Pyridinium alkylation reaction

Fig. 7-1. Flammett correlation between ir-values and the logarithms of the relative rate constants of the Sn2 alkylation reaction of substituted pyridinium iV-phenolate betaines with iodomethane in trichloro-methane at 25 °C [16].

Rebeiro and later Seddon described an improved methodology to synthesize ionic liquids in an efficient way by carrying out the alkylation reaction in sealed vessels. Rebeiro et al. [109] reported a simple and quick method of preparation of alkyl pyridinium and l-alkyl-3-methyl imidazolium salts on a large scale in a closed vessel under microwave irradiation in a microwave digestor ... 

Xiao Y, Malhotra SV (2005) Friedel-Crafts alkylation reactions in pyridinium-based ionic liquids. J Mol Catal A Chem 230 129-133... 

Deoxygenation of aUyBc and benzyUc alcohols. Allylic and benzylic alcohols are conveniently reduced to the corresponding hydrocarbons in two steps. The alcohol is first converted into a pyridinium alkyl sulfate by reaction with sulfur trioxide-pyridine in THF at 0-3° (3-20 hours). Then lithium aluminum hydride (or LiAIH -AlClj, 3 1) in THF is added and the mixture stirred for I hour at 0° and then at 25° for 3-5 hours. Yields are high. In the case of allylic alcohols... 

For the unsubstituted pyridinium cation, reaction at the 2- and at the 4-position is predicted according to the theory. Indeed, reaction of protonated pyridine with the tcrt-butyl radical at low conversions (<30%) afforded selectively the ortho- and para-substituted derivatives without any alkylation at the meta position [16], It turned out that the ortho-para ratio is highly solvent dependent. If the reaction is conducted in H2O, the para product is formed as the major compound (see 10, ortho. para — 23 77). The same reaction in benzene afforded mainly the ortho compound [ortho-.para = 11 29). The reversal of the selectivity can be explained by assuming a reversible initial radical addition, especially if the reaction is conducted in H2O [16]. Similar results were obtained for the reaction with the tetrahydrofuryl radical [16]. The alkylations are generally stopped at low conversions. Since the alkylated pyridinium cations are only slightly less electrophilic than the starting pyridinium cations, overalkylation competes at higher conversion. For example, ethylation of the pyridinium cation at 100% conversion afforded a mixture of mono-, double- and tri-ethylated pyridinium salts (—> 11a e) [17]. 

The bicyclic and tricyclic tetrazoles ((1), (9), and (10)) could also be arylated <85M1227> directly by diphenyliodonium tetrafluoroborate with a similar regioselectivity as was shown in the alkylation reactions. Thus, l-phenyltetrazolo[l,5-u]pyridinium fluoroborate (17 R = Ph, X = Bp4) and 2-phenyltetrazolo[5,l-u]isoquinolinium fluoroborate (19 R = Ph, X = BF4) were prepared. 

A range of PILs was trialed in the Friedel—Craft alkylation of phenol with tert-butyl alcohol to produce tert-butyl alcohol as mentioned in section 6.1. These included a series of pyridinium PILs specifically designed for use as acid catalysts by Duan et al. and SO3H functionalized Bronsted acidic AILs. " It was shown successfully from the pyridinium PILs that a range of PILs could be easily produced that modified the acidities, catalytic activities, and, hence, selectivities and conversions for this reaction type, with the best performance by 2-methylpyridinium, with a conversion of 95%, and a selectivity toward 2,4-di- r butylphenol of 82%. In general, the SO3H functionalized AILs led to comparable selectivities and conversions for this reaction as the PILs. " Some nonstoichiometric salts containing pyridinium cations with HF anions have been used successfully as the catalyst and reaction media for the isobutane—olefin alkylation reactions. 

Fig. 11. Non-correlation between the Erp-values and the logarithms of the rate constants of the S 2 alkylation reaction of 2,4,6-triphenyl-N-(2,6-diphenyl-4-phenoxide)-pyridinium betaine with methyl iodide, measured in 15 solvents at 25°C (26).

Usually, organoboranes are sensitive to oxygen. Simple trialkylboranes are spontaneously flammable in contact with air. Nevertheless, under carefully controlled conditions the reaction of organoboranes with oxygen can be used for the preparation of alcohols or alkyl hydroperoxides (228,229). Aldehydes are produced by oxidation of primary alkylboranes with pyridinium chi orochrom ate (188). Chromic acid at pH < 3 transforms secondary alkyl and cycloalkylboranes into ketones pyridinium chi orochrom ate can also be used (230,231). A convenient procedure for the direct conversion of terminal alkenes into carboxyUc acids employs hydroboration with dibromoborane—dimethyl sulfide and oxidation of the intermediate alkyldibromoborane with chromium trioxide in 90% aqueous acetic acid (232,233). 

Organometallic reagents react with iminium salts to give C-alkylated products. The reactions can be divided into two categories the reactions of pyridinium, quinolinium, and isoquinolinium salts and the reactions of... 

The Zincke reaction is an overall amine exchange process that converts N- 2,A-dinitrophenyl)pyridinium salts (e.g, 1), known as Zincke salts, to iV-aryl or iV-alkyl pyridiniums 2 upon treatment with the appropriate aniline or alkyl amine. The Zincke salts are produced by reaction of pyridine or its derivatives with 2,4-dinitrochlorobenzene. This venerable reaction, first reported in 1904 and independently explored by Konig, proceeds via nucleophilic addition, ring opening, amine exchange, and electrocyclic reclosure, a sequence that also requires a series of proton transfers. By... 

Reaction of pyridinium-A -(2-pyridyl)amidine (402) and alkyl haloace-tates in the presence of K2CO3 afforded a mixture of 4-oxo-4/f-pyrido[l, 2-u]pyrimidine-2-carboxylates 407 and 2-aminopyridine derivatives 406 through intermediers 403- 05, as depicted in Scheme 15 (00TL5837). Compound 406 could be cyclized on the action of heat or silica gel into 407. The best yield was achieved in the case of ethyl bromoacetate. 

In an attempt to study the behavior and chemistry of coal in ionic liquids, 1,2-diphenylethane was chosen as a model compound and its reaction in acidic pyri-dinium chloroaluminate(III) melts ([PyHjCl/AlCb was investigated [69]. At 40 °C, 1,2-diphenylethane undergoes a series of alkylation and dealkylation reactions to give a mixture of products. Some of the products are shown in Scheme 5.1-40. Newman also investigated the reactions of 1,2-diphenylethane with acylating agents such as acetyl chloride or acetic anhydride in the pyridinium ionic liquid [70] and with alcohols such as isopropanol [71]. 

Primary alkyl amines RNHi can be convertedto alkyl halides by (1) conversion to RNTs2 (p. 447) and treatment of this with I or Br in DMF, or to N(Ts)—NH2 derivatives followed by treatment with NBS under photolysis conditions, (2) diazotization with terr-butyl nitrite and a metal halide such as TiCU in DMF, or (3) the Katritzky pyrylium-pyridinium method (pp. 447,489). Alkyl groups can be cleaved from secondary and tertiary aromatic amines by concentrated HBr in a reaction similar to 10-71, for example,... 

Carbon alkylation of simple nitronate anions is also possible by the reaction with /V-substi-tuted pyridiniums, as exemplified in Eq. 5.41. Such types of reactions are classified as Srm2 reactions, in which electron transfer reactions from nitronate anions to pyridiniums are involved as key steps.59... 

Another classic reaction of pyridinium salts is reduction of the pyridine ring. Donohoe and co-workers reported the partial reduction of A-alkylpyridinium salts <060BC1071>, which is accompanied by subsequent alkylation and hydrolysis to furnish a range of 2,3-dihydropyrid-4-ones. This sequence has the potential to introduce a variety of functional groups at the C-2 position of 2,3-dihydropyrid-4-ones. Reduction of pyridinium ylides with sodium borohydride has also been reported in fair to good yields <06JHC709>. 

Towards the end of this section it may be worthwhile to point out some new reactions with high-valent metals and TBHP. The first is a pyridinium dichromate PDC-TBHP system134. Nonsubstituted or alkyl-substituted conjugated dienes, such as 1,3-cyclooctadiene (87) and others (also linear dienes), yield keto allyl peroxides 88 (equation 18), whereas phenyl-substituted dienes such as 1,4-diphenylbutadiene (89) gave diketo compounds, 90 (equation 19). In further research into a GIF-type system135 with iron and TBHP, limonene gave a mixture of products with carvone as the major product. The mechanism is thought to proceed initially by formation of a Fe(V)-carbon... 

The key intermediate 124 was prepared starting with tryptophyl bromide alkylation of 3-acetylpyridine, to give 128 in 95% yield (Fig. 37) [87]. Reduction of 128 with sodium dithionite under buffered (sodium bicarbonate) conditions lead to dihydropyridine 129, which could be cyclized to 130 upon treatment with methanolic HC1. Alternatively, 128 could be converted directly to 130 by sodium dithionite if the sodium bicarbonate was omitted. Oxidation with palladium on carbon produced pyridinium salt 131, which could then be reduced to 124 (as a mixture of isomers) upon reaction with sodium boro-hydride. Alternatively, direct reduction of 128 with sodium borohydride gave a mixture of compounds, from which cyclized derivative 132 could be isolated in 30% yield after column chromatography [88]. Reduction of 132 with lithium tri-f-butoxyaluminum hydride then gave 124 (once again as a mixture of isomers) in 90% yield. 

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