Acid- and base-sensitive

APA may be either obtained directly from special Penicillium strains or by hydrolysis of penicillin Q with the aid of amidase enzymes. A major problem in the synthesis of different amides from 6-APA is the acid- and base-sensitivity of its -lactam ring which is usually very unstable outside of the pH range from 3 to 6. One synthesis of ampidllin applies the condensation of 6-APA with a mixed anhydride of N-protected phenylglydne. Catalytic hydrogenation removes the N-protecting group. Yields are low (2 30%) (without scheme). 

These reagents exhibit a high selectivity for the attack of aldehydic over ketonic oxo groups26. The triethylammonium salt of 2-(bromomethyl)acrylic acid and base-sensitive aldehydes, under these conditions, can be used for the synthesis of lactones27. 

Bismuth(III) triflate is also a powerful acylation catalyst that catalyzes reactions with acetic anhydride and other less reactive anhydrides such as benzoic and pivalic anhydrides.113 Good results are achieved with tertiary and hindered secondary alcohols, as well as with alcohols containing acid- and base-sensitive functional groups. 

The residue is washed with diethyl ether (4 x 30 mL), and the combined organic layers are washed with water (3 x 30 mL), 1 N hydrochloric acid (3 x 30 mL), saturated sodium bicarbonate solution (3 x 30 mL), water (30 mL), and brine (3 x 30 ml), and finally dried over anhydrous sodium sulfate. Filtration and removal of the solvent on a rotary evaporator at 25°C yields 24.1-25.5 g (90-95%) of the Knoevenagel product as a colorless oil. The crude product is pure enough to be used in the ene reaction. An analytically pure sample of 3 (Note 8) is obtained by column chromatography (SI02) (Note 9) with petroleum ether/acetone, 98 2. Compound 3 is acid and base sensitive and should be stored under argon in a freezer. 

Acid- and base-sensitive lipidated peptides can be selectively deprotected by enzymatic hydrolysis of choline esters.[13al Choline esters of simple peptides, but also of sensitive peptide conjugates like phos-phorylated and glycosylated peptides,1141 nucleopep-tides1151 and lipidated peptides,113,1631 can be cleaved with acetyl choline esterase (AChE) and butyryl choline esterase (BChE) under virtually neutral conditions with complete chemoselectivity. Acid-labile farnesyl groups and base-sensitive thioesters are not attacked. 

An acid- and base-sensitive siloxycarboxylic acid was treated with AW -carbonyldi-imidazole and the resulting imidazolide (51) transformed into the desired ylide using one equivalent of salt-free methylenetriphenylphosphorane in benzene, rather than two equivalents as usually recommended. Coupling, under neutral conditions, with two equivalents of aldehyde (52) gave a mixture of diastereomeric epoxythiolates (Scheme 15).68... 

A selection of cases in which 2 has been found to be particularly efficacious is given in the Table. Additional examples are cited in references 1 and 5. Particularly noteworthy examples include the oxidation of acid- and base-sensitive systems, systems containing sulfur and selenium, and 1,3-diols to 1,3-dicarbonyl compounds. Use of chromium reagents in these latter cases often leads to fragmentation products. 

TEMPO-mediated oxidations can be performed under almost neutral conditions. Therefore, acid- and base-sensitive functionalities and protecting groups can remain unchanged during TEMPO-mediated oxidations. 

As Fetizon s oxidation is carried out under neutral conditions, acid-and base-sensitive protecting groups resist its action. The oxidation-sensitive p-methoxybenzyl (PMB) protecting group resists the action of Fetizon s reagent.12... 

Silver acetylides also reacted with epoxides yielding propargylic alcohols.27 As for related alkylations with silver acetylides (see Section 10.6.1), this reaction required zirconocene dichloride and catalytic amount of silver triflate. This method proved useful for both electron-rich and electron-deficient alkynes and compatible with various acid- and base-sensitive functional groups (Table 10.2). 

Tosyl chloride 361 can be applied similarly (entry 23) [404], Here the best cobalt complex was dependent on the structure of the starting olefin. For terminal alkenes 2 mol% of the (salen)Co complex 357a was preferred. Secondary alkyl chlorides were obtained with complete regioselectivity in 73-94% yield, while the catalyst derived from Co(BF4)2 and /V-salicylidene diphenylglycinate 353 proved to be better for the hydrochlorination of 1,1-disubstituted olefins (entry 22). Tertiary alkyl chlorides 362 were obtained in 67-96% yield. The reaction conditions are mild so that acid- and base-sensitive protecting groups are compatible. 

NOH - -CNH1. TiCl, is known to reduce oximes to imines (4,506). If this reduction is conducted in the presence of NaBHjCN (buffered), the inline is reduced to an amine before it is hydrolyzed to a ketone. This mild method is particularly useful for complex substrates with acid- and base-sensitive groups.1... 

The acid and base sensitivity of condensation polymers whether or not under stress, e.g. polycarbonate, polyesters, polyamides and polysilanes under influence of acid or base the condensation bonds are hydrolysed under the cooperative action of mechanical stresses and the environment. A striking example is shown in Fig. 26.11, where the strength retention of PpPTA fibres is plotted versus pH after an exposure of 3 months at room temperature (Van den Heuvel and Klop). The hydrolysis of the polyamide is acid or alkali catalysed, in particular below pH = 3 and above pH = 9. 

Indoles 371 are selectively acylated at the 3-position to give high yields of compounds 372 on treatment with a wide variety of acyl chlorides in dichloromethane in the presence of chloro(diethyl)aluminium or chloro(dimethyl)-aluminium. The reaction proceeds under mild conditions (at 0 °C or rt, mainly for 1.5 h) and is applicable to indoles bearing various functional groups (both acid and base sensitive indoles) without NH protection (Equation 84) <20000L1485>. 

HF pyridine complex in methanol or THF is commonly used for the removal of TBS ethers. With acid- and base-sensitive substrates, the reaction can be buffered with additional pyridine.65 At a late stage in the synthesis of Calyculin A, a potent protein phosphatase inhibitor, a primary TBS ether was cleaved selectively in the presence of three secondary TBS ethers by using HF pyridine complex in THF-pyridine [Scheme 4.43].66... 

The final series of five procedures presents optimized preparations of a variety of useful organic compounds. The first procedure in this group describes the preparation of 3-BROMO-2(H)-PYRAN-2-ONE, a heterodiene useful for (4+2] cycloaddition reactions. An optimized large scale preparation of 1,3,5-CYCLOOCTATRIENE, another diene useful for [4+2] cycloaddition, is detailed from the readily available 1,5-cyclooctadiene. Previously, the availability of this material has depended on the commercial availability of cyclooctatetraene at reasonable cost. A simple large scale procedure for the preparation of 3-PYRROLINE is then presented via initial alkylation of hexamethylenetetramine with (Z)-1,4-dichloro-2-butene. This material serves as an intermediate for the preparation of 2,5-disubstituted pyrroles and pyrrolidines via heteroatom-directed metalation and alkylation of suitable derivatives. The preparation of extremely acid- and base-sensitive materials by use of the retro Diels-Alder reaction is illustrated in the preparation of 2-CYCLOHEXENE-1.4-DIONE, a useful reactive dienophile and substrate for photochemical [2+2] cycloadditions. Functionalized ferrocene derivatives... 

Bromohydrins. The reagent reacts with epoxides regioselcctively to yield a trans-bromohydrin with bromine predominantly at the less hindered position. Acid- and base-sensitive functional groups are stable to the reagent. 

The ethylene thioketal of the unstable, acid- and base-sensitive ketone 1 can be obtained in 85% yield with zinc triflate as catalyst in CHjClj at 23°. ... 

F420 774 0.2-3.4 Air- and heat-stable somewhat acid- and base-sensitive reduced form air-stable for hours in absence of flavins... 

The C-acylation reactions of magnesium monomethyl malonate proceed in the presence of acid- and base-sensitive functionality, as illustrated in the reaction sequence shown belowH ... 

Applying the same principle, 2- and 4-pyridylethoxycarbonyl (2- and 4-Pyoc) structures can be sensitized by methylation of the pyridine nitrogen. Subsequent treatment with the weak base morpholine (pKa 8.3) in dichloromethane already induces fragmentation and the formerly protected amino group is liberated (Scheme 8). This method proved to be successful in the synthesis of acid- and base-sensitive O-glycopeptides with tumor-associated antigen structure. ... 

MgE, ether, AC2O, rt, 90-100% yield. Cleavage occurs to give a mixture of acetate and an acetoxymethyl ether that is reported to be very acid- and base- sensitive. ... 

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