Lithium methoxide formation

Formation of Lithium Methoxide and Butane in the polymerization of MMA with BuLi(7c,14). Pndeuterated MMA was polymerized in toluene with BuLi and the reaction was terminated by a small amount of acetic acid. The reaction mixture was analyzed for methanol and butane by gas-liquid chromatography (Table V). The amount of... 

Fig. 6. Formation of lithium methoxide in the polymerization of methylmethacrylate (0.125 molar) in toluene at—30 . Initiator O 3.2 x 10 molar diphenyl-bexyllithium, 3.85 X 10 molar butyllithium...

It is reported that isotactic polymer is formed from styrene polymerized by butyllithium in hydrocarbon solvents at low temperatures (7,51). The formation of isotactic polymers is however dependent on the presence of adventitious lithium hydroxide caused by part of the catalyst being destroyed by moisture (125). No isotactic polymer is formed in rigorously purified systems and the microstructure is in fact fairly highly syndiotactic (10). Lithium methoxide or isobutoxide do not induce isotactic polymer formation. 

The structure of the hydrocarbon group also affects reactions leading to the start of polymerization. Initiation by butyllithium leads to the rapid formation of a relatively large amount of lithium methoxide, whereas by the reaction of diphenylhexyllithium with methyl methacrylate only a small amount of methoxide is formed slowly in both cases, the reaction proceeds according to scheme (36) or by cyclization or termination of the active centres [170] by 1,2 addition [i. e. again in analogy to reaction (36)]... 

Some indications of what may be happening are gained from analysis of the acetic acid terminated products at various reaction times (Fig. 18). With butyllithium initiation a large amount of methanol (based on initiator) can be isolated at very short reaction times, whereas in the diphenylhexyllithium initiated process only a slower and smaller methanol formation is observed. Now this must correspond to lithium methoxide formed either directly in step (20), or in the termination of product (20), or from the cyclization reaction, or from termination of active chains [177] in reaction (21),... 

Several methyl 2-cyclopropylacetate derivatives were converted to the corresponding methyl 2-azido-2-cyclopropylacetates by treating the starting material with lithium or potassium hexa-methyldisilazanide, followed by 2,4,6-triisopropylbenzenesulfonyl (trisyl) azide and acetic acid. F or example, formation of 1. It is noteworthy that treatment of the methyl 2-azido-2-cyclopropylacetates with lithium methoxide afforded the corresponding 2-iminoacetates in good yield. " ... 

Lithium alkyls initiate polymerization of polar monomers like methyl-methacrylate, vinyl pyridine, acrylo-nitrile, etc. However, these reactions are more complex. The desired addition to the C=C bond is accompanied by other processes, e.g., attack on the -COOEt group with the formation of ketones and lithium methoxide, or in vinyl pyridine polymerization by the metalation of the pyridine moiety. 

Non-aqueous conductiometric titration has been used181 to determine trialkylsilyl phosphates and bis(trialkylsilyl)sulphates. Methanol, ethanol, butanol, acetone, ethyl methyl ketone, nitromethane, nitrobenzene, methyl cyanide, dimethylformamide, tetra-hydrofuran, butyl acetate and ethyl formate were used as solvents, and methanolic sodium, potassium and lithium methoxides and tetraethylammonium hydroxide as titrants. For the phosphates, characteristic curves were obtained only in nitromethane and methyl cyanide. Titrating in nitromethane with 0.15 N-methanolic potassium methoxide gave the best results. Alcohols, ketones, nitromethane and methyl cyanide were... 

Some abnormalities were reported in the initiations of methyl methacrylate polymerizations in toluene by butyllithium. Their nature is such that they suggest the possibility of more than one reaction taking place simultaneously. One, which must be the major one, is that of the oiganomet-allic compound reacting with the carbon-to-carbon double bond as shown above. The other, minor one, may be with the carbon-to-oxygen double bond. The major reaction produces methyl methacrylate anions. The minor reaction, however, yields butyl isopropenyl ketone with an accompanying formation of lithium methoxide ... 

Lithium methoxide does not initiate polymerizations of methyl methacrylate. The ketone molecules, however, react with carbanions on the growing chain. The resultant anions are less reactive than methyl methacrylate anions and can only add new methyl methacrylate monomers slowly. Once added, however, the reaction proceeds at a normal rate. Polymerizations of methyl methacrylate in polar solvents, on the other hand, proceed in what might be described as an ideal manner with formations of only one kind of ion pair. ... 

In 1996 Castanet et al. developed a CO-free procedure for the oxidative carbonylation of alkenes [32]. Instead of a MeOH/CO mixture, methyl formate was used in the presence of a Pd VCu system and unsaturated esters were produced in one step. During the reaction, methyl formate acted as the source of both alcohol and CO, but an initial partial pressure of CO was required in order to obtain high yields. Moreover, they demonstrated that by the addition of lithium methoxide, the handling of CO could be avoided. 

More than two decades after the preparation of a large nnmber of the so-caUed alkoxo salts by Meerwein and Bersin in 1929, U Al(OPr )4 4 was synthesized in 1952 by Albers et al. and evidence for the formation of M U(OEt)6 n (M = Na, Ca, Al) was obtained by Jones et al in 1956. Similarly, formation of a number of anionic methoxide species was indicated in the potentiometric titrations of chlorides of metals (B, Al, Ti, Nb, Ta) with lithium methoxide in methanol by Gut in 1964. Ludman and Waddington studied the conductometric titrations of a wide variety of Lewis acids with basic metal methoxides and reported the formation of alkoxo salts of the type KB(OMe)4 and K3Fe(OMe)e. Schloder and Protzer also synthesized a number of bimetallic alkoxides of aluminium with the formulae, MAl(OMe)4 and M Al(OMe)4 2 where M and M are alkali and alkaline earth metals respectively. 

C) this white precipitate dissolves with slow formation of another white precipitate of lithium methoxide. The pure organoborane is isolated by decantation of the liquid from the insoluble lithium methoxide and removal of the solvent (Chart 23.3) [1]. It is necessary that the stoichiometry of the B-OMe-9-BBN is carefully controlled to achieve high yields. 

Firestone and Christensen (1973) employed phenyllithium rather than lithium methoxide to achieve direct introduction. Penicillin G benzyl ester (81), when reacted with phenyllithium in THF at -78 C, followed by /ert-butyl hypochlorite and finally quenched with methanol, gave 6a-methoxypenicillin G benzyl ester (82). Analogously, quenching of the acylimine intermediate with water or triethylammonium formate gave 83 and 84, respectively. Hydrogenolysis of these materials was achieved with 10% Pd-C, NaHCOj, and methanol-water, at 40 psi. The resulting sodium salts exhibited markedly lower antimicrobial activity than 37. A major by-product always formed in these conversions was assigned structure 85. 

Considerable effort has been expended in exploring the scope of ke-tenimine formation as it pertains to the introduction of 7(6)-methoxy substituents. Carrol et al. (1974) reported the facile construction of ke-tenimines derived from penicillin G and demonstrated deuterium incorporation at C-6 by base-catalyzed exchange of a related imino chloride. Workers at Sankyo later reported a method (Sugimura et al., 1976) by which an imine 145 was produced from an a-haloimino chloride (144) via base-catalyzed 1,4-elimination. The resulting imine was stereospe-cifically converted to methoxyketenimine 146 by the addition of meth-oxide anion (—78°C). Exposure to lithium methoxide at -20°C then led to iminoether 147, which was transformed to amide 148 by a new reaction with trimethylchlorosilane and I equiv of quinoline. 

Formation of Bis(trimethylsilyl)methyllithium. The carbon-silicon bond of tris(trimethylsilyl)methane can be cleaved by lithium methoxide in HMPA to formbis(trimethylsilyl)methyl-lithium, which subsequently reacts with carbonyl compounds to form alkenes (eq 4). ... 

The reaction between ethyl Hthiopropiolate and the N-acylpyridinium salt formed by reaction of 4-methoxy-3-methyl-5-(triisopropylsilyl)pyridine 2363 with (+)-frafis-2-(a-cumyl)-cyclohexyl chloroformate (TCC chloro-formate) was the starting point in the synthesis of (-l-)-aUopumihotoxin 267A (1718) by Comins et al. (Scheme 301). The dihydropyridone product (—)- 2364 was obtained diastereoselectively (>96%) before hydrogenation to the saturated ester (+)-2365. However, some epimerization of the methyl substituent was apparent after cleavage of the TCC carbamate with lithium methoxide and cyclization to the indolizidinone (—)-2366 (dr 8 1). Acetoxylation at C-8 with lead tetraacetate was stereoselective, and introduced the acetate from the axial direction, possibly by stereoelec-tronicaUy-controUed intramolecular transfer of acetate from a lead—enol intermediate. The acetoxy product (—)-2367 was protodesilylated with formic acid, after which a one-pot tandem reduction with K-Selectride followed by hthium aluminum hydride gave diol (- -)-2368 with complete... 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

Fithium tetrahydroaluminate, Fluoroamides, 0075 Lithium tetrahydroaluminate, Water, 0075 Lithium, 1,2-Diaminoethane, Tetralin, 4675 Magnesium, Barium carbonate, Water, 4685 Maleic anhydride, Bases, or Cations, 1400 Mercaptoacetonitrile, 0763 t Methanol, Hydrogen, Raney nickel catalyst, 0482 4-Methoxy-3-nitrobenzoyl chloride, 2911 Methoxyacetyl chloride, 1161 t Methyl formate, Methanol, Sodium methoxide, 0830 3-Methyl-2-penten-4-yn-l-ol, 2378 Nitric acid, 4430... 

The described behaviour of both initiators can be interpreted by the preferential reaction of diphenylhexyllithium according to scheme (34) and of butyl-lithium according to scheme (36). The subsequent phases of macromolecule formation are affected by the liberated methoxide. 

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