Amines aryl hahdes

PMMA is not affected by most inorganic solutions, mineral oils, animal oils, low concentrations of alcohols paraffins, olefins, amines, alkyl monohahdes and ahphatic hydrocarbons and higher esters, ie, >10 carbon atoms. However, PMMA is attacked by lower esters, eg, ethyl acetate, isopropyl acetate aromatic hydrocarbons, eg, benzene, toluene, xylene phenols, eg, cresol, carboHc acid aryl hahdes, eg, chlorobenzene, bromobenzene ahphatic acids, eg, butyric acid, acetic acid alkyl polyhaHdes, eg, ethylene dichloride, methylene chloride high concentrations of alcohols, eg, methanol, ethanol 2-propanol and high concentrations of alkahes and oxidizing agents. 

There has heen a review of the effects of high pressure on the substitution reactions of amines with haloaromatic compoimds, including polyhalohenzenes. Nucleophilic suhstitutions hy amines often proceed readily in dimethyl sulfoxide (DMSO). The p a values, in DMSO, have been reported for some ammonium ions derived from amines widely used as nucleophiles in 5nAt reactions. Correlations have been established between the oxidation potentials and the basicities of some arylamine and diarylamine anions and the rate constants for their reactions with aryl hahdes in DMSO. 

There are interesting transition metal-catalyzed-reactions that lead to aryl amides. The use of POCI3 and DMF, with a palladium catalyst, converts aryl iodides to benzamides. A palladium-catalyzed reaction of aryl hahdes and for-mamide leads to benzamide derivatives. Carbonylation is another method that generates amides. When an aryl iodide was treated with a secondary amine and Mo(CO)e, in the presence of 3 equivalents of DBU, 10% Pd(OAc)2, with micro-wave irradiation at 100°C, the corresponding benzamide was obtained. 

The transition-metal catalyzed cross-coupling reaction of (hetero)aryl hahdes and triflates with primary and secondary amines or (hetero)aryl amines is know as the Buchwald-Hartwig reaction [144]. Mechanistically, this reaction is related to the crosscoupling reactions outlined thus far (Fig. 4.6). The modification arises at the point of transmetalation. This step in the process is substituted with the coordination of the amine reactant. Deprotonation of the amine nitrogen now precedes the reductive elimination step to generate the aryl amine product. This reaction has foimd utility in the academic setting, for use in natural product total synthesis, and in industry, for the preparation of materials up to the multi-hundred kilogram scale. 

CPG material was used as support instead of silica gel for a Heck/SAPC system [6]. There, iodobenzene was coupled with different olefins. The dependencies of different substrates and different bases on the activity were examined. The system was active for several types of olefins. The reactivity of the aryl hahdes was comparable to that of the homogeneous catalysis. Iodides reacted easily, while bromobenzene was converted inefficiently. No reaction occurred using chlorobenzene. With EtjN as base, the highest conversions were achieved. However, leaching of palladium was observed and an /Z mixture of products was isolated. When the amine was replaced by KOAc, the Heck reaction gave selectively the -isomer. No leaching was observed (detection limit approx. 0.1 ppm), but the conversion dropped to 80%. The catalytic system with KOAc as base was successfully used for five consecutive rims, with an overall TON of > 1,200. In all cases, conversion ranged from 70 to 80% and 100% selectivity of the -isomer was achieved. 

These complexes show high catalytic activity (0.5 mol% loading) in short reaction times for the aryl amination of aryl chlorides, triflates, and bromides. Primary and secondary amines, both alkyl and aryl, are well tolerated. The mirroring of results can be emphasized if these palladacycles are compared to the (NHC)Pd(allyl)Cl systems, supporting the idea of identical active species [NHC-Pd] during the catalytic cycle. One of the limitations of these catalytic procedures or catalysts is their hmited activity for the couphng of electron-rich heterocycles with aryl hahdes. 

In the presence of a catalyst system of [Pd2dba3] and proazaphospha-trane (107) Verkade and Nandakumar [94,95] have achieved a double-amination-intermolecular Heck reaction sequence in a one-pot fashion with 4-amino styrene and various aryl hahdes to furnish the triarylated products 108 in moderate to excellent yields (Scheme 37). 

Scheme 16. Amination of polymer-bound aryl hahdes.l ...

A versatile family of structurally related dialkylbiaryl phosphines L15-L25 has been subsequently developed for the coupling of aryl hahdes with variety of amines (Fig. 20.2) [12-21]. BrettPhos and RuPhos found to be the most effective for coupling of 1° and 2° amines (Scheme 20.10). The main advantages of this class of hgands are its air stability, easy handling, crystallinity, and commercial availability. 

FIGURE 20.3 Ligands of the Cu-catalyzed cross-coupling of alkyl amines with aryl hahdes. 

Aryl hahdes with a strong electron-attracting group ortho or para to the halogen are substituted by nucleophiles such as hydroxide, alkoxides, ammonia, and amines. Suitable groups that facditate the reaction are nitro > cyano > carbonyl. The reactions occur under relatively ntild conditions. 

This chapter covers the C(aryl)-N bond formation via copper-catalyzed coupling of nitrogen nucleophiles (N-heterocycles, amines, anilines, amides, ammonia, azides, hydroxylamines, nitrite salts, phosphonic amides) with aryl hahdes. The C(aryl)-N bond formation as a result of the coupling between these nucleophiles and arylboronic acids (the Chan-Lam reaction) will be presented, too. 

Glucose-linked 1,2,3-triazolium ionic liquid 122 was prepared by copper(I)-catalyzed regioselective cycloaddition of a glucose azide with a glucose alkyne followed by quaternization with methyl iodide (Scheme 6.32). This IL was used as reusable ligand and solvent in copper(I)-catalyzed amination of aryl hahdes with aqueous ammonia [71]. Similar chemistry, that is, chcking of P-propargylxyloside with phenyl azide, followed by acetate removal and methylation was employed for the syntheses of D-xylose-based ionic hquids [72]. 

Another method for the conversion of alkyl hahdes to carboxylic esters is treatment of a halide with nickel carbonyl Ni(CO)4 in the presence of an alcohol and its conjugate base. When R is primary, RX may only be a vinylic or an aryl halide retention of configuration is observed at a vinylic R. Consequently, a carbocation intermediate is not involved here. When R is tertiary, R may be primary alkyl as well as vinylic or aryl. This is thus one of the few methods for preparing esters of tertiary alcohols. Alkyl iodides give the best results, then bromides. In the presence of an amine, an amide can be isolated directly, at least in some instances. 

The hazardous nature (see Tetrazoles below) of some alkyl azides limits the method in these cases, however A-alkyl- (benzyl) -1,2,3-triazoles can be obtained by preparing the azide in situ, for example using a mixture of sodium azide, the alkyne and a benzyl hahde in situ preparation of aryl azides is also feasible. An alternative method in which the alkyl azide is also generated in situ, is to use a diazo transfer to a primary amine the diazo transfer requires Cu(II) and the cycloaddition needs Cu(I) so a reducing agent is added together with the alkyne following the first phase. ... 

Double iV-arylation and S-arylation complete the assembly of phenothiazines from an amine and two aryl halides, one of the hahdes being an obromoarenethiol. 

The aminations of aryl halides were the first to be studied in palladium-catalyzed C—N bond formations, and are thus well developed nowadays. As the oxidative addition of the C—X bond of the aryl halide often constitutes the rate-limiting step in catalytic aminations, a relative reactivity is usually observed that is comparable to that obtained in most transition metal-catalyzed cross-couphngs. Thus, due to the decreasing bond dissociation energies, the reactivity order for hahdes is as follows Ph-Cl > Ph-Br > Ph-I [149]. 

Aryl sulfonates are often an alternative in cross-coupling reactions, if the corresponding hahdes are not available. In this context, the coupling of aryl triflates with amines catalyzed by the BINAP (1) system is a well-established methodology [18] to access valuable compounds (Scheme 13.29) [90]. 

To overcome the ring closure of intermediate 10 giving rise to by-product 8 that was particularly encountered with secondary alkyl halides. Tautens and coworkers [22] developed conditions that favor the oxidative addition of alkyl hahdes. The methodology was widely applied to the intramolecular (Scheme 19.12) and intermolecular ortho alkylation of aromatic C-H bonds with secondary alkyl iodides and bromides [23]. Depending on the terminating reactions employed (the Heck reaction, direct arylation of heterocycles, and the Buchwald-Hartwig amination), a variety of valuable heterocydes were efficiently prepared. It should be pointed out that the reaction of enantioenriched substrates occurred with... 

---