Lithium aromatics

Crystallisable salts and related compounds. Almost all crystallisable catalysts, such as sodium and lithium aromatic compounds (e.g. sodium naphthalide), -oyl salts such as aroyl hexafluorophosphates, alkoxides, and many others can be prepared in a vacuum system and then purified by repeated crystallisations and washings in a closed system (see Chapter 5) thereafter they can be distributed into breakable phials or other devices as described in Chapter 3. 

The other structures all represent cases in which the Group IV element is interacting with 3 lithium atoms, and in each case a three-dimensional lithium aggregate is formed. The lithium-lithium and lithium-carbon distances are summarized in Table VIII for those structures that have been determined. In addition, lithium-carbon distances in several lithium-aromatic ion pair systems are included in Table VIII for comparison (18, 19), as well as the observed distances in the hexamer of trimethylsilyllithium. In the dimeric molecule, the Li—Li distance of... 

These systems nitrate aromatie eompounds by a proeess of electro-philie substitution, the eharacter of whieh is now understood in some detail ( 6.1). It should be noted, however, that some of them ean eause nitration and various other reactions by less well understood processes. Among sueh nitrations that of nitration via nitrosation is especially important when the aromatic substrate is a reactive one ( 4.3). In reaetion with lithium nitrate in aeetie anhydride, or with fuming nitrie aeid, quinoline gives a small yield of 3-nitroquinoline this untypieal orientation (ef. 10.4.2 ) may be a eonsequenee of nitration following nucleophilic addition. ... 

The effects of added species. The rate of nitration of benzene, according to a rate law kinetically of the first order in the concentration of aromatic, was reduced by sodium nitrate, a concentration of io mol 1 of the latter retarding nitration by a factor of about Lithium nitrate... 

The kinetics of the nitration of benzene, toluene and mesitylene in mixtures prepared from nitric acid and acetic anhydride have been studied by Hartshorn and Thompson. Under zeroth order conditions, the dependence of the rate of nitration of mesitylene on the stoichiometric concentrations of nitric acid, acetic acid and lithium nitrate were found to be as described in section 5.3.5. When the conditions were such that the rate depended upon the first power of the concentration of the aromatic substrate, the first order rate constant was found to vary with the stoichiometric concentration of nitric acid as shown on the graph below. An approximately third order dependence on this quantity was found with mesitylene and toluene, but with benzene, increasing the stoichiometric concentration of nitric acid caused a change to an approximately second order dependence. Relative reactivities, however, were found to be insensitive... 

Finally the chemical aromatization of Ring A which occurs in nature in the biosynthesis of estrogens must be mentioned. It can be done by thermal cleavage of the C-19 methyl group in 1,4-dien-3-ones (H.H. Inhoffen, 1940 C. Djerassi, 1950) and was later achieved at lower temperatures with lithium — biphenyl in THF (H.L. Dryden, Jr., 1964). 

Technora. In 1985, Teijin Ltd. introduced Technora fiber, previously known as HM-50, into the high performance fiber market. Technora is based on the 1 1 copolyterephthalamide of 3,4 -diaminodiphenyl ether and/ -phenylenediamine (8). Technora is a whoUy aromatic copolyamide of PPT, modified with a crankshaft-shaped comonomer, which results in the formation of isotropic solutions that then become anisotropic during the shear alignment during spinning. The polymer is synthesized by the low temperature polymerization of/ -phenylenediamine, 3,4 -diaminophenyl ether, and terephthaloyl chloride in an amide solvent containing a small amount of an alkaU salt. Calcium chloride or lithium chloride is used as the alkaU salt. The solvents used are hexamethylphosphoramide (HMPA), A/-methyl-2-pyrrohdinone (NMP), and dimethyl acetamide (DMAc). The stmcture of Technora is as follows ... 

Aromatic radical anions, such as lithium naphthalene or sodium naphthalene, are efficient difunctional initiators (eqs. 6,7) (3,20,64). However, the necessity of using polar solvents for their formation and use limits their utility for diene polymerization, since the unique abiUty of lithium to provide high 1,4-polydiene microstmcture is lost in polar media (1,33,34,57,63,64). Consequentiy, a significant research challenge has been to discover a hydrocarbon-soluble dilithium initiator which would initiate the polymerization of styrene and diene monomers to form monomodal a, CO-dianionic polymers at rates which are faster or comparable to the rates of polymerization, ie, to form narrow molecular weight distribution polymers (61,65,66). 

AletalHydrides. Metal hydrides can sometimes be used to prepare amines by reduction of various functional groups, but they are seldom the preferred method. Most metal hydrides do not reduce nitro compounds at all (64), although aUphatic nitro compounds can be reduced to amines with lithium aluminum hydride. When aromatic amines are reduced with this reagent, a2o compounds are produced. Nitriles, on the other hand, can be reduced to amines with lithium aluminum hydride or sodium borohydride under certain conditions. Other functional groups which can be reduced to amines using metal hydrides include amides, oximes, isocyanates, isothiocyanates, and a2ides (64). 

Sulfonic acids are prone to reduction with iodine [7553-56-2] in the presence of triphenylphosphine [603-35-0] to produce the corresponding iodides. This type of reduction is also facile with alkyl sulfonates (16). Aromatic sulfonic acids may also be reduced electrochemicaHy to give the parent arene. However, sulfonic acids, when reduced with iodine and phosphoms [7723-14-0] produce thiols (qv). Amination of sulfonates has also been reported, in which the carbon—sulfur bond is cleaved (17). Ortho-Hthiation of sulfonic acid lithium salts has proven to be a useful technique for organic syntheses, but has Httie commercial importance. Optically active sulfonates have been used in asymmetric syntheses to selectively O-alkylate alcohols and phenols, typically on a laboratory scale. Aromatic sulfonates are cleaved, ie, desulfonated, by uv radiation to give the parent aromatic compound and a coupling product of the aromatic compound, as shown, where Ar represents an aryl group (18). 

Aromatic polysulfites can be produced if bisphenols, eg, bisphenol A, are heated with diphenyl sulfite in the presence of lithium hydride (112). Halosulfates and Halosulfites. A general method for the preparation of alkyl halosulfates and halosulfites is the treatment of the alcohol with sulfuryl or thionyl chloride at low temperatures while passing an inert gas through the mixture to remove hydrogen chloride (113). 

A novel method for preparing amino heterocycles is illustrated by the preparation of 2-amino-5-methylthiophene (159). In this approach vinyl azides act as NH2 equivalents in reaction with aromatic or heteroaromatic lithium derivatives (82TL699). A further variant for the preparation of amino heterocycles is by azide reduction the latter compounds are obtained by reaction of lithio derivatives with p- toluenesulfonyl azide and decomposition of the resulting lithium salt with tetrasodium pyrophosphate (Scheme 66) (82JOC3177). 

An aiyl methane- or toluenesulfonate ester is stable to reduction with lithium aluminum hydride, to the acidic conditions used for nitration of an aromatic ring (HNO3/HOAC), and to the high temperatures (200-250°) of an Ullman reaction. Aiyl sulfonate esters, formed by reaction of a phenol with a sulfonyl chloride in pyridine or aqueous sodium hydroxide, are cleaved by warming in aqueous sodium hydroxide. ... 

Hydroxymethylferrocene has been made by condensing ferrocene with N-methylformanilide to give ferrocenecarboxalde-hyde, and reducing the latter with lithium aluminum hydride, sodium borohydride, or formaldehyde and alkali. The present procedure is based on the method of Lindsay and Hauser. A similar procedure has been used to convert gramine methiodide to 3-hydroxymethylindole, and the method could probably be used to prepare other hydroxymethyl aromatic compounds. 

The rates of the reactions of several aromatic ketones with alkyllithium reagents have been examined. The reaction of 2,4-dimethyl-4 -(methylthio)benzophenone with methyl-lithium in ether exhibits the rate expression ... 

The styrene double bond in 9(ll)-dehydroestradiol 3-methyI ether (1) or its 8-dehydro counterpart is reduced by potassium or lithium in ammonia without affecting the aromatic ring estradiol 3-methyl ether (2) is formed from both compounds. Reduction of the corresponding 17-ketones occurs with partial or complete reduction of the carbonyl group. Lithium... 

Krapcho and Bothner-By made additional findings that are valuable ii understanding the Birch reduction. The relative rates of reduction o benzene by lithium, sodium and potassium (ethanol as proton donor) wer found to be approximately 180 1 0.5. In addition, they found that ben zene is reduced fourteen times more rapidly when methanol is the protoi donor than when /-butyl alcohol is used. Finally, the relative rates of reduc tion of various simple aromatic compounds by lithium were deteiTnined these data are given in Table 1-2. Taken together, the above data sho that the rate of a given Birch reduction is strikingly controlled by the meta... 

Various other observations of Krapcho and Bothner-By are accommodated by the radical-anion reduction mechanism. Thus, the position of the initial equilibrium [Eq. (3g)] would be expected to be determined by the reduction potential of the metal and the oxidation potential of the aromatic compound. In spite of small differences in their reduction potentials, lithium, sodium, potassium and calcium afford sufficiently high concentrations of the radical-anion so that all four metals can effect Birch reductions. The few compounds for which comparative data are available are reduced in nearly identical yields by the four metals. However, lithium ion can coordinate strongly with the radical-anion, unlike sodium and potassium ions, and consequently equilibrium (3g) for lithium is shifted considerably... 

A major advance in the art of effecting Birch reductions was the discovery by Wilds and Nelson that lithium reduced aromatic steroids much more efficiently than had hitherto been possible with sodium or potassium. The superiority originally was attributed to the somewhat higher reduction potential of lithium as compared to the other alkali metals. Later work showed that the following explanation is more probable. ... 

A remarkable feature of the Birch reduction of estradiol 3-methyl ether derivatives, as well as of other metal-ammonia reductions, is the extreme rapidity of reaction. Sodium and -butyl alcohol, a metal-alcohol combination having a comparatively slow rate of reduction, effects the reduction of estradiol 3-methyl ether to the extent of 96% in 5 minutes at —33° lithium also effects complete reduction under the same conditions as is to be expected. Shorter reaction times were not studied. At —70°, reduction with sodium occurs to the extent of 56 % in 5 minutes, although reduction with lithium is virtually complete (96%) in the same time. (The slow rates of reduction of compounds of the 5-methoxytetralin type is exemplified by 5-methoxy-tetralin itself with sodium and f-butyl alcohol reduction occurs to the extent of only 50% in 6 hours vs. 99+% with lithium.) The iron catalyzed reaction of sodium with alcohols must be very fast since it competes so well with the rapid Birch reduction. One cannot compensate for the presence of iron in a Birch reduction mixture containing sodium by adding additional metal to extend the reaction time. The iron catalyzed sodium-alcohol reaction is sufficiently rapid that the aromatic steroid still remains largely unreduced. 

Aromatic steroids are virtually insoluble in liquid ammonia and a cosolvent must be added to solubilize them or reduction will not occur. Ether, ethylene glycol dimethyl ether, dioxane and tetrahydrofuran have been used and, of these, tetrahydrofuran is the preferred solvent. Although dioxane is often a better solvent for steroids at room temperature, it freezes at 12° and its solvent effectiveness in ammonia is diminished. Tetrahydrofuran is infinitely miscible with liquid ammonia, but the addition of lithium to a 1 1 mixture causes the separation of two liquid phases, one blue and one colorless, together with the separation of a lithium-ammonia bronze phase. Thus tetrahydrofuran and lithium depress the solubilities of each other in ammonia. A tetrahydrofuran-ammonia mixture containing much over 50 % of tetrahydrofuran does not become blue when lithium is added. In general, a 1 1 ratio of ammonia to organic solvents represents a reasonable compromise between maximum solubility of steroid and dissolution of the metal with ionization. 

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