Liquid ammonia neutralization reactions

The benzyl group has been widely used for the protection of hydroxyl functions in carbohydrate and nucleotide chemistry (C.M. McCloskey, 1957 C.B. Reese, 1965 B.E. Griffin, 1966). A common benzylation procedure involves heating with neat benzyl chloride and strong bases. A milder procedure is the reaction in DMF solution at room temperatiue with the aid of silver oxide (E. Reinefeld, 1971). Benzyl ethers are not affected by hydroxides and are stable towards oxidants (e.g. periodate, lead tetraacetate), LiAIH, amd weak acids. They are, however, readily cleaved in neutral solution at room temperature by palladium-catalyzed bydrogenolysis (S. Tejima, 1963) or by sodium in liquid ammonia or alcohols (E.J. Rcist, 1964). 

Ammonolysis of 2-chlorobenzothiazole in liquid ammonia was studied by Lemons et al. and found to be approximately first-order with respect to this substrate at the fairly high concentrations used. The actual nucleophilic reagent was, as expected, the neutral species NH3, and reaction via the amide ion NH2 arising from the autoprotolysis equilibrium [Eq. (5)] was excluded on the grounds that addition of ammonium chloride did not depress the reaction rate. In accordance with this interpretation and in connection with the existence of aromatic substitutions other than normal it is of interest that 2-chlorobenzothiazole was found to react difiFerently with sodamide, although the products were unidentified in this case. 

In about 250 cc of liquid ammonia (cooled with dry ice and acetone) are dissolved about 7.5 g of potassium and into the solution acetylene is passed until the blue color has disappeared (about 3 hours). Then slowly a solution or suspension of 3 g of estrone in 150 cc of benzene and 50 cc of ether is added. The freezing mixture is removed, the whole allowed to stand for about 2 hours and the solution further stirred overnight. Thereupon the reaction solution is treated with ice and water, acidified with sulfuric acid to an acid reaction to Congo red and the solution extracted five times with ether. The combined ether extracts are washed twice with water, once with 5% sodium carbonate solution and again with water until the washing water is neutral. Then the ether is evaporated, the residue dissolved in a little methanol and diluted with water. The separated product is recrystallized from aqueous methanol. The yield amounts to 2.77 g. The 17-ethiny I-estradiol-3,17 thus obtained melts at 142°C to 144°C . 

According to the Arrhenius theory of acids and bases, the acidic species in water is the solvated proton (which we write as H30+). This shows that the acidic species is the cation characteristic of the solvent. In water, the basic species is the anion characteristic of the solvent, OH-. By extending the Arrhenius definitions of acid and base to liquid ammonia, it becomes apparent from Eq. (10.3) that the acidic species is NH4+ and the basic species is Nl I,. It is apparent that any substance that leads to an increase in the concentration of NH4+ is an acid in liquid ammonia. A substance that leads to an increase in concentration of NH2- is a base in liquid ammonia. For other solvents, autoionization (if it occurs) leads to different ions, but in each case presumed ionization leads to a cation and an anion. Generalization of the nature of the acidic and basic species leads to the idea that in a solvent, the cation characteristic of the solvent is the acidic species and the anion characteristic of the solvent is the basic species. This is known as the solvent concept. Neutralization can be considered as the reaction of the cation and anion from the solvent. For example, the cation and anion react to produce unionized solvent ... 

When anisole is reduced by an alkali metal in liquid ammonia either a stable, conjugated diolefin or a less stable, unconjugated diolefin can be isolated, the latter being the product when the reaction mixture is neutralized with a strong acid such as ammonium chloride. The free ions, whether they are present to any great extent or not, are the resonance hybrid LXVI. 

The Arrhenius theory also has limitations for explaining certain reactions. For example, aqueous solutions of ammonia are basic. They react with acids in neutralization reactions, even though ammonia does not contain the hydroxide ion. Many aqueous solutions of salts with no hydroxide ions are basic, too. Some reactions take place without any liquid solvent. For example, ammonium chloride can be formed by the reaction between ammonia and hydrogen chloride, which are both gases ... 

Attempts to detect the uncharged intermediates 6-amino-4-phenyl-l,6-dihydro-4-phenylpyrimidine (66), 2-amino-4-phenyl-l, 2-dihydropyrimidine (68), and the aminodiazahexatriene 67, by recording the NMR spectra of the solution during the stepwise addition of the ammonium chloride were not successful. The facile ring opening of the pyrimidine ring in 66 is not unexpected. It has also been observed in the reaction of A-methylpyrimi-dinium salts with liquid ammonia, which also involves as neutral covalent... 

Study of the aminodeethoxylation with N-labeled liquid ammonia shows that in the 4-imino compound no incorporation of the label has taken place, proving that in the replacement of the ethoxy group no ring opening is involved. It is unknown whether the aminodeethoxylation occurs according to routes (a) and (b) in the a-adduct 22 or in the starting material 21, which is present in only a small equilibrium concentration with 22 (Scheme III.13). One can expect, however, that despite its low concentration, the aminodeethoxylation reaction takes place in the pyrimidinium salt 21, being more reactive towards to nucleophiles than the neutral adduct 22. 

Most effort over the electrochemical reduction of benzene hydrocarbons has centred on finding a reaction medium, which is also a better solvent for the substrate than liquid ammonia. Aliphatic amines have proved useful solvents and they may be used in an undivided electrochemical cell. Base is generated at the cathode while an equivalent of acid is generated in the anode reaction so that mixing of the cel contents maintains a neutral solution. An alcohol is usually added as a proton donor to prevent the build-up of a localised highly basic environment. The simultaneous anode reaction is oxidation of the amine. Electrodes of platinum, aluminium or graphite have been used. Under these conditions, benzene [38] is converted... 

Similar neutralization reactions occur with phosphoric, acetic and other acids. Liquid ammonia reacts with alkah metals forming amides and liberating H2. The reaction occurs in presence of a catalyst (e.g., Pt black). Alternatively, heating alkah metals in a stream of ammonia yields their amides. 

In a number of elimination reactions carried out in liquid ammonia, an alkali alkynylide is formed. In these cases the ammonia has to be removed completely or partly by evaporation before the acetylene is liberated by hydrolysing the reaction mixture. The beat produced in the remaining solid mass by this hydrolysis must be "neutralized efficiently and this is realized by adding a large amount of finely crushed ice over a very short period. For this reason, the reaction must be earned out in a wide-necked round-bottomed flask (fig. 8). Examples are the preparation of HOCOR and HC=CCH(OR>2 (Chap. IX, exps. 10 and 11). 

The neutral parent amido species [In(NH2)3] was synthesized by reaction of KNH2 with Ini, in liquid ammonia.Its manner of polymerization in the solid is unknown because diffraction studies were inconclusive as a result of crystal twinning. It was shown to decompose cleanly and quantitatively at moderate temperature to yield InN with liberation... 

There are three groups of substrates for which SNH reactions are especially characteristic (i) neutral azines and azoles (ii) azinium and azolium salts and (iii) nitro-arenes. Their electron-deficiency and, thus, their ability to react with nucleophiles strongly differ from each other. Azinium salts are the more electrophilic and are able to add even neutral nucleophiles very easily. Triazines,. v-tetrazines and polynitro-arenes also possess high electrophilicity. At the same time substrates such as pyridine (82JHC1285, 72JA682) and cinnoline (03CHE87), at a low temperature (e.g. in liquid ammonia as a solvent), do not react even with sodium amide. It should also be... 

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