Amines, cyclic dimethylamine

The corresponding reaction of 23 with dimethylamine and with cyclic secondary amines (piperidine and morpholine) is less facile and gives the thermodynamically more favored C-3 addition product (Equation 13) <1999RCB1150>. Using ethylenediamine, the cyclization product 29 is obtained in 80% yield (Scheme 12), although with 1,3-propane-diamine, 1,4-butanediamine, and 1,2-cyclohexanediamine the yields are reduced (70%, 25%, and 1%, respectively), consistent with the importance of entropy as a driving force for the second (intramolecular) amination. 

The formation of a-naphthols of type 189 from 1-alkyl-substituted salts 30, on heating with dimethylamine hydrochloride in ethanol, occurs by another mechanism and will be explained in Section III,C,4,b,i. The interaction of l-aryl-3-carboxy-substituted salts 62 with secondary amines in benzene is initiated probably as in the reaction of these salts with primary amines, and the attack by the secondary amine on position 3 is the primary step of this reaction. However, since protonation of the intermediate anion 190, a masked acyl anion, becomes difficult, an interaction of this anion with the carbonyl group of the benzophenone fragment occurs (86KGS125). The enamines 191 thus formed are usually hydrolyzed on purification, yielding five-membered cyclic acyloins 192. 

Aminomethylation of alkenes affords a quite large range of products, the aminomethylated ones being reported in Fig. 62, as substantial amounts of nonbasic materials are also formed. Alkenes used as substrates (Table 11) are usually allowed to react with dimethylamine other amines - - tend to complicate the reaction further. Cyclic... 

Takczaki et al. studied (he same reaction but used palJadium(ll) chloride and bases as the catalyst system. The most effective bases were KHCO3, KjCOj and cyclic letiiary amines. When the reaction is carried out in methyl ccllosolve as solvent, yields of DMF up to 99 mo % were obtained, based on charged dimethylamine [171] and so the reaction path shown in Scheme 5 is conceivable. 

Compound (17) is synthesized by the treatment of the appropriate cyclic amine with tris(dimethylamino)phosphine at 100 °C, resulting in the elimination of three moles of dimethylamine. The products obtained are dependent on the number of methylene groups bridging the nitrogen atoms. When all four bridges are ethylene, (CH2)2, only (17a) is observed when all are trimethylene, (CH2)s, only (17b) is found. When there are two of each type, both tautomers are present. 

The use of cyclic enamines" > " " b.436,441,443,446.447, 456.457,470-480 (-g g UQ o ) or dieneamines (e.g., 141 ) yields fused bicyclic systems, although the latter may also yield bis-thietane sulfones. Enamines derived from morpholine, piperidine, pyrrolidine, and dimethylamine are most commonly used, but derivatives of diethylamine, di- -propyl-amine, piperazine, 4-benzylpiperidine, methylpyrrolidines, hexahydroazepin, N-methylaniline, and indoline have also been treated with sulfenes to give thietane sulfones. Asymmetric induction has been observed with the optically active enamine, 142. ... 

The aliphatic starting material 10 ring closes to a cyclopropane product. Treatment with silver tetrafluoroborate and dimethylamine in dichloromethane gave a complex reaction mixture consisting of 20% cyclic aminal 11, 56% substitution product 12 and the oxidation products 13 (7%) and 14 (10%). However, the same reaction in diethyl ether afforded the cyclopropanone aminal 11 quantitatively. ... 

Secondary amines used for reactions with cyclic ketones may be aziridine (52X azetidine (53), pyrrolidine (54), piperidine (55), hexamethylenimine (56), morpholine (57), //-methylpiperazinc (58) and acyclic amines like dimethyla-mine (59). The general order of electrophilic attack of enamines as dependent on the nature of the amine moiety decreases in the sequence pyrrolidine (54) > dimethylamine (59) > hexamethylenimine (56) > piperidine (55) sk azetidine (53) > morpholine (57). This sequence seems to parallel the magnitude of conjugative interaction between the amino group and the C=C double bond as indicated by the H NMR chemical shift of the hydrogen at the jS-carbon. 

The pyrrole molecule possesses the NH group typical of secondary amines. The basicity of pyrrole, pX a = -3.8 for the conjugated acid is, however, much less than that of dimethylamine (pX = 10.87). This large difference is due to the incorporation of the nonbonding electron pair of the N-atom into the cyclic conjugated system of the pyrrole molecule. The protonation, moreover, does not occur on the N-atom, but to the extent of 80% on C-2 and of 20% on C-3. 

The preparation of tertiary amines from alkyl halides and a secondary amine, or a primary amine in which both TV-hydre en atoms are to be replaced by identical alkyl groups, can be carried out with favourable yields in many cases, as evidenced by preparations of diethyl-n-hexadecylamine (from diethylamine) and of dimethyl-n-docosylamine (from dimethylamine) . Alkyl sulphonates have similarly been used, and the reaction extended to the preparation of cyclic tertiary amines from primary amines and appropriate terminal di-sulphonates (reaction 38) . Satisfactory conditions have been reported... 

Reaction of a nucleoside with thiophosphoryl chloride, followed by base-promoted cyclization, provides a direct synthesis of nucleoside-3, 5 -cycllc phosphorothioates (both epimers at phosphorus). 125 Treatment of cyclic AMP with dlphenylphosphoiyl chloride produces the mixed anhydride, predominantly of Rp configuration (62), due to the greater basicity of the axial oxygen in the cAMP. The anhydride reacted with dimethylamine with inversion to give the cyclic phosphoramidate.i26 Activation of cAMP with POCI3 in (MeOlaPO, followed by treatment with an amine, also gave predominantly the Sp-phosphoramidate (63),127 and in the case of a protected cAMP, oxalyl chloride activation achieved a similar result. 128 The hydrolysis of... 

The role of hybridization and basicity in the gas phase has been discussed further by Aue [25], who draws attention to the low basicity of aziridine as against dimethylamine when compared with the other pairs of cyclic and acyclic compounds, and points out that acetonitrile is about 34kcalmol lower in proton affinity than is ethylamine. Beauchamp [26] has considered the importance of hybridization in comparing the effects of alkyl substitution on phosphines compared to amines. 

Mustard for this work was prepared by a Clark method [11]. The properties of the amines used dictated the conditions for each reaction. Thus, in the case of dimethylamine, the reaction was carried out in water at 140-150 "C under pressure of 20-25 atm., in an autoclave. Ethanolamine for reaction with mustard contained 10% of ethylene glycol, to moderate the exothermic effect [1]. The reaction was conducted at about 105-110 C. In the case of ethylenediamine, no solvent or diluent was needed the reaction proceeded well at 90-110 C. When cyclic compounds I and III were prepared, the order of addition of reactants was important. Addition of amines to mustard favored formation of the products mentioned above. The formation of undesired, bioactive quaternary ammonium compounds was thereby avoided. All the reactions were exothermic temperature was controlled by the rate of addition of amine. 

Secondary amines also yield linear polypeptides, when their nucleophilicity is not reduced by steric hindrance (e.g., dimethylamine or piperidine). Imidazole is an exception mainly yielding cyclic polypeptides. Cyclic polypeptides are also formed by sterically hindered secondary amines and by tertiary amines. Thermal polymerizations also yield cyclic polypeptides. Mechanisms and preparative aspects of aU these polymerizations are discussed in Chap. 15. 

Nuclear aminomethyl derivatives are obtained by the Mannich synthesis when phenols or napthols are reacted with secondary cyclic and acyclic a%l amines. p-HydroxydimethylbenzylamLne (m.p. 200°C) is obtained from dimethylamine, formaldehyde, and phenoP - . ... 

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