Benzamide arylation

We reasoned that the arylation of benzamide derivatives should also be possible under Pd(II)-Pd(IV) couple conditions. Gratifyingly, conditions that were developed for anilide arylation worked well for benzamide arylation (Scheme 12) [57],... 

Poly(arylene thioether)s, 363-364 Poly(arylene thioether sulfone)s, 364 Poly(aryl sulfone) derivatives, 354 Poly(p-benzamide), synthesis of, 188-189 Polybenzimidazoles (PBIs), 265 ferrocene-containing, 315 synthesis of, 313... 

Amides and sulfonamides undergo intramolecular chemistry to form aryl amides and aryl sulfonamides (Equations (17)—(19)) in the presence of palladium catalysts ligated by arylphos-phines.35,89 Initially, complexes of P(furyl)3 and P(o-tol)3 were most effective catalysts, but complexes of Hayashi s MOP and van Leeuwen s DPEphos and xantphos have lately been shown to be more active.90 In the presence of catalysts containing one of these ligand systems, five-, six-, and seven-membered rings were formed from halogenated benzamides or from substrates containing an acetamide, an A-carbobenzyloxy, or a t-butylcarbamate substituent tethered to the aryl halide (Equations (18) and (19)) ... 

Tandem mass spectrometry has been used to demonstrate that M+ as well as MH+ of substituted A-(ort/zo-cyclopropylphenyl)benzamides isomerizes before the fragmentation, with formation of 3-aryl-1-ethyl-lH-benzoxazines and 5-ethyl-2-oxodi-benzoazepines (Scheme 5.14). The methyl group in /V-[ortho-( 1 -methylcvclopropyl )-phenyl]benzamides quenches the latter process, leaving the formation of benzoxazines as the only cyclization reaction. A subsequent chemical experiment in solution confirmed the mass spectral predictions [24]. A similar study confirmed the analogy of cyclization of substituted A-(ort/zo-cyclopropylphenyl)-A -aryl ureas and N- ortho-cyclopropylphenyl)-A -aiyl thioureas in the ion source of mass a spectrometer and in solution [25]. 

Synthetic applications of the asymmetric Birch reduction and reduction-alkylation are reported. Synthetically useful chiral Intermediates have been obtained from chiral 2-alkoxy-, 2-alkyl-, 2-aryl- and 2-trialkylsllyl-benzamides I and the pyrrolobenzodlazeplne-5,ll-diones II. The availability of a wide range of substituents on the precursor benzoic acid derivative, the uniformly high degree of dlastereoselection in the chiral enolate alkylation step, and the opportunity for further development of stereogenic centers by way of olefin addition reactions make this method unusually versatile for the asymmetric synthesis of natural products and related materials. 

It has been shown that, in the presence of lithium diethylamide at —70 °C, bromoben-zoic acids form arynes which may react with arylacetonitriles to yield, predominantly, 2-cyanobenzoic acids. The reaction of alkyl and aryl isocyanides with benzyne may yield benzamide derivatives, showing their ability to act as charge-reversed equivalents to isocyanates. The generation and cyclization of a benzyne-tethered alkyllithium have been reported, and lead to a convenient synthetic route for 4-substituted indans. ... 

An Ir(l)-catalyzed asymmetric intermolecular hydroarylation of norbornene with benzamide was reported in good to excellent enantiomeric excess, albeit in low yields, via the aryl C—H activation (Scheme 5.14). In some cases, the hydroami-nation products of norbornene were also formed in high enantioselectivities. 

Benzamides constitute a fourth dass of HDAC inhibitors. One example, MS-275, is a phenylenediamine derivative that exhibits robust HDAC inhibition in patients with advanced myeloid leukemia as well as refractory solid tumors or lymphoma in Phase I studies [72]. MS-275 is currently in Phase II trials. In a recent study aimed at optimizing the benzamide scaffold, several bis-(aryl) type analogs were synthesized and evaluated for their activity against a panel of HDACs [85]. Moradei et al. found that a thienyl substitution para to the free amino group in the phenylenediamine core rendered inhibitors specific for HDACsl, 2 with potency superior to that of MS-275. Isoform-specific inhibitors should aid in dissecting the roles of HDACs in normal cellular fundioning and cancer. 

The iodo benzamide derivative of pyrrolo[2,l-c][l,4]benzodiazepine 367 (R = I, Scheme 75, Section 5.1.1) reacts with bis(tributyl)tin, lithium chloride and tetrakis(triphenylphosphine) palladium(O) in refluxing dioxane to yield the stannyl derivative 370. The latter couples with substituted aryl bromides in the presence of... 

As mentioned earlier, the synthesis of primary amides is rather challenging due to technical difficulty in handling gaseous ammonia. Thus, the use of ammonia substitutes such as HMDS and formamide has been studied (see Schemes 21 and 22). With the use of microwave irradiation, however, it has been shown that it is possible to generate both CO and ammonia at the same time for the synthesis of primary amides from aryl bromides. This protocol is very useful for laboratory organic syntheses, especially combinatorial syntheses. As Scheme 29 illustrates, the Pd-catalyzed aminocarbonylation of aryl bromides 200 with formamide (33.5 equiv.) in the presence of KOBu (1.5 equiv.) and imidazole (1 equiv.) with microwave irradiation for 400 s (6.7 min) gave the corresponding benzamides... 

The concept of in situ liberation of carbon monoxide would be even more attractive if a metal-free material could serve as the carbon monoxide source. In the ideal carbonylation method, the organic solvent itself could be exploited for controlled generation of carbon monoxide. In 2002, Wan et al. addressed this issue and developed a microwave-promoted carbamoylation process based on the commonly used solvent dimethylformamide (DMF) as the carbon monoxide precursor75. Firstly, it was discovered that aryl dimethyl amides were accessible from the corresponding bromides in the presence of a nucleophilic catalyst, imidazole (Scheme 2.34). Secondly, tertiary benzamides other than dimethylamides were synthesised by addition of 3 equiv of an external amine (Scheme 2.34). 

Formylation of the aryl group of MSMA benzamide to produce o-formylbenzamides has also been performed without observation of side reactions.137,152... 

Detailed proton NMR spectroscopic data on a variety of fused and spiro thietane and thiete derivatives was tabulated in the corresponding sections of CHEC(1984) and CHEC-II(1996). Therefore, only limited, newer information is presented here. A series of iV-(4-methoxyphenyl), iV-(l -naphthyl), iV-benzyl, and iV-(4-nitrophenyl)-,/V-(thietan-3-yl)benzene- or methanesulfonamides 13 as well as the analogous iV-aryl-iV-(thietan-3-yl)-2-nitroben-zenesulfonamides 14, 3-arylaminothietanes 15, iV-(4-aryl)-iV-(l-oxothietan-3-yl)-2-nitrobenzenesulfonamides 16, iV-(l,l-dioxothietan-3-yl)-Ar-(aryl)-2-nitrobenzenesulfonamides 17, 3-(4-arylamino)thietane 1,1-dioxides 18, and iV-(4-aryl)-iV-(thietan-2-yl)benzamides 19 were identified on the basis of their H NMR spectra <2005RJ01023>. 

Scheme 2 Preparation of primary benzamides from aryl iodides and bromides by in situ carbonylation...

Aryl-l,2,4-dithiazole-3-thiones react with phenylacetylene giving two compounds, namely, A-(4-aryl-l,3-dithiol-2-ylidene) thiobenz-amide (52) and 2,5-diaryl- 1,6,6a IV-trithia-3-azapentalene, which may also be considered as AT-(5-aryl-l -dithiohS-ylideneJthiobenz-amide (53). This compound is converted into the corresponding benzamide (54) by mercuric acetate oxidation, the opposite reaction being realized with phosphorus pentasulfide.79... 

Chang et al. [84] reported on the unprecedented aminocarbonylation of aryl iodide. In this case, the Ru3(CO)12-PdCl2 cooperative catalyst system is effective. The reaction of 4-acetyliodobenzene with N-(2-pyridyl)formamide with the aid of Ru3(CO)12 and PdCl2 gives 4-acetyl-N-(2-pyridyl)benzamide in 83% yield (Eq. 57). 

Treating A-aryl-2-(benzylthio)benzamides 215 with [bis(trifluoroacetoxy)iodo]benzene containing TFA results in an interrupted Pummerer-type reaction to give 2-aryl-l,2-benzisothiazolo-3(2//)-ones 216 (Scheme 125) <2001H(55) 1231, CHEC-III(4.05.9.1)596>. 

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