Sodium dialkylamide

Sodium alkylamides (AlkNH Na+) (but not sodium dialkylamides) under heterogeneous conditions convert pyridine into 2-alkylamino derivatives an intramolecular example of the reaction is shown in Scheme 29. 

The homoleptic metal dialkylamides are an important class of compounds in inorganic chemistry. They are typically synthesized by treatment of the corresponding halide with lithium or sodium dialkylamide. Although involving an extra synthetic step, there are numerous examples where metal dialkylamide intermediates are useful in the synthesis of metal aryloxide compounds. The reaction normally involves the simple addition of the parent phenol to the metal dialkylamide in a nonprotic, typically hydrocarbon, solvent (Eqs 6.36, 6.37, and 6.38 ). 

To a solution of the lithium dialkylamide (1.1 mmol) in THF (2 ml) cooled to -78°C was added a solution to TMSC1 (5-10mmoI) in THF (2ml), also cooled to -78 °C. This was followed by dropwise addition of the carbonyl compound (lmmol) in THF (2ml). After lmin, triethylamine (2ml) was added, followed by quenching with saturated sodium hydrogen carbonate solution. The product was extracted into pentane, and these extracts were... 

This important synthetic problem has been satisfactorily solved with the introduction of lithium dialkylamide bases. Lithium diisopropylamide (LDA, Creger s base ) has already been mentioned for the a-alkylation of acids by means of their dianions1. This method has been further improved through the use of hexamethylphosphoric triamide (HMPA)2 and then extended to the a-alkylation of esters3. Generally, LDA became the most widely used base for the preparation of lactone enolates. In some cases lithium amides of other secondary amines like cyclo-hexylisopropylamine, diethylamine or hexamethyldisilazane have been used. The sodium or potassium salts of the latter have also been used but only as exceptions (vide infra). Other methods for the preparation of y-Iactone enolates. e.g., in a tetrahydrofuran solution of potassium, containing K anions and K+ cations complexed by 18-crown-6, and their alkylation have been successfully demonstrated (yields 80 95 %)4 but they probably cannot compete with the simplicity and proven reliability of the lithium amide method. 

It is interesting to note that aliphatic azo compounds have been prepared in good yield from A,A -dialkylamides of sulfuric acid with 2 moles of sodium hypochlorite in a 1 A alkaline solution [38a, b]. The proposed course of the reaction is shown in Eq. (17). 

Nucleophilic substitution of dibenzofurans has been little studied. Bromo and iodo compounds are converted into the amino compounds on autoclaving with aqueous ammonia in the presence of copper(I) bromide (730PP125). Iodo compounds can be converted into phenols with aqueous potassium hydroxide at 250 °C (65MI31100), but dibenzofuran is cleaved to 2,2 -dihydroxybiphenyl on fusion with sodium hydroxide. Animation of halo compounds can be achieved with sodamide but 4-halo compounds undergo cine substitution on treatment with sodamide or lithium dialkylamides and the 2-substituted compounds result (56JOC457). 1,2,3,4-Tetrafluoro- and octafluoro-dibenzofuran react with nucleophiles at the 3-position (Scheme 101) (67T4041,68JCS(C)1560). 

LDA and related, sterically hindered, lithium dialkylamides, first investigated by Levine [1], have completely replaced the more nucleophilic sodium amide, which had been the base of choice for many years [2], Because the reactivity of an organo-metallic compound depends to a large extent on its state of aggregation (i.e. on the solvent and on additives) and on the metal, transmetalation of the lithiated intermediates and the choice of different solvents and additives emerged as powerful strategies for fine-tuning the reactivity of these valuable nucleophiles. 

Dithiocarbamate and dithiophosphinate complexes have important uses. The former are used as fungicides and for solvent extraction and the latter as high pressure lubricants. Dithiocarbamates stabilize high oxidation states as in [FeIV(dtc)3]+ or [NiIV(dtc)3]+. Although dithiocarbamates are usually made from sodium salts such as NaS2CNMe2 or by oxidations using thiuram disulfides, they can also be made by insertion reactions of CS2 with dialkylamides, for example,... 

The reaction of lithium enolates with molecular oxygen has been used for the a-hydroxylation of several substrates. The carbanion generated in the reaction of N,N-dialkylamides or esters with alkyl lithium reagents undergoes rapid oxidation under mild conditions when treated with molecular oxygen. The reaction produces an a-hydroperoxide intermediate which is cleanly reduced with sodium sulphite to the a-hydroxo derivatives" (equation 1). 

Lithium amide in liquid ammonia has been as successful as sodium amide in inducing dehydrohalogenation of dihaloalkyl ethers and halovinyl ethers to 1-alkynyl ethers . Lithium dialkylamides have also found use in the preparation of aryl- and alkylacetylenes in high yields , and of protected acetylenic sugars . They have also been utilized for concurrent elimination and substitution in the synthesis of ynamines , obtained in 30-40% overall yield from the corresponding aldehydes... 

A filled sp orbital is lower in energy than filled sp or sp orbitals since it is closer to the positively charged nucleus. This imparts sufficiently greater acidity to acetylene and 1-alkynes (pA a 24-26) so that bases such as alkyllithiums, lithium dialkylamides, sodium amide in liquid ammonia, and ethylmagnesium bromide may be used to generate the alkynyl anions (see Section 8.2). 

Deprotonation of carbonyl compounds by lithium dialkylamide bases is the single most common method of forming alkali enolates. Four excellent reviews have already been published. " Sterically hindered amide bases are employed to retard nucleophilic attack on the carbonyl group. The most common and generally useful bases are (i) lithium diisopropylamide (LDA 5) (ii) lithium isopropylcyclo-hexylamide (LICA 6) (iii) lithium 2,2,6,6-tetramethylpiperidide (LITMP 7) (iv) lithium hexamethyldisilylamide (LHMDS 8) and (v) lithium tetramethyldiphenyldisilylamide (LTDDS 9). Bases that are not amides include sodium hydride, potassium hydride and triphenylmethyllithium. 

Zinc ester enolates may also be obtained by the addition of ZnX2 to lithium or sodium enolates as first described by Hauser and Puterbaugh (equation 6)P This approach has so far received little attention but similar reactions have been used to obtain zinc ketone enolates. In this regard, it should be noted that Heathcock and coworkers have shown that deprotonation reactions of ketones with zinc dialkylamide bases reach equilibrium at only about 50% conversion (equation 7). This result implies that attempts to prepare zinc enolates from solutions of amide-generated lithium enolates will be successful only when the lithium enolate is made amine-free. 

Alkylamines of petrochemical, vegetable or tallow origin react with maleic anhydride at a temperature below 100 °C forming maleic monoalkyl- or dialkylamides followed by sulphonation with aqueous sodium bisulphite in the same manner as of maleic esters [10, 79]. The long-chain sulphosuccinamates obtained have enhanced hydrolytical stability (but more expensive) in comparison to sulfosuccinates that offer ample scope for their use in soaps bars, carpet cleaning, textile and wool finishing, and some other specialties. 

During the period 1965-1975 the chemistry of the 1,2-dithiolene complexes of the transition metals was the subject of considerable study. However, during this period of great activity few complexes of the early transition metals were reported aside from those of vanadium. The problem had much to do with synthetic procedures, since reaction of, say, the anhydrous metal chlorides with the dithiolene or its sodium salt did not prove successful. However, the use of metal dialkylamides did result in clean reactions (e.g. equation 21). 

One of the most useful applications of the alkoxy reagents is in the preparation of aldehydes from carboxylic acids by partial reduction of the acid chlorides or dialkylamides. Acid chlorides are readily reduced with lithium aluminium hydride or with sodium borohydride to the corresponding alcohols, but with one equivalent of lithium tri-t-butoxyaluminium hydride, high yields of the aldehyde can be obtained, even in the presence of other functional groups (7.74). 

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