Isocyanates intermediate

Special reactions of hydrazides and azides are illustrated by the conversion of the hydrazide (205) into the azide (206) by nitrous acid (60JOC1950) and thence into the urethane (207) by ethanol (64FES(19)105Q) the conversion of the same azide (206) into the N-alkylamide (208) by ethylamine the formation of the hydrazone (209) from acetaldehyde and the hydrazide (205) and the IV-acylation of the hydrazide (205) to give, for example, the formylhydrazide (210) (65FES(20)259). It is evident that there is an isocyanate intermediate between (206) and (207) such compounds have been isolated sometimes, e.g. (211). Several of the above reactions are involved in some Curtius degradations. 

A novel chemoenzymatic route to polyester polyurethanes was developed without employing highly toxic isocyanate intermediates. First, diurethane diols were prepared from cyclic carbonates and primary diamines, which were subsequently polymerized with dicarboxylic acids and glycols by using lipase CA as catalyst, yielding the polyurethanes under mild reaction conditions. 

Another reaction that can be used for conversion of carboxylic acids to the corresponding amines with loss of carbon dioxide is the Hofmann rearrangement. The classic reagent is hypobromite ion, which reacts to form an A-bromoamide intermediate. Like the Curtius reaction, this rearrangement is believed to be a concerted process and proceeds through an isocyanate intermediate. 

Use of A-bromosuccinimide in the presence of sodium methoxide or DBU in methanol traps the isocyanate intermediate as a carbamate.271... 

Entries 12 and 13 also involve cyclization of the isocyanate intermediates. 

Another way to obtain a carbamate via an isocyanate intermediate is the conversion of an imidazolide RCOIm into the azide RCON3, followed by the Curtius-Schmidt rearrangement and treatment with an alcohol [2241... 

An isocyanate intermediate may also be involved in the selenium-catalyzed process, which starts with the formation of carbonyl selenide from the reaction between selenium and CO, followed by nucleophilic attack by NuH (Scheme 28). When NuH = primary amine, the resulting RNH(CO)SeH intermediate may eliminate H2Se to give the isocyanate, which then reacts with Nu H to give the final product (Scheme 28, path a). Alternatively, oxidation of Nu(CO)SeH by 02 may lead to a bis(carbamoyl)diselenide species, which is attacked by NuH (Scheme 28, path b). 

The methodology did not work for secondary amines, thus suggesting the formation of an isocyanate as intermediate (Scheme 27, MX2 = Pdl2, [OX] = (1/2) O2]. However, by reacting a primary amine in the presence of a secondary nucleophilic amine, a general and selective synthesis of trisubstituted ureas has been achieved, through trapping of the isocyanate intermediate by the secondary amine (Eq. 52) [274,275]. 

Thermal or photochemical rearrangement of acyl azides into amines via isocyanate intermediates. While the thermal rearrangement is a concerted process, the photochemical rearrangement goes through a nitrene intermediate. 

Dihydro-2-quinazolinones are available from diphenylamine-2-acetic acids via isocyanate intermediates, and thus the nonsteroidal anti-inflammatory agent diclofenac 745 gave the dihydro derivative 746 in 63% yield on treatment with diphenylphosphoryl azide <2004BML357>. 

Aryl-2,4-quinazolinediones 980 can be prepared from 3-arylimino-2-indolinones 978 by oxidation with OT-chloroperbenzoic at 0°C <2000TL5265>. The reaction proceeds through benzoxazinone and isocyanate intermediates 979. 

Ion pairs (contd.) intimate, 91, 249, 291 solvation, 45, 57, 81, 390 solvent separated, 91 Ipso substitution, 161, 169 steric effects in, 162 Isocyanate intermediates, 49, 122 Isomer distribution, 158 Isomerisation, cis- trans, 315 Isoprene, 323... 

As with thtHofmann, Schmidt and Lossen Rearrangements, there is a common isocyanate intermediate. 

Triazines (60) have been prepared by reaction of KOCN with an alkyl chloride, involving trimerization of alkyl isocyanate intermediates formed in solid-liquid PTC.109... 

Compound 610 was transformed thermally to the tetrazolo[5,l-b]purin-7(8//)-one 639 through Curtius rearrangement via the isocyanate intermediate 638 (86H1899). Reaction of 626 (R = Ph) with bromine or sulfuryl chloride led by ring opening and decarboxylation to the halogenated tetra-... 

The first step in the overall synthetic scheme (Scheme 6) is the condensation of an appropriate carboxylic acid with trifluoroacetaldehyde. The carboxylic acid is chosen to impart specificity for the target enzyme. In one example,[28 the dianion of cyclohexanepropanoic acid (29) was formed by the addition of LDA and then quickly condensed with trifluoroacetaldehyde to form the p-hydroxy acid 30 as a racemic mixture of erythro- and threo-isomers. The p-hydroxy acid 30 is then protected with TBDMSOTf forming 31. Diphenyl phosphorazidate, TEA, and benzyl alcohol were then utilized in a Curtius rearrangement of the protected alcohol 31, which proceeds through an isocyanate intermediate that yields the protected amino alcohol 32 upon reaction with benzyl alcohol. In order for this step to occur at an appreciable rate, a second equivalent of triethylamine had to be added. The amino alcohol 32 was then deprotected and coupled with Boc-Phe-Leu-OH to give the trifluoromethyl alcohol 33, which was oxidized to the corresponding trifluoromethyl ketone 34 as a 1 1.2 mixture of diastereomers using the Dess-Martin periodinane procedure. Thus far, the compound shown in Scheme 6 is the only compound that has been synthesized by this method, but it is reasonable to assume that many other similar fluoro ketones can be produced by this scheme. 

If the reaction is carried out by treating the amide with bromine and sodium methoxide in methanol, the alkyl isocyanate intermediate is trapped as the N-alkylurethane (3) which can subsequently be hydrolysed to the primary amine. 

The 2-aminonicotinamides 67 react with [fe(trifluoroacetoxy)iodo]ben-zene (BTIB) in aqueous DMF to give the pyrazolopyridines 68 under the same conditions, the amidopyridones 69 are converted to the isoxazolopyridines 70 (97SC2217). These results are somewhat suprising, since BTIB, DAIB, and HTIB are useful reagents for the Hofmann rearrangement (Section III.A.6), and the formation of 71 and 72 from isocyanate intermediates might have been expected. 

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