Alkyl metal hydroxide

Solid super bases, prepared by successive treatment of y-alumina with alkali metal hydroxide and alkali metal, are highly active catalysts for reactions involving reactive carbanions, and have been commercialised by Sumitomo (Suzukamo et al, 1997). For example, t.vobutylbenzene, the. starting material for ibuprofen (see earlier) is produced by side-chain alkylation of toluene with propylene over a K/KOH/AI2O3 catalyst (Eqn. (14)). 

In the general context of donor/acceptor formulation, the carbonyl derivatives (especially ketones) are utilized as electron acceptors in a wide variety of reactions such as additions with Grignard reagents, alkyl metals, enolates (aldol condensation), hydroxide (Cannizzaro reaction), alkoxides (Meerwein-Pondorff-Verley reduction), thiolates, phenolates, etc. reduction to alcohols with lithium aluminum hydride, sodium borohydride, trialkyltin hydrides, etc. and cyloadditions with electron-rich olefins (Paterno-Buchi reaction), acetylenes, and dienes.46... 

As far as propargyl thioethers are concerned, the substrates in this section follow all the principles discussed for propargyl ethers and propargylamines in the two preceding sections. For alkyl propargyl thioethers typical bases used are sodium amide in liquid ammonia, alcoholate or alkali metal hydroxide [178, 186-189, 191, 287-291], and again some derivatives of carbohydrates have been used successfully [292, 293], If an ester group is also present in the molecule, the reaction can be accompanied by a hydrolysis to the carboxylate [294]. 

The catalysed A/-alkylation of the potassium salt of sulphoximines in l, 2-dimethoxyethane produces yields in excess of 90% [48]. Similarly, azacrown ethers have been synthesized by alkylation of bis(tosyIamino)alkyl ethers under catalysed basic two-phase conditions [49] (Scheme 5.12). The yields of the cyclic products (Table 5.24) are influenced by the choice of the alkali metal hydroxide employed, suggesting that there is a degree of template control in the ring closure step. This is not the case in the analogous reaction of p-toluenesulphonamide with a, co-dihaloalkanes [50], which leads to the formation of a mixture of l l and 2 2 cyclic products... 

The presence of three nitro groups on the aromatic ring of picryl chloride makes the chloro group extremely reactive towards nucleophiles. Picryl chloride (87) is hydrolyzed to picric acid (4) in the presence of hot water or aqueous sodium hydroxide. Aminolysis of picryl chloride in the presence of primary and secondary amines is complete in minutes at room temperature. Picryl chloride is therefore a very useful starting material for the synthesis of a range of other picryl derivatives. The reaction of picryl chloride (87) with ammonia can be used to synthesize 2,4,6-trinitroaniline (53) (picramide). Treatment of picryl chloride with alcohols under reflux forms picric acid and the alkyl chloride of the corresponding alcohol, whereas the same reaction in the presence of alkali metal hydroxides, or the alkoxide anion of... 

The total yield of 2-vinylpyridine formed from 2-methylpyridine can be as high as 90%. 2-Vinylpyridine may also be obtained in almost quantitative yields by heating 2-alkylaminopyridine derivatives (which are directly available by cobalt catalysis) with a supported (e.g., AI2O3) alkali metal hydroxide [Eq.(8) R = R = alkyl, cyloalkyl, etc., RR N = heterocycle] (76SZP14399 78MI1). 

The anionic polymerization of epoxides such as ethylene and propylene oxides can be initiated by metal hydroxides, alkoxides, oxides, and amides as well as metal alkyls and aryls, including radical-anion species such as sodium naphthalene [Boileau, 1989 Dreyfuss and Drefyfuss, 1976 Inoue and Aida, 1984 Ishii and Sakai, 1969]. Thus the polymerization of ethylene oxide by M+A involves initiation... 

The anionic polymerization of cyclic siloxanes can be initiated by alkali metal hydroxides, alkyls, and alkoxides, silanolates such as potassium trimethylsilanoate, (CH3)3SiOK, and other bases. Both initiation... 

Alkyl halides undergo Sn2 reactions with a variety of nucleophiles, e.g. metal hydroxides (NaOH or KOH), metal alkoxides (NaOR or KOR) or metal cyanides (NaCN or KCN), to produce alcohols, ethers or nitriles, respectively. They react with metal amides (NaNH2) or NH3, 1° amines and 2° amines to give 1°, 2° or 3° amines, respectively. Alkyl halides react with metal acetylides (R C=CNa), metal azides (NaN3) and metal carboxylate (R C02Na) to produce internal alkynes, azides and esters, respectively. Most of these transformations are limited to primary alkyl halides (see Section 5.5.2). Higher alkyl halides tend to react via elimination. 

We have already learnt that alkyl halides react with alcohols and metal hydroxide (NaOH or KOH) to give ethers and alcohols, respectively. Depending on the alkyl halides and the reaction conditions, both S l and Sn2 reactions can occur. Alkyl halides undergo a variety of transformation through Sn2 reactions with a wide range of nucleophiles (alkoxides, cyanides, acetylides, alkynides, amides and carboxylates) to produce other functional groups. 

A further possibility for side-chain alkylation of toluene is oxidative methylation with methane. Catalysts with occluded alkali metal oxides, prepared by impregnating zeolites with alkali metal hydroxides followed by calcination, usually exhibit better performance.441 Further enhancement was achieved by impregnating ion-exchanged zeolites 442 Significant improvements in stability and the yields of Cg hydrocarbons were also observed when NaX was impregnated with 13% MgO which was found to increase the amounts of active sites.443... 

The reactions of C02 with metal-hydroxides, -alkoxides, and -amides to provide metallobicarbonates, -alkyl carbonates, and -carbamates [Eqs. (27)—(29)] in general do not involve activation of carbon dioxide by prior coordination to the metal center. These processes generally entail either... 

Bis(alkylideniminoxy)ethanes (124,128,131,135,140) are of potential value, particularly as chelating ligands for metal cations. A special investigation has been undertaken in order to increase their yields in the reaction of ketoximes with dichloroethane (88ZOR2538). As a result, special conditions have been found which allow l,2-bis(organylideniminoxy)ethanes to be synthesized from oximes of dialkyl or alkyl aryl (hetaryl) ketoximes and 1,2-dichloroethane and an alkali metal hydroxide suspension in DMSO in yields up to 78%. 

Alkali metal salts of the O-alkyl dithiocarbonates (e.g. RO-CS-SeK , the xanthates) are prepared by the reaction of carbon disulphide with an alcohol and an alkali metal hydroxide. 

Metal-based asymmetric phase-transfer catalysts have mainly been used to catalyze two carbon-carbon bond-forming reactions (1) the asymmetric alkylation of amino acid-derived enolates and (2) Darzens condensations [5]. The alkylation ofprochiral glycine or alanine derivatives [3] is a popular and successful strategy for the preparation of acyclic a-amino acids and a-methyl-a-amino acids respectively (Scheme 8.1). In order to facilitate the generation of these enolates and to protect the amine substituent, an imine moiety is used to increase the acidity of the a-hydrogens, and therefore allow the use of relatively mild bases (such as metal hydroxides) to achieve the alkylation. In the case of a prochiral glycine-derived imine (Scheme 8.1 R3 = H), if monoalkylation is desired, the new chiral methine group... 

Lactams or related cyclic, conformationally fixed amides are more readily N-alkylated than acyclic amides [96], As illustrated by the examples in Scheme 6.23, structurally elaborate alkylating agents can be used to alkylate lactams. During the workup of such reactions it should be kept in mind that four- and six-membered lactams are readily hydrolyzed by aqueous base (Scheme 3.8), and most lactams are also readily hydrolyzed by aqueous acids. Prolonged treatment of lactams with alkali metal hydroxides or acids during the work-up should therefore be avoided. 

Halogenated compounds such as bis(alkyl ether)tetrabromobisphenol A or decabromodiphenyl oxide (DECA) may be used as flame-retardants for polyolefin foams, eventually using antimony oxide, metal oxides, boric acid salts, and metal hydroxides as synergist.92 For example Weil and Levchik93 reported that using suitable amounts of DECA and Sb203, polyethylene foams rated UL94 HF-1 are obtained. 

Most metal alkyls react vigorously (some explosively) with water to produce a hydrocarbon and a metal hydroxide. Typical reactions are the following ... 

Preparation of gem-Dinitroalkanes. A methanolic solution of alkali metal hydroxide (Li, Na, or K) was treated with 10% excess nitroalkane and stirred for 30 minutes. The solution was evaporated to dryness in vacuo, and the alkali metal alkyl nitronate was aned over phosphorus pentoxide at reduced pressure (0.1 mm.) for 24 hours. (Caution nitronate salts may be shock sensitive and have been known to explode after prolonged storage.) A slurry of 3.3 grams (0.02 mole) of lithium 1-nitro-cyclohexane in 50 ml. of acetonitrile was cooled to —40°C., and 2.7 grams (0.02 mole) of nitronium tetrafluoroborate were slowly added. The reaction was not exothermic, and the reaction mixture turned brilliant blue upon adding nitronium tetrafluoroborate. The reaction mixture was stirred for 2 hours at —30° to —40°C., then filtered to give a quantitative yield of lithium tetrafluoroborate. The filtrate was quenched into 100... 

Allyl bromide, methyl iodide and benzyl bromide are the triumvirate of common alkyl halides that alkylate metal alkoxides readily. In the case of phenols, potassium carbonate [Scheme 4.230]438 or cesium carbonate are competent bases whereas primary and secondary alcohols require potassium hydroxide [Scheme 4.231J,402 but the strongly basic conditions limit the scope of the method. For example, attempts to alkylate the secondary and phenolic hydroxyl groups of the intermediate 232.1 in a synthesis of the antibiotic Nogalamycin using the traditional metal alkoxide alkylation failed owing to competing sec-... 

Thiols are more acidic than the corresponding alcohols and are converted into their salts using alkali metal hydroxides or alkoxides. The thiolate salts are powerful nucleophiles, a property which has been used in the cleavage of methyl esters and methyl ethers. The combination of a hard acid and a soft base such as lithium propanethiolate (Li SPr) may favour attack on the methyl group of an ester and lead to alkyl-oxygen fission of the ester, rather than the more common addition of a nucleophile to the carbonyl group and consequently acyl-oxygen fission. This is particularly useful in the hydrolysis of hindered esters. 

The deprotonation can be achieved using solid or aqueous alkali metal hydroxides, or sodium hydride in DMF or acetonitrile. The approach has, however, only limited synthetic application to unsymmetrically substituted imidazoles which give mixtures on alkylation. Quatemization (see later) can... 

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