Phase cyanation

Alkylation. Ben2otrifluoride can also be alkylated, eg, chloromethyl methyl ether—chlorosulfonic acid forms 3-(trifluoromethyl)ben2yl chloride [705-29-3] (303,304), which can also be made from / -xylene by a chlorination—fluorination sequence (305). Exchange cyanation of this product in the presence of phase-transfer catalysts gives 3-(trifluoromethylphenyl)acetonitrile [2338-76-3] (304,305), a key intermediate to the herbicides flurtamone... 

The vapor-phase chlorination reaction occurs at approximately 200-300°C. The dichlorobutene mixture is then treated with NaCN or HCN in presence of copper cyanide. The product 1,4-dicyano-2-butene is obtained in high yield because allylic rearrangement to the more thermodynamically stable isomer occurs during the cyanation reaction ... 

The same group also described the rapid cyanation of aryl iodides in water using CuCN (Scheme 72) [82]. The addition of the phase-transfer agent TBAB was crucial for the reactions otherwise, no reaction occurred. CuCN can also be generated in situ from NaCN and Cul (Scheme 72). While aryl iodides gave good results, the yield obtained with 3-pyridinyl iodide was poor. 

The pyrene molecule is transferred by irradiation to its cation radical [29]. This reacts at the oil/water interface by nucleophilic attack from the cyanide ion. Typically, the cyanated product remains in the organic phase. 

OS 43] [R 14] ]P 32]The cyanated pyrene product leaves the reaction channel completely via the organic phase ]29]. Since the reaction occurs with aqueous dissolved NaCN, one can draw the conclusion that complete extraction of the product was achieved. 

Nickel-catalyzed carbonylation of a-ketoalkynes has also been reported by Arzoumanian et al. under phase-transfer conditions.94 The carbonylation gave either furanone or unsaturated carboxylic acids depending on the substituents of substrates (Eq. 4.53). A similar reaction, nickel-catalyzed cyanation of a-ketoalkynes with KCN in water, was also reported to afford unsaturated hydroxylactams (Eq. 4.54).95... 

There are many other examples in the literature where sealed-vessel microwave conditions have been employed to heat water as a reaction solvent well above its boiling point. Examples include transition metal catalyzed transformations such as Suzuki [43], Heck [44], Sonogashira [45], and Stille [46] cross-coupling reactions, in addition to cyanation reactions [47], phenylations [48], heterocycle formation [49], and even solid-phase organic syntheses [50] (see Chapters 6 and 7 for details). In many of these studies, reaction temperatures lower than those normally considered near-critical (Table 4.2) have been employed (100-150 °C). This is due in part to the fact that with single-mode microwave reactors (see Section 3.5) 200-220 °C is the current limit to which water can be safely heated under pressure since these instruments generally have a 20 bar pressure limit. For generating truly near-critical conditions around 280 °C, special microwave reactors able to withstand pressures of up to 80 bar have to be utilized (see Section 3.4.4). 

A typical phase transfer catalytic reaction of the liquid/liquid type is the cyanation of an alkyl halide in an organic phase using sodium or potassium cyanide in an aqueous phase. When these phases are stirred and heated together very little reaction occurs. However, addition of a small amount of crown ether (or cryptand) results in the reaction occurring to yield the required nitrile. The crown serves to transport the cyanide ion, as its ion pair with the complexed potassium cation, into the organic phase allowing the reaction to proceed. 

The OCN ligand can attach to the XH3 group to form either the cyanate (—OCN) or isocyanate (—NCO) species. Experimental gas-phase geometric structures have been... 

Yamamura and Murahashi (1977) have studied the crown ether-catalysed cyanation of vinyl halides under solid—liquid phase-transfer conditions (20). The reaction of /rans-/ -bromostyrene [140] with sodium cyanide in benzene,... 

A phase-transfer catalysed nucleophilic displacement reaction on chloro-acetanilides by cyanate ions, followed by ring-closure (Scheme 5.10), provides a simple and viable synthesis of hydantoins [41], The formation of the hydantoins is inhibited by substituents in the orf/to-position of the aryl ring, but the addition of potassium iodide, or tetra-n-butylammonium iodide, generally increases the overall rate of formation of the cyclic compounds, presumably by facilitating the initial nucleophilic substitution step. 

Autoxidation of secondary acetonitriles under phase-transfer catalytic conditions [2] avoids the use of hazardous and/or expensive materials required for the classical conversion of the nitriles into ketones. In the course of C-alkylation of secondary acetonitriles (see Chapter 6), it had been noted that oxidative cleavage of the nitrile group frequently occurred (Scheme 10.7) [3]. In both cases, oxidation of the anionic intermediate presumably proceeds via the peroxy derivative with the extrusion of the cyanate ion [2], Advantage of the direct oxidation reaction has been made in the synthesis of aryl ketones [3], particularly of benzoylheteroarenes. The cyanomethylheteroarenes, obtained by a photochemically induced reaction of halo-heteroarenes with phenylacetonitrile, are oxidized by air under the basic conditions. Oxidative coupling of bromoacetonitriles under basic catalytic conditions has been also observed (see Chapter 6). 

Cyanation of iodoarenes with NaCN was catalyzed by [PdCl2(TPPMS)2] in the presence ofNaBH4 and ZnC in water/heptane, toluene or anisole biphasic systems (Scheme 9.11) [37]. Lipophilic catalysts prepared with P(p-tolyl)3 or PPhs showed negligible activities for the biphasic cyanation, due to the lack of CN in the organic phase. The reaction provided good to excellent yields of the respective benzonitriles with several substituted iodoarenes. 

Experimentally a cyanate ester precursor mixture consisting of BPEC, 1 wt % BPE, and 100 ppm cobaltacetylacetonate was prepared and subsequently mixed with the cyclohexane phase separating solvent [86]. Essentially the same procedure as for the epoxy is used for sample preparation with the difference that the curing was done at 80 °C and post drying at 240 °C. 

On the other hand, the mechanochemical solid-state reaction was found to be the most suitable for this purpose. Thus, when the solid-state reaction was conducted for Cgo in the presence of one equivalent or less of KCN under the HSVM conditions for 30 min, a clean reaction took place to give the [2-1-2] fullerene dimer C120 (3) in 30% yield while 70% of Cgo was recovered unchanged (Scheme 2) [20]. It is to be noted that no cyanated fullerene such as 4 was obtained in comparison to the result of a liquid-phase reaction in o-dichloroben-zene (ODCB)-DMF [21]. This is apparently ascribed to the difference in reactivity of the initially formed cyanated Cgo anion with or without solvation. 

The effect of halide, cyanate, cyanide, and thiocyanate ions on the partitioning of Hg in [BMIM][PF6]/aqueous systems (Figure 3.3-2) has been studied [8]. The results indicate that the metal ion transfer to the IL phase depends on the relative hydrophobicity of the metal complex. Hg-I complexes have the highest formation constants, decreasing to those of Hg-F [42]. Results from pseudohalides, however, suggest a more complex partitioning mechanism, since Hg-CN complexes have even higher formation constants [42], but display the lowest distribution ratios. 

The solubility of the components in the solvent must be sufficient. To improve the solubility, cosolvents can be used. Another possibility is the application of a two-phase system or an emulsion in the presence of phase-transfer catalysts. A two-phase system also has advantages in product isolation and continuous electrolysis procedures. A typical example is the synthesis of p-methoxy benzonitrile by anodic substitution of one methoxy group in 1,4-dimethoxybenzene by the cyanide ion (Eq. 22.21). The homogeneous cyanation system (acetonitrile, tetraethylammonium cyanide) [24] can be efficiently replaced by a phase-transfer system (dichloro-methane, water, sodium cyanide, tetrabutylammonium hydrogen sulfate) [71]. 

The potential for novel phase behaviour in rod-coil block copolymers is illustrated by the recent work of Thomas and co-workers on poly(hexyl iso-cyanate)(PHIC)-PS rod-coil diblock copolymers (Chen etal. 1996). PHIC, which adopts a helical conformation in the solid state, has a long persistence length (50-60 A) (Bur and Fetters 1976) and can form lyotropic liquid crystal phases in solution (Aharoni 1980). The polymer studied by Thomas and co-workers has a short PS block attached to a long PHIC block. A number of morphologies were reported—wavy lamellar, zigzag and arrowhead structures—where the rod block is tilted with respect to the layers, and there are different alternations of tilt between domains (Chen et al. 1996) (Fig. 2.37). These structures are analogous to tilted smectic thermotropic liquid crystalline phases (Chen et al. 1996). 

A solution of potassium cyanate (11 mg) in water (1.36 ml) was added portionwise during 1 hour to a solution of the above hydrazide (118 mg) in a 20 1 v/v mixture of water and acetic acid (10 ml). The mixture was freeze-dried and the residue was purified by reverse-phase column chromatography (Dynamax 60 ANG, C18, 1 inch diameter) using a gradient of 10% to 40% by volume of acetonitrile in water containing 0.1% trifluoroacetic acid. There was thus obtained goserelin (100 mg, 25% yield overall), the structure of which was confirmed by mass spectroscopy. 

As has already been pointed out, the Finkelstein reaction can be conducted in situ in the absence of solvents. For example, alkylations of purine and pyrimidine bases with alkyl halides and dimethyl sulfate have been carried out by solid/liquid phase-transfer catalysis in the absence of any additional solvent [48], as have cyanation of haloalkanes [49] and / -eliminations [50]. Noteworthy is the synthesis of glycosyl isothiocyanates by the reaction of potassium thiocyanate with molten glycosyl bromide at 190 °C [51]. 

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