Anilides cleavage

Cacciapaglia, R., Di Stefano, S. and Mandolini, L. (2002) Size selective catalysis of ester and anilide cleavage by the dinuclear barium(ll) complexes of cis- and trRns-stilbeno-bis-18-crown-6. J. Org. Chem., 67, 521. 

Dinuclear Ba(II) complexes of cis- and trans-stilbenobis(18-crown-6) have been prepared [105]. These complexes catalyzed size-selective ester and anilide cleavage. 

Hydrazine, EtOH, 85% yield. Note that the cleavage of an anilide and a benzoylpyrrole is much more facile than that of a typical aliphatic benzamide. 

A, A-Diethylaminomethyl)anilidate 3-[(C2H5)2NCH2]C6H4NH-Cleavage is effected with isoamyl nitrite in Pyr/AcOH." "... 

The mechanism for the conversion of the A -oxide (94) to the o-methylaminophenylquinoxaline (96) involves an initial protonation of the A -oxide function. This enhances the electrophilic reactivity of the a-carbon atom which then effects an intramolecular electrophilic substitution at an ortho position of the anilide ring to give the spiro-lactam (98). Hydrolytic ring cleavage of (98) gives the acid (99), which undergoes ready dehydration and decarboxylation to (96), the availability of the cyclic transition state facilitating these processes. ... 

It is intriguing to note that this reaction scheme for the reduction of a sulphone to a sulphide leads to the same reaction stoichiometry as proposed originally by Bordwell in 1951. Which of the three reaction pathways predominates will depend on the relative activation barriers for each process in any given molecule. All are known. Process (1) is preferred in somewhat strained cyclic sulphones (equations 22 and 24), process (2) occurs in the strained naphtho[l, 8-hc]thiete 1,1-dioxide, 2, cleavage of which leads to a reasonably stabilized aryl carbanion (equation 29) and process (3) occurs in unstrained sulphones, as outlined in equations (26) to (28). Examples of other nucleophiles attacking strained sulphones are in fact known. For instance, the very strained sulphone, 2, is cleaved by hydride from LAH, by methyllithium in ether at 20°, by sodium hydroxide in refluxing aqueous dioxane, and by lithium anilide in ether/THF at room temperature. In each case, the product resulted from a nucleophilic attack at the sulphonyl sulphur atom. Other examples of this process include the attack of hydroxide ion on highly strained thiirene S, S-dioxides , and an attack on norbornadienyl sulphone by methyllithium in ice-cold THF . ... 

Anilide herbicides are metabolized in plants via cleavage of acylamide moiety. 

There is little mention in the literature of the use of amide salts in substitution reactions on chlorophosphazene precursors. The anilide anion was shown to be a powerful nucleophile in substitution reactions on various trimer derivatives, but investigations of such reactions with the high polymer have not been reported.22 Where strong nucleophiles (such as amide salts) with low steric requirements are employed, the usual pentacoordinate transition state (Scheme 1), may be a viable reaction intermediate which can undergo alternative modes of decomposition, perhaps involving chain cleavage and/or cross-linking. 

The bis-barium complex of pure trans-28 (0.10 mM) increases the rate of ethano-lysisof29 (65/35 EtOH/MeCN, 1 mM Me4NOEt, 25 °C) by 230-fold. The corresponding figures for quasi-trans-28-Ba2 and quasi-cis-28-Ba2 are 420- and 1280-fold, respectively. Thus, the behavior of trans and ds isomeric catalysts based on azobenzene closely parallels the behavior of the corresponding stilbene derivatives 26 and 27, in that in both cases the ds form is a superior catalyst in the cleavage of anilide 29. 

A wide range of linker groups are currently used with SynPhase crowns. They accommodate formation of the following functional groups upon cleavage carboxylic acids, primary and secondary amides, sulfonamides, alcohols, phenols, amines, anilines, anilides, hydroxymates, aldehydes, ketones, and thiols. 

Table 3.26 lists illustrative examples of cleavage reactions of support-bound N-aryl-carbamates, anilides, and /V-arylsulfonamidcs. /V-Arylcarbamatcs are more susceptible to attack by nucleophiles than /V-alkylcarbamates, and, if strong bases or nucleophiles are to be used in a reaction sequence, it might be a better choice to link the aniline to the support as an /V-bcnzyl derivative. Entry 7 (Table 3.26) is an example of a safety-catch linker for anilines, in which activation is achieved by enzymatic hydrolysis of a phenylacetamide to liberate a primary amine, which then cleaves the anilide. 

The anilide substrates J -A1 a-J -Ala-pNA (36) and -Ala-L-Pro-pNA (37) are hydrolyzed via a different rate-determining step by the serine protease, dipeptidyl-peptidase IV (12, 13). For 36, the rate-determining-step is the formation of the acyl-enzyme and for 37, it is the cleavage of this intermediate. This different behavior has been rationalized on the basis of arguments derived from the principle of stereoelectronic control in the hydrolytic process. 

Nitrations of phenyl derivatives of small ring heterocycles have been little studied. The nitration of 3-(4-nitrophenyI)-l-phenyl-2,2-dichloroaziri-dine (90) using potassium nitrate in sulfuric and acetic acids yields 1,3-bis(4-nitrophenyl)-2,2-dichloroaziridine and 3-(4-nitrophenyl)-l-(2-nitro-phenyl)-2,2-dichloroaziridine in 65 35 ratio. Under the same conditions the diphenyl derivative undergoes cleavage of the aziridine ring to give a mixture of nitrated anilides. 

Acidic work-up of 18 furnishes ketone 22. Further addition of HC1 and acetic acid at 70 °C results in cleavage of the pivaloyl anilide to yield the unprotected orf/io-ketoaniline as hydrochloride hydrate 5, since ketones with neighboring electron-withdrawing groups undergo nucleophilic addition of water. 5 directly crystallized from the reaction mixture and was obtained in 87 % yield with a purity of > 98 %. These three steps were carried out on a 3,700 g scale. 

Dimeric 7r-arene-bridged samarium anilide [Sm(NHArl Pr,H)3]2 was employed in the isolation and characterization of a dimeric amido-imido compound. Addition of 4 equivalents of TMA led to (1) cleavage of one of the Ln-NHPh bonds, (2) deprotonation, and (3) adduct formation. Density functional theory calculations, carried out in order better to understand the nature of the imido bonding, revealed the presence of Sm - N 7r-bonding interactions involving the samarium 5d orbitals [218]. 

The reaction proved to be quite flexible both electron-rich and electron-poor substituted benzanilides worked well, as did heteroaroyl anilides, saturated heterocycle anilides, and alkyl anihdes. The presence of competitive acidic a-hydrogens or of a,P-unsaturated acyl residues did not lead to good results. For greater diversity, the cyano group of the original aniline could be efficiently replaced by a tert-butyl ester or a dimethylamide. Cleavage from the resin was performed with GH2Gl2/TFA/triethylsilane (94 5 1, v/v/v). The product (603) was then dried in vacuo at 40 °C. 

As mentioned in the discussion of the pathways to indoles (Scheme 27), a detailed indole synthesis with two points of diversity based on the Heck reaction has been reported [164]. The indole core structure was synthesized via a 5-exo-tng transition state, which provided the exocyclic double bond that subsequently underwent exo to endo double-bond migration. The anthranilate building block was prepared in solution and immobilized by a method previously described for the loading of 2-aminobenzophenones [Ij. After Fmoc cleavage, the resulting 4-bromo-3-amino-phenyl ether was treated with acid chlorides and pyridine in CH2CI2. As outlined in Scheme 29, alkylation of the anilide with substituted allyl bromides was achieved in the presence of lithium benzyloxazoHdinone in THF. The reaction mixture was treated with base for 1 h and then an aUylic halide was added and the mixture was vortexed for 6 h at room temperature. The alkylation reactions were... 

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