Lithium methods

The alkyl lithium method gives high yields of -olefins from 17-ketones via the tosylhydrazones. A -Olefins are formed from 6- and 7-ketones. (Compare with the Bamford-Stevens reaction which gives A - and A -olefins, respectively.) In the presence of an excess of alkyl lithium, alkylation may occur. 

B. J. Wakefield, Best Synthetic Methods Organo-lithium Methods I, p 38, Academic, London 1988. 

Formyl-3-thienyl Methyl Tellurium3 (Organo Lithium Method) A mixture of 55 mmol of butyl lithium and... 

Formyl-3-thienyl Methyl Tellurium (Organo Lithium Method) A mixture of 55 mmol of butyl lithium and 7.8 g (50 mmol) of 4-formylthiophcnc ethylene acetal in diethyl ether is cooled at — 78° for 20 min. A solution of 14.5 g (50 mmol) of dimethyl ditellurium in diethyl ether is added dropwise until the orange color of the ditellurium persists in the mixture. The mixture is allowed to warm to 20° and is then poured onto ice/water. The product is extracted with diethyl ether, the extract is dried with anhydrous magnesium sulfate, filtered, the solvent is distilled from the filtrate and the residue is distilled under vacuum yield 6.3 g (50%) b.p. 120°/0.8 torr m.p. 55°. 

Three units of the sterically crowded substituent, 2,4,6-(CF3)3CgH2, have been introduced by the lithium method on the bismuth atom to form 5 (equation 7). ... 

It can be prepared by addition of an ethyl group to 2,6-dimethylpyrazine (0.7) with the alkyl-lithium method described by Klein and Spoerri (1951). 

An active titanium metal can be prepared by reaction of TiCIa slurried in THF or DME with potassium or lithium (method of Rieke, 4, 315). 

A problem in the conventional process resides in the difficulty in removing the b5 roduct sodium chloride from resins by washing, since sodium chloride is insoluble in the solvents, such as NMP, and incorporated in the resins. A process using a lithium salt instead of the sodium salt is attracting attention as a process for overcoming this problem. Lithium chloride is produced as a side product in the polymerization reaction. It is soluble in many of the aprotic organic solvents, such as NMP. Therefore, it is relatively easy to reduce the hthium content in the resin. However, lithium is far more expensive than sodium, so it is essential to recover and to reuse the lithium. Methods to recycle the lithium have been proposed. ... 

Only a small proportion of the salt added to water for cooking foods is eaten. A value of 24% was obtained by the lithium method for the average intake per head of the purchased cooking salt used in cooking in the UK. The only other data using traditional methods come from Hungary where 41% of the salt purchased by households was actually ingested. 

Boron forms a whole series of hydrides. The simplest of these is diborane, BjH. It may be prepared by the reduction of boron trichloride in ether by lithium aluminium hydride. This is a general method for the preparation of non-metallic hydrides. 

To meet the needs of the advanced students, preparations have now been included to illustrate, for example, reduction by lithium aluminium hydride and by the Meerwein-Ponndorf-Verley method, oxidation by selenium dioxide and by periodate, the Michael, Hoesch, Leuckart and Doebner-Miller Reactions, the Knorr pyrrole and the Hantzsch collidine syntheses, various Free Radical reactions, the Pinacol-Pinacolone, Beckmann and Arbusov Rearrangements, and the Bart and the Meyer Reactions, together with many others. 

Trimethylene dibromide (Section 111,35) is easily prepared from commercial trimethj lene glycol, whilst hexamethylene dibromide (1 O dibromohexane) is obtained by the red P - Br reaction upon the glycol 1 6-hexanediol is prepared by the reduction of diethyl adipate (sodium and alcohol lithium aluminium hydride or copper-chromium oxide and hydrogen under pressure). Penta-methylene dibromide (1 5-dibromopentane) is readily produced by the red P-Brj method from the commercially available 1 5 pentanediol or tetra-hydropyran (Section 111,37). Pentamethylene dibromide is also formed by the action of phosphorus pentabromide upon benzoyl piperidine (I) (from benzoyl chloride and piperidine) ... 

That means that this method is a neat little way one can get the ever lovely MDEA (Methylenedioxyethyl amphetamine, the softer cousin of X). Strike hears you asking So if one uses lithium tri-methylborohydride can one get methamphetamine out of that nitro group . Good question. Unfortunately the answer is no. The authors say Interestingly, N-alkylated products were not produced when other alkylborohydrides were used." Fair enough. Here s the recipe ... 

With Phenylpropanolamine at hand (or ephedrine and pseudo-ephedrine) one would next need to reduce that alpha carbon OH group to get the final amine. Strike understands that the current favorite methods for doing this involve lithium and amine. HI and red P or other iodine related protocols. So when you meth heads ruin every aspect of those methods as well, what will you do then The following are a couple of OH reduction methods (Strike thinks) that have applicable use [99-100]. 

Treatment of geminal dihalocyclopropyl compounds with a strong base such as butyl lithium has been for several years the most versatile method for cumulenes. The dihalo compounds are easily obtained by addition of dihalocarbenes to double--bond systems If the dihalocyclopropanes are reacted at low temperatures with alkyllithium, a cyclopropane carbenoid is formed, which in general decomposes above -40 to -50°C to afford the cumulene. Although at present a number of alternative methods are available , the above-mentioned synthesis is the only suitable one for cyclic cumulenes [e.g. 1,2-cyclononadiene and 1,2,3-cyclodecatriene] and substituted non-cyclic cumulenes [e.g. (CH3)2C=C=C=C(CH3)2]. 

In the first method a secondary acetylenic bromide is warmed in THF with an equivalent amount of copper(I) cyanide. We found that a small amount of anhydrous lithium bromide is necessary to effect solubilization of the copper cyanide. Primary acetylenic bromides, RCECCH Br, under these conditions afford mainly the acetylenic nitriles, RCsCCHjCsN (see Chapter VIII). The aqueous procedure for the allenic nitriles is more attractive, in our opinion, because only a catalytic amount of copper cyanide is required the reaction of the acetylenic bromide with the KClV.CuCN complex is faster than the reaction with KCN. Excellent yields of allenic nitriles can be obtained if the potassium cyanide is added at a moderate rate during the reaction. Excess of KCN has to be avoided, as it causes resinifi-cation of the allenic nitrile. In the case of propargyl bromide 1,1-substitution may also occur, but the propargyl cyanide immediately isomerizes under the influence of the potassium cyanide. 

There are a wide variety of methods for introduction of substituents at C3. Since this is the preferred site for electrophilic substitution, direct alkylation and acylation procedures are often effective. Even mild electrophiles such as alkenes with EW substituents can react at the 3-position of the indole ring. Techniques for preparation of 3-lithioindoles, usually by halogen-metal exchange, have been developed and this provides access not only to the lithium reagents but also to other organometallic reagents derived from them. The 3-position is also reactive toward electrophilic mercuration. 

Reduction with sodium in alcohol was unsuccessful (54). The introduction of lithium aluminium hydride has provided an elegant method for the reduction of thiazole esters to hydroxythiazoles for example, ethyl 2-methyl-4-thiazolecarboxylate (11 with lithium aluminium hydride in diethyl ether gives 2-methyl-4-(hydroxymethyl)thiazole (12) in 66 to 69% yield (Scheme 7) (53),... 

For most laboratory scale reductions of aldehydes and ketones catalytic hydro genation has been replaced by methods based on metal hydride reducing agents The two most common reagents are sodium borohydride and lithium aluminum hydride... 

In contrast to alcohols with their nch chemical reactivity ethers (compounds contain mg a C—O—C unit) undergo relatively few chemical reactions As you saw when we discussed Grignard reagents m Chapter 14 and lithium aluminum hydride reduc tions m Chapter 15 this lack of reactivity of ethers makes them valuable as solvents m a number of synthetically important transformations In the present chapter you will learn of the conditions m which an ether linkage acts as a functional group as well as the methods by which ethers are prepared... 

Reduction to alcohols (Section 15 2) Aide hydes are reduced to primary alcohols and ketones are reduced to secondary alcohols by a variety of reducing agents Catalytic hydrogenation over a metal catalyst and reduction with sodium borohydride or lithium aluminum hydride are general methods... 

Reduction of an azide a nitrile or a nitro compound furnishes a primary amine A method that provides access to primary secondary or tertiary amines is reduction of the carbonyl group of an amide by lithium aluminum hydride... 

Ammonium and Lithium Fluoroborates. Ammonia reacts with fluoroboric acid to produce ammonium fluoroborate (53). An alternative method is the fusion of ammonium bifluoride and boric acid (54) ... 

Trifluoroethanol was first prepared by the catalytic reduction of trifluoroacetic anhydride [407-25-0] (58). Other methods iaclude the catalytic hydrogeaatioa of trifluoroacetamide [354-38-1] (59), the lithium aluminum hydride reductioa of trifluoroacetyl chloride [354-32-5] (60) or of trifluoroacetic acid or its esters (61,62), and the acetolysis of 2-chloro-l,l,l-trifluoroethane [75-88-7] followed by hydrolysis (60). More recently, the hydrogenation of... 

Several alternative methods followed this early work. In one, aromati2ation is effected by treating the ketal of androstadienedione with the radical anion obtained from lithium and diphenyl in refluxing tetrahydrofuran. Diphenylmethane is added to quench the methyllithium produced from the... 

Preparation. Commercial manufacture of LiAlH uses the original synthetic method (44), ie, addition of a diethyl ether solution of aluminum chloride to a slurry of lithium hydride (Fig. 2). 

Quantitative Analysis of All llithium Initiator Solutions. Solutions of alkyUithium compounds frequentiy show turbidity associated with the formation of lithium alkoxides by oxidation reactions or lithium hydroxide by reaction with moisture. Although these species contribute to the total basicity of the solution as determined by simple acid titration, they do not react with allyhc and henzylic chlorides or ethylene dibromide rapidly in ether solvents. This difference is the basis for the double titration method of determining the amount of active carbon-bound lithium reagent in a given sample (55,56). Thus the amount of carbon-bound lithium is calculated from the difference between the total amount of base determined by acid titration and the amount of base remaining after the solution reacts with either benzyl chloride, allyl chloride, or ethylene dibromide. 

From the time that isoprene was isolated from the pyrolysis products of natural mbber (1), scientific researchers have been attempting to reverse the process. In 1879, Bouchardat prepared a synthetic mbbery product by treating isoprene with hydrochloric acid (2). It was not until 1954—1955 that methods were found to prepare a high i i -polyisoprene which dupHcates the stmcture of natural mbber. In one method (3,4) a Ziegler-type catalyst of tri alkyl aluminum and titanium tetrachloride was used to polymerize isoprene in an air-free, moisture-free hydrocarbon solvent to an all i7j -l,4-polyisoprene. A polyisoprene with 90% 1,4-units was synthesized with lithium catalysts as early as 1949 (5). 

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