Carbodiimide derivatives

NCD-4 is a nonfluorescent carbodiimide derivative that forms a fluorescent adduct with the Ca -ATPase, accompanied by inhibition of ATPase activity and phos-phoenzyme formation [376-378]. Ca protected the enzyme against the inhibition by NCD-4 and reduced the extent of labeling, suggesting that the reaction may involve the Ca " " binding site. The stoichiometry of the Ca -protected labeling was i 2mole/mol ATPase. The fluorescence emission of the modified Ca -ATPase is consistent with the formation of a protein bound A-acylurea adduct in a relatively hydrophobic environment. After tryptic proteolysis of the NCD-4 labeled ATPase the fluorescence was associated with the A2 band of 24 kDa [376,379]. 

Another possible approach to the synthesis of this type of dinucleotide utilizes transesterification by means of carbodiimide derivatives.93 ... 

Extension of these studies to benzologues of tetrazolo[l,5- ]pyridine, that is, for tetrazolo[l,5- ]quinoline 21 and tetrazolo[5,l- ]isoquinoline 22, led to interesting results <2003JOC1470> as shown in Scheme 7. Both of these fused tetrazoles resulted in formation of a nitrene 23 and 24, respectively, which could be interconverted via formation of the fused cyclic carbodiimide derivative 25. Isoquinolylnitrene 24, furthermore, was found to undergo subsequent reactions ring opening afforded the vinylnitrene 26, which was transformed to o-cyanophe-nylacetonitrile 27 by a 1,2-H shift and to 4-cyanoindole 28 by an intramolecular cyclization in 40% and 25% yields, respectively. 

The carboxylic functionalities inserted onto the tubes can be used as platforms to obtain further transformations (Fig. 3.5). A commonly utilized route is the reaction of carboxylic groups with thionyl chloride or oxalyl chloride to prepare the corresponding acyl chlorides, which are useful intermediates for amidation or esterification reactions. Amides can also be prepared directly from the acids by means of standard solution chemistry conditions, using carbodiimide derivatives in the presence of the selected amine. 

Reaction of the carbodiimide derived from the aza-Wittig reaction with ammonia generates the gaunidine, which under basic conditions, attacks the nitrile moiety in a nucleophilic manner. 

In the next protocol, the carbodiimide derived from the aza-Wittig reaction reacts with the a-sulfonyl anion in an electrophilic manner to generate the indole shown. 

A spin labeled carbodiimide derivative 8 is synthesized from the thiourea 7 and HgO. ... 

Transition metal carbodiimides, such as MnNCN and CuNCN, and carbodiimides derived from zinc, mercury,silver and thallium are also known. A preceramic polymeric titanium carbodiimide is obtained in the reaction of TiCU with bis(trimethyl-silyl)carbodiimide. Liganded carbodiimidotitanium complexes are obtained in the reaction of CpaTiCla with Me3SnN=C=NSi(i-Pr)3. ° Also, dicyclopentadienyl titanium (IV) diisocyanates are converted into carbodiimides with LiN(SrMe3)2. ... 

Dicarbodiimides are also obtained from gem diisocyanates or bis-iminophosphoranes, but due to the proximity of the functional groups such monomers are not useful as monomers for carbodiimide derived polymers. For example, reaction of phenylfrifluoromethyl diisocyanate with triphenyliminophosphoranes affords gem dicarbodiimides 40. ... 

Cellular poly(carbodiimides) derived from polymeric isocyanate (PMDI) can be continuously produced using a phospholene oxide catalyst. As the component temperature is increased from 25 °C to 80 °C at a constant catalyst level, foam densities decrease with increasing component temperatures, with an expected corresponding decrease in compressive strength. The foam friability also decreases with increasing component temperature. 

Oligomeric carbodiimides derived from sterically hindered aromatic diisocyanates are used as stabilizers for polyester based polymers because the carbodiimide groups in the oligomers, or in sterically hindered diisocyanates, mop up HCl, which catalyzes the depolymerization of polyesters. The carbodiimide stabilizers are commercially available under the tradename Stabaxol from Rhein Chemie, a subsidiary of Bayer. 

Mascini and Mazzei (1986) succeeded in the covalent immobilization of PyOD to a Biodyne Immunoaffinity Membrane (Pall Biodyne, USA) containing carboxylic groups on the surface. The membrane was preactivated with a carbodiimide derivative. The enzyme membrane was fixed on the tip of a hydrogen peroxide-indicating Pt electrode between a cellulose acetate membrane and a further dialysis membrane. This pyruvate sensor has been applied to serum measurement. Over 30 days the sensitivity dropped by only 13%. 

An N-protected amino aldehyde can be prepared by Swem oxidation of an N-pro-tected amino alcohol in the presence of an oxidizing agent comprising DMSO and a water-soluble carbodiimide derivative as l-ethyl-3-(3-dimethylaminopropyl)carbo-diimide hydrochloride (EDC) in an organic solvent. The N-protected amino alcohol can be derived from an L-, D-, or L-/D-amino acid, but usually is the N-protected-(S)-a-amino alcohol derived from an N-protected L-amino acid. 

The first book on the reactions of carbon cumulenes, treating the cycloaddition reactions of ketenes in depth, was written by Staudinger in 1912 Staudinger already realized that cycloaddition reactions of ketenes are common, and often ketenes were only isolated as cyclodimers. The cyclodimers of isocyanates became prominent in the development of polyurethanes in the IG Farben Laboratory in Leverkusen, Germany in the early 1930s and the cyclotrimerization of diisocyanates led to the development of polyisocyanurate foams, with thermal stability superior to rigid polyurethane foams in the 1960s. Today, polyisocyanurate foams are used in the insulation of the fuel tank of the space shuttle. Also, carbodiimide derived cellular plastics with improved thermal stability are of interest. In recent years, cumulene derived polymers became of interest as one-dimensional molecular wires. 

This method could also be applied for the formation of iminopyridines and pyridones using carbodiimide derivatives and isocyanate instead of nitriles (Eq.69) [78b]. 

Another potential problem with DCC is that at the completion of the reaction some DCU remains in solution with the product, necessitating additional purification. Water-soluble carbodiimide derivatives such as l-Cyclohexyl-3-(2-morpholinoethyl)carbodiimide Metho-p-toluenesulffonate and l-Ethyl-3-(3 -dimethylaminopropyl)carbodiimide Hydrochloride (EDCI) obviate this problem, as they are removed by a simple extraction. Many newer coupling agents have been developed for peptide synthesis and other acylation reactions. These include Benzotriazol-l-yloxytris(dimethylamino)phosphonium Hexafluorophosphate (BOP)," 0-Benzotriazol-l-yl-N,N,N, N -tetramethyluronium Hexafluorophosphate (HBTU)," Bis(2-oxo-3-oxazolidinyl)phosphinic Chloride (BOP-Cl), and (1 //-1,2,3-benzotriazol-1 -yloxy)tris(pyrTolidino)phosphonium hexafluorophosphate (PyBOP). In addition to linear and polymeric amides, lactams of various ring sizes have been synthesized using these methods (eq 1)."... 

Ester and Thioester Formation. These reactions occur through the same O-acylurea or anhydride active intermediate as in the amide coupling reactions, and the discussion of associated problems applies here as well. In general, alkyl and (particularly) aryl thiols can be efficiently coupled to carboxylic acids using DCC. Reactions of primary and secondary alcohols proceed reliably, but require the presence of an acylation catalyst. This is usually 4-Dimethylaminopyridine (DMAP), " (see also 1,3-Dicyclohexylcarbodiimide—4-Dimethylaminopyridine), but others have been used including 4-pyrrolidinopyridine and pyridine (.solvent) with catalytic p-Toluenesulfonic Acid The acylation of more hindered alcohols often re.sults in reduced yields however, even f-butanol can be acylated, providing a useful route to t-butyl esters. Various other carbodiimide derivatives have also been used in the preparation of esters. As with amides, which are not limited to intermolecular reactions, a wide variety of lactones can also be synthesized. ... 

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