Amines diaryl, reaction with

Bromination of the methyl group of (249) with A -bromosuccinimide, followed by reaction with excess secondary amine gave (250) which shows combined analgesic and antitussive properties. The Reformatsky reaction has also been used for the preparation of 2-amino-ethyl 3,3-diaryl-3-hydroxypropanates (251) as well as their dehydration products. The propene amides (252) have also been prepared for pharmacological evaluation. In l-methyl-3-bis (2-thienyl)-... 

Secondary amines have been converted to tertiary amines by treatment with lithium dialkylcuprate reagents R2CuLi -t- NHR RNR2 The reaction was also used to convert primary amines to secondary, but yields were lower. However, primary aromatic amines (ArNH2) were converted to diaryl amines (ArNHPh) by treatment with Ph3Bi(OAc)2 and a copper powder catalyst. 

When secondary amines are treated with nitrous acid, N-nitroso compounds (also called nitrosamines) are formed. The reaction can be accomplished with dialkyl-, diaryl-, or alkylarylamines, and even with mono-N-substituted amides RCONHR -I-HONO RCON(NO)R. Tertiary amines have also been N-nitrosated, but in these cases one group cleaves, so that the product is the nitroso derivative of a secondary amine.The group that cleaves appears as an aldehyde or... 

In contrast, when excess amounts of the HHTs derived from simple aliphatic glycinate esters, such as 25, were used in excess in reactions with diaryl phosphites (SO), the related glyphosate aminals containing aryl phosphonate esters 46 were isolated in low yield (5-15%). Like many aminals, these triesters 46 were acid-sensitive and were quantitatively converted to the corresponding triester strong acid salts 47 upon treatment with either HCl or methanesulf onic acid (27). 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

Nucleophilic Perfluoroalkylation of Nitrones The reaction of a,N-diaryl nitrones with (trifluoromethyl)trimethylsilane (TMSCF3) gives O-trimethylsilyl ethers of a-(trifluoromethyl)-hydroxylamines. This reaction is initiated by potassium ten -butoxide. Removal of the trimethylsilyl group on acid treatment leads to a-(trifluoromethyl)hydroxylamines, whereas catalytic hydrogenation gives a-(trifluoromethyl)amines (Scheme 2.194). 

Symmetrical dialkyl and diaryl thioureas have been prepared in generally good yield (60-90%) from the reaction of the amine with thiophosgene, formed in situ from the catalysed reaction of carbon tetrachloride with sodium sulphide [5], Reaction with diamines yields cyclic ureas. 

The palladium-catalyzed amination reaction with a monofunctional primary amine 167 effects i / -diarylation to afford the tertiary amine polymers 168. Hence, polycondensation of 167 with bifunctional arylene dihalides leads to 168 (Equation (81)). Polycondensation of a primary amine bearing an azobenzene moiety with dibromides in the presence of Pd2(dba)3 (2.5mol%)- Bu3P (P/Pd = 3 l) and NaO Bu at 100°G for 24h in toluene gives 168 in 81-93% yields, as reported by Kanbara. 

Other nucleophiles than amines which have been employed in the reaction are malononitrile and cyanoacetic ester anions. Both of these anions undergo a preliminary reaction with the aryl halide to form the C-aryl derivatives before they attack the ir-allylpalladium intermediate, so that diarylated products are formed (equation 31).86 Phenylmalononitrile anion reacts with iodobenzene and butadiene to give the same product in 70% yield. 

Fig. 16.6. Copper-mediated nucleophilic substititon reactions with aryl iodides or bromides for the preparation of diaryl ethers, diaryl sulfides, diaryl amines and arylmalonic esters (A). Often, these reactions are also referred to as Ullmann reactions.

The relative rates of these reaction sequences were found to depend on the nature of the medium (homogeneous or heterogeneous), rate of addition of water, temperature, reactivity of the amine (formed by the decomposition of the carbamic acid) with the isocyanate, concentration, and other factors. For example, in the reaction with phenyl isocyanate, cold water and heterogeneous medium favored the formation of diaryl urea while with boiling water the main product was aniline. Dilution also favored aniline formation. 

Molybdate esters These compounds are prepared by reaction of alkanols and molybdenum sources such as ammonium molybdate and molybdenum oxides, and are believed to form mononuclear mono- and dioxo- structures, as in Reaction (4.44) [54,55], These preparations are condensation reactions and require removal of water to drive the reaction to completion. Molybdate esters, like molybdenum carboxylates, show synergistic effects with diaryl amines [52] and with combinations of diaryl amines and sulphurised hindered phenols and/or sulphurised olefins [53],... 

Diaryl-isoindoles can be constructed from 1,2-diaroyl-benzenes by reaction with an amine and a reducing agent. °... 

Nucleophilic displacement of chlorine, in a stepwise manner, from cyanuric chloride leads to triazines with heteroatom substituents (see Section 6.12.5.2.4) in symmetrical or unsymmetrical substitution patterns. New reactions for introduction of carbon nucleophiles are useful for the preparation of unsymmetrical 2,4,6-trisubstituted 1,3,5-triazines. The reaction of silyl enol ethers with cyanuric chloride replaces only one of the chlorine atoms and the remaining chlorines can be subjected to further nucleophilic substitution, but the ketone produced from the silyl enol ether reaction may need protection or transformation first. Palladium-catalyzed cross-coupling of 2-substituted 4,6-dichloro-l,3,5-triazine with phenylboronic acid gives 2,4-diaryl-6-substituted 1,3,5-triazines <93S33>. Cyanuric fluoride can be used in a similar manner to cyanuric chloride but has the added advantage of the reactions with aromatic amines, which react as carbon nucleophiles. New 2,4,6-trisubstituted 1,3,5-triazines are therefore available with aryl or heteroaryl and fluoro substituents (see Section 6.12.5.2.4). 

Transition metal catalyzed processes are useful tools for the synthesis of functionalized thiophenes. Thus for instance, a phosphine-free, palladium catalyzed coupling protocol for the synthesis of 2-arylbenzo[d]thiophenes from various 3-substituted benzo[6]thiophenes and aryl bromides or iodides has been reported <04T3221>. Likewise, 2,2 -bithiophenes have been 5,5 -diarylated directly with aryl bromides in the presence of Pd(OAc)2, bulky phosphine ligands and CS2CO3 <04T6757>. A series of electron-deficient and relatively electron-rich benzo[6]thienyl bromides have been shown to participate in palladium catalyzed amination reactions, as exemplified by the interesting conversion of 63 to the tetracyclic system 64 upon reaction with 2-aminopyridine 65 <04EJO3679>. 

Arylamines and diaryl ethers. Polyhaloarenes have been employed in A-arylation. By using certain carbene ligands, rapid reaction with chloroarenes at room temperature has been demonstrated. The (dba)2Pd-t-BujP system has a wide scope of arylation including that of indole and carbamates." (Formation of Al-dimethylaminoindole from 2-chlorophenylacetaldehyde MA-dimethylbydrazone is novel." ) A more complicated ligand for arylation of amines by aryl chlorides is 1."... 

Scheme 10.3 Generation of reactive free radicals with the aid of type II initiators, exemplified by the reaction of a triplet-excited diaryl ketone with a tertiary amine.

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