Potassium Amide in Liquid Ammonia

Apparatus 21 round-bottomed, one-necked flask (without stirrer) and 2 1 round-bottomed three-necked flask, equipped with a funnel containing a plug of glass wool. 

The required amount of ferric nitrate is considerably less than that necessary for the preparation of the other alkali amides, possibly because potassium amide is soluble, and thus the zero-valent iron is not inactivated by adsorption. 

Before cutting, the lumps of potassium (10-20 g each) are freed from paraffin oil by means of a tissue. To compensate for some loss due to the presence of thin oxide crusts, 41 g instead of 1 mol is weighed, then immediately cut and the pieces put into a beaker containing 100-150 ml of dry diethyl ether. Potassium which has been stored for a very long time may contain a thick crust of oxide. 

This can be removed by means of scissors. It is advisable to carry out this operation before removal of the paraffin oil this protects the metal against oxidation. After the introduction of the potassium into the ammonia, the diethyl ether containing minute pieces of metal, has to be removed in our opinion the safest way is to pour the ether away on a piece of waste ground. Addition of f-butylalcohol to the ether does not give sufficient guarantee that the potassium is destroyed, since the potassium particles may be covered by t-butoxide when the ether is poured into the waste container, the particles may react with the other material in the container, causing fire hazards. 

No frothing will occur in contrast to the preparation of lithium amide the heat of dissolution of potassium (to K+ and e ) is less than that of lithium. 

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The enyne system in the amines 828=88-8 8-882 can be reversed by potassium amide in liquid ammonia. Addition of the enyne amines to an equivalent amount of this reagent gives the potassium acetylides, K-8e8-88=88-8R2, from which the ynene" amines can be obtained in excellent yields by addition of solid ammonium chloride. 

Cyanopyrazole is obtained from treatment of 4-amino-3-halopyridazines with potassium amide in liquid ammonia, while 4-amino-3,6-dihalopyridazines are rearranged under the same conditions to 3-cyanomethyl-l,2,4-triazole. 

In a series of reactions with potassium amide in liquid ammonia, 6-chloropyrido[2,3-f)]pyrazine gave reduction and ring contraction (Section 2.15.13.3), the 6-bromo analogue underwent only reduction, whilst the 6-fluoro derivative gave only the 6-amino substitution product (79JHC305). 

Reactions with strongly basic nucleophiles such as potassium amide in liquid ammonia may prove much more complex than direct substitution. 2-Chloro-4,6,7-triphenylpteridine reacts under these conditions via an S ANRORC mechanism to form 2-amino-4,6,7-triphenylpteridine and the dechlorinated analogue (78TL2021). The attack of the nucleophile exclusively at C-4 is thereby in good accord with the general observation that the presence of a chloro substituent on a carbon position adjacent to a ring nitrogen activates the position meta to the chlorine atom for amide attack. 

An earlier report (126) which assigned the irons configuration to the enamine (175) derived from the cyanamine (176) upon reaction with potassium amide in liquid ammonia has been questioned by Munk and Kim (725). They also have doubts about the structures (177 and 178) proposed for the products obtained by the reduction of acetonitrile with sodium (727). 

Arynes are intermediates in certain reactions of aromatic compounds, especially in some nucleophilic substitution reactions. They are generated by abstraction of atoms or atomic groups from adjacent positions in the nucleus and react as strong electrophiles and as dienophiles in fast addition reactions. An example of a reaction occurring via an aryne is the amination of o-chlorotoluene (1) with potassium amide in liquid ammonia. According to the mechanism given, the intermediate 3-methylbenzyne (2) is first formed and subsequent addition of ammonia to the triple bond yields o-amino-toluene (3) and m-aminotoluene (4). It was found that partial rearrangement of the ortho to the meta isomer actually occurs. 

Evidence for symmetrical intermediates such as benzyne cannot be established by quantitative analysis of the reaction mixture unless a labelled starting substance is used. By applying labeling techniques, Roberts and his collaborators obtained results which indicated that benzyne (13) occurs as an intermediate in the amination of chlorobenzene with potassium amide in liquid ammonia. From chlorobenzene-1-C (12) about equal amounts of anUine-l-C (14) and aniline-2-C (15) were formed. More or less probable alternative... 

The amination of 2-chloropyridine-A-oxide (53) with potassium amide in liquid ammonia yielded a mixture of 2-(55) and 3-amino-pyridine-A-oxide (56) in 5-10% total yield.This rearrangement might be explained by an aryne mechanism involving 2,3-pyridyne-A-oxide (54). Since the structure of 56, with its quaternary nitrogen atom, is more analogous to that of 3-methoxybenzyne (39) than to that of 2,3-pyridyne (26), an orientation effect directing the amide ion to C-3 can be expected here. 

In an extensive investigation of the behavior of halogeno-pyridines and -quinolines towards potassium amide in liquid ammonia, tendencies to react according to the hetaryne type and other mechanisms were compared. The following results may be mentioned. 3-Fluoropyridine does not react via 3,4-pyridyne, but yields fluoro derivatives of 4,4 - and 2,4 -bipyridine. 3,6-Dibromopyridine is converted first into 6-bromo-3,4-pyridyne and not into 6-amino-3-bromopyridine. 2-Bromoquinoline yields 2-methylquinazoline together with 2-aminoquinohne. ... 

Cf. the formation of o-diaminobenzene from m-aminobromobenzene and of m-diaminobenzene from p-aminobromobenzene by the action of potassium amide in liquid ammonia (unpublished result of G. B. R. de Graaff, W. C. Melger, and H. J. den Hertog). 

This pyridine-pyrimidine ring transformation has also been observed on treatment of 2-bromoquinoline with potassium amide in liquid ammonia, 2-methylquinazoline being obtained (67RTC187). Similarly, 8-bromo-l,7-phenanthroline gives 2-methyl-l,3,5-triazaphenanthrene (83JHC447)... 

The carbanion 5, formed from V,V-diethyl-5-phenyl-3//-azepin-2-amine (4) with potassium amide in liquid ammonia, or with lithium 2,2,6,6-tetramethylpiperidide in tetrahydrofuran, is thiolated by dialkyl or diaryl disulfides to yield 3-(alkylsulfanyl)-3//-azepines, e.g. 6.38... 

It is important to learn if the same intermediate forms in several reactions, for if so its identity will very likely be manifest by the common features that can be observed. Here is an example cited by Bunnett.6 It was suspected that the reaction of chlorobenzene with potassium amide in liquid ammonia occurs by way of benzyne. Experiments were done with a I4C label (blackened) at the 1-position.14 The reaction gives equal amounts of aniline-1-14C and aniline-2-l4C,... 

Both the a- and a -hydrogens of dibenzyl sulfone were shown to be ionized by means of two equivalents of potassium amide in liquid ammonia. ... 

Like thallium(I) amide from which it is derived by treatment with potassium amide in liquid ammonia, the ammoniated salt (x = 2 or less) explodes violently on heating, friction, or contact with dilute acids or water. 

The [S2N2H] anion (22) is formed by the treatment of S4N4H4 with potassium amide in liquid ammonia.76 Although the [S2N2II] anion has not been isolated as an ionic salt, numerous metal complexes in which 22 acts as a bidentate (S,N) ligand are known. 

Cyanobenzocyclobutene has been prepared from sodium cyanide and 1-bromobenzocyclobutene,5 formed by reaction of benzocyclobutene with N-bromosuccinimide,6 and by ring closure of o-chlorohydrocinnamonitrile with potassium amide in liquid ammonia.7 The present procedure is a modification of the latter method and was previously described by one of the submitters.8... 

It is possible to illustrate the kinetics of anionic polymerisation by the polymerisation of styrene with potassium amide in liquid ammonia. The first step involves the bread-down of initiators into ions. 

The brief survey of various catalysts for the isomerization of vinylnorbomene 408 into ethylidenenorbomene 394 as well as the effectiveness of potassium amide in liquid ammonia for this purpose were described (equation 192)250. One step in the synthesis... 

In a similar way, Kim and Bunnett (1970) demonstrated that the substitution of amino group for iodine in iodotrimethylbenzene proceeds via the ion-radical mechanism, in contrast to the bromo and chloro analogs. The reaction of 5- and 6-halo-l,2,4-trimethylbenzenes with potassium amide in liquid ammonia gives rise to 5- and 6-aminoderivatives. This is the cine-substitution reaction (see Scheme 4.12). 

Amination of 2-chloro-, 2-bromo-, and 2-iodopyridine with potassium amide in liquid ammonia gave exclusively 2-aminopyridine. In this case an Addition-Mimination mechanism (Sn(AE) mechanism) has been proposed. The intermediacy of 2,3-pyridyne was considered to be highly unlikely (65AHC121). 

When 2-chloro-5-nitropyridine reacted with potassium amide in liquid ammonia at -33°C, a mixture of compounds was obtained as main prod-... 

It is of interest to mention that 2-bromoquinoIine, when treated with potassium amide in liquid ammonia, reacts very differently from 3-bromoisoquinoline hardly any 2-aminoquinoline is obtained, but as main product 2-methylquinazoline has been isolated (65RTC1569 67RTC187). This ring transformation involves breaking of the bond between C-3 and C-4 in the covalent o-amino adduct at C-4 (Scheme II.IO). Since this ring transformation cannot be considered degenerate, it is beyond the scope of this book to discuss this reaction in more detail. 

As we have seen in Section II,A, 6-bromo-4-phenylpyrimidine reacts on treatment with potassium amide in liquid ammonia at -75°C into the corresponding 6-amino compound nearly quantitatively according to the Sn(ANRORC) mechanism (71RTC1239). Extensive investigations have been carried out on the scope and limitations of this mechanism and on the several factors that influence the occurrence of the Sn(ANRORC) mechanism in the aminodehalogenation of 4-substituted-6-halogenopyrimidines. 

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