4-Nitrophthalic anhydride synthesis

T Wieland, C Birr, H Wissenbach. 3-Nitrophthalic anhydride as blocking agent in Merrifield polypeptide synthesis. Angew Chem 8, 764, 1969. 

Kricheldorf has reported the synthesis of lyotropic poly(amide-imide)s and poly(benzoxazole-amide)s. These were prepared by the polycondensation of N,N-bis(trimethylsilyl)-p-phenylenediamine or N,AT -bis(trimethylsilyl)-3,3 -dim-ethylbenzidine with the diacyl chloride of trimellitimide of p-aminobenzoic acid, or the imide formed from p-amino benzoic acid and terephthalic acid. Lyotropic behaviour was observed in cone, sulphuric acid solution [38]. A series of thermotropic poly(imide-amide)s was prepared based on trimellitimides formed from trimellitic anhydride and an a, -bis(4-aminophenoxy) alkane with carbon chain lengths 9-12. Melting points were in the range 250-300 °C. They formed smectic A phases and tended to degrade around the isotropisation temperatures (around 350 °C). Pendant methyl groups or occupied meta- groups tended to prevent mesophase formation [39]. Novel LC poly(imide-amides) have also been synthesised from new diamine spacers derived from linear diaminoalkanes and 4-nitrophthalic anhydride. A smectic and nematic phase were observed when 4,4 -biphenyl dicarboxylic acid was used as co-monomer [40]. 

The first step of this synthesis is to form a bis-imide monomer formed by the reaction of nitrophthalic anhydride and a diamine (see Figure 4.21). The second step of polyetherimide synthesis involves the formation of a bisphenol dianion by treatment of a diphenol with two equivalents of base, followed by... 

Today we routinely use the 3-nitrophthalic anhydride blocker It is applicated in a single dose of a ten- to twenty fold excess on estimated amounts of remaining amino functions and added as a 0.1 niolar solution in pure pyridine with ten minutes reaction time at the end of each peptide synthesis stage, in which all chemical operations are monitored by photometric control and forced to approach completion. We have no indications to date that the acidically marked, blocked sequences on polymer cause undesired side reactions in subsequent stages of the synthesis, particularly in further peptide coupUngs, probably because of the acidity of the blocker functions (pK 2), which in their anionic salt form possess only a very diminished nucleophilicity. 

The construction of isocoumarin natural products offers another instructive comparison between DoM and more conventional methodologies. Thus, in the synthesis of hydrangenol 37 (Scheme 12), [31a] a five-step, one-pot process directly furnishes the heteroannelated product 36, a sequence involving a low-temperature DoM of a dimethyl amide, an LDA-induced chain extension, and a base-mediated cyclization. BBr3 treatment leads to the natural product 37 in good overall yield. The chosen classical alternative, [31b] involving Claisen condensation of 39 with 40 to give 38, is achieved in low over l yield due to the an inefficient preparation of the homophthalic ester 39 (from 3-nitrophthalic anhydride), a memento of an earlier DoM- classical route comparison (Scheme 3). 

Thermal stability of PEI is significantly deteriorated by the use of unpurified monomers. PEI obtained using unpurified dianhydride A possesses poorer molecular-mass characteristics even if all production conditions are maintained (PEI 7, Table 2). Mass-spectrometry analysis of dianhydride A allowed detection of three admixtures bisphenol A, nitrophthalic anhydride (initial monomers for dianhydride A synthesis), and phthalic anhydride. Moreover, PEI thermal stability may be definitely reduced by solvent traces (PEI 8) increased Cf ion content at insulficient washing off of methylene chloride. As known, inorganic admixtures (metal ions) may occur in the polymer both from raw materials (monomers and solvents) and directly from the equipment. In case of iron increments, PEI thermal stability is decreased by its 10-fold exceeding of the permissible level only (PEI 3 compared to PEI 2). 

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