Ethyl isocyanoacetate

The foregoing examples show that the nucleophilic attack to nitroarenes at theorr/io-posidcn followed by cyclizadon is a generid method for the synthesis of various heterocycles. When nucleophiles have an electrophilic center, heterocyclic compounds are obtained in one step. Ono and coworkers have used the anion dedved from ethyl isocyanoacetate as the reacdve anion for the preparadon of heterocyclic compounds. The carbanion reacts with various nitroarenes to give isoindoles or pyriirddines depending on the stnicture of nitroarenes fEqs. 9.56 and9.57. The synthesis of pyrroles is discussed in detail in Chapter 10. 

This strategy using super nonionic strong base is also applied to less reac compounds The reaction of Tnitronaphthalenev/ith ethyl isocyanoacetate proceeds very slowly in the presence of DBU, but this reaction is accelerated by the use of phosphazene base to give the corresponding pyrrole in reasonable yield fEq 10 36 ... 

The 3-nitroindoles show interesting reactivity toward the anion of ethyl isocyanoacetate iV-sulfonyl derivatives give the pyrrolo[3,3-b indole ring system lEq. 10.38. " On the other hand, iV-alkoxycarbonyl derivatives give the normal product, the pyrrolo[3,4-li indole ring system fEq, 10,39, ... 

Reaction of l-diethylaimno-2-tutroalkenes with ethyl isocyanoacetate in the presence of DBU at room temperanire, followed by quenching with HCl, leads to l-hydtoxypyra2oles m good yield fEq 10 89 ... 

Alternatively, the 3-carboethoxy derivatives 35 are synthesized by the reaction of nitroenamines 34 with ethyl isocyanoacetate 6JCR(S)76>. 

Treatment of N-benzoyl-L-alanine with oxalyl chloride, followed by methanolic triethylamine, yields methyl 4-methyl-2-phenyloxazole-5-carboxylate 32 <95CC2335>. a-Keto imidoyl chlorides, obtained from acyl chlorides and ethyl isocyanoacetate, cyclise to 5-ethoxyoxazoles by the action of triethylamine (e.g.. Scheme 8) <96SC1149>. The azetidinone 33 is converted into the oxazole 34 when heated with sodium azide and titanium chloride in acetonitrile <95JHC1409>. Another unusual reaction is the cyclisation of compound 35 to the oxazole 36 on sequential treatment with trifluoroacetic anhydride and methanol <95JFC(75)221>. 

Essentially no forerun need be taken prior to collection of the product. The last few milliliters of distillate were slightly yellow, and 2-3 g. of intractable material remained in the distillation flask. A boiling point of 76-78° (4 mm.) has been reported for ethyl isocyanoacetate. The submitters have found the distilled product to be stable for up to 6 months when stored under nitrogen in a freezer at -20°. 

Ethylenedioxybutyl)-3-trichloro-acetamido-l-cyclohexene, 58, 9, 11 Ethylene glycol, 56, 44 Ethyl a-fluoro-l-naphthaleneacetate, 57, 73 Ethyl 2-fluoropropanoate, 57, 73 3-Ethylhexane, 58, 3, 4 3-ETHYL-l-HEXYNE, 58, 1, 2, 3, 4 Ethylidenecyclohexane, 59, 46 Ethyliodide, 59, 133 Ethyl 2-iodo-3-nitropropionate, 56,65 Ethyl isocyanide, 55, 98 Ethyl isocyanoacetate, 59,184 l-Ethyl-4-isopropylbenzene, 55,10 Ethyl levulinates, 5-substituted, 58, 81 ETHYL 2-METHYL1NDOLE-5CARBOXY-LATE, 56, 72... 

Thiol protection, 59, 190 Thiono esters, reaction with ethyl isocyanoacetate, 59,187 Thionyl chloride, 55, 27 Thiophenol, 55, 122 58, 144 Thorium dodecanedioate, 56,110 Toluene, 56, 86 58,125 p-Toluenesulfonates, reaction with organo-cuprates, 55,112 p-Toluenesulfonic acid, 58, 57, 63 p-Toluenesulfonic acid, monohydrate, 56,44... 

Thiazoles from Ethyl Isocyanoacetate and Thiono Esters Ethyl Thiazole-... 

THIAZOLES FROM ETHYL ISOCYANOACETATE AND THIONO ESTERS ETHYL THIAZOLE-4-CARBOXYLATE... 

The present procedure is illustrative of a mild and general method for preparing thiazoles substituted in the 4-position with electron-withdrawing substitutents such as carbethoxy, cyano, and p-toluenesulfonyl. Thus condensation of ethyl isocyanoacetate with various thiono esters affords the parent ethyl thiazole-4-carboxylate as well as a series of analogs bearing substituents in the... 

Methyl formate Formic acid, methyl ester (8,9) (107-31-3) Ethyl isocyanoacetate Acetic acid, isocyano-, ethyl ester (8,9) (2999-46-4)... 

The commercially available biphei rl ketone and ethyl isocyanoacetate underwent a smooth condensation reaction and following protecting group manipulations the hydrogenation snbstrate was produced in excellent yield. ° Examination of the asymmetric hydrogenation of material produced using this protocol revealed that the... 

Monocyclic nitro aromatics such as m-dinitrobenzene and its derivatives also react with ethyl isocyanoacetate to give the corresponding isoindoles (Eq. 10.40).44... 

Similar treatment of 5-nitrobenzothiadiazole 97 with ethyl isocyanoacetate and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave the thiadiazolo[3,4-< ]isoindole 93 (21%), but when a phosphazene base was employed the major isolated product was the pyrimidine fV-oxide 98 (46%) (Equation 13) <1996J(P1)1403, 1996TL8391>. 

Pyrrolyl)-4,5-dihydroisoxazole derivatives 402 have been synthesized (Scheme 1.48) in good yields (66%-78%) by regioselective 1,3-dipolar cycloaddition of nitrile oxides to 1-phenylsulfony 1-1,3-dienes, followed by Barton-Zard pyrrole annulation using ethyl isocyanoacetate anion (444). 

Cyclization of 3-nitroindoles 127 with ethyl isocyanoacetate and DBU (conditions of Barton-Zard pyrrole synthesis) gave the corresponding pyrrolo 3,4-fc]indoles 128 (Scheme 22) [35],... 

In the case of quinoxalines 169a,b, benzothiadiazole 172a and benzoselenodiazole 172b the reaction exhibits a remarkable dependence on the base. Whereas in the presence of DBU all these substrates react with ethyl isocyanoacetate to yield pyrimidine Y-oxides 170 and 173 only, the use of phosphorane 164 provides pyrroles 171 and 174 predominantly (Scheme 51) (96TL8391). 

Reaction of 4-nitro-2,l,3-benzoselenadiazole 143 with ethyl isocyanoacetate in the presence of 1,8-diazabicy-clo[5.4.0]undec-7-ene (DBU) in tetrahydrofuran (THF) at room temperature gave the pyrrole-fused product 146 in 56% yield as the sole product (Scheme 9) <1996J(P1)1403>. Reaction of 5-nitro-2,l,3-benzoselenadiazole 147 with ethyl isocyanoacetate under similar reaction conditions gave the pyridimine iV-oxide-fused product 150 in 28% yield as the sole product. Proposed mechanism for the formation of pyrrole and pyrimidine rings involves initial attack of the ethyl isocyanoacetate anion at the /3-position to the nitro groups forming the anionic intermediates 145 and 148 and the resonance structure intermediate 149. The reactivity and chemoselectivity were explained by the steric effect in the intermediates. 

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