N-hydroxybenzotriazole

Photosensitive functions are in many cases also heat sensitive, so the preparation of photosensitive polyimides needs smooth conditions for the condensations and imidization reactions. Some chemical reactants, which can be used for polyamide preparation, have been patented for the synthesis of polyimides and polyimide precursors. For example, chemical imidization takes place at room temperature by using phosphonic derivative of a thiabenzothiazoline.102 A mixture of N -hydroxybenzotriazole and dicyclohexylcarbodiimide allows the room temperature condensation of diacid di(photosensitive) ester with a diamine.103 Dimethyl-2-chloro-imidazolinium chloride (Fig. 5.25) has been patented for the cyclization of a maleamic acid in toluene at 90°C.104 The chemistry of imidazolide has been recently investigated for the synthesis of polyimide precursor.105 As shown in Fig. 5.26, a secondary amine reacts with a dianhydride giving meta- and para-diamide diacid. The carbonyldiimidazole... 

The earliest published example of microwave-assisted SPOS involved diisopropyl-carbodiimide (DlC)-mediated solid-phase peptide couplings [24], Numerous Fmoc-protected amino acids and peptide fragments were coupled with glycine-preloaded polystyrene Wang resin (PS-Wang) in DMF, using either the symmetric anhydride or preformed N-hydroxybenzotriazole active esters (HOBt) as precursors (Scheme 12.1). 

For the preparation of large compound libraries, the cost of reagents and resins is a further issue that must be considered. Some supports, e.g. resin-bound phenols or N-hydroxybenzotriazole, which enable the preparation of resin-bound, reactive esters (Section 3.3.3), can be reused many times without the need to dismantle the reactor, and are therefore much more cost-efficient than supports that can only be used once [136,137], Reactions such as the acylation of amines with resin-bound acylating agents have the additional advantage that only one equivalent of amine is needed, which again leads to a substantial reduction of costs. 

The mixture of (2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-amino-l,6-diphenylhexane (100 g, 0.22 mol), 2S-(l-tetrahydro-pyrimid-2-onyl)-3-methyl butanoic acid methyl ester (44.8 g, 0.22 mol) and 750 ml DMF was cooled in an ice/water bath. N-Hydroxybenzotriazole (90.9 g, 0.67 mol), l-ethyl-3-[3-dimethylaminopropyl]carbodiimide (86 g, 0.45 mol) and triethylamine (62.5 ml, 0.45 mol) were added and the ice bath was removed, allowing the reaction mixture to stir with warming to room temperature for 5 hours. The mixture was diluted with 1000 ml of IPAC and quenched with 1000 ml of water. The mixture was shaken and separated, the aq. layer was extracted IPAC, the organics were washed with 10% HCI, solution of NaHC03 with 100 ml hexanes, then washed 500 ml water, and brine, dried over MgS04, filtered and concentrated to provide. (2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(2S-(l-tetrahydro-pyrimid-2-onyl)-3-methylbutanoyl)amino-l,6-diphenylhexane as a white foam. 

The incorporation of the amino acids for obtaining of Boc-D-Phe-Cys-(Trt)-D-Trp-Lys(Boc)-Thr(tBu)-Cys(Trt)-2-CI-trityl-resin is carried out following a synthesis program such as that described below, using an excess of 2.5 equivalents of Fmoc-amino acid, N-hydroxybenzotriazol (HOBt) and diisopropylcarbodiimide (DIPCDI). Later the Fmoc group is deprotected with 20% of piperidine/DMF for 1 min + 5 min. 

Coupling reagents diisopropylcarbodiimide (DIPC, DIC Fluka) and N-hydroxybenzotriazole (FlOBt EMD Biosciences). Coupling reagents are only necessary if preactivated amino acid derivatives are not used (see Note 1). 

Condensation of peptide units is also often carried out in one step by treating the two components with N-hydroxysuccinimide or N-hydroxybenzotriazole and DCCI since coupling with DCCI alone, as originally described,(39) may entail a significant degree of racemiz-ation(40) an example is shown.(41)... 

The modified carbodiimide method, using N-hydroxysuccinimide is called the Wuensch-Weygand method. " Koenig and Geiger, in 1970 proposed the use of N-hydroxybenzotriazole. " 3-Hydroxy-4-oxo-3,4-dihydroquinazohne and 3-hydroxy-4-oxo-... 

The deblocking can be conducted in quantitavive yield, using trifluoroacetic acid at room temperature. Another protection group used in combination with EDC is the 3-(3-pyridyl)allyloxycarbonyl (Paloc) group. In this reaction DAEC is used in combination with N-hydroxybenzotriazole. 

Using the automated stepwise method of synthesis on a solid phase allows the synthesis of polypeptides consisting of up to 120 amino acids. The final polypeptide is purified by HLPC (high pressure liquid chromatography). O-glycopeptides are also constructed on a solid phase using DCC and N-hydroxybenzotriazole in DMF. ... 

N-f-butoxycarbonyl group (e.g., 25% HBr-HOAc, TFA-anisole), but is removed by TFA in the presence of dimethyl sulfide within 40-60 minutes at 23°. The N -tosyl protecting group is also removed under these conditions, but at a slower rate. The p-methoxysulfonyl group is also removed by N-hydroxybenzotriazole or by 1 Af NaOH within 1 hour, but only partially by 80% hydrazine hydrate after 24 hours. 

Mediators essential for laccase bleaching of pulp have been the subject of coupled experimental and computational research by Sealy et al. [55]. This study examined the effect of substitution on N-hydroxybenzotriazole, and the activity of phthalim-ides. N-hydroxybenzotriazole itself was more effective in lowering kappa numbers than any of the derivatives that were tested. Computationally, the bond dissociation energy was generally lower for N-hydroxybenzotriazole than the derivatives. Similarly, the most active of the phthalimide mediators had the lowest bond dissociation energy. 

J Sealey, AJ Ragauskas. Investigation of laccase/N-hydroxybenzotriazole delignifica-tion of kraft pulp. J. Wood Chem. Technol. 18(4) 403 16, 1998. 

There are examples of the use of supported carbodiimide 2 (R = Cy) for the formation of N-hydroxybenzotriazole (HOBt)-derived active esters from N-Boc-protected amino acids (see below), which have been subsequently employed in coupling reactions for the synthesis of dipeptide p-nitroanilides and dipeptide diphenyl phosphonates [12, 13]. Such HOBt-active esters have also been generated from pyrazinone-derived acids using 2 (R = Cy) [14], as well as from difluorophenyl acetic acids [15] for further amidation reactions in the parallel synthesis of tissue factor Vila inhibitors. 

C H5CH20, or by trifluororacetic acid, when R = /-C4H90, gives 3-aminomonophosphamic acids. Coupling using [N, IV-dicyclohexylcarbodiimide (DCC)-N-hydroxybenzotriazole] or mixed anhydride with carboxylic acids formed 3-acylamino derivatives for screening (27). 

N,N-dicyclohexylcarbodiimide and similar condensing agents, activated esters with A/-hydroxysuccinimide, and N-hydroxybenzotriazole together with other acylating agents commonly used in peptide synthesis. The choice of coupling reaction is invariably dependent on the side chain. The efficiency of the reaction varies considerably between side chains so that optimization of the coupling procedure is often a matter of trial and error. 

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