Treatment with isocyanates

Both PMPPIC and PS contain benzene rings, and their delocalized II electrons provide strong interactions. As a result, that there is an adhesion between PMPPIC and PS (Fig. 8). Comparing both methods, treatment with silanes or treatment with isocyanates, it is obvious that the isocyanatic treatment is more effec-... 

Yen and Chu subsequently also disclosed a related Pictet-Spengler reaction involving tryptophan and ketones for the preparation of 1,1-disubstituted indole alkaloids [417]. In the approach shown in Scheme 6.234, tryptophan was reacted with numerous ketones (12 equivalents) in toluene in the presence of 10 mol% of trifluoroacetic acid catalyst. Using microwave irradiation at 60 °C under open-vessel conditions, the desired products were obtained in high yields. Compared to transformations carried out at room temperature, reaction times were typically reduced from days to minutes. Subsequent treatment with isocyanates or isothiocyanates led to tetrahydro-/8-carbolinehydantoins. 

Conjugated heterocumulenes generated in situ by an aza-Wittig reaction are also capable of electrocyclic-ring closure with a subsequent 1,3-H shift. This principle, applied for the first time by Saito et al. on butadiene iminophosphorane 51 (Scheme 28) by treatment with isocyanate and isothiocya-... 

Oxadiazoles are obtained by reaction of aromatic isocyanates or CS2 with N-acylaminoiminophosphoranes (151), as shown in Scheme 60. Upon treatment with isocyanate, an unstable carbodiimide 152 is generated, which cyclizes spontaneously in 80-84% yield. With CS2 as reagent, the corresponding isocyanate cyclizes without isolation of any intermediates to 2-mercapto-l,3,4-oxadiazole 154 in 72-90% yield [91PS(57)11]. 

Resin-bound triazenes with a free NH group can be acylated by treatment with acyl halides, or carbamoylated by treatment with isocyanates [342]. The resulting triazene derivatives are stable towards strong bases, but undergo acidolysis when treated with TFA or TMSC1, yielding amides and ureas, respectively (Entries 1 and 2, Table 3.16). Polystyrene-bound triazenes devoid of a free NH group or carbamates can be cleaved from the support by treatment with acyl halides to yield amides (Entries 3 and 4, Table 3.16). 

Because many more alcohols than alkyl halides are commercially available, the Mitsu-nobu reaction enables the synthesis of larger and more diverse compound arrays than alkylation with alkyl halides. A -AcyIsuIfonamides are strongly acidic and can be alkylated with diazomethane (Entry 6, Table 8.9) or trimethylsilyldiazomethane [137]. Resin-bound sulfonamides have been N-acylated by treatment with acyl halides, and N-carbamoylated by treatment with isocyanates [138]. 

Support-bound C,F I-acidic compounds, such as acetoacetamides, react with isocyanates under basic conditions to yield amides through C-carbamoylation [71]. Similarly, polystyrene-bound aryllithium compounds can be converted into benzamides by treatment with isocyanates [111]. These reactions are closely related to C-thiocarbamoyla-tion, which has been used for the solid-phase synthesis of thioamides (see Section 13.9). Amides have also been prepared by C-alkylation of resin-bound N-acylaminals with allyltrimethylsilane or diethylzinc (Entry 11, Table 13.7). 

Hydroxy-n-propylhydrazine (3-hydrazylpropanol) was cyclized with ethyl carbonate to yield 17 (R = NH2). The reaction was followed by treatment with isocyanate, RNCO, to form a urea derivative 19.85... 

Primary or secondary aminopyrazines may be converted directly into ureido- or thioureidopyrazines by treatment with isocyanates or isothiocyanates primary aminopyrazines may also be converted into such products indirectly via the corresponding isocyanato- or isothiocyanatopyrazines piperazines may be converted into 1/4-carbamoyl- or thiocarbamoylpiperazines by treatment with isocyanates, A-nitrourea, or isothiocyanates and aminopyrazines may be converted into guani-dinopyrazines by treatment with. S -methylisothiourcas or cyanamide. These processes (and some subsequent intramolecular cyclizations or other reactions) are illustrated in the following examples ... 

Phosphonylated aminoquinolines are prepared from phosphonylated arylamines obtained as above in refluxing toluene from diethyl 2-phenyl-2-oxoethylphosphonate and arylamines [mixture of the P-imino- and (Z)-P-enamino derivatives]. Metallation of p-unino and p-enaminophosohonates with n-BuLi in THF followed by sequential treatment with isocyanates, triphenylphosphine, hexachloroethane, Et3N, and aqueous workup produces, after deprotection, 3-phosphonylated-4-aminoquinolines (Scheme 7.1 IS). - ... 

Ring closures to three different benzologues of the bicyclic system discussed in the previous section have been published. Thus, reaction of (164) with triphenylphosphine followed by treatment with isocyanate gave [l,2,3]oxadiazolo[3,4-a]quinoxalinium-3-olate (165) (Equation (40)) <91S745>, ring transformation of (166) in the presence of aqueous triethylamine afforded the [ 1,2,4]triazolo[4,5-a]quinoxalinone compound (167) (Equation (41)) <87JHC1013>, and treatment of (168) with sodium alkoxide resulted in formation of the unsubstituted tricyclic compound (25) (Equation (42)) <87JPC101>. 

The synthesis of Primisulfuron-methyl (299) started from reaction of diethyl malonate and thiourea (Scheme 77) [284]. The resulting pyrimidine derivative 348 was methylated, difluoromethylated and then oxidized to give sulfone 351. Reaction of 351 with aqueous ammonia gave heteroaromatic amine 352, which was transformed to Primisulfuron-methyl (299) upon treatment with isocyanate 353. 

A three component condensation involving aryl amines, aldehydes, and olefins was used to assemble a variety of tetrahydroquinolines [83]. Dihydropyrimidine-2,4-diones were prepared from condensing amines with resin bound acrylates followed by treatment with isocyanates [84]. Two additional groups have published their work using the Pictet-Spengler reaction to prepare tetrahydro- -carbolines [85], tetrahydroisoquinolines [86] and... 

A special problem arises in the preparation of secondary amines. These compounds are highly nucleophilic, and alkylation of an amine with alkyl halides cannot be expected to stop at any specifle stage. Secondary amides, however, can be monoalkylated and lydrolyzed or be reduced to secondary amines (p. 11 If.). In the elegant synthesis of phenyl- phrine an intermediate -hydroxy isocyanate (from a hydrazide and nitrous acid) cyclizes to pve an oxazolidinone which is monomethylated. Treatment with strong acid cleaves the cyclic irethan. 

Treatment of 2-imino-3-phenyl-4-amino-(5-amido)-4-thiazoline with isocyanates or isothiocyanates yields the expected product (139) resulting from attack of the exocyclic nitrogen on the electrophilic center (276). Since 139 may be acetylated to thiazolo[4,5-d]pyrimidine-7-ones or 7-thiones (140). this reaction provides a route to condensed he erocycles (Scheme 92). 

Rea.ctlons, As with other tertiary alcohols, esterification with carboxyUc acids is difficult and esters are prepared with anhydrides (181), acid chlorides (182), or ketene (183). Carbamic esters may be prepared by treatment with an isocyanate (184) or with phosgene followed by ammonia or an amine (185). 

Chlorosulfonyl isocyanate is an excellent alternative to alkaline cyanates ia the preparation of hydantoias from stericaHy hindered or labile amino nitriles (62). Imino derivatives similar to (18) can also be obtained by addition of sonitnles to imines followed by treatment with a cyanate (63). 

Propargyl alcohol (332) and (328) react readily with isocyanates in the presence of a basic catalyst to give 4-methylene-2-oxazolidinones (334) and 4-methylene-2-imidazolinones (336), respectively (63JOC991). In the absence of sodium methoxide the intermediate methanes (333) and ureas (335) were obtained and on treatment with sodium methoxide underwent ring closure. Moderate to excellent yields were obtained. 

Iodine isocyanate was used to synthesize the first steroidal aziridine, 2, 3 -iminocholestane (95). from 5a-cholest-2-ene (91). This reaction sequence which is believed to proceed through a three-membered ring iodonium ion (92) illustrates the limitation of pseudohalogen additions for the synthesis of -aziridines. The iodonium complex forms from the least hindered side (usually alpha) and is opened tmK5-diaxially to give a -oriented nitrogen function. The 3a-iodo-2 -isocyanate (93) is converted by treatment with... 

Incorporation of the phenethyl moiety into a carbocyclic ring was at first sight compatible with amphetamine-like activity. Clinical experience with one of these agents, tranylcypromine (79), revealed the interesting fact that this drug in fact possessed considerable activity as a monamine oxidase inhibitor and as such was useful in the treatment of depression. Decomposition of ethyl diazoacetate in the presence of styrene affords a mixture of cyclopropanes in which the trans isomer predominates. Saponification gives acid 77. Conversion to the acid chloride followed by treatment with sodium azide leads to the isocyanate, 78, via Curtius rearrangement. Saponification of 78 affords tranylcypromine (79). 

A variation on this overall synthetic approach allows the formation of related TSIL ureas by initial conversion of l-(3-aminopropyl)imida2ole into an isocyanate, followed by treatment with an amine and allcylating agent. This approach has been used to append both amino acids and nucleic acids onto the imidazolium cation skeleton [14]. 

A new ionic polymeric polycarbamate was synthesized after steps of polyurethane chemistry using 3-iso-cyanatemethyl-3,5,5-trimethylcyclohexyl isocyanate, 2,5-dimethyl-2,5-dihydroperoxyhexane, 1,6-butanediol, 2,4-tolylenediisocyanate, and N,N -bis(j3-Hydroxy-ethyOpiperazine [27]. Modification of the nitrogen of the piperazine ring into quaternary ammonium salt by treatment with methyliodide gave the MPI high electroconductivity. 

Reductive ring opening of the [i-lactam 10 (X = O), obtained by [2 + 2] cycloaddition of chloro-sulfonyl isocyanate and tetraphenylcyclopentadiene followed by treatment with /7-cresol, with sodium hydride in anhydrous tetrahydrofuran yields 3,5,6,7-tetraphenyl-2//-azepin-2-one (11, X = O).41 Surprisingly, similar treatment of the reduced /Mactam 10 (X = H2) is reported to yield 3,5,6,7-letraphenyl-2//-azepine (11, X = H2), the first monocyclic 277-azepine to be isolated and characterized. Physical data for this compound, however, are inconclusive and attempts to reproduce this synthesis have failed.291... 

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