Ammonia dipolar aprotic solvent

The use of dimethyl sulphoxide as a dipolar aprotic solvent is well known,7 and the present method can be regarded as a model procedure and has been applied to the preparation of a number of N-w-alkyl-pyrroles and N-w-alkyl indoles.8 The yield of N-benzylindole is considerably higher than in previously reported preparations and is as good as that reported for the preparation of N-methylindole in liquid ammonia.4 The present method is, however, less laborious and quicker to carry out. Very high yields are obtained in reactions using w-alkyl halides and moderately good yields with secondary alkyl halides. The reactions should be compared with those recently reported for pyrryl-thallium.9... 

The transformation termed propargylic rearrangement attracted much attention, and detailed discussions are available in review papers.134-141 Suitable reagents to bring about this rearrangement are metal alkoxides and metal amides in alcohols and dipolar aprotic solvents (DMSO, HMPT), and metal amides in ammonia. Reactivities are strongly dependent on the base employed, the solvent, and the reaction conditions. 

The principles underlying the N- alkylation of indoles are the same as those for pyrroles (67T3771). Development of synthetic techniques for maximizing yields has resulted in procedures using dipolar aprotic solvents, crown ether and phase transfer catalysis, as well as reactions in liquid ammonia. These techniques are illustrated by some representative examples given in Table 8. 

A comparison of the suitability of solvents for use in Srn 1 reactions was made in benzenoid systems46 and in heteroaromatic systems.47 The marked dependence of solvent effect on the nature of the aromatic substrate, the nucleophile, its counterion and the temperature at which the reaction is carried out, however, often make comparisons difficult. Bunnett and coworkers46 chose to study the reaction of iodoben-zene with potassium diethyl phosphite, sodium benzenethiolate, the potassium enolate of acetone, and lithium r-butylamide. From extensive data based on the reactions with K+ (EtO)2PO (an extremely reactive nucleophile in Srn 1 reactions and a relatively weak base) the solvents of choice (based on yields of diethyl phenylphosphonate, given in parentheses) were found to be liquid ammonia (96%), acetonitrile (94%), r-butyl alcohol (74%), DMSO (68%), DMF (63%), DME (56%) and DMA (53%). The powerful dipolar aprotic solvents HMPA (4%), sulfolane (20%) and NMP (10%) were found not to be suitable. A similar but more discriminating trend was found in reactions of iodobenzene with the other nucleophilic salts listed above.46 Nearly comparable suitability of liquid ammonia and DMSO have been found with other substrate/nucleophile combinations. For example, the reaction of p-iodotoluene with Ph2P (equation (14) gives 89% and 78% isolated yields (of the corresponding phosphine oxide) in liquid ammonia and DMSO respectively.4 ... 

The acetylide so formed can be directly alkylated to an internal acetylene without work-up. A further advantage of dehydrohalogenation of vinyl halides with NaNH in liquid ammonia or in a dipolar aprotic solvent (e.g. DMSO) is that both the cis and trans haloolehns furnish the acetylene, in contrast to reaction with oxygen bases (see Section II.A.2, equation 19). Bromoolefins 9 and cis-10 are converted to... 

MeO , OH , or EtO and methyl fluoride, anisole, and 4-fluoroanisole on the gas-phase 5 2 reactions between dimethylmethylphosphonate and methylformate and HOO versus HO , MeO , or EtO in an attempt to discover the origin of the O -effect on the Sf 2 reaction of carbanions with 4-substituted benzyl chlorides in liquid ammonia " on the solvolysis reaction and the 2 reaction between phenoxide ions, and both neutral and negatively charged amines and 4-substituted benzyl chlorides in liquid ammonia on the ionization rates (the step) of the 5" 1 reactions of many substituted trityl halides and carboxylates in aqueous acetone and in aqueous and pure acetonitrile in the presence of piperidine on the ionization rates ( i) of the 5 reactions of various diarylmethyl chlorides in the presence of piperidine, pyridine, or PPh3 in several dipolar aprotic solvents on the solvolyses of X,Y-substituted benzhydryl acetates in various aqueous MeOH and EtOH solutions and on the dispersions observed in Grunwald-Winstein correlations of 5 solvolyses of substrates with substituents containing adjacent tt-electrons. ... 

The high volatility of liquid ammonia, which makes it easily separable from water, makes it a potentially attractive alternative to the conventional dipolar aprotic solvents. 

The success of carbonates depends on the full deprotonation of pronucleophile Nu-H by liberated alkoxide anion. Otherwise, attack of alkoxide on the cationic i7 -allylpalladium(n) complex would afford aUyl ethers, and this is sometimes a side reaction. Allylation of nucleophiles by allylic carbonates is customarily carried out in more or less polar aprotic solvents (THF, DMSO, DMF), and less frequently in dichloromethane, toluene, and even in water. The orders of acidity in dipolar aprotic solvents and in water are quite different, and this should be taken into account to know the position of the acid-base equilibrium. Lists of pA values in DMSO are availablc. - Orders of acidities in THF and in DMSO are probably not different. Examples of pA (DMSO) are MeCOCH2COOEt (14.4), CH2(COOEt)2 (16.4), PhOH (18.0), methanol (29.0), aniline (30.6), water (31.2), and ammonia (estimated 40). 

For the VNS reaction to proceed satisfactorily, the carbanions should be in the form of loose ion pairs when they form tight ion pairs or aggregates with countercations, the addition does not proceed. The most convenient base-solvent systems are therefore f-BuOK, NaOH, or NaH in dipolar aprotic solvents, such as DMF, DMSO, or their mixtures with THF. An excellent solvent for this reaction is liquid ammonia. According to stoichiometry of the reaction, the base should be used in an excess. In majority of cases, the reaction is carried ont preferably at low temperatures of-20to-70°C [35]. 

Ji et al. (2010,2012) discuss a number of types of reactions of organic substances in liquid ammonia, and provide many references to recent and earlier work. They compare the equilibrium constants of phenols and carbonyl-activated carbon adds in ammonia and water, and describe work that is part of an ongoing study of the kinetics of a variety of reactions, including aromatic substitutions and solvolyses in ammonia. They point out that owing to its weakness as an add and as a hydrogen-bond donor, in many respects ammonia behaves as a dipolar aprotic solvent. It solvates cations strongly, but anions hardly at all (Marcus, 1983,1985). The low value of the autoprotolysis constant ( 10 at -33°C) is chiefly due to the weakness of ammonia as an acid. The mobility of the NH ion in liquid ammonia is not anomalous (Lagowski,... 

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