Mild base

Formation - tbutylacetyl chloride or t-butylacetic anhydride Cleavage - removed with mild base... 

Cleaved with mild base such as piperidine, morpholine or dicyclohexylamine... 

The anion B is just the enolate anion of a carbonyl compound, actually the same as A. So there is no need to use a Grignard reagent or any other synthetic equivalent in this reaction anion B itself can be the intermediate and we simply treat the aldehyde with mild base ... 

Synthesis A mild base must be used to avoid the Cannizzaro reaction. The hydroxy acid A caimotbe isolated and cyclises spontaneously. (Fleming p.92). 

In the alcohol oxidations, the sulfonium intermediate (2, nucleophile = R2C(OH)) loses a proton and dimethyl sulfide to give the carbonyl compound (42). The most common mechanism for the decomposition of (2) is attack by a mild base to remove a proton from one of the methyl groups. Subsequent cycHc coUapse leads to the carbonyl compound and dimethyl sulfide (eq. 9) ... 

Heating TCNE with an alcohol in the presence of a mild base such as urea causes replacement of either one (19) or two (20) cyano groups by alkoxyl. The products with ethanol are 1-ethoxy-1,2,2-tricyanoethylene [69155-32-4] and l,l-bisethoxy-2,2-dicyanoethylene [17618-65-4]. 

Mild base does not effect isoxazolidine ring cleavage by fission of the N—O bond rather, C—O bond cleavage takes place <77AHC(2l)207). The reaction of iV-trimethyl-silylisoxazolidine (185) with KOH produced a /3-hydroxyketone oxime (Scheme 59) (74DOK109). 

Cleavage occurs by prior activation with peracetic acid to the bissulfone followed by mild base treatment. ... 

This derivative is stable to trifluoroacetic acid it is cleaved by mild bases (pH 8.4 0.1 NNaOH, 1 min, 100% yield). ... 

The most intensively studied oxidizing system is that developed by Pfitzner and Moflatt in which the oxidation is carried out at room temperature in the presence of dicyclohexylcarbodiimide (DCC) and a weak acid such as pyridinium trifluoroacetate or phosphoric acid. The DCC activates the DMSO which in turn reacts with the carbinol to give an oxysulfonium intermediate. This breaks down under mild base catalysis to give the desired ketone and dimethyl sulfide. 

Base-catalyzed fragmentation also occurs on treatment of 5,6j9-epoxy-19-aldehyde (hemiacetal, hemiacetal-acetate or 3)5,6/ -acetal) accessible from nitrous acid-acetic acid treatment of 5a-bromo-6jS-hydroxy-19-oximes followed by mild base hydrolysis (yield not reported)... 

Trimethylsilyl ethers are readily cleaved by fluoride ion, mild acids, and mild bases. If the TMS derivative is somewhat hindered, it also becomes less susceptible to cleavage. A phenolic TMS ether can be cleaved in the presence of an alkyl TMS ether [Dowex l-x8 (HO ), EtOH, rt, 6 h, 78% yield]. ... 

This ester, developed for peptide synthesis, is prepared by the standard DCC coupling protocol and is cleaved reductively with SnCl2 (MeOH, 25°, 5 h) followed by treatment with mild base to effect quinonemethide formation with release of the acid in 75-95% yield. ... 

MISCELLANEOUS FUSED HETEROCYCLES with mild base causes internal alkylation and consequent... 

O-isopropylidene derivative (57) must exist in pyridine solution in a conformation which favors anhydro-ring formation rather than elimination. Considerable degradation occurred when the 5-iodo derivative (63) was treated with silver fluoride in pyridine (36). The products, which were isolated in small yield, were identified as thymine and l-[2-(5-methylfuryl)]-thymine (65). This same compound (65) was formed in high yield when the 5 -mesylate 64 was treated with potassium tert-hx Xy -ate in dimethyl sulfoxide (16). The formation of 65 from 63 or 64 clearly involves the rearrangement of an intermediate 2, 4 -diene. In a different approach to the problem of introducing terminal unsaturation into pento-furanoid nucleosides, Robins and co-workers (32,37) have employed mild base catalyzed E2 elimination reactions. Thus, treatment of the 5 -tosylate (59) with potassium tert-butylate in tert-butyl alcohol afforded a high yield of the 4 -ene (60) (37). This reaction may proceed via the 2,5 ... 

A useful variation of the Williamson synthesis involves silver oxide, Ag20, as a mild base rather than NaH. Under these conditions, the free alcohol reacts directly with alkyl halide, so there is no need to preform the metal alkoxide intermediate. Sugars react particularly well glucose, for example, reacts with excess iodomethane in the presence of Ag20 to generate a pentaether in 85% yield. 

Both the malonic ester synthesis and the acetoacetic ester synthesis are easy to cany out because they involve unusually acidic dicarbonyi compounds. As a result, relatively mild bases such as sodium ethoxide in ethanol as solvent can be used to prepare the necessary enolate ions. Alternatively, however, it s also possible in many cases to directly alkylate the a position of monocarbonyl compounds. A strong, stericaliy hindered base such as LDA is needed so that complete conversion to the enolate ion takes place rather than a nucleophilic addition, and a nonprotic solvent must be used. 

Ferrous bicarbonate is a mild base and, as corrosion proceeds, the ratio of bicarbonate to carbonic acid increases to produce a corresponding increase in pH. The high pH is therefore not necessarily... 

Key features of the cyclopropanation include the ylide acting as a mild base to isomerize the 1,2-dioxines into cis-y-hydroxy enones, followed by Michael addition of the ylide and last by cyclization of the intermediate enolate [35]. It must be noted that the trans-y-hydroxyenones do not give the cyclopropanation. 

Aldehyde (4) can be made by chloromethylation (P 9), the condensation with nitromethane with mild base gives an excellent yield of crystalline (3) and LiAlH can be used for the reduction. 

Alkyl-CON H2/-CON H R 9-7 Often broad but frequently couple. Primary amides often appear as two broad signals due to partial double bond character of amide bond. Often slow to exchange and may require warming/mild base... 

Alkyl-SH 5-1 Usually sharp and couple to adjacent protons. May need mild base to exchange (e.g., drop of NaHC03/D20 solution) Beware easy oxidation to -S-S-. Therefore important to locate ... 

Palladium-catalyzed reactions have been used for the formation of thienoindolizines the following reaction, which is carried out in presence of a mild base, gives different ratios of the endo- (thienopyridone) and exo- (thienoindolizine) products according to the specific catalyst and base used (Equation 36). The latter is almost exclusively formed when the base used is sodium formate or piperidine <1997TL1057>. For the conditions favoring the 5 6 6-fused product, see Section 11.17.4.1.1.3. 

In cross-coupling with arylboronic acids, some Cu1 carboxylates were found to provide a way to realize a very mild, base-free procedure, which is helpful in cases when added base can induce side reactions (59).222... 

Compounds of this type with an electron-withdrawing substituent at C-a can be easily prepared by condensation of 2-(benzotriazol-l-yl)acetophenone 869 with aldehydes. Exclusively (E) isomers of a,(l-unsaturated ketones 870 are formed. Treatment with hydrazines converts derivatives 870 into pyrazolines 871. Elimination of benzotriazole from 871 in the presence of mild bases furnishes pyrazoles 872. When in these reactions hydroxylamine is used instead of hydrazines, the corresponding isoxazoles are obtained (Scheme 141) <2001JOC6787>. 

Carbonyl oxygen atoms of aldehydes can also be efficiently acylated by 1-acylbenzotriazoles 915 in the presence of mild bases (K2CO3, Et3N). The released benzotriazolide anions are consecutively attached to the aldehyde carbonyl carbon atoms to produce esters 944 (Equation 20). Aliphatic aldehydes react quickly at room temperature, but aromatic aldehydes require elevated temperatures. The yields are good to quantitative. The amounts of benzotriazol-2-yl isomers of esters 944 in the products mixtures is strongly dependent on the reaction conditions and the character of groups R1 and Rz, and it may vary from 5% to 25% <1999JHC777>. 

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