Anilido

Morphine has certain undesirable side effects. Among these are respiratory depression, nausea, and vomiting, depression of the cough reflex, cardiovascular depression and hypotension, smooth muscle contraction (constipation), and histamine release (93). Morphine s onset of action, duration, and low therapeutic indices have prompted a search for a more effective opiate iv anesthetic. Extreme simplification of the complex morphine molecule has resulted in anilido —piperidines, the fentanyl class of extremely potent opiate iv anesthetics (118,119). 

Reduction of low-spin Fe(m) imide 165 with hydrogen (1 atm, 20 °C) proceeds stepwise leading first to anilido complex 168 and then to 77-cyclohexadienyl complex 169 via hydrogenolysis of the Fe=NR linkage (Scheme 64). It should be mentioned that the similar low-spin cobalt complex [PhB(CH2PPh2)3]Co N-/>-Tol is stable to hydrogen pressure (1-3 atm) up to 70 °C <2004JA4538>. 

Scheme 6.6 Preparation of anionic and neutral anilido bridged ir(i) complexes.

The Os— N(amido) bond (1.859 A) is significantly shorter than the corresponding distance in the anilido complex [Os (NHPh)(Tp)(Cl)2] (1.919A), suggesting that the bicyclic amide is a stronger rr-donor than the anilide. 

Remarkably robust dialkylthorium complexes [Th(L)(CH2SiMe3)2] (L 13 or 14), supported by bulky bis(anilido) ligands based on a xanthene or 2,6-dimethylpyridine framework, were prepared by salt elimination from [ThCl2(L)(dme)] and 2LiCH2SiMe3 or by alkane elimination from [Th(CH2SiMe3)4] and H2(13) or H2(14). ... 

Anatoxin-a, via enyne metathesis, 11, 297 Ancillary ligands, in alkene polymerization, 11, 697 Anilides, or/itf-alkenylations, 10, 144 Anilido complexes, with mono-Cp Ti(IV), 4, 415 Anilines... 

The dimeric amido complexes underwent reductive elimination after cleavage to form two monomeric, 3-coordinate, 14-electron amido complexes. In the case of the anilido dimer 20, a half-order rate dependence in the palladium complex showed that the reductive elimination occurred after reversible cleavage of the dimer to form two monomers. In the case of the f-butylamido complex 21, rapid reductive elimination occurred after irreversible dimer cleavage. This conclusion was supported by reaction rates that were first order in palladium dimer and by the lack of crossover during the reductive elimination reactions containing two doubly-labeled dimers. 

A QSAR study(50) of the series 13-15 showed that their analgesic action was positively dependent on the lipophilicity and molecular mass of the N-substituent but negatively dependent on the lipid affinity of the 4-substituent additional to the anilido function. A Chinese group has studied a variety of cis-3 - methylfentanyl derivatives with modified N-phenethyl substituents. Some of the compounds approached the potency of the parent and one exceeded it (see 18).(51) All compounds had high lipid solubilities as judged... 

In contrast to these failures, several derivatives in which the anilido nitrogen of fentanyl is doubly linked to C-4 of the piperidine ring, forming a spirane (19), are highly potent, although unusual in requiring an a-methyl-benzyl rather than phenethyl substituent attached to the piperidine nitrogen. 

The spirane ring is formed by treating amides derived from 16 with formamide and reducing the product.(20,56) In the solid state the 4-NPh moiety adopts an equatorial rather than an axial conformation in relation to the piperidine ring,(57) akin to the solid and probable solute state conformation of fentanyl, for which there is X-ray<58) and H-nmr evidence (see 20). The activities of the spiranes 19 also provide evidence that anilido phenyl is a- rather than /3-oriented in active conformations of fentanyl derivatives (21). This aromatic feature is confined to the /3-orientation in the bicyclo analogs 22, neither of... 

Derivatives of fentanyl and sufentanil with chemo- and photoaffinity functionalities attached to the anilido nitrogen (e.g., NCOCH2Br, NCOCH=N2) have been reported, but affinity labeling experiments performed with theses compounds on brain tissue met with little success. Some of the compounds, notably the diazoacetyl analog of cis 3-methylfentanyl, displayed high binding affinities.(60)... 

SYNS 5-CARBOXANILIDO-2,3-DIHYDRO-6-METHYD 1,4-OXATHIIN aCARBOXIN (USDA) D 735 DCMO 2,3-DIHYDRO-5-CARBOXANILIDO-6-METHYL-l, 4-OXATHIIN 5.6-DIHYDRO-2-METHYL-3-CARBOX-ANILIDO-l,4-OXATHIIN (GERMAN) 2.3-DIHYDRO-6-... 

If, however, there is insufficient aniline, a mixture, of phenyl isocyanate and anilido-formyl chloride is formed ... 

It is also interesting to note that -svlien the amino gi oup in aniline is substituted by basic groups, mercury compounds have always been obtained having the metal in the para position to the amino group, but in the case of the esters of the a-anilido fatty acids, the mercury always enters the ortho position to the substituted amino group, and in some eases the para position as well. 

In the ease of the esters of a-anilido fatty acids and tolylglycine esters, the acetoxymercuri compounds when saponified by sodium hydroxide, eliminate water between the bydroxymercuri residue and the carboxyl group, thus forming anhydrides of the type... 

Derivatives of a-ANiLiDO Fatty Acids and their Esters. -... 

In this series of compounds the substitution of mercury becomes more easy as the series is ascended. Whilst the ethyl a-anilido acetate... 

From this the higher indulines are formed by introduction of anilido-groups, by phenylation, and by introduction of the rest of paraphenylenediamine. This latter reaction always takes place in a normal induline melt, the paraphenylenediamine being formed from decomposition of amidoazobenzene. 

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