Alkylations ferf-butoxide

Similarly, sodium methoxide (NaOCHj) is a suitable base and is used in methyl alcohol. Potassium hydroxide in ethyl alcohol is another base-solvent combination often employed in the dehydrohalogenation of alkyl halides. Potassium ferf-butoxide [K0C(CH3)3] is the prefened base when the alkyl halide is primary it is used in either terf-butyl alcohol or dimethyl sulfoxide as solvent. 

If, however, the base itself is a crowded one, such as potassium ferf-butoxide, even primary alkyl halides undergo elimination rather than substitution ... 

As a practical matter, elimination can always be made to occur quantitatively. Strong bases, especially bulky ones such as ferf-butoxide ion, react even with primary alkyl halides by an E2 process at elevated temperatures. The more difficult task is to find conditions that promote substitution. In general, the best approach is to choose conditions that favor the SN2 mechanism—an unhindered substrate, a good nucleophile that is not strongly basic, and the lowest practical temperature consistent with reasonable reaction rates. 

Exercise 8-26 a. Why is potassium ferf-butoxide, KOC(CH3)3, an excellent base for promoting elimination reactions of alkyl halides, whereas ethylamine, CH3CH2NH2, is relatively poor for the same purpose ... 

Use of a Bulky Base If the substrate is prone to substitution, a bulky base can minimize the amount of substitution. Large alkyl groups on a bulky base hinder its approach to attack a carbon atom (substitution), yet it can easily abstract a proton (elimination). Some of the bulky strong bases commonly used for elimination are ferf-butoxide ion, diisopropylamine, triethylamine, and 2,6-dimethylpyridine. 

Alkali metal salts with nucleophilic anions are notably good initiators for chloral anionic polymerization (Fig. 26). The most studied initiator is lithium ferf-butoxide. When 0.2 mole % of lithium ferf-butoxide (based on chloral) was added to neat chloral monomer at 60°C the alkoxide (CH3)3C0CH(CCl3)0 Li was formed instantaneously, but no further addition of chloral occurred. This reaction was observed by an NMR study of the system and confirmed by the chemical reactions of the product alkoxide, which acted as the initiator. Tertiary amines such as pyridine and NR3 where R is an alkyl group have been found to be good initiators for chloral polymerization. They are slower initiators than lithium... 

The application of strong bases to hydrocarbons which contain a sp3 hybridized carbon and a conjugated system may abstract a proton and form a fully conjugated carbanion. This reaction has several synonyms such as deprotonation, proton abstraction or metalation reactions. The most common bases are alkyl lithium derivatives, e.g., butyl lithium21 24). Sometimes the addition of tetramethylethylenediamine (TMEDA) or potassium ferf-butoxide is required especially when dianions and polyanions are prepared 24e,f). Ether solvents or hydrocarbon solvents are most common. This process can be demonstrated by the preparation of anthraene dianion 22 from 9,10-dihydroanthracene (1)25). The metalation reaction can also be carried out in the NMR tube. 

Alkylpyrido[2,3-d]pyridazin-5(6//)-one and 5-alkylpyrido[2,3-t/]pyridazin-8(7//)-one, converted into their anions by potassium ferf-butoxide or sodium hydride in dimethylfor-mamide, are, V-alkylated at position 6 or 7 respectively by alkyl or arylalkyl halides, 9 90 e.g. formation of 8 or 9.90... 

But if the alkyl groups, R or R, are sufficiently bulky, steric interaction between them may limit the degree of association actually obtained to values less than "normal . Thus di-fso-propylaluminum fluoride is trimeric, dimethylaluminum phenoxide equilibrates to a mixture of dimers and trimers dimethylaluminum-ferf-butoxide is dimeric and so is dimethylaluminum dimethylamide ... 

METHYL HYDRATE (67-56-1) CH O CH3OH Flammable liquid. Forms explosive mixture with air [explosion limits in air (vol %) 6.0 to 36.5 flash point 52 F/11 C autoignition temp 725°F/385°C 867°F/464°C " Fire Rating 3]. Violent reaction (possible fire and/or explosion) with strong oxidizers strong mineral acids (e.g., nitric, sulfuric, perchloric) acetyl bromide alkyl aluminum salts beryllium dihydride bromine, chromic acid l-chloro-3,3-difluoro-2-methoxycyclopropene, cyanuric chloride diethylzinc, isophthaloyl chloride potassium-ferf-butoxide phosphorus trioxide platinum-black catalyst (ignition) potassium sulfur diimide Raney-nickel catalysts 2,4,6-trichlorotriazine, triethylaluminum, 1,3,3 -trifluor o-2 -... 

A secondary alkyl halide can form both substitution and elimination products under Sn2/E2 conditions. The relative amounts of the two products depend on the base strength and the bulk of the nucleophile/base. The stronger and bulkier the base, the greater the percentage of the elimination product. For example, acetic acid is a stronger acid = 4.76) than ethanol (pA a = 15.9), which means that acetate ion is a weaker base than ethoxide ion. The elimination product is the main product formed from the reaction of 2-chloropropane with the strongly basic ethoxide ion, whereas no elimination product is formed with the weakly basic acetate ion. The percentage of elimination product produced would be increased further if the bulky ferf-butoxide ion were used instead of ethoxide ion (Section 10.3). 

If, however, you want to synthesize tert-butyl ethyl ether, the starting materials must be an ethyl halide and ferf-butoxide ion. If you tried to use a tert-butyl halide and ethoxide ion as reactants, you would obtain the elimination product and little or no ether because the reaction of a tertiary alkyl halide under Sn2/E2 conditions forms primarily the elimination product. So, in carrying out a Williamson ether synthesis, the... 

Ethyl acetoacetate refluxed 1 hr. with u-butyl chloride in dimethyl sulfoxide as a dipolar aprotic solvent in the presence of anhydrous K-carbonate ethyl y -butoxycrotonate. Y 69%. G. Brieger and W. M. Pelletier, Tetrah. Let. 1965, 3555 with K-ferf-butoxide and dimethyl sulfate s. G. J. Heiszwolf and H. Kloosterziel, Chem. Commun. 1966,51 from ethyl sodioacetoacetate, alkyl group effect, cf. W. J. le Noble and J. E. Puerta, Tetrah. Let. 1966, 1087. 

Write structural formulas for all the products that would be obtained when each of the following alkyl halides is heated with potassium ferf-butoxide in terf-butyl alcohol. When more than one product results, you should indicate which would be the major product and which would be the minor product(s). You may neglect cis-trans isomerism of the products when answering this question. 

With larger, sterically hindered bases such as ferf-butoxide, however, where isomeric alkenes are possible, the major product is often the less substituted alkene because reaction occurs primarily at the most accessible H atom. Sterically hindered bases such as fert-butoxide are also noteworthy because the steric hindrance prevents them from reacting as nucleophiles, even with primary alkyl halides. 

The chiral E-R -9-BBN alkylates the chloroacetonitrile to afford in good yields the corresponding chiral nitriles. Sodium ferf-butoxide in THF is best suited for the a-alkylation of chloroacetonitrile (Eq. 10.4) [4]. 

The regioselectivity (a vs. y) is controlledby many factors, such as the nature of the heteroatom, the base, the substituents bonded to the heteroatom, the electrophile, the solvent, and the reaction conditions. It has been proposed, as a rule of thumb, that for a given counter ion, e.g., lithium, anion-destabilizing substituents (e.g., OR, NR2) favor the attack by alkyl halides and protons at the y-position, while carbonyl compounds undergo reaction preferentially at the a-position. The complementary regioselectivity is encountered when anion-stabilizing substituents (e.g., SR, BR2) are bonded to the allyl moiety. A list of n-butyllithium/potassium ferf-butoxide metalated heterosubstituted alkenes is shown in Table 3. 

Alkylation of ketones. 2-n-Butylthiomethylene-6-methylcyclohexanone allowed to react with methyl iodide in ferf-butanol in the presence of K-ferf-butoxide 2-n-butylthiomethylene-6,6-dimethylcyclohexanone (Y 84%) refluxed with KOH in aq. diethylene glycol -> 2,2-dimethylcyclohexanone (Y 77%).— The n-butylthiomethylene group does not deactivate the carbonyl and can be easily removed. F. e. s. R. E. Ireland and J. A. Marshall, Am. Soc. 81, 6336 (1959). 

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