Ammonium salts, alkyl reaction

The catalytic effect of quaternary ammonium salts in the basic liquid liquid two-phase alkylation of amines [1-3] is somewhat unexpected in view of the low acidity of most amines (pKfl>30). Aqueous sodium hydroxide is not a sufficiently strong base to deprotonate non-activated amines in aqueous solution and the hydroxide ion is not readily transferred into the organic phase to facilitate the homogeneous alkylation (see Chapter 1). Additionally, it is known that ion-pairs of quaternary ammonium cations with deprotonated amines are decomposed extremely rapidly by traces of water [4]. However, under solidrliquid two-phase conditions, the addition of a quaternary ammonium salt has been found to increase the rate of alkylation of non-activated amines by a factor of ca. 3-4 [5]. Similarly, the alkylation of aromatic amines is accelerated by the addition of the quaternary ammonium salt the reaction is accelerated even in the absence of an inorganic base, although under such conditions the amine is deactivated by the formation of the hydrohalide salt, and the rate of the reaction gradually decreases. Hence, the addition of even a weak base, such as... 

This conversion produces as the bye product through direct reduction of H. The p-CdTe and p-InP electrodes have also been Investigated (12) while the reaction scheme Is essentially as indicated above, the net formation of formic acid is demonstrated to be a function of the pH of the medium. Hence using the solutions of supporting electrolytes such as carbonates, sulphates, phosphates and perchlorates of alkali salts or tetra alkyl ammonium salts, the reaction (4) has been effected. 

Further investigation of phase transfer catalysis, a phenomenon where quaternary ammonium salts catalyse reactions in aqueous-organic two-phase systems, has confirmed that the function of the ammonium ion is to solubilize the reagent/substrate in the organic phase. The use of phase transfer catalysis in the alkylation of weak acids such as diethyl malonate has been described other examples - - of this phenomenon are cited above. 

Amines are powerful nucleophiles which react under neutral or slightly basic conditions with several electron-accepting carbon reagents. The reaction of alkyl halides with amines is useful for the preparation of tertiary amines or quaternary ammonium salts. The conversion of primary amines into secondary amines is usually not feasible since the secondary amine tends towards further alkylation. 

The Leuckart reaction uses formic acid as reducing agent. Reductive alkylation using formaldehyde, hydrogen, and catalyst, usually nickel, is used commercially to prepare methylated amines. These tertiary amines are used to prepare quaternary ammonium salts. 

Quaternary ammonium alkyl ethers are prepared similarly an alkaline starch is reacted with a quaternary ammonium salt containing a 3-chloto-2-hydtoxyptopyl or 2,3-epoxyptopyl radical. Alternatively, such derivatives can be prepared by simple quaternization of tertiary aminoalkyl ethers by reaction with methyl iodide. Sulfonium (107) and phosphonium (108) starch salts have also been prepared and investigated. Further work has explained the synthesis of diethyl aminoethyl starch (109) as well as the production of cationic starches from the reaction of alkaline starch with... 

In the case of the bases derived from quaternary heterocyclic ammonium salts, the carbinolamines (5) can react as cyclic aldehyde-ammonias with many reagents with which the amino-aldehyde (7) could react. However, reactions of the carbinolamines which are not characteristic of amino-aldehydes are also known. Carbinolamines can easily be reconverted into the quaternary salts by the action of dilute acids, and they form alkyl ethers very easily with alcohols. If these last reactions do not occur, then this is convincing evidence for the base possessing the amino-aldehyde structure. However, if these reactions do occur this does not provide unambiguous confirmation of the carbinolamine structure. They are also given by the bi-molecular ethers (8), and, in the case of a tautomeric equilibrium... 

Diphenylisoinclole (29) can be prepared by a modified Leuckart reaction of o-dibenzoylbenzene (46), using an ammonium salt of formic acid the process is essentially a reductive alkylation of ammonia, accompanied by cyclization, and leads to 29 in 44% yield with ammonium formate, and 47 in 28% yield with methylammonium formate. 1,3-Diphenylisoindole. (29) can also be obtained in good yield by the reaction of 46 with 1,1-dimethylhydrazine. ... 

An alkyl halide 1 reacts with hexamethylenetetramine 2 to the quaternary ammonium salt 4, which crystallizes from the reaction mixture ... 

Generally the desired substituted carbonyl compound 3 is obtained after hydrolytic workup under acidic conditions. With simple alkyl halides an irreversible A-alkylation may take place as a side-reaction to give a quaternary ammonium salt 7 ... 

Ammonia and other amines are good nucleophiles in SN2 reactions. As a result, the simplest method of alkylamine synthesis is by Sn2 alkylation of ammonia or an alkylamine with an alky) halide. If ammonia is used, a primary amine results if a primary amine is used, a secondary amine results and so on. Even tertiary amines react rapidly with alkyl halides to yield quaternary ammonium salts, R4N+ X-... 

We ve already studied the two most general reactions of amines—alkylation and acylation. As we saw earlier in this chapter, primary, secondary, and tertiary amines can be alkylated by reaction with a primary alkyl halide. Alkylations of primary and secondary amines are difficult to control and often give mixtures of products, but tertiary amines are cleanly alkylated to give quaternary ammonium salts. Primary and secondary (but not tertiary) amines can also be acylated by nucleophilic acyl substitution reaction with an acid chloride or an acid anhydride to yield an amide (Sections 21.4 and 21.5). Note that overacylation of the nitrogen does not occur because the amide product is much less nucleophilic and less reactive than the starting amine. 

Arai and co-workers have used chiral ammonium salts 89 and 90 (Scheme 1.25) derived from cinchona alkaloids as phase-transfer catalysts for asymmetric Dar-zens reactions (Table 1.12). They obtained moderate enantioselectivities for the addition of cyclic 92 (Entries 4—6) [43] and acyclic 91 (Entries 1-3) chloroketones [44] to a range of alkyl and aromatic aldehydes [45] and also obtained moderate selectivities on treatment of chlorosulfone 93 with aromatic aldehydes (Entries 7-9) [46, 47]. Treatment of chlorosulfone 93 with ketones resulted in low enantioselectivities. 

Tertiary aliphatic amines are also cleaved by HI, but useful products are seldom obtained. Tertiary amines can be cleaved by reaction with phenyl chloroformate R3N -h ClCOOPh —> RCl 4- R2NCOOPh. a-Chloroethyl chloroformate behaves similarly.Alkyl halides may be formed when quaternary ammonium salts are heated R4N+X" R3N -)- RX. ... 

The higher solubility of several quaternary ammonium salts of glyphosate in polar aprotic organic solvents such as acetonitrile was discovered (2), which permitted their reaction in solution with various alkyl halides. For example, GLY(n-Bu4N)2H reacted with either o-xylylene dichloride or 1,5-dibromopentane to produce the interesting quaternary glyphosate derivatives 81 and 82, whose structures have been confirmed by x-ray analysis (2). 

Certain quaternary ammonium salts will alkylate [Co (DMG)2py] . The addition of PhCH2NMc3 I to a solution of the complex in methanol gives the PhCH2Co complex in 45% yield. The reaction works more slowly with dimethylpiperidinium iodide to give the CH3—Co complex 15). There is no alkylation with tertiary amines alone 164), but in the presence of equimolar amounts of dimethylacetylenedicarboxylate certain aliphatic tertiary amines can alkylate [Co (DMG)2py] in methanol solution. The reaction also produces the enamine derivative of a maleic ester, and the mechanism appears to involve addition of the amine to the triple bond to form an ammonium salt, which can then attack the Co(I) derivative (75). 

H). On the other hand, the synthesis of unsymmetricaUy iV,iV -substituted congeners is less straightforward as a functionalised imidazole has to be isolated prior to alkylation or arylation. Two main methods are available for imidazole functionaU-sation deprotonation with metalUc Na or K leading to an imidazoUde (I) followed by reaction with RX or reaction of glyoxal with a primary amine, an ammonium salt and formaldehyde (J). Al-functionalised imidazole can then be alkylated or... 

A thio-substituted, quaternary ammonium salt can be synthesized by the Michael addition of an alkyl thiol to acrylamide in the presence of benzyl trimethyl ammonium hydroxide as a catalyst [793-795]. The reaction leads to the crystallization of the adducts in essentially quantitative yield. Reduction of the amides by lithium aluminum hydride in tetrahydrofuran solution produces the desired amines, which are converted to desired halide by reaction of the methyl iodide with the amines. The inhibitor is useful in controlling corrosion such as that caused by CO2 and H2S. 

The nitrogen atom in quinolizidine derivatives behaves as a tertiary amine and hence it can undergo quaternization by reaction with alkyl halides. For instance, berberine derivative 101 was transformed into 102 by treatment with 3-iodopropanol followed by anion exchange. Compound 102 was then transformed into intermediate 103, which was employed as a precursor for the the preparation of bis-ammonium salt 104 (Scheme 10). This compound showed ultrashort curare-like activity in rhesus monkeys <2001JOC3495>. 

In the following example, although the synthesis of the azoniaspirocycle does not involve an acyclic compound, the reaction itself is very similar to those described in this section, hence its inclusion here (Equation 34). Maruoka and co-workers have designed a C2-symmetric chiral quarternary ammonium salt, which is then employed as a phase-transfer catalyst in an enantioselective alkylation <1999JA6519, 2001JFC(112)95, 2004TA1243>. 

Dithiophosphato metal complexes are usually prepared by metathesis of metal halides with alkali metal or ammonium salts. A convenient method uses the redox reaction of his th iophosphory 1 )d is ulfanes (RO)2(S)PSSP(S)(OR)2, with metal species in low oxidation states resulting in the insertion of the metal into the sulfur-sulfur bond.24 Recently it was used for the synthesis of long alkyl chain, liquid platinum(II) dithiophosphates25 and for the synthesis of Ru (CO)2[S2P(OPr%]2 from Ru3(CO)i2 with (Pr 0)2(S)PSSP(S)(0Pr,)2.26... 

In addition to substitution N-bromosuccinimide also forms addition compounds although in small amounts. Such addition reactions are catalysed by tetra-alkyl ammonium salts. Thus while with cyclohexene allylic substitution occurs, in presence of tetramethylammonium bromide, 1 2 dibromocyclohexane is obtained as the main product. 

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