Amine ditosylates

Since no other stereoisomer but that of iditol, mannitol or sorbitol can exist in the as-fused ring series of l,4 3,6-dianhydrohexitols and since amination experiments on the ditosyl derivatives of each isomer have given three different amino derivatives, it is reasonable to assume that the two diamines which have been isolated are of the same configuration as their parent dianhydrohexitols. These two diamines LXXIV and LXXV on treatment with nitrous acid suffered deamination as expected but instead of obtaining in one case isomannide and in the other isosorbide, only one dianhydrohexitol was isolated and that was dian-hydro-L-iditol. The deamination must of course lead to the transitory carbonium cation LXXVIII and this on hydroxylation can take on any of the configurations, L-iditol, D-mannitol or D-sorbitol. That it preferentially takes on the configuration of L-iditol indicates that this is in some ways a more stable structure than the others. This behavior is paralleled... 

A small amount of an unsaturated amine derivative 110 was isolated by Cope and Shen193 it was probably formed as a result of the elimination of the less reactive tosylate group of isosorbide 2,5-ditosylate (108) under the influence of the dimethylamine reagent at 120° (see Scheme 22). 

Sometimes this deactivation is so great that co-ordinated amines are non-nucleophilic. This is particularly likely when the ligand is co-ordinated to a non-labile metal centre. However, even in these cases, all is not lost. We may also use the enhanced acidity of ligands co-ordinated to a metal centre to generate reactive nucleophiles which would not otherwise be readily accessible. For example, nickel(n) complexes of deprotonated diamines may be prepared, and react with dialkylating agents to yield macrocyclic complexes (Fig. 6-10). To clarify this, consider the reaction in Fig. 6-10 in a little more detail. The amine 6.14 is reactive and unselective, and does not give the desired macrocycle upon reaction with the ditosylate. Deprotonation of the amine under mild conditions is not pos-... 

Cyclization of the ditosylate 194 under dilute conditions gave iV-tosyl azonine 87 in 62% yield (Scheme 40, Section 14.10.7.5) <1999CC309, 2001 J(P1)2161 >. Similarly, monosubstituted ditosyl 1,4,7-triazonanes are readily available from the corresponding 1,8-ditosylate 56 and amine, for example, Scheme 4 (Section 14.10.5.2.1) <2002JME3458> ... 

Tosyl groups can easily be substituted by the azide moiety, and the products subsequently transformed into synthetically useful amines. For example, both tosyl groups in the ditosylate 14 can be exchanged almost quantitatively. ... 

Bridged or reinforced azamacrocycles, which have pairs of nitrogen atoms of an aza-macrocycle linked, usually by an a,cu-alkandiyl bridge, 154 are prepared by reaction of a cyclic amine with a bifunctional nucleophile, such as an a,cu-dibromoalkane or an a,cu-ditosyl-alkane-diol. Bis(acyl esters), amides, and halides react with amines to form bicyclic amides which can be reduced to the bicyclic amines.155 The bridge can have internal functions, such as C=C or o-C6H4 (or include hetero atoms, thus forming clathrochelates).156... 

This group is compatible with BOC, Cbz, and phthalimide cleavage conditions TFA, hydrogenolysis, and hydrazine, respectively. The DPSide group is introduced by alkylation of the amine with the ditosylate in the presence of TEA in DMF (85-96% yield). Cleavage requires a combination of TBAF and CsF in DMF or THF (80-92% yield). 

Additional type Ilae cyclizations have been reported between primary amines and four-carbon materials at the 1,4-dicarbonyl oxidation level. Copper-mediated cyclizations of 2,7-ditosyl-... 

Ruthenium-based catalysts display some utility for electrophilic amination of heteroaromatic substrates. Che and coworkers have found that [Ru(TTP)(CO)J in combination with PhI=NTs will oxidize arenes such as furan, indole, and pyrrole (Fig. 13) [68]. Reactions occur optimally under the action of ultrasound, a rather unusual addendum to the standard protocol for C-H amination. More intriguingly still, iV,A-ditosylated products are isolated in most instances, a finding that is not easily resolved mechanistically. As the substrate profile for this amination process involves only electron-rich heteroaromatics, aziridination of the arene nucleus would seem a likely step along the reaction coordinate. Interestingly, no amination product is observed when stoichiometric [Ru(TMP)(NTs)2] (TMP = tetra(2,4,-6-trimethylphenyl)porphyrin) is mixed with either furan or /V-phenylpyrrole. though a reduction of the starting Ru(VI) complex to a Ru(IV) species is noted... 

D. RING CLOSURE TO FORM A C—N—C LINKAGE FROM THE REACTION OF A PRIMARY AMINE OR AMIDE AND A DIHALIDE OR DITOSYLATE... 

The larger dichloro precursors needed to make the diiodides by the sodium iodide/acetone process are generally not available. On the other hand, the ditosylate derivatives of the available tetra- and pentaethylene glycols can be produced and reacted directly with the amine to form the aza-15-crown-5 and aza-18-crown-6 ligands. The ditosylates also can be converted to the more reactive diiodides by reaction with sodium iodide in acetone or acetonitrile. 

The cyclization reaction of dihalogen or ditosylate compounds with bis primary or bis secondary amines is similar to the diacid dichloride reaction except that the diaza-crown is obtained in a single step. This is a convenient procedure particularly since the dihalide is usually readily available and inexpensive. This cyclization process does not need high-dilution techniques because of template effects by metal ions. It is important to note that when using a bis primary amine and a dihalide, many side products such as the cryptands and bis-crown ethers can be formed (Alfa et al., 1988 Krakowiak and Bradshaw, 1991). 

Formation of two C—N bonds by a 1 1 cyclization reaction of a bis secondary amine and a dihalide or a ditosylate. The N,N -dialkyl-substi-... 

Diamine (or Primary Amine) and a Dihalide or Ditosylate Ester. 407... 

O—C bonds by a 1 1 cyclization of a bis-phenol and an aliphatic dihalide or ditosylate ester (method T) (3) ring closure to form two aliphatic N—C bonds by a 1 1 cyclization of a diamine (or primary amine) and a dihalide or ditosylate ester (method U) (4) ring closure to form two anilinic N—C bonds by a 1 1 cyclization of a diaminobenzene derivative and a dihalide, ditosylate ester, or bis-carboxylyl dichloride (method V) (5) ring closure to form one phenolic O—C bond and one anilinic N—C bond by a 1 1 cyclization of... 

The preparation of macrocyclic ligands by a direct alkylation of metal-coordinated amines using a template effect is rare because the complexed amine is seldom a good nucleophile. The complexed anilines, on the other hand, can be deprotonated, which enhances the nucleophilicity of the nitrogen atom. Such a reaction of a complexed diphosphorous-containing bisaniline with a ditosylate ester gave the complexed macrocyclic ligand (method AC-1) (Ansell et al., 1985). 

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