Carbodi-imides

Carbodi-itnides have been obtained from thioureas upon treatment 

Carbodi-imides also resulted from photolyses of -substituted 

Carbodi-imides can be prepared in high yields from 

The synthesis of N-(tosylmethyl)carbodi-imides, and their application to the synthesis of 2-amino-1,3-oxazoles, has been reported. 

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BuOH, EDCI (EDCI = l-ethyl-3-[3-(dimethylamino)propyl]carbodi-imide hydrochloride), DMAP, CH2CI2, 88% yield.Cbz-Proline was protected without racemization. 

In addition, isocyanates may, under appropriate conditions, react with themselves to give dimers, trimers (isocyanurates) and carbodi-imides. 

Not only are these reactions of importance in the development of the cross-linked polyurethane networks which are involved in the manufacture of most polyurethane products but many are now also being used to produce modified isocycuiates. For example, modified TDI types containing allophanate, urethane and urea groups are now being used in flexible foam manufacture. For flexible integral foams and for reaction injection moulding, modified MDIs and carbodi-imide MDI modifications cU"e employed. 

In the absence of solvents and with suitable catalysts the evolution of carbon dioxide simultaneously with the polycarbodi-imide formation gives rise to a foamed product. These foams are cross-linked because of reactions between carbodi-imide groups and free isocyanate groups. Raw materials for such foams are now available from Bayer (Baymid). 

The use of the triphenylphosphine-carbon tetrachloride adduct for dehydration reactions appears to be a very simple way of synthesizing nitriles from amides, carbodi-imides from ureas, and isocyanides from monosubstituted formamides. All of these reactions involve the simultaneous addition of triphenylphosphine, carbon tetrachloride, and tri-ethylamine to the compound to be dehydrated. The elimination of the elements of water is stepwise. An adduct, e.g. (46), is first formed, chloroform being eliminated, which decomposes to produce hydrogen chloride and the dehydrated product. 

The efficient conversion of the furazans (70) into 1,4-dinitriles (71) is thought to occur via the nitrile oxides (72). Thermal decomposition of the diaziridones (73) in the presence of triethyl phosphite gives the phosphine-imine (75) and the isocyanate (74), which subsequently react together to give the carbodi-imide (76). ... 

Carbodi-imides are used to mediate the formation of amide linkage betwen a carboxylate and an amine or phosphoramidate linkages between a phosphate and an amine [12]. The following is essentially the method of Rockwood [13] and is modified to give a phospho-diester link between the terminal monophosphate of the oligonucleotide and the hydroxyl group of 2-hydroxyethyl disulfide (HEDS) [14]. 

Calf thymus (CT) DNA was first fragmented by sonication, then purified by a standard procedure. Agarose gel electrophoresis for the sonicated CT DNA revealed a distribution in molecular weight ranging from 30 kDa to 260 kDa which is equivalent in base pairs (bp) from 40 to 400 (1 bp = 660 Da). The DNA fragments were reacted with HEDS in the presence of l-cyclohexyl-3-(2-morpholinoethyl) carbodi-imide metho-p-toluenesulfonate (CMC/jTs). Finally, the reaction mixture was gel-filtered and the macro-molecular fractions, when displayed the characteristic absorption of 260 nm of the nucleic bases, were collected. 

As reported by Nelissen [58], unreacted carbodi-imides (Stabaxol I, P and P100), used as hydrolysis stabilisers in e.g. polyesters, are readily detected by IR analysis on the basis of the —N=C=N—absorption at 2140 cm 1, but without further discrimination within... 

Most proteins contain an abundance of carboxylic acid groups from C-terminal functionalities and aspartic and glutamic acid side chains. These groups are readily modified with bis-hydrazide compounds to yield useful hydrazide-activated derivatives. Both carbohydrazide and adipic acid dihydrazide have been employed in forming these modifications using the carbodi-imide reaction (Wilchek and Bayer, 1987). 

Figure 1.112 Phosphate groups can be modified with adipic acid dihydrazide in the presence of a carbodi-imide to produce hydrazide derivatives. This is a common modification route for the 5 -phosphate group of oligonucleotides.

The Derivative, 5-(biotinamido)pentylamine, contains a 5-carbon cadaverine spacer group attached to the valeric acid side chain of biotin (Thermo Fisher). The compound can be used in a carbodi-imide reaction process to label carboxylate groups in proteins and other molecules, forming amide bond linkages (Chapter 3, Section 1). However, the main use of this biotinylation reagent is in the determination of factor XHIa or transglutaminase enzymes in plasma, cell, or tissue extracts. 

FIGURE 2.11 Structures and nomenclature of compounds that serve as auxiliary nucleophiles. Generation of activated esters. Substituted hydroxamic acids are sometimes added to carbodi-imides or other reactions to improve the efficiency of couplings. The additive suppresses side reactions by converting activated species into activated esters (see Section 2.10) before they have time to undergo secondary reactions, p(Me2SO) HOBt 9.30, HOAt 8.70. 

NL Benoiton, FMF Chen. Reaction of JV-t-butoxycarbonylamino acid anhydrides with tertiary amines and carbodi-imides. New precursors for 2-t-butoxyoxazol-5(4//)-one and A-acylureas. J Chem Soc Chem Commun 1225, 1981. 

Amides [41,44], thioamides [41 ] and amidines [45] are converted into nitriles by the reaction with dichlorocarbenes generated by Makosza s procedure (Table 7.16). Under similar conditions, monosubstituted and A.A-disubstituted ureas are converted into cyanamides (Table 7.17) JV,(V -disubstituted ureas produce carbodi-imides in low yield [41,46,47]. /V-Carbamoyl derivatives of dibenzo[/ /]diazepines and the related 10, l l-oxirane derivatives are converted into the corresponding... 

The first publications to describe the phosphane oxide-catalyzed carbodi-imide synthesis from isocyanate appeared in 1962. In this case iminophos-phoranes were recognized as important intermediates. The first mechanistic studies also appeared at this time. Scheme 24 depicts the proposed two-step mechanism (62JA3673, 62JA4288 66CJC2793). 

The rate-determining first step is the reaction of the isocyanate with phosphane oxide, resulting in the formation of isocyanate and CO2. Once the isocyanate is formed, it reacts with additional isocyanate to give carbodi-imide and regenerate the catalyst. A more detailed investigation of the reaction mechanism (Scheme 25) followed years later (69ACSA2697 72ACSA1777). 

Guanidines have been prepared by the reaction between an amine, or an amine salt, and a host of other reagents, such as a thiourea in the presence of lead or mercuric oxide [83, 157, 158], carbodi-imides [140, 174, 175],calcium cyanamide [176, 177], isonitrile dichlorides [178—180], chloroformamidines [181], dialkyl imidocarbonates [182], orthocarbonate esters [183], trichloro-methanesulphenyl chloride [184], and nitro- or nitroso-guanidines [185-188]. Substituted ureas can furnish guanidines, either by treatment with amines and phosphorus oxychloride [189], or by reaction with phenylisocyanate [190] or phosgene [191]. 

The structure of [p-2,3- 2,3-diazabicyclo[2,2,l]heptane diyl-bis(tricarbonyl-iron)] (28) has been reported the Fe—Fe distance is 2.490 Treatment of dialkyl carbodi-imides (RN=C=NR) with Fe(CO)j in refluxing heptane... 

Guanidines may also be formed by reaction of amines with carbodi-imides. This reaction is limited by the availability of carbodiimides, which are usually formed by several methods,24 including dehydration of ureas with the Edward Burgess reagent 11 (Scheme 9).25-27... 

Barvian, M. R. Showalter, H. D. H. Doherty, A. M. Preparation of N,N Bis(aryl)guanidines from Electron Deficient Amines Via Masked Carbodi-imides, Tetrahedron Lett. 1997, 38, 6799-6802. 

A very useful preparation of 1,3,5-thiadiazine type rings involves the report of Goerdeler and Ludke167 that 154 undergoes reaction with phenyl isocyanate to give 162 (X = Ph, Y = 0) and with carbodi-imides to give 162 (X = R, Y = NR ). Other compounds 163 may be prepared by treatment of 154 with benzaldehyde imines,167 a process which was also recently utilized by Kristian et al.3oa... 

The modification of carboxyl groups has been carried out (1) by esterification with dry methanol and HC1, (2) by esterification with aliphatic diazo compounds, (3) by the formation of adducts with carbodi-imides, or (4) by the formation of amides through activation with carbodiimides. Both complete and, apparently specific, partial modification of the 11 free carboxyl groups have been obtained. In general, the first method suffers from the denaturing medium, the second from incomplete reaction, and the third from the uncertain nature of the products. The fourth procedure is perhaps subject to the least question. There are a total of 11 free carboxyl groups in native RNase-A l (Val), 5/ (Asp), 5y(Glu). A summary of the derivatives is given in Table V. 

Yoshida, T., Maeda, K., Kobayashi, M., and Ichishima, E. (1994). Chemical modification of Penicillium 1,2-a-D-mannosidase by water-soluble carbodi-imide identification of a catalytic important aspartic acid residue. Biochem. J., 303, 97-103. 

Regiospecific, Pd(II) catalysed, cycloaddition reactions of azetidines to yield ring-enlarged products include the formation of tetrahydro-2-iminopyrimidines (e.g. 10) by reaction with carbodi-imides (95JOC253) and tetrahydro-l,3-thiazin-2-imines (e.g. 11) from isothiocyanates (95JOC3092). 

Carbodi-imide (RN=C=NR) may potentially co-ordinate via the 71-bond or the N lone pair. Palladium complexes of this ligand have been obtained as diamagnetic, monomeric complexes of type [PdX2L2] [X = Cl or Br L = (Bu N)C or MeNCNBu1] according to equation (15).75 The retention of the antisymmetric N=C=N stretch at 2130 cm-1 is evidence for N lone-pair co-ordination. Although... 

Hubert and co-workers have reported that alkyl diazoacetates react with A -diisopropylcarbodiimide in the presence of transition metal salts to give 2-isopropylimino-3-isopropyl-5-alkoxy-4-oxazolines.115 For example, treatment of ethyl diazoacetate with rhodium(II) acetate in the presence of A,A -diisopropylcarbodiimide (215) produced 2-iso-propylimino-3-isopropyl-5-ethoxy-4-oxazoline (217) in good yield. The formation of oxazoline 217 was interpreted in terms of an addition of ethoxycarbonylcarbene onto one of the nitrogen atoms of the carbodi-imide to give the transient ylide 216 which then cyclized to produce the observed heterocycle. 

Methyl isocyanate and all isocyanic acid esters are an interesting and highly reactive class of organic compounds, since the isocyanate group (-NC0) reacts readily with a wide variety of compounds as well as with itself to form dimers, trimers, ureas, and carbodi-imides. Methyl isocyanate (MIC) is an intermediate in the preparation of carbamate pesticides and conceivably could be applied to the production of special heterocyclic polymers and derivatives. 

Es ist bekannt, daB tert. Phosphanoxide die Umwandlung von Isocyanaten in Carbodi-imide katalysieren702 703. Am besten geeignet sind 2,5-Dihydro-phosphol-1-oxide ... 

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