Isocyanates alternative method

Low boiling isocyanates, such as methyl isocyanate, are difficult to prepare via conventional phosgenation due to Ihe fact that the /V-alkyl carhamovl chlorides are volatile below their decomposition point. A convenient method for the synthesis of these low boiling materials eonsisls of live reaction of JV. Al -dimeihylurea with toluene diisocyanate to yield an aliphatic -aromatic urea which is pymlyycd to yield the desired isocyanate. Alternatively, an appropriate aliphatic-aromatic urea can he prepared by the reaction of dipltenylcarbamoyl chloride with methylanune. 

The following alternative method may be used. Dissolve 0.01 mol of the phenol and 0.01 mol of 1-naphthyl isocyanate in 20 ml of light petroleum (b.p. 60-80 °C), add 2 drops of triethylamine (or, less satisfactorily, 2 drops of pyridine), reflux for 5 minutes and allow to crystallise. Filter olf the crystalline solid through a sintered glass funnel. 

An alternative method for preparing isocyano carboxylic esters using methyl isocyanate, acetone, and chloroformic acid benzyl ester was also described by the author and illustrated in Eq. 1 ... 

Curtius reaction. The overall process of converting an acid through the azide and isocyanate into an amine is known as the Curtius reaction. For application of the Curtius reaction to Cii-2-phenylcyclopropanecarboxylic acid, J. Weinstock found the route to the azide through the acid chloride unsatisfactory because of ready isomerization to the trans acid chloride. An efficient alternative method utilizes a mixed anhydride intermediate of a type found serviceable in the synthesis of peptides. A solution of the acid in aqueous acetone was treated with triethylamine to... 

The Bucherer-Bergs synthesis has been successfully applied to a great variety of cyclic ketones, ranging from cyclopropanone to steroidal ketones. However, the difficulty of preparing small-ring ketones has led to the development of alternative methods to obtain the corresponding spirohy-dantoins. Isocyanate intermediate 27 may be prepared in several steps from malonic ester typical Bucherer-Bergs chemistry follows.51... 

Because of the importance of /3-lactam antibiotics, a number of solid-phase approaches to this class of compounds have recently been reported [140]. In particular, [2 + 2] cycloadditions between ketenes and resin-bound imines have attracted the attention of many laboratories [140]. The alternative method, based on [2 -i- 2]cycloaddition of isocyanates to olefins has been reported by our laboratory only. 

An important plant protection agent based on catechol is carbofuran, manufactured by Bayer diViA FMC, It is obtained by the reaction of catechol with methallyl chloride, followed by Claisen rearrangement at around 200 °C and ring closure to the respective benzofuran, with subsequent reaction of the hydroxyl group with methyl isocyanate in the presence of triethanolamine. (An alternative method of synthesis is based on o-nitrophenol). 

Isocyanates and polyisocyanates are manufactured on a commercial scale by the reaction of gaseous phosgene with amines or amine salt precursors [141-143]. As restrictions upon the use of very toxic materials such as phosgene and other chlorine-containing compounds within the chemical industry have become more rigorously enforced, there has been increasing interest in developing alternative methods for isocyanate production [144]. Alternative methods, such as the thermolysis of carbamates (urethanes), very often require rather drastic reaction conditions [139, 140]. 

In pursuit of alternative methods of isocyanate production, the results of investigations with simple boron halides, BX3 (X = Cl, Br), in converting carbamate esters to isocyanates of industrial importance were reported. Additionally, it has previously been shown that BX3 can be generated in the production of benzyl esters by reaction of trialkyl borates with benzylic halides and CO in the presence of catalytic quantities of Pd° or Rh [244-246]. This offers the rather attractive option of two concomitant processes achieving commercially valuable ends, together with constant recycling of boron. 

A convenient method for the synthesis of these low boiling materials consists of the reaction of /V,/V-dimethy1iirea [96-31-1] with toluene diisocyanate to yield an aUphatic—aromatic urea (84). Alternatively, an appropriate aUphatic—aromatic urea can be prepared by the reaction of diphenylcarbamoyl chloride [83-01-2] with methylamine. Thermolysis of either of the mixed ureas produces methyl isocyanate ia high yield (3,85). 

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). 

In a modification of the original method. Read replaced a-ammo acids with o-amino nitriles. Chlorosulfonyl isocyanate is an excellent alternative lo alkaline eyanates in the preparation of hydanloins from sterically hindered or lahile amino nitriles. 

Cycloaddition reactions of thioketene and isocyanic acid forming four-membered ring products have been studied by means of the ab initio RHF/6-31G method. The two alternative reactions are concerted but nonsynchronous, taking place through twisted or planar four-membered cyclic transition states. The activation barriers were calculated to be... 

Pentafluorosulfanyl isocyanate, SF5NCO and SF5NCS, were first reported in 1964 by Tullock et al. (8). They are obtained from the reaction of pentafluorosulfanyl(trifluoromethyl)amine with benzoic acid and thiobenzoic acid, respectively. An alternative preparative method of F5SNCS involves thiolysis of F5SN=CC12 with H2S in the presence of NaF. 

An alternative common method of nitrile oxide synthesis, frequently referred to as the Mukaiyama method (60JA5339), involves dehydration of primary nitroalkanes using, for example, phenyl isocyanate in the presence of a catalytic amount of triethylamine (Scheme 5). Phosphorus oxychloride (730S59 90S817), chloroformate esters (86BCJ2827), aryl... 

Despite this they should be considered as possible alternatives in cases where more familiar methods fail. Amongst this group of activators are p-toluenesulfonyl chloride, tiifluoromethanesulfonic anhy-dride,silver tetrafluoroborate, molybdenum oxide, phosphorous pentoxide, trichloromethyl chloroformate, 2-fluoro-l-methylpyridiniumsulfonate, chlorosulfonyl isocyanate, antimony penta-chloride (for which an X-ray structure of the DMSO-SbCb conqilex was obtained) and phenyl dichlo-rophosphate. ... 

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