Alkylating-like agents

A very significant mortality in Western countries is associated with cardiac arrhythmias Consequently an intensive search is underway for agents to combat this condition - particularly for compounds with an unusual mode of action A class Ic (local anesthetic-like) agent of interest in ihis context is Indecainide (50) One of several routes to this compound covered by patents begins with sodium amide mediated alkylation of 9 cyanofluorene (48) with 3 isopropylamino-1 chloropropane to give amine 49 The synthesis concludes by partial hydrolysis of the nitnle func tion to a carboxamide linkage with sulfunc acid to produce indecainide (50) [15]... 

The development of bifunetional drugs with a nonsteriodal anti-inflammatory agent, dielofenac or ibuprofen, and a cholinesterase inhibitor like pyridostigmine may be beneficial for both nerve and alkylating chemical agents (Amitai et al, 2005,2006). Anti-inflammatory drugs reduce... 

The drug essentially cross-links DNA and, therefore, behaves like alkylating antineoplastic agents. In general, the platinum complex acts as apotent inhibitor of DNA polymerase. Based on adequate... 

Acyclic a,a-disubstituted tin enolates 6 inevitably form as cis/trans-mixtures. Nevertheless, application of the chromium alkylation protocol with the modified salen complex 7 provides fair enantioselectivity with various alkylating agents R CH2X hke allyl bromide, benzyl bromide, allyl iodide, and ethyl iodoacetate, as outlined in Scheme 5.5. A plausible explanation is based on the assumption of a rapid cis/trans-isomerization of the tin enolates 6 through the C-bound tautomer and the postulate that one of the enolate diastereomers reacts distinctly faster than the other. The role of the additive BugSnOMe, which has a beneficial effect on the enantioselectivity, might be to catalyze the cis/trans-isomerization of the enolate. Several models have been proposed for the mechanisms of the enantioselective enolate alkylation like transmetallation of tin into a chromium enolate, formation of a stannate by iodine transfer from chromium to tin, as well as activation of the alkyl halide by chromium [5]. 

FS(0)20CH3. Colourless liquid, b.p. 94°C. Functions as a powerful methylating agent, even for amides and nitriles which are not attacked by conventional alkylating agents like dialkyl sulphates. 

Geranyl pyrophosphate is an allylic pyrophosphate and like dimethylallyl pyrophosphate can act as an alkylating agent toward a molecule of isopentenyl pyrophosphate A 15 carbon carbocation is formed which on deprotonation gives/ar nesyl pyrophosphate... 

Qu tern iy S Its. The ring nitrogen of quinoline reacts with a wide variety of alkylating and acylating agents to produce useful intermediates like A/-benzoylquinolinium chloride [4903-36-0] (8). The quinoline 1,2-adducts, eg, A/-benzyl-2-cyano-l,2-dihydroquinoline [13721 -17-0] (9), or Reissert compounds (28), formed with potassium cyanide can produce 2-carboxyquinoline [93-10-7] (10) or 2-cyanoquinoline [11436-43-7] (11). 

AdeninyUiydroxypropanoic acid alkyl esters [(R,5)-AHPA esters, (30)] represent a new class of broad-spectmm antiviral agents, which are, like (3)-DHPA, targeted at SAH hydrolase (62). The free acid, (R,3)-AHPA, is only weakly active as an antiviral agent. Thus the alkyl moiety merely serves as a protecting group to faciUtate uptake of AHPA by the cells. Within the cells, the AHPA alkyl esters would be hydroly2ed to release the free acid, which should then interact with SAH hydrolase. 

Another possibility is that both nitrogen atoms react with a double alkylating agent. In this way fused pyrazole derivatives (pyrazolo[l,2-a]pyrazoles) like (237) can be obtained by reaction of 3,5-dimethylpyrazole with 1,3-dichloropropane or l-chloro-3-propanol (69BSF2064). More surprising is the reaction with a-chlorocarbonylphenylketene which yields the paraionic compound (238) (80JA3971) which can also be obtained from 3,5-dihydroxy-4-phenylpyrazole and /3-dicarbonyl compounds (82JOC295). 

The behaviour of pyrazoles towards nitrosation is similar to their behaviour described above towards diazo coupling, i.e. aminopyrazoles and pyrazolones readily react with nitrosation agents, like alkyl nitrites (81FES1019), to afford stable nitroso derivatives. Some simple nitrosopyrazoles have been isolated, for example the blue-green 3,5-dimethyl-4-nitrosopyrazole, and many others have been proposed as reactive intermediates in the direct conversion of pyrazoles into diazonium or diazo derivatives (Scheme 25) (B-76MI40402). 

The mechanism of oxidation has not been studied in detail. In aqueous media it may be assumed that hypobromous acid is formed and that this is the true oxidizing agent. Indeed, Deno" has shown that the rate of oxidation of alcohols by aqueous bromine closely parallels the HOBr concentration and that the alkyl hypohalide is a most likely intermediate. Rate studies and... 

Epoxides are found in thousands of biological molecules and constitute vital functional entities. They can impart localized structural rigidity, confer cytotoxicity through their role as alkylating agents, or act as reactive intermediates in complex synthetic sequences. The widespread occurrence of epoxides is contrasted by only a handful of aziridines that are known to date. In this chapter we would like to introduce the different mechanisms by which enzymes produce epoxides. 

Ammonium salts of alkenyl succinic half-amides have teen described for use as corrosion inhibitors in oil and gas production technology to combat corrosion by media containing CO2, H2S, and elemental sulfur [1366]. The inhibitor composition may contain a dispersing agent, such as a low molecular weight or polymeric anionic surfactant like an alkylsulfonic acid or an alkyl-aryl sulfonic acid. 

This chapter compares the reaction of gas-phase methylation of phenol with methanol in basic and in acid catalysis, with the aim of investigating how the transformations occurring on methanol affect the catalytic performance and the reaction mechanism. It is proposed that with the basic catalyst, Mg/Fe/0, the tme alkylating agent is formaldehyde, obtained by dehydrogenation of methanol. Formaldehyde reacts with phenol to yield salicyl alcohol, which rapidly dehydrogenates to salicyladehyde. The latter was isolated in tests made by feeding directly a formalin/phenol aqueous solution. Salicylaldehyde then transforms to o-cresol, the main product of the basic-catalyzed methylation of phenol, likely by means of an intramolecular H-transfer with formaldehyde. With an acid catalyst, H-mordenite, the main products were anisole and cresols moreover, methanol was transformed to alkylaromatics. 

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