Isocyanates nucleophilic reaction

Chemical Properties The formation of salts with acids is the most characteristic reaction of amines. Since the amines are soluble in organic solvents and the salts are usually not soluble, acidic products can be conveniendy separated by the reaction with an amine, the unshared electron pair on the amine nitrogen acting as proton acceptor. Amines are good nucleophiles reactions of amines at the nitrogen atom have as a first step the formation of a bond with the unshared electron pair of nitrogen, eg, reactions with acid anhydrides, haUdes, and esters, with carbon dioxide or carbon disulfide, and with isocyanic or isothiocyanic acid derivatives. 

The use of dicarbodiimides as monomers in polyaddition reactions have not as yet found wide utility. However, polymers containing carbodiimide groups are known, and further nucleophilic reactions of these polymers with numerous substrates are reported. Carbodiimides, generated in situ from isocyanates are used as catalyst in the formation of polyamides from diisocyanates and dicarboxylic acids. Also, homoleptic lanthanide amidinates, made from carbodiimides, exhibit high catalytic activity for the ring opening polymerization of e-caprolactone at room temperature. ... 

A much less likely first step is nucleophilic reaction of the carbonyl oxygen of the isocyanate with the carbon attached to bromine ... 

Tertiary amines are catalysts for both isocyanate-hydroxyl and isocyanate-water reactions. Generally, an increase in base strength in tertiary amines increases the catalytic strength. However, in the case of triethylene diamine (DABCO) the nucleophilicity is enhanced by the steric configuration. Electron-donating substituents enhance catalytic activity. Some tertiary amines are illustrated in Figure 2.20. 

Other Nucleophilic Reactions. Fluorous thiol can react with alkoxysulfonyl or aryloxysulfonyl isocyanates to give the corresponding sulfonyl thiocarbamates under mild reaction conditions (eq 9).ll... 

Isocyanates are susceptible, however, to nucleophilic as well as electrophilic attacks. Typical nucleophilic reactions of isocyanates are urethane (carbamate) formation with alcohols ... 

Rapid growth of urethane technology can be attributed to the development of catalysts. Catalysts for the isocyanate-alcohol reaction can be nucleophilic (e.g., bases such as tertiary amines, salts and weak acids) or electrophilic (e.g., organometallic compounds). In the traditional applications of polyurethanes (cast elastomers, block foams, etc.) the usual catalysts are trialkylamines, peralkylated aliphatic amines, triethylenediamine or diazobiscyclooctane (known as DABCO), N-alkyl morpholin, tindioctoate, dibutyl-tindioctoate, dibutyltindilaurate etc. 

Like isocyanates, isothiocyanates react rapidly with nucleophiles. Reactions of isocyanates with ammonia or amines yield ureas. In a similar fashion, isothiocyanates give a thiourea as the first formed intermediate (Fig. 23.35). 

Nucleophilic Reactions. M,C)-Bis(trimethylsilyl)hydroxyl-amine is a protected, lipophilic form of hydroxylamine. It reacts with a variety of electrophiles predominantly by attack on the nitrogen nucleophilic center. Reaction with acid chlorides (1 equiv) in the presence of triethylamine gives M<9-bis(trimethylsilyl)-hydroxamic acids by iV-acylation. A related reagent, tris(tri-methylsilyl)hydroxylamine, gives the same product in high yields, also by iV-acylation. Hydrolysis gives the free hydroxamic acids, whereas thermal fragmentation affords isocyanates (eq 1). ... 

Often the initially formed bonds at low temperature are not the ones that are isolated at room temperature. Also the electronic configurations play a part in product formation. For example, in the [2+2] cycloaddition reaction involving two carbodiimides the more nucleophilic carbodiimide attacks the more electrophilic carbodiimide giving rise to the formation of only one reaction product. The latter reactions proceed stepwise, while sometimes concerted reactions are observed. Sterical hindrance also plays an important role in product formation. We have utilized A-methyl-A -t-butylcarbodiimide as a probe in determining the structure of the derived cycloadducts, because the reaction always proceeds via addition across the C=N bond with the methyl substituent. For example, in the [2+2] cycloaddition reaction with benzoyl isocyanate the reaction proceeds across the C=0 bond of the isocyanate, because t-butyl isocyanate is the only product generated in the retro reaction... 

The chemical reactivity of the cumulenes under discussion ranges from highly reactive species to almost inert compounds. While some cumulenes can only be generated in a matrix at low temperatures, others are indefinitely stable at room temperature. For example, sulfines and sulfenes are only generated in situ, but some cumulenes with bulky substituents are sometimes isolated at room temperature for example, C=C=S was detected in interstellar space by microwave spectroscopy, and its spectrum was later verified by matrix isolation spectroscopy. In contrast, some cumulenes, such as carbon dioxide and carbon disulfide, are often used as solvents in organic reactions or in the extraction of natural products. The reactivity of some center carbon heterocumulenes in nucleophilic reactions is as follows isocyanates > ketenes > carbodiimides > isothiocyanates. However these reactivities do not relate to the reactivities in cycloaddition reactions. Often reactive cumulenes are isolated as their cyclodimers. Aromatic diisocyanates are more reactive than aliphatic diisocyanates in nucleophilic as well as cycloaddition reactions. 

The chemistry of isothiocyanates resembles very much the chemistry of isocyanates. In addition to the widely known nucleophilic reactions of isothiocyanates, cycloaddition reactions are also prominent. The cycloaddition reactions can occur across either the 0=N or the C=S double bond but the latter is often preferred. The polarization of the N=0=S bond is shown in the following resonance forms ... 

Urea derivadves are of general interest in medicinal chemistry. They may be obtained cither from urea itself (barbiturates, sec p. 306) or from amines and isocyanates. The latter are usually prepared from amines and phosgene under evolution of hydrogen chloride. Alkyl isocyanates are highly reactive in nucleophilic addidon reactions. Even amides, e.g. sulfonamides, are nucleophilic enough to produce urea derivatives. 

The cyclic carbamate (oxazoIidin-2-one) 313 is formed by the reaction of phenyl isocyanate (312) with vinyloxirane[I92]. Nitrogen serves as a nucleophile and attacks the carbon vicinal to the oxygen exclusively. The thermodynamically less stable Z-isomer 315 was obtained as a major product (10 I) by the reaction of 2-methoxy-l-naphthyI isocyanate (314) with a vinyloxir-... 

Pd-cataly2ed reactions of butadiene are different from those catalyzed by other transition metal complexes. Unlike Ni(0) catalysts, neither the well known cyclodimerization nor cyclotrimerization to form COD or CDT[1,2] takes place with Pd(0) catalysts. Pd(0) complexes catalyze two important reactions of conjugated dienes[3,4]. The first type is linear dimerization. The most characteristic and useful reaction of butadiene catalyzed by Pd(0) is dimerization with incorporation of nucleophiles. The bis-rr-allylpalladium complex 3 is believed to be an intermediate of 1,3,7-octatriene (7j and telomers 5 and 6[5,6]. The complex 3 is the resonance form of 2,5-divinylpalladacyclopentane (1) and pallada-3,7-cyclononadiene (2) formed by the oxidative cyclization of butadiene. The second reaction characteristic of Pd is the co-cyclization of butadiene with C = 0 bonds of aldehydes[7-9] and CO jlO] and C = N bonds of Schiff bases[ll] and isocyanate[12] to form the six-membered heterocyclic compounds 9 with two vinyl groups. The cyclization is explained by the insertion of these unsaturated bonds into the complex 1 to generate 8 and its reductive elimination to give 9. 

Because of their relative instabiUty, primary phosphine oxides caimot be isolated and must be converted direcdy to derivatives. Primary and secondary phosphine oxides undergo reactions characteristic of the presence of P—H bonds, eg, the base-cataly2ed nucleophilic addition to unsaturated compounds such as olefins, ketones, and isocyanates (95). 

Primary cycloaUphatic amines react with phosgene to form isocyanates. Reaction of isocyanates with primary and secondary amines forms ureas. Dehydration of ureas or dehydrosulfuri2ation of thioureas results in carhodiimides. The nucleophilicity that deterrnines rapid amine reactivity with acid chlorides and isocyanates also promotes epoxide ring opening to form hydroxyalkyl- and dihydroxyalkylaniines. Michael addition to acrylonitrile yields stable cyanoethylcycloalkylarnines. 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

A urethane is typically prepared by nucleophilic addition reaction between an alcohol and an isocyanate (R—N = C=0), so a polyurethane is prepared by reaction between a cliol and a diisocyanate. The diol is usually a low-molecular-weight polymer (MW 1000 amu) with hydroxyl end-groups the diisocyanate is often toluene-2,4-diisocyanate. 

Problem 31.9 Show the mechanism of the nucleophilic addition reaction of an alcohol with an isocyanate to yield a urethane. 

The nitrogen atoms in ADC compounds are highly electrophilic. Nucleophilic attack on nitrogen is easy, and as with electrophilic acetylenes, such as dimethyl acetylenedicarboxylate, it seems likely that some cycloaddition reactions of ADC compounds with unsymmetrical substrates proceed via a stepwise mechanism. PTAD is a powerful electrophile, although TCNE is more reactive, and chlorosulfonyl isocyanate is more reactive still.58... 

A straightforward preparation of pyrimidinones and pyrimidinethiones 45 involved reaction of isocyanates or isothiocyanates with the readily available starting material 44, which had previously been described by the same authors. A particularly interesting application was the use of sugar isothiocyanates to give nucleosides. Nucleophilic displacements of the sulfur groups in the products were also reported <06EJO634>. 

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