Quaternary-salt formation

Primary halides are more reactive than secondary compounds quaternary salt formation does not occur with tertiary halides, elimination always occurring to give the hydriodide and an olefln, Also, the larger the alkyl group the slower is the reaction this is shown by the very slow reaction of dodecyl bromide with quinoline, and even butyl iodide is much slower to react than methyl iodide. The longer chain primary halides commonly undergo elimination rather than cause quaternization for example, n-octyl and cetyl iodides give only the hydriodides when heated with 9-aminoacridine. ... 

Quaternary salt formation in a 1-substituted pyrazole ring (cf. 23) can occur only at N-2 to give the fully resonance-stabilized symmetrical salt 24. This reaction, which proceeds very readily, has been known for many years and therefore will not be commented on here. 

The 5H-imidazole ring (37) possesses two nitrogen atoms with lone pairs e,vailable for quaternary salt formation, but unlike those in the... 

Quaternary salt formation in 4-quinazoline 3-oxide and its 4-amino and 4-methyl derivatives has been studied by Adachi. These N-oxides, prepared by reaction of the simple quinazoline with hydroxylamine, react with ethyl iodide at N-1, although only in the case of the 4-amino derivative could the ethiodide be purified. The salts are degraded by alkali yielding derivatives of ethylaniline [Eq. (4)]. 

In a 1-substituted 1,2,3-triazole (79), both the 2- and 3-nitrogen atoms possess lone pairs of electrons that are available for quaternary salt formation, and quatemization is known to occur at the 3-nitrogen atom to give the symmetrical cation (80). Thus, the reaction between 1-methyl-l,2,3-triazole and benzyl iodide yields the same salt as is obtained from the interaction of 1-benzyl-1,2,3-triazole and methyl iodide the salt must therefore be 80 (R = Me, R = PhCH2,... 

Two interesting cases of quaternary salt formation are illustrated by compounds 88 and 90 (Z = CH) which contain fused quinoline and triazole rings. In these compounds both of the nitrogen atoms unique to the triazole ring possess lone pairs of electrons which are available for reaction. With compound 88 reaction occurs to give 89, but in... 

The introduction of a nitrogen atom into the benzene ring of indole affords a center, not present in indole itself, at which quaternary salt formation occurs readily, and the base 95 is converted into a quaternary salt (96) on the pyridine-type nitrogen atom. ... 

Quaternary salt formation by the l,5-diaza-3H-indene 103 is reported to take place only at N-5 to give 104. This information is... 

As a rule, the annular nitrogen atoms in 1,3,4-thiadiazoles are very reactive towards electrophiles as shown by facile alkylation reactions and quaternary salt formation. A thorough study on the quaternization of 2,5-disubstituted thiadiazoles, and its comparison with pyridazines has been published <84CHEC-i(4)545>. Electrophilic attack by benzyl chloride on 2-aminothiadiazole to give (44) in a regiospecific manner was utilized in the synthesis of an antiviral candidate <92MI 4io-oi>. 

The normal-propylamine NPT has been made by the oxalylamide route, with the amide with a mp 179-181 °C (75%) from benzene and NPT hydrochloride mp 186-187 °C (33%) from MeOH/benzene. An attempt to make NPT by the alkyl halide procedure failed. Using these same ratios of reactants, there was the formation of a sizable quantity of DPT with appreciable unreacted tryptamine presence (T NPT DPT/1 5 4). A recycling under the same conditions gave T NPT DPT/0 3 7) and a third cycle gave only DPT, but with a loss of almost 90% of the material presumably to quaternary salt formation. Interestingly NPT is less toxic than DPT in experimental mice, but has not been assayed yet in man. 

Quaternary-salt formation can also occur, particularly at elevated temperatures, if the sulfonylation product has a primary sulfonyloxy group. Thus, 2,3-0-isopropylidene-l-0-tosyl-D,L-glyceritol readily reacts86 with hot pyridine to give the corresponding pyridinium p-toluenesulfonate ... 

Configuration examination073 by H-nmr of the quaternary precursor of pentazocine (213a and b) and related compounds demonstrate that during quaternary salt formation, axial attack of the electrophile (from 3-methyl-2-butenyl bromide) occurs to yield predominantly 213b. This was consistent with earlier observations/174 175 An extensive study of the metazocines (base, HC1 salt, and methiodide) has been published,076 some results of which were later revised.077 178 ... 

Alkyl-5-phenyltetrazoles are converted into 2-alkyl isomers on heating with alkyl iodide, presumably by quaternary salt formation followed by elimination of alkyl iodide to give the thermodynamically more stable isomer (Scheme 5) (77AHC(21)323). 

Dialkylation (quaternary salt formation) can be avoided by ensuring that the sum of the alkylation potentials is lower than the of the 1-alkylazole. When the pTsT values of the imidazole and 1-... 

It is very difficult and probably of little value to try to separate the work of these three pioneers. At the time Makosza reported the two-phase carbene reaction [11] the process was described in a patent issued to Starks [8]. While Brandstrom was pushing back the frontiers of alkylation in nonpolar homogeneous solution [12], Makosza had alkylated a massive number of carbon acids under catalytic conditions [13]. Hennis (Dow, Midland, Michigan) working in a more limited way, was successfully alkylating carboxylates under conditions favorable for in situ quaternary salt formation [14]. And so it goes. It is, in our opinion, of value to credit and compliment these early workers in the field now known as phase transfer catalysis and draw attention to the important work each, in his own way, accomplished. 

Dinitrochlorobenzene reacts readily with pyridine, giving l-(2,4-dinitrophenyl) pyridinium chloride. Since Zincke s original observation of this reaction, several activated halogenobenzenes have been used, and activated nitro groups have also been replaced in quaternary salt formation. Examples are given in Table 5.16. 

Finally there are a number of examples of quaternary salt formation from pyridine and reactive halogen derivatives of other heterocyclic nuclei " . 

A related intramolecular substitution occurs when a pyridine 1-oxide reacts with 2-bromopyridine or 2-bromoquinoline. Initial quaternary salt formation, assisted by the presence of hydrobromic acid, is followed by... 

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