Nitrogen, phthalimides

Carbamates are allylated in the presenee of strong bases in DMSO or HMPA[197], Phthalimide (320) and succimide are allylated with the allyl-isoureu 321 at room temperature or the allylic acetate 322 at 100 C[I98.I99], Di-/-butyl iminodicarbonate is used as a nitrogen nucleophile[200]. 

Phthalimide with a of 8 3 can be quantitatively converted to its potassium salt with potassium hydroxide The potassium salt of phthalimide has a negatively charged nitrogen atom which acts as a nucleophile toward primary alkyl halides m a bimolecu lar nucleophilic substitution (Sn2) process... 

Gabriel synthesis (Section 22 8) Method for the synthesis of primary alkylamines in which a key step is the formation of a carbon-nitrogen bond by alkylation of the potassium salt of phthalimide... 

In a typical experiment, triethylene glycol was treated with two equivalents of sodium toluenesulfonamide in dry DMF solution. After 6 h at reflux, the solution was distilled and product obtained by a standard work-up procedure. By this procedure, 9 was obtained in about 10% yield. The transformation is illustrated below as Eq. (4.10). Note also that Vogtle and his coworkers have also utilized phthalimide as a source of nitrogen in the preparation of such azacrown precursors as H2N(CH2CH2 0)2CH2CH2NH2 In such reactions, a standard hydrazine cleavage was used to remove the phthaloyl residue. 

A further alkylation of the nitrogen is not possible. In a second step the TV-substituted phthalimide 3 is hydrolyzed to give the desired amine 5 and phthalic acid 4 ... 

Phthalic anhydride derivatives are also not typical precursors in phthalocyanine formation. Their use is of interest in cases where the substituents prohibit conversion of the anhydride to nitrogen-containing derivatives like phthalimides or phthalonitriles. 

Imide-terminated telechelics are also synthesized by metathesis depolymerization, and it is found that phthalimide-substituted olefins allow for productive depolymerization when only one methylene spacer separates the nitrogen atom and the olefin (Fig. 8.21). This combination of steric hindrance around the nitrogen lone pair and decreased electron donation from resonance prevents the negative neighboring group effect. However, secondary acyclic amines are unable to produce telechelics through metathesis depolymerization because of unfavorable catalyst-amine interactions. 

Indeed, the choice of a nitrogen compound to be used as carrier in such O-alkyl prodrugs is not restricted to benzamides. Other amides were examined, e.g., phthalimide, succinimide, and saccharin. Thus, the saccharin prodrug of estradiol (11.50, R = 17/J-estradiol) underwent rapid nonenzymatic hydrolysis in rat and human plasma [85]. Administration of the prodrug to rats led to an impressive fivefold increase in the oral bioavailability of estradiol, and it was approximately nine times more potent orally, based on the 50% effective dose. 

Diastereoselective tandem conjugate addition of both oxygen- and nitrogen-centred nucleophiles (potassium phthalimide, TsNHK, MeONa, and MesSiOK) to the novel (IN)-lO-camphorsulfonic acid-derived nitroalkenes (139 R = Me, Pr, and... 

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... 

Formaldehyde and acetic acid convert carbazole and the 3,6-dihalocar-bazoles to the 9,9 -dicarbazolylmethanes 67 (R = H or Hal). The phthalimidomethyl group can be introduced onto the carbazole nitrogen, giving 68 by reaction with phthalimide-formaldehyde in ethanol, or more elaborately by reacting carbazol-9-ylpotassium with the salt 69 in dimethyl-formamide. ... 

Bromine trifluoride has found application in the conversion of (methylsulfanyl)thiocar-bonyl groups, bonded to carbon atoms in aromatic rings, oxygen atoms in alcohols and phenols, or to the phthalimide nitrogen atom, into trifluoromethyl groups.125... 

Despite the expenditure of a tremendous amount of effort throughout the world, the two original methods employed in the manufacture of copper phthalocyanine are still used. In the first, a mixture of phthalic anhydride, urea and copper(I) chloride is heated in a high-boiling solvent such as nitrobenzene or trichlorobenzene in the presence of a catalytic amount of ammonium molybdate. The crude copper phthalocyanine is filtered off and the solvent recovered by distillation. The urea acts as a source of nitrogen and the first step in the overall reaction (equation 18) is conversion of phthalic anhydride to phthalimide (219) by ammonia liberated by the urea. More ammonia then converts the phthalimide to l-keto-3-iminoisoindoline (220) and finally to l-amino-3-iminoisoin-dolenine (221). All three intermediates have been isolated and identified. In the presence of copper chloride the l-amino-3-iminoisoindolenine undergoes conversion to the copper complex of phthalocyanine. 

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