Syntheses with Isocyanates

Starch reacts with isocyanates to produce carbamates (urethanes), which are esters of carbamic acid. Several reactions of starch with phenyl-, various aryl-, 1-naphthyl-isocyanates or 1,6-hexamethylene- and 2,4-tolyl-diisocyanates were conducted either in pyridine or morpholine below the boiling point of these solvents.2546-2548 In each case all three hydroxyl groups of the glucose units reacted to give tricarbanilates, provided a sufficient amount of the isocyanate reagent was used. 

The carbamates have hydrophobic surfaces and are resistant to swelling not only in water, but also in the presence of such strongly swelling reagents as 4 M aqueous 

Phenyl- and other aryl-carbamates of starch appeared to be nontoxic to Aspergillus oryzae, Aspergillus niger, and Penicillium expansum.2550 2-(Hydroxypropyl)starch carbamate was also tested without any particular success in enzyme-immobilizaton studies.2553 Improvements in the weight gain of ruminants upon feeding with fodder supplemented with carbamates was reported.2554 

Dialkylcarbamates were produced by the reaction of starch with dialkylacar-bamoyl chlorides in aqueous suspensions, with reaction yields as high as 83%.2555 These reactions are localized at the surface of starch granule.2556 

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More convenient is the use of aryl a2ides which are readily converted into isocyanates upon heating in nonreactive solvents via the loss of nitrogen. The latter method is useful for the synthesis of isocyanates with additional substituents which could not be prepared with phosgene (20). 

H-pyran synthesis from, 3, 759 bis(trimethylsiloxy) in pyrrole synthesis, 4, 333 chromene synthesis from, 3, 750 cycloaddition reactions with isocyanates, azetidin-2-ones from, 7, 261 dihydropyran synthesis from, 3, 771 fuiyl... 

Waste PETP was depolymerised by glycolysis to give hydroxyl-terminated oligomers(DPET), which were used in the synthesis of urethane oils. The effect of depolymerisation temps., the type of glycol and the amount of catalyst on the yield and composition of the depolymerisation products was studied. The physical properties of the urethane oils were compared with those of a commercially-available product. The reaction of DPET with isocyanates produced random linkage between different molecules with or without terephthaloyl groups. 15 refs. 

The anionic method of polymerization is most useful for the synthesis of low molecular weight hydroxy-terminated oligomers and polymers that are to be further processed. For example, the treatment of hydroxy-terminated oligomers with isocyanates has been used to obtain polyester-urethanes (9,20), while triblock copolymers (PCL-PEG-PCL) are prepared by initiating the polymerization of e-caprolactone with the disodium alcoholate from polyethylene glycol (26). 

Analogous to the synthesis of isocyanates, isothiocyanates are obtained in good yield by reacting AyV -thiocarbonyldiimidazole (ImCSIm) with primary aliphatic or aromatic amines in equimolar amount. In chloroform at room temperature the dissociation equilibrium of imidazole-A-thiocarboxamides is shifted completely to isocyanates. 

Reaction of pyridines with dialkyl acetylenedicarboxylates in the presence of isocyanates in dry CH2C12 at room temperature produced 1-substituted 2-oxo-l,9a-dihydro-2/7-pyrido[l,2-tf]pyrimidine-3,4-dicarboxylates <2004TL1803>. One-pot, three-component synthesis of 1-substituted 2-oxo-l,llb-dihydro-2//-pyrimido[2,l- ]iso-quinoline-3,4-dicarboxylates and 4-(3-chloro-4-methylphenyl)-3-oxo-4,4a-dihydro-3/7-pyrimido[l,2-tf]quinoline-l,2-dicarboxylate was realized by the reaction of isoquinoline and quinoline with isocyanates and dialkyl acetylenedicarboxylates <2004S861>. Diastereomeric mixtures of l-tosyl-2-aryl-l,llb-dihydro-2/7-pyrimido[2,Ttf]isoquinoline-3,4-dicarboxylates were obtained from isoquinoline, iV-tosyl-benzaldehyde imines, and DMAD <2002OL3575>. 

Synthesis of a pyrimidopyrrolopyrimidine central core of alkaloid variolin B has been achieved by the reaction of ylide 226 with isocyanates. The product 227 is formed in excellent yield (Equation 26) <2000TL4777, 2002TL1005, 2003JOC489>. 

A synthesis of l,3-pyrrolo[l,2-f]imidazoles 148 has been obtained by reacting 147 with isocyanates in THF under reflux for 4h in the presence of DBU. This reaction gave high yields of l,3-dioxo-l,2,3,4-tetrahydropyrrolo[l,2-f]-imidazoles (Equation 20) <2004JOC9313>. 

The same research group has also published the synthesis of the related benzologue <2005BMC295>. The synthesis of this tricyclic ring system 157 has been accomplished in analogous way the indole-azine 156 was prepared first and was then reacted with isocyanates. 

The aza-Wittig/67r-electrocyclization strategy for the synthesis of 1-arylaminoisoquinolines 220 was applied for the first time by Saito et al. (86CL135). This sequence (Scheme 81) is induced by an aza-Wittig reaction of A-vinyliminophosphoranes 218 with isocyanates. The vinylcarbodiimides 219, once formed, spontaneously undergo thermal 67r-electrocyclization (86CL135). 

Taylor and Patel describe a quinazoline synthesis (Scheme 93) transforming the iminophosphorane of anthranonitrile with isocyanate to car-bodiimide 254. Addition of ammonia in tetrahydrofuran (THF) leads to guanidine 255, which affords with the adjacent nitrile function quinazoline derivatives 256 (91JHC1857). 

An interesting variation of this quinoxaline synthesis is outlined by the synthesis of sydnoquinoxalines shown in Scheme 103. The starting material is phenylsydnone 288 with an iminophosphorane group in an o-position. With isocyanate or isothiocyanate carbodiimide intermediates 289 are formed by an electrophilic aromatic substitution at the sydnone ring (4 position), the 4-(arylamino)sydno[3,4-a]quinoxalines (290) are obtained (91S745). 

There are few examples of this type of synthesis. Typically, an azirine reacts with isocyanates or isothiocyanates to yield the triazine via a series of dipolar intermediates. The products may be contaminated with the isocyanate trimer the example of Scheme 114 below is typical. The novel spiro compound (188) is formed by a similar route (Scheme 115) (79HCA1429, 81LA264). 

Diones are normally synthesized from /3-hydroxy acids in two steps first, conversion into carbamates by reaction with sodium cyanate, and then cyclization with thionyl chloride (Scheme 103) (54JCS839). Alternative preparations utilize oxetanes, which may be combined either with isocyanates in the presence of boron trifluoride (68JAP6808278) or with S-alkylthioureas (Scheme 104) (69ZOR1844). In the last example the initial products are imines (224) which may readily be hydrolyzed to the required diones. Similar methods can be applied to the synthesis of tetrahydro-l,3-thiazine-2,4-diones, and, for instance, the 4-oxo-2-thioxo derivative (225) is obtained from /3-propiolactone and dithiocarbamic acid (Scheme 105) (48JA1001). 

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). 

The reversed reaction, i.e. attack of CO on the corresponding transition metal azido complex, sometimes also provides an attractive route for the synthesis of isocyanate complexes, e.g. the reaction of CO with, for example, Co(N3)(DH)2(PPh3),344 Rh(f/5-C5Me5)(N3)4276 or Rh(N3)(cod).344... 

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