With alkali amides

Mono-metallation of most simple acetylenic compounds in organic solvents can be accomplished without complications. The same holds for reactions of RCsCH with alkali amides in liquid ammonia. However, HCsCSiR3 and HC=CSnR3 cannot be metallated in this way, because the bonds between C and Si and between C and Sn are cleaved. HCsCSeR and HC=CPR2 disproportionate into HCsCH and RSeCsCSeR or R2PCsCPR2, respectively, under the influence of alkali amides [40,102],... 

In liquid ammonia with alkali amides, or in Et20 or THF with lithium dialkylamides, these complications do not occur, because these bases are considerably weaker than BuLi. 

Treatment of "skipped" enynes H CCH2CH=CHR with alkali amides presumably will lead to extensive isomerization into C>CCH=CHCH2R. With alkyllithium bases inverse addition has to be applied to avoid dimetallation. This isomerization reaction is likely to be even more serious in the case of the diynes HC=CCH2OCR, since the CH2-protons have kinetic acidities comparable with that of the ethynyl proton. 

For enyne ethers HC=CCH=CHOR, the 1,4-elimination with alkali amides is a very attractive method because the starting compounds ROCH2CsCCH2OR can be readily prepared from the commercially available butynediol... 

Since CH2CI2 is attacked by strong bases, this solvent has to be removed completely if the dehydrohalogenation is carried out with alkali amides or (-BuOK. 

Alkylation, of 2-acetamidothiazoles, 35, 37 with alkali amides, 34, 35 of alkylaminothiazole, 34 with alcohols, 47, 80, 90 of aminothiazoles, with alcohols, 38 with benzyl chloride. 33 with chloracetic acid, 33 with chloracetic esters, 33 with 3-chloropropionic acid, 33 with dimethylaminoethylchloride, 35 with ethylene oxide, 34, 38 with ethyl iodide, 33 with phenethyl chloride, 35 with 2-propynyl bromide. 32 in aprotic solvents, 35 of azothiazoles, 105... 

Alkali metal phenylhydrazines, ArN(Na)NH, which are prepared by the direct reaction of primary hydrazines with alkali amide in liquid... 

The degree of rearrangement in the amination of substituted halobenzenes with alkali amides is influenced by the position of the substituent, relative to the halogen. Whereas... 

Vinylic hydrogen atoms in strained ring systems have an increased acidity [65]. Cyclopropenes can be smoothly metallated with alkyllithium [66] (in the case of the unsubstituted hydrocarbon, addition across the double bond occurs), lithium dialkylamides in THF [9], or with alkali amides in liquid ammonia [16]. Whereas reaction of propene with strong bases results in the exclusive formation of the allylic derivative, the kinetically preferred process with 1-methylcyclopropene is vinylic deprotonation ... 

We have carried out the procedure for 1-methylcyclopropene several times with freshly prepared sodamide (see Chap. I, Exp. 7). In most cases the ratio of 1-methylcyclopropene to methylenecyclopropane was greater than 3, in one experiment even 10. The original paper reports the formation of almost pure 1-methylcyclopropene. The authors used commercial sodamide, which might be less reactive than the freshly prepared base, and therefore unable to cause isomerization. Since the protons in methylenecyclopropane are less acidic than the vinylic proton in 1-methylcyclopropene, the exocyclic isomer is not likely to interfere in metallation reactions with alkali amides in liquid ammonia or with LD A... 

Although a-metallated allenic thioethers are readily formed from the corresponding thioethers and strong bases, it is in general more practical to generate these intermediates from the isomeric acetylenic sulfides. This can be done either with butyllithium (or BuLi TMEDA) [9] in THF or with alkali amides in liquid ammonia [44] ... 

Treatment of Z-bis-thioethers RS—CH=CH—SR with alkali amides or organo-lithium result s in a smooth elimination of thiol with formation of metallated ethynyl sulfides M—C=C—SR [203]. If Z-bis(methylthio)ethene and the reactive basic system BuLi TMEDA in THF are allowed to interact at very low temperatures, no elimination occurs, but a precipitate of the lithio derivative is formed. It has a reasonable stability below — 100°C, thus permitting functionalizations... 

Metallation of Carboxylic Esters with Alkali Amides... 

Conjugated or skipped dienes and trienes undergo ionization with alkali amides in liquid ammonia. In the cases of allylbenzene, heptatriene, indene, and cyclopentadiene, the equilibrium RH + MNH2 RM +NH3 is probably completely on the right side (with M = Na or K), but the thermodynamic acidities of cyclohexadiene and pentadiene are probably very close to that of ammonia, so that metallation with alkali amides (even potassium amide) may be incomplete. 

With alkali amides in liquid ammonia, abstraction of a methylene or the methyne proton is the only process observed ... 

Dialkyl and alkyl arylsulfones are much more acidic than the corresponding sulfoxides. Interaction with alkali amides in liquid ammonia or LDA in THF-hexane mixtures gives rise to a complete metallation, but also butyllithium can be successfully used [2], e.g. ... 

A group with strong inductively withdrawing properties can cause a considerable increase of the acidity of a methyl proton if the CH3-group and this substituent are in suitable (ortho- or para-) relative positions. Compounds 15, for example, can be metallated with alkali amides in liquid ammonia or with LDA in organic solvents [13] ... 

Metallation of o- and /i-Tolunitrile with Alkali Amides in Liquid Ammonia and Alkali Diisopropylamide in THF-Hexane Mixtures... 

In the procedure described in this experiment, o- and p-tolunitrile are metallated with alkali amides in liquid ammonia and with KDA in THF and the intermediary anions alkylated with butyl bromide. Side-reactions such as selfcondensation or addition of the base across the C=N function only take place during the reactions with lithium amide, but to a lesser extent than with LDA in THF. 

Although we had good results in some subsequent reactions with alkyl halides, the metallation of imines by alkali amides has a limited applicability. We assume, on the basis of our results, that the pK values of the imines are close to that of ammonia. Thus, the reaction with alkali amides in this solvent will give rise to certain... 

Complete and fast metallation of nitriles RR CHC N (R and R =H, alkyl or aryl) is effected by alkali amides in liquid ammonia (see, for instance, Ref. [1]). Also N,A/-dialkylaminonitriles R2NCH(R )C=N (R = H, alkyl or aryl) react smoothly [2], In organic solvents, e.g., toluene, addition of the alkali amide across the C=N bond (formation of H—C—C(NH2)=NM) may seriously compete with the deprotonation [3], Attempts to metallate ally cyanides, H2C=CHCH2C=N, with alkali amides in liquid ammonia gave mainly resinous material [2]. 

Metallation of Nitriles with Alkali Amides in Liquid Ammonia... 

---