Nucleophile ammonia

It has been found that the cupric sulfate-mediated aminolysis of 3-bromo[ N]isoquinoline with ethanolic ammonia (130°C, 7 days reaction time) yields a mixture of 13 and 14, ratio 75 25 (74RTC198). It shows that also with the weaker nucleophile ammonia a part of 3-bromoisoquinoline can undergone a ring-opening, ring-closure process. 

The additions of ammonia equivalents, i.e. nitrogen nucleophiles like dibenzylamine (Scheme 27) which are essentially a protected primary amino group, are of special synthetic interest with respect to their possible subsequent chemical transformations. Poorly nucleophilic ammonia equivalents like acetamide or the classical phthalimide, did not add or originally gave low yields of 92a (Scheme 28) [9],but later phthalimide was found to add to 1-Me very well under mild conditions [53]. However, the a-chlorine in 92a could neither be substituted nor could the phthalimido group be cleaved without destroying the cyclopropane ring. The potassium bis(alkoxycarbonyl)amides (Boc)2NK and (Moc)(Boc)NK add to 1-Me in satisfactory yields, but the a-chlorine atom in... 

A detailed study of the conversion of 3,4-dichloro-l,2,5-thiadiazole into 3,4-diamino-l,2,5-thia-diazole has been carried out <76JHC13>. Reaction with lithium or sodium amide produces only 4% of the diamine together with cyano-containing by-products, a consequence of direct attack on sulfur. Use of a less powerful nucleophile, ammonia or potassium phthalimide, resulted in an increased attack on carbon and produced the diamine in 24% and 66% yields, respectively. Secondary amines, e.g. morpholine <76JOC3l2l> and dimethylamine <72JMC315>, produce the normal displacement products. The reaction of dichlorothiadiazole with potassium fluoride in sulfolane gives a mixture of 3-chloro-4-fluoro and 3,4-difluoro-l,2,5-thiadiazole <82CB2135>. 

Enamines or imines can form pyridines by cyclization to a nitrile group, as shown in the production of compound (48). Alternatively, the nitrogen atpm of the nitrile can be made more nucleophilic by attack on the carbon atom by an external nucleophile. Ammonia causes cyclization of the dienamines (53) (77JHC1077) and (54) (78JAP(K)786878l) in both cases, elimination of the amine introduces the extra double bond. Dimethylamine or piperidine cause cyclization of l-cyano-2,5,5-trimethylhex-l-en-3-yne to the f-butyl-pyridine (55). There are a few other examples of the synthesis of bicyclic compounds from... 

The first step in this minimalistic transcription/translation process that mimic genealogical criteria in Fig. 46 involves Michael addition of methyl acrylate to the nucleophilic ammonia surface to produce an electrophilic, carbomethoxy functionalized surface, followed by reaction with ethylenediamine to translate the functionalized dendrimer surface back to a nucleophilic primary amine functionalized surface. This iterative sequence is the key in providing alternating nucleophilic... 

Interestingly, reaction of 157 with other nucleophiles (ammonia, amines, Grignard reagents, alkyllithiums, KCN, triphenylphosphine, and trimethylphosphite) did not give any expected products and trimer 162 was the only identifiable compound. 

The third reaction is different because it has more than one step. It is a carbonyl substitution the kind we met in Chapter 12. The nucleophile (ammonia) attacks the carbonyl group to fonr. tetrahedral intermediate that decomposes with the loss of the better leaving group. 

Opening the epoxide with a nitrogen nucleophile makes one isomer. At least the alkene is symmetrical so it doesn t matter which end of the epoxide is attacked by the nucleophile. We have chosen azide ion (N ) as the nucleophile. Ammonia wdll also do as, although it can react repeatedly, it usually behaves itself with epoxides. You were not asked to make both diastereoisomers, so we can stop there. 

It was observed that ammonolysis of B(C2H,Si(R)H2)3 (Scheme 2, route A) requires basic catalysts such as n-butyl lithium. The reaction is performed in analogy to the potassium hydride-catalyzed cross-linking of cyclic silazanes described by Seyferth et al. [8]. Most probably, n-BuLi initially deprotonates the weak nucleophile ammonia with the formation of lithiiun amide and evaporation of n-butane. The stronger nucleophilic amide then replaces a silicon-bonded hydride, which subsequently deprotonates ammonia, leading to the evolution of molecular hydrogen. The silylamines that arise are not stable under the reaction conditions applied (refluxing solvent), and by fast condensation of ammonia the polymeric precursors form [6]. 

Ammonolysis of halides belongs to the class of reactions that we have called nucleophilic substitution. The organic halide is attacked by the nucleophilic ammonia molecule in the same way that it is attacked by hydroxide ion, alkoxide ion, cyanide ion, acetylide ion, and water ... 

Prop-2-ynyl)-5-(trifluoromethyl)-l, 3,4-thiadiazol-2(3//)-one (19) reacts with nucleophiles (ammonia, pyrrolidine, or potassium methylthiolate) with formation of 6-methylene-2-(trifluo-romethyl)-5,6-dihydro-4//-l,3,4-thiadiazine-4-carboxamides 20a, b or S-methyl 6-mcthylene-2-(trifluoromethyl)-5,6-dihydro-4//-l,3,4-thiadiazine-4-thiocarboxylate (20c).82 The action of aqueous sodium hydroxide on 19 gives rise to the 4//-1,3,4-thiadiazine 20d, which also bears an exocyclic methylene group.82... 

The second step is displacement of the tosylate group by the nucleophile ammonia. The reaction occurs at a primary carbon, so it may be safely assumed to proceed by the Sn2 mechanism. Therefore in this step the C—O bond of the original alcohol molecule breaks, with inversion, to give a product with the (S) configuration at Cl ... 

In the next example, neither the nucleophile (ammonia, NH3) nor the electrophile (borane, ... 

The mechanism for the decomposition of NH4NO3 is similar. Once again, the nucleophile ammonia is generated via proton transfer from NH4" to N03. It may seem strange that nitrate, an extremely weak base, should pick up a proton from NH4. Remember, however, that this is a heat-induced solid-state reaction reactivity patterns are expected to be different under such conditions, relative to lower temperature solution-phase chemistry. Once the N-N bond has formed, we need to do a few proton transfers and eliminate two water molecules to arrive at the final product N2O, as depicted below ... 

The aldehyde is attacked by the nucleophilic ammonia, which after a series of proton transfers and loss of water, leads to the formation of an imminium ion which is in turn intercepted by the nucleophile, cyanide. This leads to formation of a aminonitrile product. 

The amidoxime route has been used for the synthesis of derivatives differently functionahzed at C(5). Amidoxime 11 treated with trichloroacetic anhydride in hot trichloroacetic acid, lead to the corresponding 5-trichloromethyl- 1,2,4-oxadiazole 27. The latter, in the presence of nitrogen nucleophiles (ammonia, primary or secondary amines), undergoes an aminolysis reaction leading to 28 (Schane 8) [17],... 

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