YV-arylation

A representative 1,3-dipolar cycloaddition process occurs with yV-aryl-C-(trifiuoromethyl)-nitrilimines, generated from the corresponding hydrazonoyl bromides, c.g. 4. under basic conditions. which can react with dimethyl fumarate and maleate,bicyclic olefins. and dipolarophiles containing cumulative double bonds. With sodium isocyanates as the dipolarophilc the cycloaddition reaction occurs across the C = N bond, while with potassium isothiocyanate it occurs through the C = S bond. ... 

Oxidation of (266 Ar = Ph) with nitrous acid produces the thiadiazole (86) which can be isolated when R is alkyl. Treatment of (86) with acid produces Hugerschoff bases (87 Scheme 93). When R of (266) is aryl, isomerization is rapid and only (87) is obtained when acidic peroxide is used as the oxidant (65AHC(5)119>. Recently the reaction has been studied using mixtures of thiourea and jV.JV -disubstituted thioureas. Products of type (267) and (268) were isolated from N-aryl-TV -alkylthioureas but only (268) was obtained from the yV-aryl-W-aryl and JV-alkyl-AT-alkyl derivatives (Scheme 94) (80IJC(B)667,75IJC(B)24l). 

Scheme 16 y-Selective conjugate addition of azlactones to yV-aryl maleimides... 

Electrophilic iV-aminations have been performed with hydroxylamine-O-sulfonic acid (HOSA)," O-(2,4-dinitrophenyl)hydroxylamine and 0-mesitylenesulfonylhydroxylamine. The use of HOSA is mainly restricted to aqueous reaction media. Imide sodium salts of some heterocycles such as theobromine (88) can be converted to hydrazine derivatives by treatment with 0-(diphenylphosphinyl)hydroxylamine (equation 35).This reaction has been extended to synthesis of -arylhydrazines, where R and R are hydrogen, alkyl or aryl (equation 36)." Similarly, trisubstituted hydrazines can be prepared by the use of yV-aryl-O-acetylhydroxylamines and secondary amines." A recent publication" concerning the synthesis of l-acyl-2-dkylhydrazines from hydroxamic acids and amines in the presence of activating agents has been found to be erroneous no N—N bond formation occurs under these conditions. "... 

A solution of the sodium salt of yV-methylaniline in HMPA can be used to cleave the methyl group from aryl methyl ethers ArOMe + PhNMe —> ArO + PhNMca- This reagent also cleaves benzylic groups. In a similar reaction, methyl groups of aryl methyl ethers can be cleaved with lithium diphenylphosphide (PH2PLi). " This reaction is specific for methyl ethers and can be carried out in the presence of ethyl ethers with high selectivity. 

It has been found that a number of bidentate ligands greatly expand the scope of copper catalysis. Copper(I) iodide used in conjunction with a chelating diamine is a good catalyst for amidation of aryl bromides. Of several diamines that were examined, rra s-yV,yV -dimethylcyclohexane-l,2-diamine was among the best. These conditions are applicable to aryl bromides and iodides with either ERG or EWG substituents, as well as to relatively hindered halides. The nucleophiles that are reactive under these conditions include acyclic and cyclic amides.149... 

The yV-benzoylhydrazones of methyl 4-aryl-2,4-dioxobutanoates 76 (R = XC6H4 = Ph) (81ZOR284) have been isolated as several isomers in the solid state (see Table XIII), depending on the substituent X. In CDCI3 solution, the equilibrium 76A-Z 76A- 76B (Table XIII) ap-... 

The Li compound 588 formed by the oz-r/w-lithiation of yv,A-dimethylaniline reacts with vinyl bromide to give the styrene derivative 589(433], The 2-phe-nylindole 591 is formed by the coupling of l-methyl-2-indolylmagnesium formed in situ from the indolyllithium 590 and MgBr2> with iodobenzene using dppb(434]. 2-Furyl- and 2-thienyllithium in the presence of MgBr2 react with alkenyl halides(435]. The arylallenes 592 and 1,2,4-alkatrienes are prepared by the coupling reaction of the allenyllithium with aryl or alkenyl halides[436]. 

Triflic acid catalyzes the arylation of Af-methyl-l,2,3,6-tetrahydropyridine 227 to give 4-phenylpiperidine 229 (Scheme 59) <2001TL5821>. The reaction is believed to proceed by initial formation of a 1,4-dication 228, which forms in preference to the 1,3-dication 231. When yV-methyl-5-phenyl-l,2,3,6-tetrahydropyridine 230 is arylated under the same conditions, 3,3-diphenylpiperidine 232 is formed as the sole product showing the stabilization of the 1,3-dication intermediate 231 by the tertiary 5-position. Intramolecular arylation of 2- and 6-benzyl-substituted 1,2,3,6-tetrahydropyridines can also be catalyzed by triflic acid <20050L4309>. 

Gabriel and Wenker type synAeses are thoroughly viable for yV-alkylaziridines, and there are examples of aziridination of alkenes, via vic-dihalides etc., where by use of a chiral amine a kinetic induction of chirality in the aziridine nucleus has been achieved. 2-Iodoalkyl azides react with alkyl and aryl dichloroboranes, forming aziridines (Scheme 17). Sequences resembling the Wittig and Wittig-Hor-... 

Triazines with three different substituents are formed by variations on the above methods. There is no efficient route to trialkyl or triaryl derivatives, although the reaction of acylimidates and amidines has met with some success (see Section 2.20.4.6.2). In general the best routes available are as follows, (a) Substitution reactions of cyanuric chloride, (b) The condensation of yV-cyanoamidine with chloromethyliminium salts, (c) 2-Aryl-l,3,5-triazin-2-ones may be efficiently prepared by ring closure reactions on yV-(a-chloroalky-lidene)carbamoyl chloride and amidines (see Section 2.20.4.4.1). 

Pyrazine yV-Oxides, their C-Alkyl and C-Aryl Derivatives... 

Aryl tellurium chlorides, prepared by halogenolysis of diaryl ditellurium compounds, combined with yv.Af-dichlorobenzenesulfonamide in carbon tetrachloride to produce an equimolar mixture of aryl tellurium chloride benzenesulfonimide and aryl tellurium trichloride. ... 

A -Aryl-iV -phenylalkynylamidines are cycitzed to quinolines by treatment with hot PPA the main product is the 2-(A -methyl-yV-phenylamino)quino]ine but cyclization on to the other benzene ring may (xxur to some extent. 3-Phenyl-aminobut-2-enoate esters are cyclized (on to a ring-carbon) at or below room temperature by the application of Vilsmeier reagents. 

Further reaction of 17 with thiolate or reaction of 8 with two equivalents of thiolate provides the stable 3,5-bis[alkyI(aryl)siilfanyl]-.W,yV-dialkylthiatriazin-l-amines 16.43... 

Aryl ortho thioesters, which can be readily prepared from the corresponding acid chlorides207 or methyl esters,208 react with yV-halo compounds, such as l,3-dibromo-5,5-dimethylhydantoin (DBH) or yV-bromosuccinimide, and hydrogen fluoride/pyridine to give aromatic trifluoromethyl compounds,236 i.e. formation of 7.207... 

Spirofused (3-lactams related to 64 were prepared from 3-hydroxy-3-arylpropanamides after activation of the hydroxyl group by formation of a phosphate ester <97JOC6412>. A similarly easy cyclization occurred when the A-aryl amide 66 was treated with potassium carbonate <97TA739>. Radical induced 4-e.w-trig cyclizations of yV-vinyl-2-bromobutan-... 

The condensation of aldehydes with thiocyanoacetic esters, catalysed by potassium fluoride or potassium carbonate, gave as minor products yV-carbamoyl-2-imino-5-alkyl(or aryl)-l, 3-oxathiolan-4-carboxylic esters, in which the 4,5-c/j-isomers predominated according to n.m.r. spectroscopy. l,3-Oxathiolan-2-thione was converted into dimethyl 1,3-dithiol-2-one-4,5-dicarboxylate and ethylene on treatment with dimethyl acetylene-dicarboxylate, and the transformation of methyl 2-methoxycarbonyl-methyl-1,3-oxathiolan-2-carboxylate into dimethyl-5,6-dihydro-l, 4-oxa-thiin-2,3-dicarboxylate by chlorination at low temperatures found analogy in the reactions of 2,2-dialkyl-l,3-oxathiolans. Thiomethoxymethyl hexachloroantimonate reacted with potassium t-butoxide to give mainly 3,5,5-trimethyl-l,3-oxathiolanium hexachloroantimonate the mechanism of this remarkable reaction was not settled. ... 

The reaction of yV-acylhydrazines with benzeneseleninic acid (29 Scheme 9) in the presence of triphe-nylphosphine afforded high yields of diverse selenol esters. Alkyl, cycloalkyl and aryl selenol esters were prepared, even in the case of the highly hindered compounds (30) and (31). 

Methods F and G are ligandless palladium-catalysed and therefore dramatically sensitive to the presence of an oxygen [28], Beside aryl bromides, the Pd(OAc)2 or Pd(SEt2)Cl2-catalysed SM reactions in Af,yV-dimethylformamide were effectively conducted with aryl chlorides [29], When appropriate precautions were taken, the SM cross-coupling reaction of phenylboronic acid (260) with 4-nitro-bromobenzene (168) or 4-nitro-iodobenzene (225) furnished 4-nitrobiphenyl (224) with a quantitative yield within 0.75 or 2.5 h. Scheme 16. 

Pryadeina MV, Burgart YV, Saloutin VI, Kodess MI, Ulomskii EN, Rusinov VL (2004) Synthesis of 7-alkyl(aryl)-6-aIkoxycarbonyl-5-fluoroalkyl-l, 2,4-tri(tetr)azolo[ 1,5-a]pyrimi-dines. Russ J Org Chem 40 902-907... 

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