Labile

Once the above restrictions on isotope, solubility, chemical lability and paramagnetism are met, then a very wide range of samples can be investigated. Gases can be studied, especially at higher pressures. Solutions for... 

Apart from the sheer complexity of the static stmctures of biomolecules, they are also rather labile. On the one hand this means that especial consideration must be given to the fact (for example in electron microscopy) that samples have to be dried, possibly stained, and then measured in high vacuum, which may introduce artifacts into the observed images [5]. On the other, apart from the vexing question of whether a protein in a crystal has the same stmcture as one freely diffusing in solution, the static stmcture resulting from an x-ray diffraction experiment gives few clues to the molecular motions on which operation of an enzyme depends [6]. 

Many inorganic and organic compounds possessing labile hydrogen atoms add acrylonitrile readily with the formation of compounds containing a cyancethyl grouping (—CH j. CH2. CN). This reaction is usually known as cyanoelhylation ... 

It has been tentatively suggested that one mechanism underlies the Willgerodt reaction and the Kindler modification of it. A labile intermediate is first formed which has a carbon—carbon bond in the side chain. The scheme is indicated below it postulates a series of steps involving the addition of ammonia or amine (R = H or alkyl), elimination of water, re addition and eUmination of ammonia or amine until the unsaturation appears at the end of the chain then an irreversible oxidation between sulphur and the nitrogen compound may occur to produce a thioamide. 

TMS silyl enol ethers are labile can also use EtsSi-, iPrsSi- etc. 

In peptide syntheses, where partial racemization of the chiral a-carbon centers is a serious problem, the application of 1-hydroxy-1 H-benzotriazole ( HBT") and DCC has been very successful in increasing yields and decreasing racemization (W. Kdnig, 1970 G.C. Windridge, 1971 H.R. Bosshard, 1973), l-(Acyloxy)-lif-benzotriazoles or l-acyl-17f-benzo-triazole 3-oxides are formed as reactive intermediates. If carboxylic or phosphoric esters are to be formed from the acids and alcohols using DCC, 4-(pyrrolidin-l -yl)pyridine ( PPY A. Hassner, 1978 K.M. Patel, 1979) and HBT are efficient catalysts even with tert-alkyl, choles-teryl, aryl, and other unreactive alcohols as well as with highly bulky or labile acids. 

The most stable protected alcohol derivatives are the methyl ethers. These are often employed in carbohydrate chemistry and can be made with dimethyl sulfate in the presence of aqueous sodium or barium hydroxides in DMF or DMSO. Simple ethers may be cleaved by treatment with BCI3 or BBr, but generally methyl ethers are too stable to be used for routine protection of alcohols. They are more useful as volatile derivatives in gas-chromatographic and mass-spectrometric analyses. So the most labile (trimethylsilyl ether) and the most stable (methyl ether) alcohol derivatives are useful in analysis, but in synthesis they can be used only in exceptional cases. In synthesis, easily accessible intermediates of medium stability are most helpful. 

The cyclic carbonate of benzoin (4,5-diphenyl-l,3-dioxol-2-one, prepared from benzoin and phosgene) blocks both hydrogen atoms of primary amines after dehydration acid stable, easily crystallizable Sheehan oxazolinones are formed, which are also called Ox derivatives. The amine is quantitatively deblocked by catalytic hydrogenation in the presence of 1 equiv. of aqueous acid (J.C Sheehan, 1972, 1973 M.J. Miller, 1983). An intelligent application to syntheses of acid labile -lactams is given in the previous section (p. 161). 

More successful are solid-phase methods in which the linear precursor is attached through a labile ester bond (e.g. o-nitrophenyl) to a polymer. 

Butyne trimerizes in the presence of aluminum chloride to give hexamethyl Dewar-benzene (W. Schafer, 1967). Its irradiation leads not only to aromatization but also to hexa-methylprismane (D.M. Lemal, 1966). Highly substituted prlsmanes may also be obtained from the corresponding benzene derivatives by irradiation with 254 nm light. The rather stable prismane itself was synthesized via another hydrocarbon, namely benzvalene, a labile molecule (T. J. Katz, 1971, 1972). 

The furanose rings of the deoxyribose units of DNA are conformationally labile. All flexible forms of cyclopentane and related rings are of nearly constant strain and pseudorotations take place by a fast wave-like motion around the ring The flexibility of the furanose rings (M, Levitt, 1978) is presumably responsible for the partial unraveling of the DNA double helix in biological processes. 

In the total synthesis of the naturally occurring big molecule of palytoxin, which has numerous labile functional groups, this coupling is the most useful for the creation of E, Z-conjugated diene part 653. In this case, thallium hydroxide as a base accelerates the reaction 1000 times more than KOH[523]. Even TECOj can be used instead of a strong base in other cases[524]. 

Since allylation with allylic carbonates proceeds under mild neutral conditions, neutral allylation has a wide application to alkylation of labile compounds which are sensitive to acids or bases. As a typical example, successful C-allylation of the rather sensitive molecule of ascorbic acid (225) to give 226 is possible only with allyl carbonate[l 37]. Similarly, Meldrum s acid is allylated smoothly[138]. Pd-catalyzed reaction of carbon nucleophiles with isopropyl 2-methylene-3,5-dioxahexylcarbomite (227)[I39] followed by hydrolysis is a good method for acetonylation of carbon nucleophiles. 

The mobility of the proton in position 2 of a quaternized molecule and the kinetics of exchange with deuterium has been studied extensively (18-20) it is increased in a basic medium (21-23). The rate of exchange is close to that obtained with the base itself, and the protonated form is supposed to be the active intermediate (236, 664). The remarkable lability of 2-H has been ascribed to a number of factors, including a possible stabilizing resonance effect with contributions of both carbene and ylid structure. This latter may result from the interaction of a d orbital at the sulfur atom with the cr orbital out of the ring at C-2 (21). 

This derivative condenses either on itself (64) or on the anhydrobase, giving the trimethine dye. Indeed, the nucleophilic a-carbon of the dye—the proton is labile and can be replaced (70, 71)—is liable to add onto the electrophilic /3-carbon of the alcene derivative. The neocyanine results from elimination of a molecule of ethanol. 

In thiazole series the application of Tchemiac s method (S). which consists of cyclizing the intermediary iminoketothioether, obtained by reaction of a thiocyanoketone upon a labile hydrogen compound, is suitable and occurs with an average yield of 50%. In selenazole series this cydization does not happen from selenocyanoketones and by using different acidic media (9). 

By reaction of a corresponding quaternary salt in the presence of a condensation agent such as amyl nitrite or with a heterocycioammonium salt possessing a labile group, such as Cl, I. or SR (6. 11) in the 2-position, cyanine dyes are obtained (Scheme 52). 

Compounds of this type possess a definite Aj-selenazoline structure, while homologous compounds with at least one labile hydrogen on the 2-amino group can exist as a tautomeric equilibrium (Scheme 64). 

Active Raney nickel induces desulfurization of many sulfur-containing heterocycles thiazoles are fairly labile toward this ring cleavage agent. The reaction occurs apparently by two competing mechanisms (481) in the first, favored by alkaline conditions, ring fission occurs before desul-, furization, whereas in the second, favored by the use of neutral catalyst, the initial desulfurization is followed by fission of a C-N bond and formation of carbonyl derivatives by hydrolysis (Scheme 95). 

The a-thiocyanatoketones are easily obtainable from a-halocarbonyl compounds and metal thiocyanates (sodium, potassium, barium, or lead thiocyanate) (416, 484, 519, 659) in an alcoholic solution. Yields ranged from 80 to 95%. They are very sensitive substances that isomerize when reacted upon by acids, bases, or labile hydrogen and sulfur compounds. 

TABLE 11-30, 2-MERCAPTOTHIAlZOLE DERIVATIVES FROM q-TH30CYANAT0KET0NES AND LABILE SULFUR"... 

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