Displacement dimethylamino

This view is supported by the fact that if diazominobenzene is dissolved in dimethylaniline in the presence of the hydrochloride of the latter, the main product is p-dimethylamino-azobenzene, CgHjN=NCgHgN(CH3)2 this is because dimethylaniline couples in the nucleus more readily than does aniline. The reaction is an electrophilic displacement of hydrogen by the diazonium ioii ... 

C. Nucleophilic Attack on Other Atoms.—Amidoximes have been shown to react with tris(dimethylamino)phosphine by displacing dimethylamine to give the phosphine oxides (52), but some N-substituted aromatic amidoximes give derivatives of (53). ... 

Bis(trifluoromethyl)nitroxide displaces the dimethylamino-group from tris(dimethylamino)phosphine to form (59). 

The reaction of 5-[2-(iV,./V-dimethylamino)ethyl]-l,2,4-oxadiazole with methyl iodide forms the quaternary ammonium salt 170 (Scheme 22), which undergoes elimination in the presence of base (diisopropylethylamine (DIEA), TEA, l,8-diazabicyclo[4.3.0]undec-7-ene, etc.) to form an intermediate 5-vinyl-l,2,4-oxadiazole 171, which undergoes in situ Michael addition with nucleophiles to furnish the Michael adducts 172. As an example, also shown in Scheme 22, 3-hydroxy-pyrrolidine allows the synthesis of compound 172a in 97% yield. Mesylation followed by deprotonation of the 1,2,4-oxadiazole methylene at C-5 enables Sn2 displacement of the mesylate to give the 5-azabicycloheptyl derivative 173, which is a potent muscarinic agonist <1996JOC3228>. 

In 1,8-bis(dimethylamino)naphthalene steric and lone pair interactions are minimised in a structure (Einspahr et al., 1973) having the amino groups twisted and displaced above and below the plane of the naphthalene ring, as in [53] in which the almost planar naphthalene ring is shown as a dashed line. In l,8-bis(dimethylamino)-2,7-dimethoxynaphthalene, steric interactions involving the methoxy substituents bring about a further distortion as in [54] (Woolf, 1980). 

Activation Parameters (kcal mole ) for Nucleophilic Displacement by the Dimethylamino-Group at 25 (Bruice and Benkovic, 1963)... 

The selective introduction of fluorine is of continuing interest not only because of the synthetic challenge but also because of the possibility of a dramatic change in biological activity. The fluoride-ion displacement of carbohydrate trifluoromethanesulfonates using tris(dimethylamino)sulfonium... 

There are several examples of the 1,2-elimination of hydrogen chloride from 9-(2-chloroethyl)carbazoles, using potassium hydroxide in ethanol, generating the 9-vinylcarbazoles. 3-Dimethylamino-9-(2-hydroxyethyl) carbazole comparably lost water on base treatment. Dimethylamine displacement of halogen, then amine N-oxide formation and elimination was utilized to produce 9-alkenylcarbazoles with four, five, and six carbon atoms from the corresponding cu-haloalkyl carbazoles. ... 

In order to introduce substituent variation on the amino group at the pyrazolo[l,5- 7]pyridine 7-position, a modified procedure was investigated where a 7-chloro substituent was carried through the synthesis. However, this procedure was compromised by the fact that dimethylamine displacement of the chlorine also occurred during formation of the enamino ketone 1000, giving the dimethylamino compound 1001 as a major by-product <2003X9001, 2005BMC5346>. 

In its reaction with aniline, 43a reveals its enaminoketone properties The presence of small quantities of acetic acid initiates an addition/elimina-tion reaction in which the dimethylamino is displaced by the phenylamino group yielding 44 at 72%. 

Other nucleophiles react readily with 57, but mixtures are obtained due to exchange at the primary amine functionality, as shown for the reaction with dimethylamine to give a low yield of 2,6-dimethylamino-3,5-dicyanopyrazine (104) as one of several products formed. A high-yield preparation of 104 is presented in Section V,E,4, along with a general discussion of the second cyanide displacement. 

The nature of the aromatic substituents is apparently not critical for SSRI activity, as indicated by the structure of duloxetine (23-5), where one ring is replaced by thiophene and the other by naphthalene. The synthesis starts as above by the formation of the Mannich base (23-1) from 1-acetyl thiophene with formaldehyde and dimethyl-amine. Treatment of that intermediate with the complex from lithium aluminum hydride and the 2R,3S entantiomer of dimethylamino-l,2-diphenyl-3-methyl-butane-2-ol gives the S isomer (23-2) in high enantiomeric excess. Treatment of the aUcoxide from (23-2) and sodium hydride with 1-fluoronaphthalene leads to the displacement of halogen and thus the formation of ether (23-2). The surplus methyl group is then removed by yet another variant of the von Braun reaction that avoids the use of a base for saponifying the intermediate urethane. Thus, reaction of (23-3) with trichloroethyl formate leads to the A -demethylated chlorinated urethane (23-4). Treatment of that intermediate with zinc leads to a loss of the carbamate and the formation of the free secondary amine duloxetine (23-5) [23]. 

If l,l-bis-dimethylamino-2.4.6-triphenyl-X -phosphorin 164 is allowed to react with 2 moles of trifluoroacetic acid and a 10-fold molar excess of methanol in refluxing benzene, one of the amino groups is displaced and 1-methoxy-l-dimethyl-amino-2.4.6-triphenyl-X -phosphorin 757 can be isolated in good yield. The phos-phonium salt 165 (H can also attack C-2) is initially formed by protonation of 164 at C-4 (or C-2). Nucleophilic substitution then leads to 167 via 166 (Hettche, >). 

Another useful reagent for the 3-alkylation of indole is the N,N-dimethylformaldiminium ion, which forms the useful intermediate gramine [87-52-5] (9). The C-3 substituent can subsequendy be modified by displacement of the dimethylamino group by a nucleophile. Alternatively, gramine can be converted to its quaternary salt prior to substitution. A variety of carbanions can function as the nucleophile. 

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