Ammonium salts elimination reactions

A second side reaction using this approach is the Hoffmann elimination of the sulfide or amine, during attempted deprotonation of the sulfonium or ammonium salt. This reaction is especially important in the case of ammonium ylides. Finally, another problem which surfaces during the deprotonation step is the formation of a mixture of ylides, e.g. (45) and (46) from (44), which undergo competing rearrangements to give (47) and (48 Scheme 12). ... 

Several limitations of this base-promoted rearrangement are worthy of mentioning (a) when structurally feasible, both Stevens and Sommelet-Hauser reactions will compete (b) certain substituents on the aromatic ring, e.g. Cl, CN, NO2, prevent the formation of the ylide and no rearrangement takes place (c) if a p-hydrogen is present on the ammonium salt, elimination becomes yet another undesirable side reaction, In an attempt to overcome these limitations, Sato has utilized the fluoride-induced desilylation of... 

Elimination of an amino group, NRj, is a difficult problem, whatever mechanism is involved. The typical pK of an amine, RjNH, is 35, so expulsion of RjN is unrealistic. If we need to do this, we must first make the amine into a quaternary ammonium salt, by reaction with methyl iodide. 

Amine activatitMi pathway has been well studied in catalysis by lanthanides, early transition metals, and alkali metals. In metal amide chemistry of late transition metals, there are mainly two pathways to synthesize metal amide complexes applicable under hydroamination conditions [54], One is oxidative addition of amines to produce a metal amide species bearing hydride (Scheme 8a). The other gives a metal amide species by deprotonation of an amine metal intermediate derived from the coordination of amines to metal center, and it often occurs as ammonium salt elimination by the second amine molecule (Scheme 8b). Although the latter type of amido metal species is rather limited in hydroamination by late transition metals, it is often proposed in the mechanism of palladium-catalyzed oxidative amination reaction, which terminates the catalytic cycle by p-hydride elimination [26]. Hydroamination through aminometallation with metal amide species demands at least two coordination sites on metal, one for amine coordination and another for C-C multiple bond coordination. Accordingly, there is a marked difference between the hydroamination via C-C multiple bond activation, which demands one coordination site on metal, and via amine activation. 

The first step of the reaction involves the formation of the S-C bond with the elimination of a molecule of ammonium salt. The fact that it has been possible to isolate the acyclic intermediate (176), R = Me or Ph, would confirm this hypothesis, particularly when the reaction is carried out for a short time in the cold in ethereal solution (27, 82). These intermediates (176) can be cyclized quantitatively on standing or on being treated by hydrochloric acid. However, no evidence has been advanced concerning their structures. 

Quaternary ammonium salts as we have seen are useful m synthetic organic chem istry as phase transfer catalysts In another more direct application quaternary ammo mum hydroxides are used as substrates m an elimination reaction to form alkenes... 

The amino functional group is not commonly encountered in steroid synthesis except perhaps in steroidal alkaloids. However, certain elimination reactions have been shown to have theoretical and limited preparative importance, largely due to the efforts of McKenna and co-workers. The Hofmann rule for 2 elimination predicts that alkaline elimination of quaternary ammonium salts will occur towards the carbon carrying the most hydrogen atoms cf. the converse Saytzeff orientation, above). In cyclohexyl systems, the requirement for diaxial elimination appears to be important, as in other 2 eliminations, and the Hofmann rule frequently is not obeyed [e.g., (116) (117)]. 

Quaternaiy ammonium salts, as we have seen, aie useful in synthetic organic chemistry as phase-transfer catalysts. In another, more direct application, quaternaiy ammonium hydroxides aie used as substrates in an elimination reaction to fonn alkenes. 

The reactions of (174) with various amines has been studied." " Hydrolysis of the hexamine salt of (174) gave not the symmetric diamine but (184) via a cyclic intermediate. The pyrolysis of 5-methyl-2-thenyltrimethyl ammonium hydroxide (185) is claimed to give (186) through a 1,6 Hofmann elimination reaction. The Bischler-Napieralski cyclization has been applied to acetyl derivatives of 2-(2-thienyl) ethylamine and 2-(3-thienyl) ethylamine for the preparation of sulfur analogs of isoquinoline. ... 

Amine oxides 2, which can be prepared by oxidation of amines 1, react upon heating to yield an olefin 3 and a hydroxylamine 4. This reaction is called the Cope elimination reaction,and as a synthetic method is a valuable alternative to the Hofmann degradation reaction of quaternary ammonium salts. 

The preparation of an alkene 3 from an amine 1 by application of a /3-elimination reaction is an important method in organic chemistry. A common procedure is the Hofmann elimination where the amine is first converted into a quaternary ammonium salt by exhaustive methylation. Another route for the conversion of amines to alkenes is offered by the Cope elimination. 

The Hofmann elimination reaction is not often used today in the laboratory, but analogous biological eliminations occur frequently, although usually with protonated ammonium ions rather than quaternary ammonium salts. In the biosynthesis of nucleic acids, for instance, a substance called adenylosuccinate... 

Calcium, iron, magnesium, alkali metals, and citrates do not affect the analysis. Ammonium salts interfere and must be eliminated by means of sodium nitrite or sodium hypobromite. The hydrochloric acid normally used in the analysis may be replaced by an equivalent amount of nitric acid without any influence on the course of the reaction. Sulphuric acid leads to high and erratic results and its use should be avoided. 

Syn elimination and the syn-anti dichotomy have also been found in open-chain systems, though to a lesser extent than in medium-ring compounds. For example, in the conversion of 3-hexyl-4-d-trimethylammonium ion to 3-hexene with potassium ec-butoxide, 67% of the reaction followed the syn-anti dichotomy. In general syn elimination in open-chain systems is only important in cases where certain types of steric effect are present. One such type is compounds in which substituents are found on both the P and the y carbons (the unprimed letter refers to the branch in which the elimination takes place). The factors that cause these results are not completely understood, but the following conformational effects have been proposed as a partial explanation. The two anti- and two syn-periplanar conformations are, for a quaternary ammonium salt ... 

The reaction of 5-[2-(iV,./V-dimethylamino)ethyl]-l,2,4-oxadiazole with methyl iodide forms the quaternary ammonium salt 170 (Scheme 22), which undergoes elimination in the presence of base (diisopropylethylamine (DIEA), TEA, l,8-diazabicyclo[4.3.0]undec-7-ene, etc.) to form an intermediate 5-vinyl-l,2,4-oxadiazole 171, which undergoes in situ Michael addition with nucleophiles to furnish the Michael adducts 172. As an example, also shown in Scheme 22, 3-hydroxy-pyrrolidine allows the synthesis of compound 172a in 97% yield. Mesylation followed by deprotonation of the 1,2,4-oxadiazole methylene at C-5 enables Sn2 displacement of the mesylate to give the 5-azabicycloheptyl derivative 173, which is a potent muscarinic agonist <1996JOC3228>. 

Trithiophosphonic acids (RPS3H2) are thermally unstable compounds, undergoing decomposition reactions at temperatures sometimes as low as — 10°C depending upon the electronic and steric properties of the R substituent. Decomposition usually occurs via a condensation reaction (similar to that observed for dithiophosphinic acids - Equation 21) to give the di-thiadiphosphatene disulfide and eliminate H2S (Equation 35).48 Similar to dithiophosphinic acids, their metal and ammonium salts are far more thermally stable and are therefore the preferred synthetic target in most cases. 

Ammonia is evolved here in the condensation process of melamine to melam whereas the respective ammonium salts are evolved in the case of the hydrobromide and nitrate. Reactions 9 and 9b show that ammonia should be neutralised by pyrosulphuric acid groups. In TG we have found that diammonium pyrosulphate eliminates ammonia above 350 C, with however complete decomposition ... 

Additional work was carried out by the GE group on optimization of the reaction yield and to eliminate unwanted linear oligomers [14], Three side reactions which interfere with synthesis of cyclics were identified reaction of the amine with acid chloride to form an acyl ammonium salt, followed by decomposition to an amide (Equation (3.2)) reaction with CH2CI2 to form a salt (Equation (3.3)) hydrolysis of the acid chloride, forming carboxylate via catalysis... 

The ammonium catalyst can also influence the reaction path and higher yields of the desired product may result, as the side reactions are eliminated. In some cases, the structure of the quaternary ammonium cation may control the product ratio with potentially tautomeric systems as, for example, with the alkylation of 2-naph-thol under basic conditions. The use of tetramethylammonium bromide leads to predominant C-alkylation at the 1-position, as a result of the strong ion-pair binding of the hard quaternary ammonium cation with the hard oxy anion, whereas with the more bulky tetra-n-butylammonium bromide O-alkylation occurs, as the binding between the cation and the oxygen centre is weaker [11], Similar effects have been observed in the alkylation of methylene ketones [e.g. 12, 13]. The stereochemistry of the Darzen s reaction and of the base-initiated formation of cyclopropanes under two-phase conditions is influenced by the presence or absence of quaternary ammonium salts [e.g. 14], whereas chiral quaternary ammonium salts are capable of influencing the enantioselectivity of several nucleophilic reactions (Chapter 12). 

The dehydrohalogenation of 1- or 2-haloalkanes, in particular of l-bromo-2-phenylethane, has been studied in considerable detail [1-9]. Less active haloalkanes react only in the presence of specific quaternary ammonium salts and frequently require stoichiometric amounts of the catalyst, particularly when Triton B is used [ 1, 2]. Elimination follows zero order kinetics [7] and can take place in the absence of base, for example, styrene, equivalent in concentration to that of the added catalyst, is obtained when 1-bromo-2-phenylethane is heated at 100°C with tetra-n-butyl-ammonium bromide [8], The reaction is reversible and 1-bromo-l-phenylethane is detected at 145°C [8]. From this evidence it is postulated that the elimination follows a reverse transfer mechanism (see Chapter 1) [5]. The liquidrliquid two-phase p-elimination from 1-bromo-2-phenylethanes is low yielding and extremely slow, compared with the PEG-catalysed reaction [4]. In contrast, solid potassium hydroxide and tetra-n-butylammonium bromide in f-butanol effects a 73% conversion in 24 hours or, in the absence of a solvent, over 4 hours [3] extended reaction times lead to polymerization of the resulting styrene. 

In an interesting catalysed conversion of trichloroethene by secondary amines into aminoacetamides, the initial steps are thought to involve the p-elimination of HC1 to produce dichloroethyne (Scheme 9.1), which reacts with the secondary amine under the wet conditions to produce the amide [35] the reaction does not work with N-alkylanilines. Such a mechanism is realistic, as it is well known [36] that trichloroethene is converted into the inflammable and explosive dichloroethyne by bases, and quaternary ammonium salts catalyse the formation of the alkyne when trichloroethene is reacted with oxiranes [37]. Chloroethynes have also been obtained by the catalysed reaction of terminal ethynes with carbon tetrachloride under basic conditions [38]. 

The same authors did not observe intramolecular cyclization by the coupling reaction of the ammonium cation and the carboxylate anion, at least in their work [81]. The presence of elimination reactions of the ammonium salt should not be ruled out, at least at high temperatures. 

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