Diisopropyl amide

Lithium aluminum tri-tert-bu-toxyhydride, 53, 53 Lithium amide, bis(trimethyl-silyl), 53, 66 Lithium amide, diisopropyl-,... 

MonofluoToalkanes and vicinal difluoroalkanes are dehydrofluonnated if strong enough bases are applied [10 12] In 5-fluorononane and fluorocyclodo-decane, elimination by means of sodium methoxide in methanol gives cis- and trans allcenes in respective yields of 8 and 21% and in ratios of 1 2 2 2 4, however, the bulky lithium diisopropyl amide m tetrahydrofuran produces trdns-isomers almost exclusively The strength of the base does not have much effect on the rate of elimination, but the lithium cation causes considerable acceleration [10] (equation 10)... 

LDA (Section 21.10) Abbreviation for lithium diisopropyl-amide LiN[CH(CH3)2]. LDA is a strong, sterically hindered base, used to convert esters to their enolates. 

Stork and Takahashi took -glyceraldehyde synthon from the chiral pool and condensed it with methyl oleate, using lithium diisopropyl amide as catalyst for the mixed aldol reaction, leading to The olefinic linkage is a latent form... 

Diisopropylamino-a.a-diphenvlbutyronitriie (60 g) was added in several portions to a mixture of sulfuric acid (150 ml) and water (15 ml) and the solution was heated 3 /i hours on the steam bath and then poured on ice and made basic with NH4OH. The 7-diisopropyl-amino-o. a-diplienylbutyramide precipitated as a solid, which was taken up in methylene chloride from an aqueous slurry. The methylene chloride was separated and dried by filtering through anhydrous KjCOj. The solvent was removed by distillation, leaving the amide which was crystallized from Skellysolve B five times and found then to have MP 87.0° to BB.5°C. 

Unlike the parent system, 5-methyl-5//-dibenz[c,e]azepine (1, R1 = Me R2 = H) on treatment with lithium diisopropyl amide fails to yield the tautomeric phenanthridine-imine (see Section 3.2.1.5.4.2.), but forms the 5-carbanion, which on quenching with deuterium oxide furnishes 5-methyl-[5-2H,]-5//-dibenz[e,e]azepine (l).83 5,7-Diphenyl-5//-dibenz[r,e]azepine (1. R1 = R2 = Ph) behaves similarly. In contrast, however, 5,7-dimethyl-5//-dibcnz[c,e]azepine (1, R1 = R2 = Me) yields theazaallyl anion 3, which on addition of deuterium oxide deuterates regiospecifically at the 7-methyl group to give derivative 4. 

The optimum conditions for obtaining a high diastereoselectivity are as follows Deprotonation of the sulfoxide must be carried out at 0 C with lithium diisopropyl amide (1 equiv). a lower temperature probably changes the organization of the lithium species and gives lower diastereoselectivity. The condensation reaction is very fast at —78 C, reaction time is usually around 10 minutes3. 

The stereochemistry of the silyl ketene acetal can be controlled by the conditions of preparation. The base that is usually used for enolate formation is lithium diisopropyl-amide (LDA). If the enolate is prepared in pure THF, the F-enolate is generated and this stereochemistry is maintained in the silyl derivative. The preferential formation of the F-enolate can be explained in terms of a cyclic TS in which the proton is abstracted from the stereoelectronically preferred orientation perpendicular to the carbonyl plane. The carboxy substituent is oriented away from the alkyl groups on the amide base. 

Using potassium bis(trimethylsilyl)amide as a solid base, N -isopropyl-l,l-dimethyl-N,N -bis(trimethylsilyl)silanediimine and 2,4-diisopropyl-1,1,3,3-tetramethylcyclodisilazane were formed, accompanied by hexa-methyldisilazane. 

DIC (or diisopropyl carbodiimide) is another water-insoluble amide bond-forming agent that has advantages over DCC (Section 1.4, this chapter). It is a liquid at room temperature and... 

It was found that in spite of the large excess of modifying amine (N-isopropyl-, -diethyl, -dipropyl, -diisopropyl, -n-hexyl, -cyclohexyl, -n-octyl), the extent of substitution did not exceed 5-10 molar %. For the case of the N-isopropyl derivative, i.e. [poly(AAm-co-NiPAAm)], the authors connected such results with the temperature-induced conformational transformation of partially hydrophobized copolymer acquiring the contracted conformation, "... which made it difficult for N-isopropylamine to react further with the amide groups [22], Unfortunately, no data on the solution behaviour of these interesting copolymers have been reported to date, although there is a high probability that they would demonstrate certain properties of the protein-like macromolecules. At least, in favour of similar supposition is supported by the results of our studies [23] of somewhat different PAAm partially hydrophobized derivative, whose preparation method is depicted in Scheme 3. 

Fig. 3.6-2. Inorganic cluster core of super inverse crown ethers of general formula [ NaMg(amide)0(THF) 6], where amide = TMP (2,2,6,6-tetramethylpiperidinide) or DPA (diisopropyl-amide).

List A, giving examples of compounds which form explosive peroxides while in storage, include diisopropyl ether, divinylacetylene, vinylidene chloride, potassium and sodium amide. Review of stocks and testing for peroxide content by given tested procedures at 3-monthly intervals is recommended, together with safe disposal of any peroxidic samples. 

An investigation of lithium diisopropyl amide (LDA) by solid state NMR led to the observation of dramatic differences between the spectra of the solid polymer and the complex crystallized from THF. Li as well as "C and "N MAS spectra showed large sideband patterns in the former case and only a few sidebands in the latter. For both materials X-ray data are available and establish a helix structure for the polymeric material, which is insoluble in hydrocarbon or ethereal solvents, and a dimer structure of the THF complex (25, 26, Scheme 4). The obvious difference between both structures, apart from the solvent coordination in the THF complex, is the magnitude of the structural N-Li-N angle, which is close to 180° in the first case and close to 90° in the second (176° and 107°, respectively). Thus, a large difference for the electric field gradient around the Li cation is expected for the different bonding situations. 

Laterally lithiated tertiary amides are more prone to self-condensation than the anions of secondary amides, so they are best lithiated at low temperature (—78 °C). N,N-Dimethyl, diethyl (495) and diisopropyl amides have all been laterally lithiated with aUcyllithiums or LDA, but, as discussed in Section I.B.l.a, these functional groups are resistant to manipulation other than by intramolecular attack" . Clark has used the addition of a laterally lithiated tertiary amide 496 to an imine to generate an amino-amide 497 product whose cyclization to lactams such as 498 is a useful (if rather low-yielding) way of building up isoquinoline portions of alkaloid structures (Scheme 194) ". The addition of laterally lithiated amines to imines needs careful control as it may be reversible at higher temperatures. ... 

Apparently a substantial spacer is also allowable between the aromatic ring and the carboxy group. Gemfibrozi 1 (52), a iiypotriglyceridemic agent which decreases the influx of steroid into the liver, is a clofibrate homologue. It is made readily by lithium diisopropyl amide-promoted alkylation of sodium iso-propionate with alkyl bromide 51. ... 

An amount of 4.1 equiv of lithium diisopropyl amide (LDA) is absolutely necessary for this reaction to go to completion. An equilibrium exists between the formation of the second anion of the B-keto ester and the formation of lithium diisopropyl amide from diisopropylamine. 

Q ,Q -disubstituted /1-ketoesters like 9, when treated with an alkoxide, can be cleaved into ordinary esters by the reverse of the condensation reaction, the retro-Claisen reaction. However the condensation of esters with only one a-hydrogen is possible in moderate yields by using a strong base, e.g lithium diisopropyl amide (LDA). ... 

Deprotonation of a dihydrothiazine ring, followed by a reaction with an electrophile, is most straightforward in benzothiazin-3-ones (general structure 35), which are deprotonated at the 2-position by lithium diisopropyl amide (LDA). The enolate can then react with a variety of electrophiles including deuterium oxide, methyl iodide, and aldehydes <1982T3059>. Compound 70 was prepared in this manner from 2,4-dimethyldihydro-l,4-benzothiazin-3-one (Equation 27) <1985T569>. 

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