Amines direct addition

So without direct amination we are confined to semi-direct ami-nation (Strike s terminology). In Strike s opinion, the direct addition of an azide (N3) counts. Once on the beta carbon, that azide is as good as an amine. But can we get an azide directly onto safrole without having to go thru the bromosafrole intermediate as was discussed earlier Maybe we can ... 

Direct addition of ammonia to olefmic bonds would be an attractive method for amine synthesis, if it could be carried out smoothly. Like water, ammonia reacts with butadiene only under particular reaction conditions. Almost no reaction takes place with pure ammonia in organic solvents. The presence of water accelerates the reaction considerably. The reaction of aqueous ammonia (28%) with butadiene in MeCN in the presence orPd(OAc)i and PhjP at 80 C for 10 h gives tri-2,7-octadienylamine (47) as the main product, accompanied by a small amount of di-2,7-octadienylamine (46)[46,47], Isomeric branched... 

Both the hquid and cured 2-cyanoacryhc esters support combustion. These adhesives should not be used near sparks, heat, or open flame, or ia areas of acute fire ha2ard. Highly exothermic polymerization can occur from direct addition of catalytic substances such as water, alcohols, and bases such as amines, ammonia, or caustics, or from contamination with any of the available surface activator solutions. 

Both primary and secondary amines add to a /S-unsaturated aldehydes and ketones to yield /3-amino aldehydes and ketones rather than the alternative imines. Under typical reaction conditions, both modes of addition occur rapidly. But because the reactions are reversible, they generally proceed with thermodynamic control rather than kinetic control (Section 14.3), so the more stable conjugate addition product is often obtained to the complete exclusion of the less stable direct addition product. 

We saw in Section 19.13 that certain nucleophiles, such as amines, react with a,/Tunsaturated aldehydes and ketones to give the conjugate addition product, rather than the direct addition product. 

When it is desired to convert a primary or secondary amine directly to the quaternary salt exhaustive alkylation), the rate can be increased by the addition of a nonnucleo-philic strong base that serves to remove the proton from RR NH2 or RR R"NH and thus liberates the amine to attack another molecule of RX. ... 

Hydroaminomethylahon of alkenes [path (c)j wiU not be considered [12]. This review deals exclusively with the hydroaminahon reaction [path (d)], i.e. the direct addition of the N-H bond of NH3 or amines across unsaturated carbon-carbon bonds. It is devoted to the state of the art for the catalytic hydroamination of alkenes and styrenes but also of alkynes, 1,3-dienes and allenes, with no mention of activated substrates (such as Michael acceptors) for which the hydroamination occurs without catalysts. Similarly, the reachon of the N-H bond of amine derivatives such as carboxamides, tosylamides, ureas, etc. will not be considered. 

In 1993, ten challenges faced the catalysis research community. One of these was the anti-Markovnikov addition of water or ammonia to olefins to directly synthesize primary alcohols or amines [323]. Despite some progress, the direct addition of N-H bonds across unsaturated C-C bonds, an apparently simple reaction, stiU remains a challenging fundamental and economic task for the coming century. 

Since the order of increasing CL intensity for alkyl amines reacted with Ru(bpy)32+ is tertiary amines > secondary amines > primary amines, pharmaceutical compounds bearing a tertiary amine function (e.g., antihistamine drugs [99], anticholinergic drugs [100], erythromycin [101], and its derivatives [102]) have been sensitively determined after HPLC separation (Table 3). The method was applied to the detection of d- and L-tryptophan (Trp) after separation by a ligand-exchange HPLC [103], The detection limits for d- and L-Trp were both 0.2 pmol per injection. Oxalate in urine and blood plasma samples has also been determined by a reversed-phase ion-pair HPLC (Fig. 18) [104], Direct addition of... 

On an industrial scale, diazotization reactions are carried out by dissolving the aromatic amine in hydrochloric or sulfuric acid. Despite the fact that 2 equivalents of acid per equivalent of amino group should theoretically suffice, as much as 2.5 to 3 equivalents per amino function are actually required to ensure complete diazonium salt formation. One equivalent of an aqueous sodium nitrite solution is added to the resulting mixture at 0 to 5°C. The exothermic nature of the reaction, combined with the heat sensitivity of most diazonium salts, makes it necessary to provide cooling, usually by direct addition of ice. 

Although the CuBr/QUINAP system is an effective chiral catalyst in alkynylation of imines or iminiums, one drawback is that enantiopure QUINAP is quite expensive. An analog of QUINAP, PINAP (Figure 5.2), was readily synthesized and found as a very effective chiral ligand in the direct addition of alkynes to iminiums generated from aldehydes and secondary amines in situ (Scheme 5.8). ... 

Numerous other derivatives could be prepared from 4 or Its 2-carbon shorter homolog and commercially available acid chlorides, or via direct addition of the amines to appropriate Isocyanates. Lower cost synthetic routes leading to the methacrylamide derivative or to 1 from acrylate esters have also been demonstrated (A. F. Nordquist, unpublished results). 

The addition of nitrenes leads predominantly to the closed [6,6] bridged isomers. The corresponding [5,6] bridged isomer is - if at all - formed only in small amounts, probably via a direct addition to the [5,6] bond [394]. Nitrenes have been generated by thermolysis of azido-formic esters [172,395 00], photolysis of aroyl azides [401] or aryl azide [402], elimination of O-4-nitrophenylsulfonylalkylhydroxamic acid [403] or reaction of amines with Pb(OAc)4 [404]. 

On the other hand, Elliott and his co-workers 4 maintain that the evidence for the nitro- structure is unsatisfactory, and that the p-nitro-dimethylaniline produced with dimethylaniline is a secondary product obtained either by oxidation of the nitroso-compound or by direct nitration of the amine. The addition of ethyl hydrogen sulphate to a solution of nitrosulphonic acid in sulphuric acid does not yield nitro -ethane. Elliott suggests that the crystalline acid is essentially the nitroso- form, ON. O. SO 2. OH, but that in the molten condition and in sulphuric acid solution this form is in equilibrium with another of yO ... 

Diamine 8 is obtained from hydrogenation of amino imine 7 which can be formed by direct addition of primary amine to amino imine [1] or to l-aza-l-cycloheptene 3. 

The majority of the complexes are decomposed by water through ligand displacement, although they are not necessarily sensitive to atmospheric moisture. They are generally prepared by direct addition of the amine TV -oxide to solutions of metal salts in organic solvents. Triethyl orthoformate or 2,2 -dimethoxypropane have often been added to the reaction media as desiccants. 

There are several methods available for the electrophilic addition of hydrogen and nitrogen to alkenes, dienes and alkynes. While the direct electrophilic addition of amines to these substrates is not feasible, aminomercuration-demercuration affords a very useful indirect approach to such amines. The addition of amides to C—C multiple bonds can be effected directly through the Ritter reaction or by the less direct, but equally useful, amidomercuration-demercuration process using either nitriles or amides. Similarly, H—N3 addition to alkenes can be carried out directly or via mercuration to produce organic azides. 

Li and coworkers have reported a novel silver-catalyzed, three-component coupling of an aldehyde, an amine, and an alkyne, and the first example of a direct addition of a silver acetylide to an aldehyde to produce propargylic alcohols (Scheme 1.41).103-105 Treatment of an aldehyde with a silver halide and secondary amine gave propargylic amines in good yields in organic solvent, water, or ionic liquids. The proposed mechanism suggests addition of a silver acetylide to the iminium ion formed in situ. 

Muller, T.E., Hultzsch, K.C., Yus, M., Foubelo, F., and Tada, M. (2008) Hydroamination direct addition of amines to alkenes and alkynes. Chemical Reviews, 108, 3795-3892 and references therein. 

The phosphorus-stabilized carbanion of 94 was generated at -100 °C with LDA (1.2 equiv.) in THF. Amination reactions were performed both with DTBAD and trisyl azide. Direct addition of a stoichiometric amount of DTBAD (1.1 equiv.) at -100 °C followed by acidic quench led to a mixture of hydrazino products 95 (major diastereomer indicated) in good yield and diastereoselectivity (Scheme 44). 

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