Ethoxycarbonyl isothiocyanate

The problem is more complicated when the ambident nucleophile. 2-aminothiazole, reacts with an ambident electrophilic center. Such an example is provided by the reaction between 2-amino-5-R-thiazole and ethoxycarbonyl isothiocyanate (144), which has been thoroughly studied by Nagano et al. (64, 78, 264) the various possibilities are summarized in Scheme 95. At 5°C, in ethyl acetate, the only observed products were 145a, 148. and 150. Product 148 must be heated to 180°C for 5 hr to give in low yield (25%) the thiazolo[3.2-a]-s-tnazine-2-thio-4-one (148a) (102). This establishes that attack 1-B is probably not possible at -5°C. When R = H the percentages of 145a. 148. and 150 are 29, 50, and 7%, respectively. These results show that ... 

The ambident reactivity of 2-amino-4,5-disubstituted thiazoles toward benzoylthiocyanate 153 has been studied (311) and parallels that of ethoxycarbonyl isothiocyanate (Scheme 98) the percentages of 154. 155. 

Aminopyridotriazinones 123 were obtained from guanidines 122 in hot hydrochloric acid-dioxane solution however, yields were moderate. The intermediates 122 could be obtained from the reaction of 2-aminopyridine 120 with ethoxycarbonyl isothiocyanate, followed by treatment of thioureas 121 with amines in the presence of HgCl2 (Scheme 12) <2002JHC1061>. 

The thiadiazolopyrimidine derivative 39 reacts with ethoxycarbonyl isothiocyanate and carbon disulfide. In the former case the bicyclic derivative 40 is formed, and with the latter reagent the pyrimido dithiazole 41 is formed (Scheme 4) <2004JHC99>. 

A novel approach to 1,2,4-thiadiazoles 112 is based on the monocyclic and cascade rearrangement of 1,2,5-oxadiazole-2-oxides 111 <2004PAC1691>. Thus, /V-oxidcs 110 upon treatment with ethoxycarbonyl isothiocyanate undergo cascade rearrangement to give 1,2,4-thiadiazoles 112 via intermediate 111 (Scheme 13). 

A typical cyclization reaction starting from a 3-aminopyrazole is the transformation of 255 <2000BML821 >. This compound was treated first with ethoxycarbonyl isothiocyanate followed by sodium methoxide to yield a cyclic intermediate which was methylated by methyl iodide to give the stable product 256. In the cases of the synthesis of 257 <1995PHA675>, the dimeric 258 <2005JHC975>, the azo-substituted 259 <2001JCM439>, and the diaryl... 

Similarly, hydrazones 148 (prepared via reaction of 147 with aroyl or with ethoxycarbonyl isothiocyanates) afforded 149 or 150 upon cyclization under various conditions [77ZN(B)430 79ZN(B)275]. 

The synthesis of 6-substituted derivatives 626 was achieved via reaction of 2-substituted-5-aminopyridine-4-car-boxylic acids and formamidine acetate in boiling 2-methoxyethanol <1996J(P1)2221>. The pyrido[3,4- lpyrimidinone 628 was prepared by amination of the thioureido derivative 627 with diisopropylamine followed by cyclization in boiling DMF <2004FRP2846657>. Pyridine 627 was prepared from the corresponding 3-amino derivative with ethoxycarbonyl isothiocyanate in DMF. 

The pyrazolo[1,5-c]pyrimidine derivative 195 is prepared by reaction of 194 with ethoxycarbonyl isothiocyanate in a 1 2 ratio. It is not clear why excess ethoxycarbonyl isothiocyanate is required (83S478). 

The Chemistry of Ethoxycarbonyl Isothiocyanate and Related Compounds R. Esmail and F. Kurzer, Synthesis, 1975, 301-314. 

Triazinethiones are formed in good yields by the condensation of isothiocyanates and amidines. The reaction between ethoxycarbonyl isothiocyanate and benzamidine is used to illustrate the method (equation 68) (71CB1606). 

The reactions of thiadiazolopyrimidines 58 (R = Me, allyl) with ethoxycarbonyl isothiocyanate and CS2 gave heterocycle 59 via thermal decomposition of 1 1 cycloadducts, which have a hypervalent sulfur (Equation 10). The mechanistic and reactivity features of these reactions were described <2004JHC99>. 

Cyclocondenzation of 2-pyridylacetonitrile and ethoxycarbonyl isothiocyanate in MeCN gave 4-cyano-l-oxo-2,3-dihydro-lH-pyrido[l,2-c]pyrimi-dine-3-thione in 18% yield (08MI2). 6-Endo-trig cyclization of anion, formed from 4-methylpyrimidine by LDA in THF at —78 °C, with methyl 3-propynoate provided 8-methyl-6H-pyrido[2,l-c]pyrimidin-6-one in 47% yield (06TL5063). 

This compound dissociates in solution to yield the starting materials, dithiocarbamic acid and ethoxycarbonyl isothiocyanate <1998EJI1025>. 

The reaction of 2-amino-2-selenazoline (34) and ethoxycarbonyl isothiocyanate affords 4-thioxo-2,3,6,7-tetrahydro-4/7-selenazolo[3,2-<2][l,3,5]triazin-2-one (99). Phenyl isothiocyanate and (34) give the 1,3,5-triazine derivative (100 Scheme 44) (74JOC1819,69T191). 

Azole approach. 2-Aminooxazoline forms a cycloadduct with ethoxycarbonyl isothiocyanate. The orientation of the substituents in the adduct shows that the reaction is initiated by isothiocyanate addition to the exocyclic nitrogen (264) (71CB3039). 

Ethoxycarbonyl isothiocyanate, as well as benzoyl isothiocyanate, interacts with 2-amino-2-thiazoIine at the ring nitrogen atom (509). The initial adducts react further to form fused 1,3,5-triazines (75JOC2000). 

Ethoxycarbonyl isothiocyanate (Et02CN = C = S) will introduce an ethoxycarbonylaminothiocarbonyl substituent (Et02CNHC = S) to a pyrrole C(2) <2001JME1217>. 

Pyrroles 779 and 781 were regioselectively acylated with ethoxycarbonyl isothiocyanate, affording acylated thioamides 780 and 782, respectively, as intermediates in the synthesis of pyrroloamidines, guanidine bioisostere analogs (Equations 184 and 185) <2001JME1217>. 

Thiophanate (81) is prepared by treating o-phenylenediamine (84) with ethoxycarbonyl isothiocyanate (prepared in situ by heating KNCS with ClCOOEt) [64] (Scheme 10). 

The reaction of ethyl 2-(l,2,3,4-tetrahydroisoquinolin-l-yl)acetate hydrochloride with potassium cyanate in boiling water gave 2,3,4,6,7,116-hexahydro-1 //-pyrimido[6,1 -a]isoquinoline-2,4-dione (69IJC684). 3,4,6,7-Tetrahydro-27/-pyrimido[6,l-fl]isoquinoline-2,4-dione and its 2-thioxo derivative were prepared in the reactions of l-methyl-3,4-dihydroisoquinoline with benzoyl isocyanate and ethoxycarbonyl isothiocyanate, respectively, in the presence of NEts (75CB1541). 

An —NH—CS group is incorporated in a new ring when ethoxycarbonyl isothiocyanate (review [2688]) reacts with an amino ester (cf. the reaction of its methyl homologue with an amino-imino ether, p. 77) [2388] other isothiocyanates give 3-substituted products. When an isocyanate is used, the product is a dione. In alkaline solution, an amino ester reacts with a dithiocarbamate to give a fused thioxopyrimidinone in good yield [3342]. 

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