Phosgene reactivity

Chemical a large part of phosgene reactivity may be accounted... 

The second type of phosgene reactivity is represented by electrophilic reactions... 

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. 

There is a significant difference in the toxicological effects of saturated and unsaturated afiphatic aldehydes. As can be seen in Table 6, the presence of the double bond considerably enhances toxicity. The precautions for handling reactive unsaturated aldehydes such as acrolein, methacrolein [78-85-3] and crotonaldehyde should be the same as those for handling other highly active eye and pulmonary irritants, as, for example, phosgene. 

Commercially important arenesulfonyl isocyanates are not directly accessible from the corresponding sulfonamides via phosgenation due to lack of reactivity or by-product formation at elevated temperatures. A convenient method for their preparation consists of the reaction of alkyl isocyanates with sulfonamides to produce mixed ureas which, upon phosgenation, yield a mixture of alkyl and arenesulfonyl isocyanates. The desired product can be obtained by simple distillation (16). Optionally, the oxalyl chloride route has been employed for the synthesis of arenesulfonyl isocyanate (87). 

Ketene Insertions. Ketenes insert into strongly polarized or polarizable single bonds, such as reactive carbon—halogen bonds, giving acid hahdes (7) and into active acid haUdes giving haUdes of p-ketoacids (8) (46). Phosgene [77-44-5] (47) and thiophosgene [463-71-8] (48) also react with ketenes. 

Ammonia reacts vigorously with phosgene. The products are urea, biuret, ammeUde (a polymer of urea), cyanuric acid, and sometimes cyameUde (a polymer of cyanic acid). The secondary products probably arise through the very reactive intermediate carbamyl chloride [463-72-9] NH2COCI (see... 

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 manufacture of crystal violet (1), however, is a special case which does not involve the isolation of the intermediate Michler s ketone (Fig. 3). Thus, phosgene is treated with excess dimethyl aniline in the presence of zinc chloride. Under these conditions, the highly reactive intermediate "ketone dichloride" is formed in good yield this intermediate further condenses with another mole of dimethyl aniline to give the dye. 

Fatty acid chlorides are very reactive and can be used instead of conventional methods to faciUtate production of amides and esters. lmida2oles are effective recyclable catalysts for the reaction with phosgene (qv) (24). 

Phosgenation. Reaction of phosgene with arylamines to form ureas, and with reactive aryl species to form substituted hen zophen ones, are special cases of acylation. They are dealt with separately siace a more specialized plant is required than for other acylations. Urea formation takes place readily with water-soluble arylamines by simply passiag phosgeae through a slightly alkaline solutioa. An important example is carbonyl-J-acid from J-acid. 

The reactivity of five-membered rings with one heteroatom to electrophilic reagents has been quantitatively compared in a variety of substitution reactions. Table 2 shows the rates of substitution compared to thiophene for formylation by phosgene and iV,AT-dimethylfor-mamide, acetylation by acetic anhydride and tin(IV) chloride, and trifluoroacetylation with trifluoroacetic anhydride (71AHC(13)235). 

PMDI is produced on an industrial scale by the phosgenation of diamin-odiphenylmethane. Structure and molar mass of PMDI depend on the number of aromatic rings in the molecule. For PMDI the distribution of the three monomeric isomers has a great influence on the quality, because the reactivities of the various isomers (4,4 -, 2,4 - and 2,2 -MDI) differ significantly. The greater the portion of the 2,2 - and 2,4 -isomers, the lower is the reactivity. This can lead to different bonding strengths as well as to residual isomers in the produced wood-based panels. 

Chemical Reactivity - Reactivity with Water Decomposes, but not vigorously Reactivity with Common Materials No reaction Stability During Transport Stable Neutralizing Agents for Acids and Caustics Can be absorbed in caustic soda solution. One ton of phosgene requires 2,480 lbs. of caustic soda dissolved in 1(X)0 gal. of water Polymerization Not pertinent Inhibitor of Polymerization Not pertinent. 

Treatment of 2,6-dimethylaniline (121) with phosgene and triethylamine affords the corre-S]ionding isocyanate (122). Condensation of that reactive intermediate with N-isopropylpropyl-cne-1,3-diamine leads to formation of urea 123. This product, recainam (123), acts as membrane Stabilizing agent and thus exhibits both local anesthetic and antiarrhythmic activity [30]. 

Treatment of a chiral amine with phosgene is the cheapest way to prepare symmetrical ureas [29]. Nevertheless, due to the toxicity and reactivity of that reagent, it can advantageously be replaced by triphosgene [30] or l,l -carbonyldiimidazole [31-34] or other derivatives such as l,l -carbonyldi-2(lH)-pyridinone [35]. This procedure can be extended to thiophosgene (Scheme 1) and its thio-analogues, such as l,l -thiocarbonyldi-2(lH)-pyridinone to produce thioureas [36] chiral diamines can thus be transformed into the corresponding monoureas or monothioureas. 

AyV -Carbonyl-2,2 -biimidazole (A V7-carbonyl-2,2 -biimidazyl) prepared from 2,2 -biimidazole and phosgene is relatively unreactive on hydrolysis, and shows reduced reactivity in reactions with carboxylic acids.[19],[2]... 

A, A /-Carbonylbis[2(3//)-benzoxazolethione], obtained from mercaptobenzoxazole and dimeric phosgene as the more thermodynamically stable A-acyl product, also represents a reactive heterocyclic diamide of carbonic acid, and is therefore used in the same way for ester syntheses as A /V -carbonyldibenzimidazole.c 1321... 

Bisphenol A, whose official chemical name is 2,2-bis(4-hydroxyphenyl)propane, is a difunctional monomer with two reactive hydroxyl groups, as shown in Fig. 20,2. It polymerizes svith dicarbonyl organic monomers, such as phosgene or diphenyl carbonate, which are illustrated in Fig. 20.3. During polymerization, shown in Fig. 20.4, the hydroxyl groups of the bisphenol A deprotonate in the presence of a base. After deprotonation, the oxygen atoms on the bisphenol A residue form ester bonds with the dicarbonyl compounds. The polymerization process terminates when a monohydric phenol reacts with the growing chain end. 

Figure 25.4 An SC derivative of mPEG was first prepared through the use of phosgene to form a chloroformate intermediate. Reaction with NHS gives the amine-reactive SC-mPEG.

A modification of Zalipsky s method by Miron and Wilchek (1993) simplifies the creation of the SC-activated species. Instead of using highly toxic phosgene to form a chloroformate intermediate and then reacting with NHS, the new procedure utilizes either N-hydroxysuccinimidyl chloroformate or N,N -disuccinimidyl carbonate (DSC Chapter 4, Section 1.7) to produce the SC-PEG in one step (Figure 25.6). Since both activation reagents are commercially available, creating an amine-reactive PEG derivative has never been easier. 

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