Trichloroacetyl isocyanate, reactions

Phosgene reacts exothermically with thiirane in two steps (Scheme 36) (77MI50602). 3,5-Dinitrobenzoyl chloride and benzoyl fluoride initiate polymerization of thiirane. A novel reaction of benzoyl isocyanate or trichloroacetyl isocyanate, which yields ethylenethiol derivatives from epithiochlorohydrin (2-chloromethylthiirane), 2-methylthiirane or cyclohexene episulfide, has been reported (Scheme 37) (71BAU2432). 

The ease with which furans react with electrophiles is forcibly demonstrated by the reaction (in CHC13 at 25°C) of 2,4-dimethylfuran with trichloroacetyl isocyanate to give the amide 56a.129 Attack at the 3-position is not easy, but still the azide of 3-(2-furyl)propenoic acid at 230°C gives an isocyanate that... 

The reaction of methyl (3-hydroxypyridin-2-yl)ketone oxime (487) with thionyl chloride, trichloroacetyl isocyanate or chlorosulfonyl isocyanate gave 3-methylisoxazolo[4,5-6]pyridine (488) in varying yields dependent upon the temperature and solvent (Equation (43)) <87H(26)292l>. Trichloroacetyl isocyanate was particularly effective in the formation of compound (488) in either diethyl ether or tetrahydrofuran, at ambient temperature or at reflux, affording 60-78% yields. The treatment of 2-acetyl-3-hydroxypyridine (489) with hydroxyamine 0-sulfonic acid afforded a 1 1 mixture of compound (488) and 2-methyloxazolo[4,5-6]pyridine (490) (Equation (44)). The formation of the isomer (490) results from a Beckmann rearrangement. 

Trichloroacetyl isocyanate (82.2 mmol) was added dropwise to a mixture of the Step 2 product (68.5 mmol) dissolved in 300 ml CH2C12, then stirred for 30 minutes. TLC monitoring indicated the presence of Step 2 product, so additional trichloroacetyl isocyanate (4.5 g) was added. After 1 hour, TLC analysis indicated that the reaction was complete and the product was isolated as a pale yellow solid using the Step 2 workup. 

Acyl isocyanates are more reactive than alkyl or aryl isocyanates. However, the presence of an additional rr-bond conjugated to the C>i-N bond of the isocyanate opens the possibility for [4 + 2] cycloadditions to compete with normal [2 + 2] additions. Reactions with alkyl and aryl substituted alkenes are rather slow. Propene, tranj-2-butene, styrene and conjugated dienes give only 3-lactams, albeit in moderate yields (Scheme 25). The strained double bond of norbomene, a reactive dienophile, adds across the conjugated 4iT-system of trichloroacetyl isocyanate (equation 51). 

Examples of the reaction of tervalent phosphorus with isocyanates and their analogues include the addition of phosphites to carbonyl isothio- and isoseleno-cyanates to give the phosphonates (32) and the reaction of dialkyl phosphoramidites with trichloroacetyl isocyanate to give the rearranged product (33). Predictably, the betaine (34) is obtained from the reaction of TDAP with fluorosulphonyl isocyanate more surprising is the relative stability of (34) to hydrolysis. ... 

The reaction of hydroxylated compounds (alcohols or phenols) and amines with trichloroacetyl isocyanate (TAI) (47) to form urethanes and ureas, respectively (48), can be performed within the NMR tube. This method, however, is restricted to compounds containing those functionalities and has not been applied widely. 

Oxazepam (116) can be converted into a range of 3-(disubstituted-amino) derivatives, in moderate yield, by its reaction with the appropriate 2-amino-4,5-dihydro-l,3,2-dioxaphosphole. A direct route to the 3-amino-derivatives has also been reported.l,3-Dihydro-2//-l,4-benzodiazepin-2-ones react with most isocyanates to give the 1-carbamoyl derivative however, (114), on reaction with trichloroacetyl isocyanate and subsequent hydrolysis, gave the 3-amido-derivative. The latter has been converted into a range of 3-esters.Continuing work on the electrolytic reduction of 2,3-dihydro-l,4-diazepinium salts has shown that the AW-dibenzyl-6-phenyl-compound gives a diazepine dimer and an unexpected rearrangement product, which is 1,4-di-imidazolidinyl-butadiene. ... 

An alternative route involves end-capping to produce a terminal hydroxyl followed by reaction with trichloroacetyl isocyanate (Equation 5.23). This new, reactive end group can be used to initiate the growth of a second block via the photoreduction method proposed by Bamford in which magnesium or ihenium carbonyls are excited by UV or visible radiation and extract a chloride atom from the terminal unit, thereby creating a radical site. As only one radical is formed, this is a much cleaner reaction compared with (1) however, block lengths are more difficult to control in both these radical reactions, and the exact structure of the product formed can depend on the mechanism of the termination reaction. 

Alkyl isocyanates, like n-butyl isocyanate, do not react with different alkyl azides and aryl azides respectively. In contrast, aryl isocyanates 131 react with alkyl azides 130 like n-butyl azide or cyclohexyl azide to yield 1-alkyl-4-aryl-A -tetrazoline-5-ones 132, however, aryl isocyanates do not react with aryl azides. The reactions take place within some hours and up to several days at elevated temperatures, ranging from 55 to 130 °C, and are performed in benzene or without solvent (Scheme 29A). The addition of aryl azides to acyl isocyanates, such as benzoyl isocyanate or carboalkoxy isocyanates like chloroacetyl isocyanate and trichloroacetyl isocyanate, was unsuccessfully attempted at different reaction conditions [107]. 

The bis-alkyne side chain was synthesized as outlined in Scheme 64. Hy-drazone 300 was alkylated, followed by hydrolysis, to give a-hydroxy ketone 301, which was converted to oxazolone by treatment with trichloroacetyl isocyanate. The oxazolyl triflate 302, prepared by reaction of the oxazolone with triflic anhydride, was coupled with alkyne 213 under Sonogashira conditions as reported by Panek [118], followed by deprotection of MPM and oxidation, to furnish the side chain precursor bisalkynyloxazole 299. 

Reaction of trichloroacetyl isocyanate (3 equivalents) in p-xylene at reflux for 3 days with norbornenes gave, after base treatment, the 2-cyanonorborn-2-ene derivative, e.g. (407) from norbornene itself. The known [4 -t- 2] cycloadduct is not formed reaction is thought to occur by way of the unsaturated imide (408), itself possibly the result of base-promoted disproportionation of an initial [2 + 2] adduct. Decomposition of t-butylazodiphenylcarbinol in benzene occurs by a radical chain mechanism involving t-butyl radicals olefinic compounds act as radical traps norbornene, for example, is hydro-t-butylated to give exo-2-t-butylnorbomane. Stable cyclic... 

Chitwood, Gott, and Martin found that when 1 was treated with trichloroacetyl isocyanate, the unsaturated amide 6 was obtained via the unstable 3-lactam 4 and the [4+2]cycloadduct 5 (Scheme 5). They observed that the reaction performed in acetonitrile proceeded ten times faster than in chloroform. Owing to their low stability, both by-products 4 and 5 were detected only by NMR. 

Polar solvents, such as acetonitile or nitromethane accelerated the reaction rate, more so the cycloaddition than the rearrangement to the amides. An increase in polarity of the solvent promoted formation of the [2+2]cycloadduct as a kinetic product. The rate of cycloaddition depends on the concentration of both components, whereas the intramolecular rearrangement of cycloadducts to 25 does not. The highest content of [2+2]cycloadduct in the reaction mixture could be achieved when the cycloaddition was performed with more concentrated solutions of benzylated glycals in a polar solvent. For example, tri-O-benzyl allal 26 (30 mg/ml) plus 3 molar equiv. of trichloroacetyl isocyanate in nitromethane produced 42% of the respective p-lactam 27 after 10 hrs, whereas at a glycal-concentra-tion of 400 mg/ml, 27 was formed in a 60% yield after 5 hrs. (Scheme 11)... 

This is illustrated in Scheme 12 by the example of the synthesis of p-lactam 28.Until now 14 structures derived from dihydro-2H-pyrans and glycals were obtained, and are shown in Scheme 13. The same procedure could be applied to the cycloaddition of trichloroacetyl isocyanate to the furanoid glycal 29.The reaction proceeded with the same high stereoselectivity to produce [2+2] and [4+2]cycloadducts having the a-D-gluco configuration (Scheme 14). J Deprotection led to the formation of stable compound 30. 

Reference is made in Chapters 13 and 24 to the synthesis of /8-lactams by the addition of trichloroacetyl isocyanate to glycal derivatives followed by periodate cleavage of the sugar rings, and bis(trichloroethyl)azodicarboxylate adds to such compounds to afford a route to 2-amino-2-deoxyglycosides (Chapter 9). A novel cycloaddition reaction is illustrated in Scheme 6A. ... 

One of the earlier [4+2] cycloaddition reactions, involving ketenimines as dienophiles, is the reaction of trichloroacetyl isocyanate with the ketenimines 110 to give the cycloadducts 111 in 91-93 % yields. In this reaction, the C=C bond of the ketenimine participates . 

Stefanova, R., D. Rankoff, S. Panayotova, S. L. Spassov, Proton NMR determination of linoleic acid mono- and diesters of polyethyleneglycols via reaction with trichloroacetyl isocyanate,/. Am. Oi/CAe/ra. Soc., 1988,65,1516-1518. 

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