Amine labilization

Substitution of aqua ligands by nitrogen donors such as the nucleic acid bases leads to mono- and disubstituted complexes whose properties, of course, have been extensively studied (Chapter 4). Once inside the cell, however, only a small proportion of the platinum is complexed to the DNA. Metabolism of the platinum complexes therefore takes place with other biomolecules besides DNA. Amino acid reactions may take place which may sequester the complex. Further, in the case of substitution by nucleophiles with strong tram influence, especially those of sulfur, displacement of amine and deactivation may occur. Interestingly, amine labilization tram to a thioether in d5-[Pt(NH3)2(Me2S)2] has been observed [107]. In vivo, thioethers such as methionine could effect the same chemistry and the characterization of [Pt(methionine)2], assigned the structure as shown, as a metabolite of cisplatin [108] confirms this view ... 

The rates (A i) indicate pronounced amine lability, in particular piperidine, while the ratio k-i/kg suggest a strong preference for CO binding. Comparison with porphyrin and phthalocyanin complexes indicates that CO dissociation rates are relatively insensitive to the nature of the in-plane ligand unlike, those of amine dissociation k which vary from 1020 s (OMBP) to 0.50 S (phthalocyanine). The binding of CO to [Fe(TAAB)L2] + is very poor in contrast to the above results which may reflect the enormous number of differences in the structure and electronic features of TAAB relative to OMBP and other related chelates. However, CO dissociation does not occur readily, while dimethylglyoxime complexes are even more... 

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. 

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). 

Tertiary amines have been shown to react with isocyanates ia an analogous fashion to form ureas (41—43). Similarly, a2iridines (three-membered rings containing nitrogen) are found to react with isocyanates to yield cycHc ureas. Tertiary amines have also been shown to form labile dipolar 1 1 adducts with isocyanates reminiscent of salt formation. In contrast, formaldehyde acetal aminals form iasertion products with sulfonyl isocyanates (44,45). 

An excess of phosgene is used during the initial reaction of amine and phosgene to retard the formation of substituted ureas. Ureas are undesirable because they serve as a source for secondary product formation which adversely affects isocyanate stabiUty and performance. By-products, such as biurets (23) and triurets (24), are formed via the reaction of the labile hydrogens of the urea with excess isocyanate. Isocyanurates (25, R = phenyl, toluyl) may subsequendy be formed from the urea oligomers via ring closure. 

Nucleophilic Addition. Reagents with labile hydrogen atoms, such as alcohols, thiols, phenols, carboxyHc acids and amines, add to ketenes giving the corresponding carboxyHc acid derivatives (1) as shown ia Figure 1 (38). Not many are of practical importance, as there are better ways to such... 

Many mercury compounds are labile and easily decomposed by light, heat, and reducing agents. In the presence of organic compounds of weak reducing activity, such as amines (qv), aldehydes (qv), and ketones (qv), compounds of lower oxidation state and mercury metal are often formed. Only a few mercury compounds, eg, mercuric bromide/77< 5 7-/7, mercurous chloride, mercuric s A ide[1344-48-5] and mercurous iodide [15385-57-6] are volatile and capable of purification by sublimation. This innate lack of stabiUty in mercury compounds makes the recovery of mercury from various wastes that accumulate with the production of compounds of economic and commercial importance relatively easy (see Recycling). 

Propylene oxide is highly reactive. It reacts exothermically with any substance that has labile hydrogen such as water, alcohols, amines, and organic acids acids, alkahes, and some salts act as catalysts. 

The influence of boron-bonded ligands on the kinetics and mechanistic pathways of hydrolysis of amine boranes has been examined (37,38). The stoichiometry of trimetbyl amine azidoborane [61652-29-7] hydrolysis in acidic solution is given in equation 10. It is suggested that protonation occurs at the azide ligand enabling its departure as the relatively labile HN species. 

In contrast to the 3-amino derivatives, 3-hydroxy-2,l-benzisoxazoles are relatively labile. With nitrous acid they undergo ring fission to anthranilic add. Its 3-acetoxy derivative (258) reacts with primary amines to form the quinazolone (259) (67AHC(8)277, p. 297). 

Ethylene oxide is a highly active intermediate. It reacts with all compounds that have a labile hydrogen such as water, alcohols, organic acids, and amines. The epoxide ring opens, and a new compound with a hydroxyethyl group is produced. The addition of a hydroxyethyl group increases the water solubility of the resulting compound. Eurther reaction of ethylene oxide produces polyethylene oxide derivatives with increased water solubility. 

The synthesis of alkoxy amines 2 by addition of organometallic reagents to the C-N double bond of oxime ethers 1 is plagued by the propensity for proton abstraction a. to the C-N double bond, the lability of the N-O bond and the poor electrophilicity of the oxime ethers. Therefore, frequently no products, undesired products or complex mixtures are obtained. The result depends on the substrate, organometallic reagent, solvent, temperature and additives1 6. 

The field of alkaloid synthesis via tandem cyclizations favors the application of (TMSlsSiH over other radical-based reagents, due to its very low toxicity and high chemoselectivity. For example, cyclization of the iodoarylazide 102, mediated by (TMSlsSiH under standard experimental conditions, produced the N-Si(TMS)3 protected alkaloid 103 that after washing with dilute acid afforded the amine 104 in an overall 83% yield from 102 (Reaction 81). ° The formation of the labile N-Si(TMS)3 bond was thought to arise from the reaction of the product amine 104 with the by-product (TMSlsSil. The skeletons of ( )-horsfiline, ( )-aspidospermidine and (+ )-vindoline have been achieved by this route. - ... 

There exist a considerable number of compounds containing labile chlorine which bring about sulfur-less vulcanization at levels of approximately 3 phr [64] as basic chemicals such as lead oxides and amines are needed. Additionally, it may be assumed that diene mbbers are cross-linked by such systems through the formation of C-C links this would mean, initially, hydrogen chloride is split off and later neutralized by the base. Examples of chemicals that act in the manner are listed below ... 

Efforts to achieve a retardation of cross-linking in elastomers are based on the general assumption of a radical mechanism for retardation cross-linking and the possibility of its inhibition by a deactivation of the reactive macromolecular radical [33]. These compounds generally contain one or more labile hydrogen atoms, which after, donation of this atom, will form relatively inactive radicals. Typical antirad agents are quinones, hydroquinones, and aromatic amines (phenyl and napthylamines). 

Compound (1) phosphorylates phosphate monoesters and alcohols, although with the latter a considerable excess of alcohol is necessary to obtain satisfactory yields. In the absence of mercuric ions the milder phosphorylating species (3) can be isolated which converts monoalkyl phosphates to pyrophosphate diesters in good yield but does not react appreciably with alcohols unless catalytic amounts of boron trifluoride are added. Amine salts of (3) are converted to phosphoramidates on heating. In the presence of silver ions, O-esters of thiophosphoric acid behave as phosphorylating agents and a very mild and convenient procedure suitable for preparing labile unsymmetrical pyrophosphate diesters, such as the... 

The reactions [OS 52], [OS 53], [OS 54] and [OS 55] were chosen as test reactions among a wide class of reagents employed for Michael additions. 1,3-Dicarbonyl compounds were chosen because of their relatively high acidity since they enable one to use weak bases instead of strong bases such as sodium efhoxide. The latter is labile to moisture and can react with the Michael acceptor [8]. Diisopropylethyl-amine was chosen as a weak base. 

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