Protonation Followed by Addition

Treatment of 109 with concentrated hydrochloric acid converts it to the hydrochloride salt 139 (R = H), presumably via protonation and covalent hydration related compounds had been reported earlier. In the presence of methanol, 139 (R = Me) is the product.  

Passage of hydrogen chloride into ether solutions of 76 and Ai-oxides 94-9765.79 results similarly in protonation and hydration. Thus, for example, 95 gives 140, convertible back to 95 with base likewise, among other examples, 94 is converted to 141 in ethanol.  

In strong hydrochloric acid, 51 is cleaved to benzil and benzamidine, perhaps via an analogous covalent hydrate ethanoic acid similarly cleaves 44.  

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The Liotta procedure involved slurrying coal in an aqueous solution of tetrabutylammonium hydroxide to remove acidic protons, followed by addition of methyl iodide as alkylating agent. This mixture was then stirred vigorously for 12-72 hrs. depending upon the extent of alkylation desired. After all lation, the moist coal sample was roto-evaporated to remove excess THF and methyl iodine, followed by exdiaustive extraction with water to remove tetrabutylammonium iodide produced during all lation. Finally, the treated coal was vacuum dried (50 C, 0.1 torr, 24 hours) before use. 

Cyclizations involving bond formation between N-1 of the piperazinedi-one and C-2 of the indole ring of tryptophan have been reported. A few cyclodipeptides incorporating tryptophan have been shown to undergo cyclization in acid medium. The mechanism probably involves initial /3-protonation followed by addition of the piperazinedione to the iminium ion (85CPB4783) (Scheme 13). 

I.5.2.I. Abstraction of laterally situated protons followed by addition of an electrophile... 

The acid-catalyzed hydration is a typical acid-catalyzed addition to the carbonyl group. Protonation, followed by addition of water, gives a protonated product. Deprotonation gives the hydrate. 

The mechanism of dealkylative quinone formation, in accord with the work of Kochi, involves one-electron removal to give a radical cation (Scheme 18). The para-disposed methoxyls are best able to stabilize the charge in this case. Addition of water, loss of methanol and a proton, followed by additional loss of an electron then gives an allyl cation 56. Water can then attaek either ortho or para to the carbonyl leading to quinone formation. Preferred attack at the ortho position seems to be due to steric factors and possible destabilization of the allyl cation at the para position. The adjacent amide may force the methyl ether to adopt a conformation that does not optimize lone-pair donation. 

The intermediate is beUeved to form through a TT-complex, which collapses into a CJ-complex, which then rearomati2es upon proton removal from the carbon. This is followed by addition of a proton to the oxygen of the alkylben2ene sulfonate. 

The reaction of 2-phenyl-l-azirine (201) with benzoic acid gaveN-benzoylphenacylamine (204) (67BCJ2938). The overall mechanism of the reaction involves initial protonation on nitrogen followed by addition of the nucleophile to the azirinium ion and finally ring opening. 

When saturated steroidal ketones are reduced in ammonia, an alcohol is usually present to act as a proton donor and high yields of steroidal alcohols are obtained. Under these conditions, reduction probably proceeds by protonation of the radical-anion (or ketyl) (61), which results from a one electron addition to the carbonyl group, followed by addition of a second electron and proton. Barton has proposed that reduction proceeds via protonation of the dianion (62) arising from addition of two electrons to the carbonyl group. This proposal implies that the ketyl (61) undergoes addition of a second electron in preference to undergoing protonation by the... 

Huffman found that treatment of cholan-12-one (65b) with lithium and ammonia for 2 hours followed by addition of propanol gives 40 % of a pinacol together with 48.5 % of 12-ols in which the ratio of 12j5 12a is 19 1. This predominance of the 12 -ol was interpreted in terms of slow formation of a dianion of type (62) followed by its equilibration to the thermodynamically most stable configuration, i.e. one which affords the 12j5-ol upon protonation. An alternative explanation is that reduction in the presence of methanol involves protonation of a ketyl such as (61) by methanol, whereas in the absence of methanol reduction proceeds via the dianion (62) which is protonated on... 

Pyridine and dimethyl acetylenedicarboxylate in methanol yield - a mixture of (33) and (34). It is tempting to assume that a zwitterion (30) is first formed and that this then adds a proton followed by a methoxide ion (Michael addition) under the influence of both the positive charge on the ring and the assisting ester group. The resulting structure (31) could then add another molecule of the ester and cyclize, as indicated, to (32). Subsequent aromatization accompanied by loss of one, or the other, substituent at position 3 would lead to the two products, (33) and (34), actually isolated. 

A meehanistie seheme that was proposed involves the sueeessive or synehronous elimination of a proton and a ehloride ion from the 5-methyl group and from the ehloroethynyl group attaehed to it, followed by addition of the nueleophile (NH3) to the intermediate bipolar earbene ion stabilized by eonjugation (Seheme 103). 

The trimerization step can then be seen as formation of the reactive cation (52) by ring-opening of protonated indole dimer (53), followed by addition of indole as shown to give the trimer (27). ... 

Chiral tetrahydroisoquinoline derivatives can be obtained by diastereoselective or enatioselective protonation. Deprotonation of lactam 87 with n-BuLi followed by addition of H2O and NH4CI afforded 88 in 92% yield and 97% ee. The stereoselectivity was highly dependent upon the proton source. Further elaboration afforded tetrahydroisoquinoline 89 in >97% ee . The enantioselective protonation of 1-substituted tetrahydroisoquinoline 90 in the presence of chiral amine 91 proceeded in 90-95% yield and 83-86% ee. This methodology was used in an asymmetric synthesis of salsolidine <00SL1640>. 

The addition of HC1 to 1,3-butadiene in the gas phase at total pressures lower than 1 atmosphere and at temperatures in the range of 294-334 K yielded mixtures of 3-chloro-l-butene and ( )- and (Z)-l-chloro-2-butenes, in a ratio close to unity44,45. Surface catalysis has been shown to be involved in the product formation (Figure 1). The reaction has been found to occur at the walls of the reaction vessel with a high order in HC1 and an order less than unity in diene. The wall-catalyzed process has been described by a multilayer adsorption of HC1, followed by addition of butadiene in this HC1 layer. This highly structured process is likely to involve near simultaneous proton and chloride transfers. 

Alvarez-Toledano has investigated149 the reactivity of tertiary amines toward vinylketene complexes of type 221 and found that a number of unusual transformations take place. The formation of 237 and 238 is not directly linked to the presence of the amine, but instead relies on a thermo-lytic coupling of two carbene complexes formed from the vinylketene ligand, with additional loss of carbon monoxide. It is thought that 239 is formed by the deprotonation of the labile C-4 proton, followed by subsequent coordination of a capping Fe(CO)3 group. 

The anion presumably plays only a minor role, if any, especially in aqueous systems. Now the formation of 3-hexene may be explained in either of two ways. The intermediate carbonium ion, written in brackets, can undergo hydride migration to form a new carbonium ion, which can then collapse by proton loss to form the 3-hexene. Such a process does not require the intermediate formation of 2-hexene. The alternate explanation involves the discrete formation of 2-hexene followed by addition and elimination of a proton to give the desired 3-hexene. There is no question but that the hydride migration occurs, and with great... 

In contrast, oxime ethers and esters are usually stable in solution but the E/Z isomerization can be induced by acids " or by irradiation ". Recently, Narasaka and colleagues"" "" studied the equilibration-isomerization of (E)-O-acyl oximes 239 in the presence of an acid in a nucleophilic solvent (equation 71). Isomerization probably proceeds via protonation of the oxime nitrogen followed by addition-elimination of a nucleophilic solvent until the equilibrium of E and Z isomers is achieved. The isomerization of the more labile 0-acyloximes occurs either by an Sjv2 substitution at the oxime nitrogen with acids and/or by acyl exchange through the formation of a mixed anhydride and the free oxime. 

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