditions developed by Moody usually give good yields[2]. This involves slow addition of the aldehyde and 3-5 equiv. of the azide to a cold solution of sodium ethoxide. While the thermolysis might be viewed as a nitrene insertion reaction, it has been demonstrated that azirine intermediates can be isolated at intermediate temperatures[3]. 

Indoles can also be alkylated by lactones[l4]. Base-catalysed reactions have been reported for (3-propiolactone[15], y-butyrolactone[10] and 5-valerolac-tone[10]. These reactions probably reflect the thermodynamic instability of the N -acylindole intermediate which would be formed by attack at the carbonyl group relative to reclosure to the lactone. The reversibility of the JV-acylation would permit the thermodynamically favourable N-alkylation to occur. 

SelenazoIidin-2-4-ciiones-2-alkylidene (or arylidene) hydrazones (III) are simply prepared by base-catalysed condensation of a-haloacids on selenosemicarbazones of acetone or benzaldehvdc (Table X-21) (71). 

Polyether Polyols. Polyether polyols are addition products derived from cyclic ethers (Table 4). The alkylene oxide polymerisation is usually initiated by alkah hydroxides, especially potassium hydroxide. In the base-catalysed polymerisation of propylene oxide, some rearrangement occurs to give aHyl alcohol. Further reaction of aHyl alcohol with propylene oxide produces a monofunctional alcohol. Therefore, polyether polyols derived from propylene oxide are not truly diftmctional. By using sine hexacyano cobaltate as catalyst, a more diftmctional polyol is obtained (20). Olin has introduced the diftmctional polyether polyols under the trade name POLY-L. Trichlorobutylene oxide-derived polyether polyols are useful as reactive fire retardants. Poly(tetramethylene glycol) (PTMG) is produced in the acid-catalysed homopolymerisation of tetrahydrofuran. Copolymers derived from tetrahydrofuran and ethylene oxide are also produced. 

Alkyl sulphoxides occur widely in small concentrations in plant and animal tissues. No gaseous sulphoxides are known and they tend to be colourless, odourless, relatively unstable solids soluble in water, ethyl alcohol and ether. They are freely basic, and with acids form salts of the type (R2S0H) X. Because sulphoxides are highly polar their boiling points are high. Their main use is as solvents for polymerization, spinning, extractions, base-catalysed chemical reactions and for pesticides. 

Ring enlargement by base catalysed rearrangement of 17-hydroxy-20-ketopregnanes... 

The base-catalysed isomerisation of thiazoles to imidazoles initially reported by Cook et al " has been further investigated more recently. One notable example reports the reaction of 2-amino-2-cyanoacetamide 37 with benzylisothiocyanate to give 5-... 

A large primary isotope effect kH/kD = 3.6 had also been found earlier by Ibne-Rasa122 in the nitrosation of 2,6-dibromophenol in the 4 position which was also shown to be base-catalysed. These values are not unexpected in view of the isotope effect found with diazonium coupling which involves a similarly unreactive electrophile, so that the rate-determining transition state will be displaced well towards products. Furthermore, the intermediate will have a quinonoid structure and will, therefore, be of low energy consequently, the energy barrier for the second step of the reaction will be high. 

Rapid base-catalysed exchange at all positions. References pp. 388-406... 

Kinetic studies of base-catalysed hydrogen exchange have been carried out by Roberts, by Shatenshtein, and by Streitweiser and their coworkers. In earlier work, potassium amide was used as base in liquid ammonia as solvent, whereas later workers used lithium and caesium cyclohexylamides in cyclohexylamine. The reaction can be represented by equilibria (239) and (240)... 

Streitweiser et al.591 have measured rates of base-catalysed dedeuteration and detritiation and have attempted to discover details of the reaction mechanism. Second-order rate coefficients for the reaction of some polycyclics with lithium cyclohexylamide in cyclohexylamine are given in Table 179, and it can be seen... 

The differences in rate for the two positions of naphthalene show clearly that an additional-elimination mechanism may be ruled out. On the other hand, the magnitude of the above isotope effect is smaller than would be expected for a reaction involving rate-determining abstraction of hydrogen, so a mechanism involving significant internal return had been proposed, equilibria (239) and (240), p. 266. In this base-catalysed (B-SE2) reaction both k and k 2 must be fast in view of the reaction path symmetry. If diffusion away of the labelled solvent molecule BH is not rapid compared with the return reaction kLt a considerable fraction of ArLi reacts with BH rather than BH, the former possibility leading to no nett isotope effect. Since the diffusion process is unlikely to have an isotope effect then the overall observed effect will be less than that for the step k. ... 

RELATIVE RATES FOR BASE-CATALYSED EXCHANGE OF ArH AT 25 °C594,... 

Kinetic studies of base-catalysed hydrogen exchange of heterocyclic compounds have been carried out. Paudler and Helmick515 measured second-order rate coefficients for deuteration of derivatives of imidazo[l,2-a]pyridine(XXXIII), imidazo[l,2-a]pyrimidine(XXXIV), and 1,2,4-triazolo[1,5-a]pyrimidine(XXXV)... 

The intense activation of ortho positions by strongly electron-withdrawing groups has produced some interesting kinetic results in the base-catalysed exchange of pyridine and its derivatives. For the neutral molecule, exchange occurs... 

The mechanism of the base-catalysed reaction was proposed as equilibria (251) and (252)... 

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