Methyl isocyanate additive reactions

Poly(phenylene oxide)s undergo many substitution reactions (25). Reactions involving the aromatic rings and the methyl groups of DMPPO include bromination (26), displacement of the resultant bromine with phosphoms or amines (27), lithiation (28), and maleic anhydride grafting (29). Additional reactions at the open 3-position on the ring include nitration, alkylation (30), and amidation with isocyanates (31). 

As already described for the all-carbon-Diels-Alder reaction, a hetero-Diels-Alder reaction can also be followed by a retro-hetero-Diels-Alder reaction. This type of process, which has long been known, is especially useful for the synthesis of heterocyclic compounds. Sanchez and coworkers described the synthesis of 2-aminopyridines [48] and 2-glycosylaminopyridines 4-144 [49] by a hetero-Diels-Alder reaction of pyrimidines as 4-143 with dimethyl acetylenedicarboxylate followed by extrusion of methyl isocyanate to give the desired compounds (Scheme 4.30). This approach represents a new method for the synthesis of 2-aminopyridine nucleoside analogues. In addition to the pyridines 4-144, small amounts of pyrimidine derivatives are formed by a Michael-type addition. 

This method was extensively reviewed in <84CHEC-I(4)545> and a brief summary is presented here interestingly, since the mid-1980s, this reaction has become less popular. A(-Aryl benzhydrazonyl chlorides react with thiobenzamides to form trisubstituted thiadiazolines which on treatment with alcohols furnish the 2-alkoxy derivative (Scheme 25). A-Arylbenzhydrazonyl chlorides also react with thioketenes to yield 5-methylene thiadiazolines (Equation (16)). Other examples involve the addition of the nitrileimine generated from A-trifluoroacetobenzhydrazonyl bromide to the 0=S of potassium isothiocyanate and methyl isocyanate <87JHC1391>. 

Zirconium and hafnium dialkylamides are highly reactive compounds. They undergo (i) protolytic substitution reactions with reagents such as alcohols, cyclopentadiene and bisftrimethylsilyOamine 63 64 (ii) insertion reactions with C02, CS2, COS, nitriles, phenyl isocyanate, methyl isothiocyanate, carbodiimides and dimethyl acetylenedicarboxylate 69-72 and (iii) addition reactions with metal carbonyls.73 These reactions are summarized with reference to Zr(NMe2)4 in Scheme 1. 

Quinoxaline 1-oxide (209) reacts with phenyl isocyanate to give 2-anilinoquinoxaline (210) together with 1,3-diphenyl-l-(2-quinoxalinyl)-urea (211) and cyclized oxidation product of the urea 212.215 2-Quinoxalinone 4-oxide (205) and its 1-methyl derivative undergo addition reactions, e.g., with phenyl isocyanate and benzyne to give compounds 214 and 216, respectively.216 These reactions are formulated as proceeding via the intermediate cycloadducts 213 and 215. Compound 216 has also been obtained by photolysis of 3-(o-hydroxy-phenyl)quinoxaline 1-oxide.51 1,3-Dipolar cycloaddition of quinoxaline... 

The toxicity of methyl isocyanate comes as a surprise if its high sensitivity to hydrolysis is considered. But actually, it may reach its site of action in the human body largely undecomposed. This is due to the reversible addition of another nucleophile to this heterocumulene. The tripeptide gluthathione, which is supposed to protect the body against oxidizing agents, adds to the C=N double bond of the isocyanate by means of its thiol group whereby the thio-carbamate is formed. When the latter decomposes in a reversal to its formation reaction, it releases the intact toxic methyl isocyanate. 

Several additional examples of the intramolecular cycloaddition of unactivated acetylenes with isomiinchnones were reported by Maier [30]. This cycloaddition approach represents an efficient method for providing rapid access to annulated furans present in several sesqui- and diterpenes, such as the panicu-lides [51],furanonaphthoquinones [52],furodysin,andfurodysinin [53,54].The decomposition of acyclic acetylenic diazoimides 102 and 103 with Rh2(OAc)4 resulted in cycloaddition and retro-Diels-Alder extrusion of methyl isocyanate to give annulated furans 104 and 105 in good yield. The overall transformation is closely related to the intramolecular Diels-Alder reactions of acetylenic oxa-zoles extensively studied by Jacobi and coworkers [55]. 

However, it is not certain whether the isocyanate or the carbamate is the acylating agent in such reaction. In fact, as depicted in scheme 138, it is possible that this reaction could proceed through a mechanism involving the transient formation of methyl isocyanate rather than through the normal addition (A- ) directly to the carbonyl group followed by loss of acetaldehyde. 

The cyclization step can also proceed via Michael addition. Thus, reaction of 4-pyridone (135) with methyl isocyanate in the presence of base afforded (136) in quantitative yield (Equation (22)) <83S593). This reaction could also be carried out with 4-quinolone <838593,82TL3i8i>. 

In the early morning of December 3, 1984, water inadvertently entered the methylisocyanate tank, where >40 metric tons of methyl isocyanate were being stored. The addition of water to the tank caused a runaway chemical reaction, resulting in a rapid rise in pressure and temperature. The heat generated by the reaction in the presence of higher than normal concentrations of chloroform and an iron catalyst, which, combined with the corrosion of the stainless steel tank wall, resulted in a reaction of such momenrnm that poisonous gases formed and could not be contained by safety systems (36). 

Additionally, reactions of isocyanate with amines provide another cross-linking approach to make nanogels. Cross-linked micelles with pH-responsive features were obtained by the addition of excess amounts of 1,8-diaminooctane to micellar aggregates consisting of poly (poly(ethylene glycol) methyl ether methacrylate)-b/oc -poly(methyl methacrylate-co-poly (3-isopropenyl-a,a-dimethylbenzyl isocyanate)) [PPEGMEMA-b-P(MMA-co-TMI)] (Figure 54.9). 

Typical procedure. Valylalanine methyl ester isocyanate [313] Reaction of valylalanine methyl ester hydrochloride (123 mg, 0.515 mmol) with triphosgene (a solution of 112 mg in 1 mL of dichloromethane, 0.38 mmol) yielded 112 mg (95%) of the crude isocyanate 454 as a colorless oily solid. NMR analysis of the product revealed the presence of 8% of hydantoin 455 and 15% of an additional impurity. 

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... 

B. Polymeric Urea [Benzene, diethenyl-, polymer with ethenylbenzene, [[[[(1 methylethyl)amino]carbonyt]amino]methyl] deriv.] A 10.0-g. portion of benzylamine polymer beads prepared as in Part A and 125 ml. of tetrahydrofuran (Note 6) are combined in a 300-ml., three-necked, round-bottomed flask equipped with a magnetic stirrer, a dropping funnel, and a condenser fitted with a gas-inlet tube A nitrogen atmosphere is established in the system, and the slurry is stirred while 1.35 g. (0.0159 mole) of isopropyl isocyanate [Propane, 2-isocyanato-] is added. This causes an exothermic reaction, which subsides after about 20 minutes. The mixture is then stirred at room temperature for 22 hours and at reflux for an additional 4 hours. The beads are collected by filtration, washed with 150-ml. portions of tetrahydrofuran (Note 6) and methanol, and dried under reduced pressure over calcium chloride to yield 9.09 g, of the isopropyl urea polymer. 

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