Alkyl hahde reaction with amines

The reactivities of alkyl halides are in the sequence RI > RBr > RCl and MeX > EtX > PrX. Benzyl hahde reactions with tin do not require catalysts (equation 2). For less reactive halides, the catalysts and promoters employed include metals (sodium, magnesium, zinc, or copper), Lewis bases (amines, triorganophosphines and -stibines, alcohols, or ethers), iodides, and onium salts (R4MX). The use of tin-sodimn alloys can result in tri- or tetraorganotin products. Electrochemical synthesis has also been reported, e.g. the formation of R2SnX2 from the oxidation of anodic tin by RX in benzene solution and the formation of ILtSn from RI (R = Me or NCCH2CH2) and cathodic tin. 

Method 7. Alkyl haHde amination reaction of ammonia or alkylamine with an alkyl haHde. 

A number of 2eohtic materials have been claimed to cataly2e this reaction and reaction temperatures are on the order of 200—350°C with pressures as high as 18000 kPa (2600 psi) reported. This is a low conversion process and recycle of the unconverted starting materials is necessary to provide an economical process. Amination of ethylene to produce ethylamines cataly2ed by ammonium iodide is reported, but not beheved to be practiced commercially (15,16). Alkyl Halide Amination (Method 7). The oldest technology for pioducing amines is the reaction of ammonia with an alkyl hahde. This... 

The reaction between alkyl hahdes and ammonia or primary amines is not usually a feasible method for the preparation of primary or secondary amines, since they are stronger bases than ammonia and preferentially attack the substrate. However, the reaction is very useful for the preparation of tertiary amines and quaternary ammonium salts. If ammonia is the nucleophile, the three or four alkyl groups on the nitrogen of the product must be identical. If a primary, secondary, or tertiary amine is used, then different alkyl groups can be placed on the same nitrogen atom. The conversion of tertiary amines to quaternary salts is called the Menshutkin reaction It is sometimes possible to use this method for the preparation of a primary amine by the use of a large excess of ammonia or a secondary amine by the use of a large excess of primary amine. The use of ammonia in methanol with microwave irradiation has also been effective. Microwave irradiation has also been used in reactions of aniline with allyl iodides. A base other than the amine... 

Menschutkin reaction. Reaction of tertiary amines with alkyl hahdes to form quaternary salts. 

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... 

To avoid the direct manipulation with hazardous azides, methods using Cu(I)situ generation of azides were developed as one-pot procedures, for example, with substitution reaction of alkyl hahdes by NaN3 [493] or with nitrosation of aromatic primary amines by tBuONO followed by trimethylsilyl azide [494]. Vice versa, the alkyne component has been generated in situ, for example, by sequential Seyferth-Gilbert reaction (homologation of aldehydes with diazophosphonates) and reaction with azides in a Cu(l)-catalyzed cycloaddition [495]. 

In prior chapters we have already discussed many general methods to synthesize amines. In this section we consider substitution reactions of alkyl hahdes with ammonia or an amine, and a variation on this method that improves yields. 

Primary, secondary, and tertiary aliphatic amines have been cleaved to give aldehydes, ketones, or carboxylic acids with aqueous bromine and with neutral permanganate. " The other product of this reaction is the amine with one less alkyl group. In a different type of procedure, primary alkyl primary amines can be converted to gem-dUialides [RCH2NH2 RCHX2 (X = Br or Cl)] by treatment with an alkyl nitrite and the anhydrous copper(I) hahde. ... 

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. 

Quatemization involves the reaction of a tertiary amine with an alkylating agent. Typically, primary and some secondary alkyl halides are used for this purpose, although alkyl sulfates have also been used. Tertiary hahdes are not useful because they undergo elimination rather than substitution. The reaction, which is an example of an Sn2 process, proceeds readily to give crystalline, stable, and still-aromatic quaternary salts (Scheme 6.6). These have been used for many years to characterize amines. Acyl halides also react in a similar manner with pyridine, but the resulting salts are unstable and generally not isolated. 

The direct photolysis of alkyl or aryl halides in solution to form carbon-centered radicals is rarely used in organic synthesis." Alkyl iodides usually afford mixtures of radical and ionic products, while alkyl bromides can produce radical-derived products but in low yield. A notable exception is the photocycliza-tion of haloarenes, which has been shown to produce carbon-centered radicals that can add to aromatic rings. A similar reaction has recently been observed on irradiation of iodoheterocycles, with substituted benzenes or electron-poor alkenes, to form arylated or alkylated heterocycles in good yield. Related reactions have also been reported on irradiation of 4-chloroanilines in the presence of (electron-rich) alkenes, although in this case, the alkylations appear to involve the formation of a phenyl cation. An alternative approach to form carbon-centered radicals is to irradiate the alkyl iodide or bromide in the presence of triethylamine this is proposed to form an amine-haHde exciplex, which cleanly breaks down to give a carbon-centered radical and a halide anion. Cossy and co-workers have shown this to be a fast, convenient, and chemoselective method of radical generation, which has recently been used to prepare the bicyclic core of ( )-bisabolangelone (Scheme 1). ... 

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