Intermediates zwitterions

Hydrogen atoms in azolium ions can be removed easily as protons (e.g. 230—>232) exchange with deuterium occurs in heavy water. The intermediate zwitterion (e.g. 231) can also be written as a carbene, and in some cases this carbenoid form can be trapped or isolated as a dimer. 

Both terminal and nonterminal acetylenes have been used. Activating groups oL to the acetylenic bond have included sulfone (131-135), sulfoxide (134), ester (28,133-139), and ketone (134,140). Whether adduct 183 Is designated as cis or trans depends on the investigators and the particular compound. If the addition reaction is carried out in aprotic solvents, the major isomer is 183 formed by cis addition (135,138,139). For example, the addition of aziridine to dimethyl acetylenedicarboxylate (182, X, Y = CO2CH3) in dimethyl sulfoxide (135) gave 75 % of a mixture containing 95 % of the Chester 185. Collapse of the intermediate zwitterion intermediate 186... 

The differenee in reaction rates of the amino alcohols to isobutyraldehyde and the secondary amine in strong acidic solutions is determined by the reactivity as well as the concentration of the intermediate zwitterions [Fig. 2, Eq. (10)]. Since several of the equilibrium constants of the foregoing reactions are unknown, an estimate of the relative concentrations of these dipolar species is difficult. As far as the reactivity is concerned, the rate of decomposition is expected to be higher, according as the basicity of the secondary amines is lower, since the necessary driving force to expel the amine will increase with increasing basicity of the secondary amine. The kinetics and mechanism of the hydrolysis of enamines demonstrate that not only resonance in the starting material is an important factor [e.g., if... 

The mechanism for the redistribution in oxidation states begins similarly to that of the Paal thiophene synthesis. However, upon formation of dithione 38, nucleophilic addition of one thiocarbonyl into the other produces the intermediate zwitterion 39. A 1,3-tautomerization of hydrogen then gives... 

In acetic acid the intermediate zwitterion is trapped by acetate affording cyclopentenones with an acylated hydroxymethylene group on C-4. Use of this sequence has been made of in the synthesis of the sesquiterpenes cyclocolorenone 347) (3.31) and a-cadinol (3.32) 348). 

The heterocycle decomposes readily, and the intermediate zwitterion alternatively rearranges to a vinylic ester that retains the phosphoryl isocyanate linkage. 

The major product (21-37%) from the reaction of benzyne with N-phenylpyrrole is the 2 1 adduct (167), the formation of which is explicable in terms of the cyclization of either one of two intermediate zwitterions, 165 or 166. Alternatively, prototropic shift within the intermediate (166) accounts for the formation of the a-naphthylamine (147) (4-6% yield). Other benz[o]carbazole derivatives (168 and 169)... 

The formation of a small amount of naphthalene as a by-product of the reaction of benzyne with iV -methylpyrrole was noted by Wittig and Behnisch. Some related examples have recently been described. The tetrachloronaphthalen-l,4-imine (108) with benz5me gave N-methylcarbazole, which it is tempting to see as arising from the reaction of an intermediate zwitterion (compare 166) with another molecule of benzyne or, more likely, a benzyne precursor. The complementary product, 1,2,3,4-tetrachloronaphthalene, was not identified in this case. 

The formation of anthracene in reactions of 185 and 186 with benzyne, which was unexplained by Wittig et aZ., possibly is due to an alternative reaction of the intermediate zwitterion (202) with another molecule of benzjme or with a benzyne precursor. Benzyne reacted with the isoindole (206) to give the tetramethyltriptycene (208) and, in a separate run using excess of the benzyne precursor, W-benzylcarbazole. The latter product would appear to be made up of the iV-benzyl group from an intermediate anthracen-9,10-imine (207) and two molecules of benzyne. Mass spectral evidence also implicated the adduct 207, and the formation of 208 was attributed to benzyne-induced deamination of 207 to 1,4,9,10-tetramethylanthracene, which was trapped by further addition of benzyne across the 9- and 10-positions. 

At low pH (acidic solution), an amino acid will exist as the protonated ammonium cation, and at high pH (basic solution) as the aminocarboxylate anion. The intermediate zwitterion form will predominate at pHs between these extremes. The uncharged amino acid has no real existence at any pH. It is ironic that we are so familiar with the terminology amino acid, yet such a structure has no real existence Amino acids are ionic compounds, solids with a high melting point. 

A plausible mechanism for the ring expansion (Scheme 65) proceeds via an intermediate zwitterion A, resulting from Michael addition of the tertiary nitrogen to the alkyne. Cleavage of the C(l)-N bond occurs via formation of the six-membered transition state B in which a molecule of alcohol facilitates the Sn reaction. 

A potentially useful route to reserpine alkaloids has been suggested by the application of the amino-Claisen reaction (Scheme 52) to the indolyl-substituted isoquinuclidine (268). Treatment of (268) with methyl propiolate gave the intermediate zwitterion (269) which rapidly rearranged to (270). This latter compound has all the necessary functionality for further elaboration into the reserpine ring system (B-82MI20700). 

Attempts to rationalize these and other photochemical reactions have been based on the nature of the lowest excited state or the stereochemistry of substituents. A wider-ranging explanation is based on stabilization of the common intermediate zwitterion (367) by either electron-releasing substituents at C-3 and C-5 or polar solvents (79JA7521). 

It was amply emphasized above that the formation of homologous ketones is the principal competing reaction in this condensa-tJoor4M,e To explain this observation it has become customary to invoke a transient intermediate zwitterion, termed by Arndt and Eistert 4 5 a diazomum betaine which can collapse into an epoxide with attendant nitrogen expulsion, or can undergo rearrangement to (me or two possible oarbonyl compounds. The process may be represented schematically as shown in Eq. (284). 

If the ester group is at the alternative position of the side chain, then the position of attack of the intermediate zwitterion is altered, leading to the first direct synthesis of 2tf-quinolizines (e.g., 34).288 Methyl propiolate gives only a trace of the corresponding 2tf-quinolizine. 

Also known are 2 + 2 cycloadditions proceeding by way of a bipolar ion, path (b) of Scheme l.28 These reactions occur in situations such as that depicted in Equation 12.14, where the intermediate zwitterion (10) is strongly stabilized. Tetracyanoethylene adds by this mechanism to /Mnethoxyphenyl-,29 alkoxyl-,30 and cyclopropyl-31 substituted olefins. The additions show large solvent effects.32 Partial loss of stereochemistry occurs as in the biradical cases, but it is much less pronounced. 

On the other hand, stereospecificity is not always complete, and many ketene cycloadditions take place only when there is a strong donor substituent on the alkene. An ionic stepwise pathway by way of an intermediate zwitterion 3.34 is therefore entirely reasonable in accounting for many ketene cycloadditions. It seems likely that some of these reactions are pericyclic and some not, with the possibility of there,being a rather blurred borderline between the two mechanisms, with one bond forming so far ahead of the other that any symmetry in the orbitals is essentially lost. But when it is pericyclic, how does it overcome the symmetry-imposed barrier ... 

A systematic study of the impact of geminal a-fluorine substitution upon the rate of decarboxylation of /1-lactones has included investigation of the thermolysis of oc,oc-difluoro /1-lactones, to give CO2 and 1,1-difluoroalkenes, in the gas phase and in solution.48 The gas-phase results have been interpreted, with reference to ab initio calculations on the fluoro- and non-fluorinated /1-lactone systems, in terms of a probable concerted, asynchronous, non-polar mechanism. However, a polar mechanism which probably involves formation of an intermediate zwitterion has been invoked to explain the solvent dependence observed. 

While both the primary and secondary ozonides have been isolated and characterized, the pair formed by the carbonyl oxide (CO) and the carbonyl compound (CC) has never been directly put into evidence. This elusive intermediate, called also Criegee intermediate zwitterion (CZ), according to this AMI study which did not take into account solvent effects, forms a tight pair or a dipolar complex (DC). The primary ozonide has an O-envelope halfchair conformation and as such two conformers are possible from a rfr-alkene 11 and 12 and only one 13 from the trans-alkene. The splitting of the primary ozonide can lead either to an anti 14 or syn 15 CO and has a determining role for the stereochemical outcome of the reaction <1997JOC2757>. 

Dimethyl-4-bromo-27/-chromenes are accessible via a boron tribromide induced cyclization of phenol derivatives 31 (Scheme 9). The reaction is proposed to proceed via O-deprotection and subsequent elimination of hydroxide to form the intermediate zwitterionic species 32. Addition of bromide, pyran ring closure and protonation provides 4-bromo-2/7-chromenes in moderate yield (Scheme 9) < 1997H(45) 1131 >. 

A tandem Michael-aldol reaction of ynone selenides with aldehydes provides a convenient route to 3-substituted selenochromen-4-ones 132 (Equation 49) <2002TL7039>. The reaction proceeds via an intermediate zwitterion formed via a 6-/ r/ -r//g-cyclization. 

In 1989, the irradiation of (E,E)-2,4-hexadiene S3 sensitized by meso-porphyrin IX dimethyl ester led to the formation of cis-3,6-dimethyl-l,2-dioxene (62), which was the major product detected at — 78 °C in Freon 11 [69]. Endoperoxide 62 was purified under vacuum at 0.75 mmHg, and collected in a trap (98% isolated yield). Dienes that can adopt a cisoid conformation, such as 53 or ( , )-l,4-di phenyl butadiene, were photooxidized by the corresponding endoperoxides in high or quantitative yield in a suprafacial Diels-Alder reaction [60, 70], Dienes that cannot readily adopt cisoid conformations, such as (fc, Z)-2,4-hexadienes and (Z, Z)-2,4-hexadienes, lose their stereochemistry in the singlet oxygen [2 + 4]-cyclo-addition [60], (E,Z)- and (Z,Z)-dienes give a complex mixture of hydroperoxides and aldehydes, which suggests the intervention of intermediate zwitterions or 1,4-diradicals [71]. 

The relatively easy decarboxylation of many azolecarboxylic acids is a result of inductive stabilization of intermediate zwitterions of type 608 (cf. Section 3.4.1.8.1). Kinetic studies show that oxazole-2- and -5-carboxylic acids are both decarboxylated via the zwitterionic tautomers. Thiazole-2-carboxylic acids, and to a lesser extent -5-carboxylic acids, are decarboxylated readily thiazole-4-carboxylic acids are relatively stable. Isothiazole-5-carboxylic acids are decarboxylated readily, the 3-isomers less so while the 4-isomers require high temperatures. The 1,2,4-, 1,2,5-, and 1,3,4-thiadiazolecar-boxylic acids are also easily decarboxylated their stability is increased by electron-donating substituents. Most 1,2,3-triazolecarboxylic acids lose carbon dioxide when heated above their melting points. Decarboxylation of 2-hydroxytetra-zole-5-carboxylic acid requires severe conditions (HC1, reflux, 90 h) to produce 2-hydroxytetrazole (40%) <1999TL6093>. 

Kuehne and Foley117 have shown that nitroethene reacts exothermically with 1-N-morpholinocyclohexene in acetonitrile to give the less substituted alkylated enamine (54), whereas the cyclobutane (53) is produced in hydrocarbon solvent. This is attributed to the increased lifetime and selectivity of the intermediate zwitterion in polar solvents, which is expressed in the proton transfer, via a six-membered transition state, to the enamine product (54, Scheme 38). 

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