Aryl derivatives amide compounds

Turning our attention first to alkyl carbamates of cyclic amides, we find interesting attempts to improve the pharmaceutical and pharmacokinetic properties of 5-fluorouracil (8.152, R = H) [194-196], This antitumor agent, while clinically useful, suffers from poor water solubility, unsatisfactory delivery properties and low tissue selectivity. A variety of prodrug candidates were prepared, in particular the alkyl and aryl carbamates presented in Table 8.12. With the exception of the more-lipophilic derivatives, these compounds exhibited somewhat improved water solubility. More importantly, both rectal and oral bioavailability were markedly improved. The activation... 

The historical sketch outlines the class of lanthanide amides this article is to deal with and which is further manifested in Scheme 1. Organometallic amides which can be classified as dialkyl (-aryl, -silyl) amides and amides derived from unsaturated heterocyclic ligands are seen with respect to N-unsubstituted (primary, inorganic) amides. The consideration of more classic coordination compounds like acid amides or sulfonamides, often ascribed as wet chemistry , is excluded. The historical data also demonstrate the relatively late start of lanthanide amide chemistry reflecting the late industrial establishment of the lanthanide elements (separation, purification, etc.) [9], However, lanthanide amides are still the youngest class in conjunction with the most important pillars of organometallic lanthanide chemistry, namely the alkyls/cyclopentadienyls (LnCp3, 1954, [10]) and the alkoxides (Ce(OR)4 1956 [11a] La(OR)3 , 1958 [lib]). Indeed most of the work has been conducted in the last ten years. 

Hydrazines.—It will readily be seen that these two compounds are not the only aromatic aryl) derivatives of di-amide or hydrazine. The following series is possible the aryl radical, when more than one is present being either like or different. 

Treatment of the amides 11 with phenacyl bromide in refluxing acetonitrile provides the 1-oxo compounds 13 without isolation of the quaternized intermediates 12. Use of 2-cyanopyridine in wet acetonitrile also yields the oxo compound 13 (R = H). Treatment of the amide 11 (R = H) with ethyl bromoacetate provides the dioxo compound 15. This was also formed when attempts were made to recrystallize the quaternary salt 14. Dehydration of the piperidine 16 gives the reduced compound 17. A variety of 3-aryl derivatives were prepared using this approach. ... 

Quinoline and isoquinoline undergo a set of reactions in which, in effect, a hydride ion is replaced by a strongly nucleophilic species. With organolithium compounds the initial adduct, on hydrolysis and mild oxidation, yields the corresponding alkyl or aryl derivative, and hydroxy or amino groups can be introduced by reaction with alkali metal (or alkaline earth) hydroxides or amides. 

The compounds (r/-CsHs)3UCl and (r/-CsHs)3ThCl are useful precursors for the synthesis of a large number of organoactinides, such as tris(cyclopentadienyl)metal alkoxides, tetrahydroborates, alkyls and aryls, halides, amides, and other derivatives,The chlorouranium compound was first synthesized by Reynolds and Wilkinson in 1956 from uranium tetrachloride and sodium cyclopentadienide in tetrahydrofuran. Vacuum sublimation, in our hands, invariably gives the pure product in low yield. The thorium analog was originally prepared in a similar manner,... 

The ureas, e.g. 28 (R = NMe2), derived from the corresponding 2-(l-arylviny )benzylamines by reaction with (dimethylamino)carbamoyl chloride (Me2NCOCl) in the presence of triethyl-amine, undergo cyclization in refluxing phosphoryl chloride to the 5-aryl-3-(dimethylamino)-l//-2-benzazepin-3-amines. e.g. 29a.84 Prepared similarly are the 3-(4-methylpiperazin-l-yl) compound 29b and the 3-methyl derivative 29c from the corresponding urea and amide, respectively. 

Carbenes from Diazo Compounds. Decomposition of diazo compounds to form carbenes is a quite general reaction that is applicable to diazomethane and other diazoalkanes, diazoalkenes, and diazo compounds with aryl and acyl substituents. The main restrictions on this method are the limitations on synthesis and limited stability of the diazo compounds. The smaller diazoalkanes are toxic and potentially explosive, and they are usually prepared immediately before use. The most general synthetic routes involve base-catalyzed decomposition of V-nitroso derivatives of amides, ureas, or sulfonamides, as illustrated by several reactions used for the preparation of diazomethane. 

The instability of 5-aminoimidazoles (96) has led to in situ acylation being used to obtain stable compounds and using this approach several derivatives have been prepared. For example, a solution of the appropriate 5-nitroimidazole (97) in ethyl acetate was reduced with Raney nickel, and the resulting solution of 5-aminoimidazole (96) then treated with an acid chloride to give the amides (118 R1 = Me, R2 = S02Me, COPh, R3 = alkyl, aryl, hetaryl) (25-45%) [82IJC(B)1087],... 

The reaction described is of considerable general utility for the preparation of benzoyloxy derivatives of unsaturated hydrocarbons.2"8 Reactions of 2-butyl perbenzoate with various other classes of compounds in the presence of catalytic amounts of copper ions produce benzoyloxy derivatives. Thus this reaction can also be used to effect one-step oxidation of saturated hydrocarbons,9, 10 esters,6,11 dialkyl and aryl alkyl ethers,12 14 benzylic ethers,11,15 cyclic ethers,13,16 straight-chain and benzylic sulfides,12, 17-19 cyclic sulfides,11,19 amides,11 and certain organo-silicon compounds.20... 

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