Phthalimides, deprotection with

Amino-6-methyl-1,6-naphthyridin-5(6//)-one (17) with (V-(4-iodopentyl) phthalimide gave 6-methyl-8-(l-methyl-4-phthalimidobutyl)amino-l,6-naphthyridin-5(6//)-one (18, R = phthalimido) (substrate, Me2NCHO, 80°C, A, synthon + NEt3 in during 4 h 85°C, 2 h 45%) and thence, by deprotection with hydrazine, 8-(4-amino-l-methylbutyl)amino-6-methyl-l,6-naphthyridin-5(6//)-one (18, R = NH2).1116... 

Theil et al. developed a method for chemoenzymatic synthesis of both enantiomers of cispentacin [89]. frans-2-Hydroxymethylcyclopentanol, obtained by the sodium borohydride reduction of ethyl 2-oxocyclopentanecarboxylate, was monosilylated with tert-butyldimethylsilyl (TBDMS) chloride to afford 55. Lipase PS-catalysed transesterification with vinyl acetate in /erf-butyl methyl ether furnished the ester 56 and the alcohol 57. The deacetylated 58 was obtained by the Mitsunobu reaction with phthalimide, triphenylphosphine and diethyl azodicarboxylate (DEAD) to furnish the cis oriented 59 with inversion of configuration (not retention as mentioned in the original article) (Scheme 9). Desilylation, Jones oxidation and subsequent deprotection with aqueous methylamine gave the ( R,2S) enantiomer 5 [89]. The (15, 2/f) enantiomer was prepared by the same route from the silyl alcohol 57. 

The use of DDQ in dichloromethane/water for the cleavage of primary allyl and benzyl ethers has been reported, and anhydrous ferric chloride in dichloromethane debenzylated sugar benzyl ethers, without affecting acetals, benzoates, phthalimides and glycosidic linkages. 4-Methoxy- and 3,4-dimethoxy-benzyl ethers have been deprotected with catalyic DDQ and ferric chloride. The combination of Ti(0 Pr)4 and BuMgCl has been used to cleave allyl ethers to the corresponding alcohols. 

Thianthrene-di-, tri-, and tetracarboxylic acids, and a variety of their derivatives, were prepared and polymerized with co-monomers to obtain thianthiene-containing polyimides, aramids and polybenzoxazoles. The multiply substituted thianthrene derivatives were prepared starting with dichloro-substituted benzamide or phthalimide via chlorine displacement by sulfur nucleophiles. The protected carboxyl groups enhanced the displacement reaction to give thianthrene bisamides and imides in good yields. Deprotection with base gave carboxylic acid derivatives. 

The 5-(aminomethyl)thiophene-2-acetic acid isomer 76 was prepared by chloromethylation in position 2 of thiophene followed by nucleophilic displacement with phthalimide to afford 81, and a second chloromethylation in position 5 to give 82 (Scheme 23). Subsequent reaction with cyanide gave 83, the hydolysis of which afforded the phthalide-protected amino acid 84 which was coupled to H-Ala-Ile-Gly-OMe using propanephosphoric anhydride, followed by hydrazine N-deprotection)110 ... 

Phthalimide protection is stable towards acids and bases, but can be cleaved with strong nucleophiles, such as hydrazines or sulfides, or by reduction with sodium boro-hydride [230]. More sensitive towards nucleophilic attack than unsubstituted phthalimide is tetrachlorophthalimide [33]. This group has been successfully used as N(a) protection of amino acids in the solid-phase synthesis of peptides (deprotection N2H4/DMF (15 85), 40 °C, 1 h coupling DIC/HOAt/amino acid (1 1 1), 3 equiv. of each, DMF, 25 °C, 4 h [294]). Typical conditions for the removal of phthaloyl protection on cross-linked polystyrene include treatment of the resin with hydrazine hydrate [295,296], with methyl hydrazine [297], or with primary aliphatic amines [298] in DMF, EtOH, or solvent mixtures for several hours at room temperature or above [296,299,300]. Illustrative examples are sketched in Figure 10.15. It has been claimed that the hydrazinolysis of polystyrene-bound phthalimides proceeds more readily in DCM or DCE than in DMF [301]. 

We have already seen various syntheses of SMA phthalimides, either through nucleophilic animation of a-chlorosilanes (see Sections III.A.l and III.A.2), hydro-silylation of A-vinyl phthalimide (see Section III.B.5.f) or by reaction of SMA with phthalic anhydride (see Section IV.A.2.h). The deprotection and recovery of free SMA has been conducted in the usual way by reaction with hydrazine.81,88,211... 

Deprotection of phthalimidesJ Phthalimides arc useful for complete protection of primary amino groups, including amino acids, oven though hydrazinolysis is usually necessary for deprotection, A mild, two-step but one-flask cleavage involves reduction with NaBHi in aqueous 2-propanol followed by eyclization to a lactone with release of the amine (equation 1). Yields are generally 80-97%. Racemization docs not occur in deprotection of amino acids (four examples). 

Laus et al. also investigated a chain extension of pSt-TEMPO with a substituted styrene, phthalimide methylstyrene (PIMS) [146], with the objective of incorporating the PIMS, then deprotecting it to produce the amino functional polymers, according to Scheme 12. 

Zwierzak and co-workers have reported on the use of a phosphoramidate as an alternative to the phthalimide in the Gabriel synthesis.22 "0 However, several drawbacks to their method led to revisions in the original method. In particular, the use of toxic benzene as a solvent, deprotection by gaseous HC1 in benzene, and low yields were discouraging. The modified procedure reaction involves nucleophilic amination by diethyl yV-sodio-./V-(r-butoxycarbonyl)phosphoramidate 37 with tetrabutylammonium bromide as a catalyst in acetonitrile. Carrying out the reactions in tetrahydrofuran led... 

Base modification at the 4-position of pyrimidines leads to loss of base-pairing properties. The thiol moiety in 91 was deprotected after ODN synthesis using 1 M DBU in acetonitrile. The modified oligothymidylate was then cleaved from the solid phase and reacted with N-(2-chloroethylthio)phthalimide to yield 92, which was subjected to further derivatization [264]. Purine base positions accessible for ligand attachment are C-8 of adenosine (93) [265] and C-2 of guanosine (94) [266]. 

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