Base-induced Reactions

Addition of triethylamine to the activated alcohol, during a Swern oxidation, may produce side reactions, beginning with a deprotonation step. As triethylamine operates at very low temperature, only substrates very sensitive to deprotonation suffer these side reactions. No base-catalyzed hydrolyses are possible because of the absence of water. 

The most common side-reactions induced by an initial deprotonation are  

The Swern oxidation of homoallylic alcohols leads to a (3,y-unsaturated carbonyl compound, which sometimes suffers an in situ base-induced isomerization of the alkene into conjugation with the carbonyl group.239 

A partial migration of an alkene into conjugation with a ketone occurs during a Swern oxidation. The isomerization into conjugation can be purposefully brought about by treat-  

Sometimes, when a Swern oxidation produces a carbonyl compound possessing a good-leaving group at the 3-position, an in situ elimination occurs, resulting in the generation of a conjugated enone or enal. 

Synthesis is the lifeforce, the sine qua non, for creating the members of chemical families. For some families of compounds the chemist must rely on Nature to achieve the task, but for many other families chemists can employ their own ingenuity in coaxing the elements into proper combinations. The ultimate utility of a family of chemical compounds is usually related to the ease with which this can be done, the calixarenes providing a good case in point. Like the cyclodex- 

Vocanson, F. Lamartine, R. Lanteri, P. Longeray, R. Gauvrit, J. Y. NewJ. Chem. 1995,19,825. The resorcinol-derived calixarenes, generally made via acid catalysis, have recently been found to be accessible by base-induced condensation as well Konishi, H. Iwasaki, Y. Morikawa, O. Okano, T. Kiji, J. Chem. Express 1990, 5, 869 Konishi, FI. Iwasaki, Y. Synlett 1995, 612. 

Many phenols have been tried, generally without success. A typical example is reported by Yilmaz, M. Vural, U. S. Synth. React. Inorg. Met.-Org. Chem. 1991, 21, 1231, who used 4-nitrophenol, 4-hydoxybenzoic acid, 4-hydroxyacetophenone, 1,4-dihydroxybenzene, 4-phenoxyphenol, 4-hydroxybenzyl alcohol, 4-cyanophenol, 4-hydroxymethylbenzoic acid and 

4-hydroxyethylbenzoic acid and in all cases obtained amorphous, unextractable material. Souley, B. Asfari, Z. Vicens, J. Pol. J. Chem. 1992,66,959. 

Interesting calixarenes and calixarene-related compounds have been obtained in one-step reactions from 1-naphthol, from the naphthalenediol disulfonate 11, and from and the bis-phenols 13, 15, and 17. Although 2-naphthol reacts with formaldehyde to yield a simple bis-naphthol, 1-naphthol produces a mixture containing 9.6% of the symmetrical cxo-OH cyclic tetramer 10 accompanied by 5% and 16% of two other cyclic tetramers in which the naphthol residues are unsymmetrically placed in the cyclic array. When the disodium salt of 1,8-dihydroxy-3,6-naphthalenedisulfonic acid (chromotropic acid) (11) is treated with an aqueous solution of formaldehyde and the mixture is allowed either to stand at room temperature for a week or is refluxed 6 h, a high yield of the endo-OH cyclic tetramer 12 is formed. The ease with which this condensation occurs is surprising in view of the deactivating effect of the sulfonic acid groups 

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The Barton-Zard reaction refers to the base-induced reaction of nitroalkenes 1 with alkyl a-isocyanoacetates 2 to afford pyrroles 3. Solvents used are THF or alcohols (or mixtures) and the reaction often proceeds at room temperature. 

Intramolecular cyclization can yield fluorinated phenoxazines by a Smiles rearrangement (86IZV1855) and 2,3-dihydro-l,4-benzodioxins by a base-induced reaction [81JFC(18)483]. 

The elimination of sulfur dioxide from thiirane dioxides leading to the corresponding alkenes is not the only result of base-induced reactions other products are also formed. This fact raises the question of the mechanistic pathway of this reaction. In general, the thiirane dioxide is treated with a large excess of the base in an appropriate solvent for several hours at room temperature or below. Bases commonly used are 2n NaOH (in water), NaOCH3 (in methanol), t-BuO-K + (in f-BuOH) and BuLi (in tetrahydrofuran) or KOH-CCU (in t-BuOH)16-19"112 113. 

Nitro-, 4-nitro-, 7-nitro-, 5,7-dinitro-, and 6,8-dinitroquinoline react with the carbanion of chloromethyl phenyl sulfone to give products of substitution of hydrogen at positions 4 3 8 6,8 and 5,7 respectively <96LA641>. The base-induced reaction of benzoyl chloride salts of quinoline iV-oxides with carbonitriles to give 2-quinolyldiacylamines as the main products has been reported <96TL(37)69>. 

Special cases of triafulvene formation were found in the base-induced reaction of the nitroso compound 91 with dimethyl fumarate85, in the thermolysis of tetra-fluorocyclopropene reported to give the perfluorinated triafulvenes 65/6668 and in the addition of bis(trifluoromethyl) ketene to bis (p-tolyl) cyclopropenone66 which gave rise to triafulvene 63 by elimination of C02 ... 

Base-induced reaction of nitroalkenes with alkyl a-isocyanoacetates to afford pyrroles. 

The C==C must be introduced by a base-induced reaction. If acid is used, such as in the dehydration of an alcohol, the product would undergo polymerization. 

The base-induced reaction of dichloromethyl methyl ether with trialkyl- and triarylboranes also provides a powerful method for the preparation of the corresponding tertiary carbinols.1617 fn this case, all three groups transfer readily from horon to carbon under mild conditions, and oxidation with alkaline hydrogen peroxide provides the tertiary alcohol ... 

One of the most useful of the base-induced reactions of esters is illustrated by the self-condensation of ethyl ethanoate under the influence of sodium ethoxide to give ethyl 3-oxobutanoate ... 

All of these substances can be reduced to benzenamine with tin and hydrochloric acid. As a result, each could be, but not necessarily is, an intermediate in the reduction of nitro compounds to amines. Formation of the bimolecular reduction products is the result of base-induced reactions between nitroso compounds and azanols or amines and possibly further reduction of the initially produced substances (see Exercise 24-18). 

One of the oldest known thermosetting synthetic polymers is made by condensation of phenols with aldehydes using basic catalysts. The resins that are formed are known as Bakelites. The initial stage is the base-induced reaction of benzenol and methanal to give a (4-hydroxyphenyl)methanol, and this reaction closely resembles an aldol addition and can take place at either the 2-or the 4-position of the benzene ring ... 

The alkylation reaction is limited to nitro-substituted arenes and heteroarenes and is highly chemoselec-tive nucleophilic displacement of activated halogens, including fluorine, was not observed. The regio-selectivity is determined by the bulkiness of the silicon reagent. With unhindered silyl derivatives a strong preference for ortho addition was observed, as in the example of equation (6). With bulkier reagents attack took place exclusively at the para position (Scheme 1). The success of this reaction, which could not be reproduced with alkali enolates, was attributed at least in part to the essentially nonbasic reaction conditions under which side processes due to base-induced reactions of nitroarenes can be effectively eliminated.12... 

The kinetics of this reaction have been monitored by pulse radiolysis, using conductivity detection. At pH 9.5, the half-life of 17 is <3.5 jus, because of the base-induced reaction 38, and the appear-... 

The action of triethylamine may cause base-induced reactions, such as a-epimerization of carbonyl compounds isomerization of alkenes into conjugation with carbonyl groups and, elimination in carbonyl compounds posssessing a good-leaving group at the (3-position... 

Normally, Oppenauer oxidations are performed employing Al3+ cations as catalyst because aluminium alkoxides possess a good balance of a desired high hydride transfer capability versus a low propensity to promote undesired base-induced reactions, like aldol condensations and Tischtschenko reactions. In the reaction, as originally described by Oppenauer, aluminium t-butoxide is used as catalyst,4 because its high basicity allows a very favourable equilibrium towards the formation of the aluminium alkoxide of the alcohol whose oxidation is desired. However,... 

The Oppenauer oxidation presents two important limitations on one side it is unable to oxidize certain alcohols because of unfavourable thermodynamics, and on the other side, base-induced reactions between the oxidant and the product may become dominant. That is why, it is seldom employed for the obtention of aldehydes because these compounds react readily under basic conditions. On the other hand, although aluminium alkoxides promote aldol condensations, many base-sensitive functional groups such as most esters but not formates—25 resist its action. 

Although aluminium alkoxides are able to promote base-induced reactions, the basic conditions involved are not extremely strong and many base-sensitive functional groups remain unaffected during Oppenauer oxidations, including alkyl halides,51 epoxides52 and most esters.53 On the other hand, the very sensitive formate esters are hydrolyzed under Oppenauer conditions and the resulting alcohols are oxidized in situ.25... 

When the pentamer (66) reacts with alkoxide anions at low temperatures (-30 to -40°C), then the products of kinetic control (102) are isolated, whereas at higher temperatures, thermodynamic control prevails and the products (103) are obtained [131,132] (Scheme 68). Similar observations have been made with sulphur nucleophiles [132], and complex products are obtained with amines, including the formation of heterocycles [132]. Reaction of (66) with ethyl acetoacetate gave a pyran derivative (104) in a reaction that may be rationalised as shown in Scheme 69 [133]. In an analogous way.furan derivatives are formed from perfluoro-2-butene and -cyclohexene in base-induced reaction with 1,3-dicarbonyl derivatives [133]. 

The Shapiro Reaction, a variation on the Bamford-Stevens Reaction, is the base-induced reaction of tosylhydrazones to afford alkenes. This reaction is carried out with two equivalents of an organolithium compound. 

In general, carbenoid reactions in which an organic molecule decomposes thermally or photochemically without the use of metal salts or organometallic reagents are thought to involve free carbenes base-induced reactions more often involve carbenoids. However, both halves of this generalization have their exceptions. 

Clean conversions to 1-bromoalkynes were recorded in base-induced reactions of [1-bromoalkenyl iodonium salts, whereas the corresponding jS-chloro-analogues afforded mixtures of 1-chloroalkynes and 1-chlorocyclopentenes [42],... 

Addition of diazomethane to 3,3-dimethylcyclopropene leads to the pyrazolines (303, R = H) but methyl diazoacetate leads to (304) and (305) the former is apparently derived by base induced reaction of the pyrazoline, while the latter may be explained in terms of rearrangement to the diazocompound (306) followed by dipolar addition to the cyclopropene 242). 

Base-Induced Reactions of 3,5-Dimethylisoxazole with Electrophilic Reagents... 

Alternatively, thiophenes have been accessed by base induced reactions involving thioacetaldehyde dimer and active methylene compounds under microwave irradiation, as illustrated by synthesis of 2-aminothiophene-3-carbonitrile 7 <07TL5261>. 

Esters undergo a reaction similar to aldol condensation called the Claisen condensation. It is a base-induced reaction of two ester molecules, which usually forms p-ketoester products. O 0 0... 

An interesting version of the rearrangement [76] is presented in Scheme 51. The base-induced reaction of 2,4-dinitrobenzenesulfonamide with various acyl chlorides provides AT-(2,4-dinitrobenzenesulfonyl) acylamide derivatives 159 that rearrange and fragment in situ to afford the respective nitriles 160. The reaction has been used for derivatization of complex crown ethers. 

An alternative synthesis of salts of 1, which proved to be suitable for large scale synthesis, soon followed and is outlined in equation 3 . In this approach the carbene is generated by a base-induced reaction, and under the conditions of the reaction the product... 

Jones and Denham found that a base-induced reaction of the nitroso compound 76 with dimethyl fumarate yielded 77 (equation 69). 

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