Halogen as Heteroatom

In 1965 with Comisarow and Cupas we reported the first fluoromethyl cation136. Since then a large variety of fluorine substituted carbocations have been prepared. Fluorine has a particular ability to stabilize carbocations via back coordination of its unshared electron pairs into the vacant p orbital of the carbocationic carbon atom. 19 F NMR spectroscopy is a particularly efficient tool for the structural investigations of these ions137. The 2-fluoro-2-propyl and 1-phenylfluoroethyl cations 79 and 80 are representative examples of the many reported similar ions138.  

Trifluormethyl139 and perfluorophenyl substituted carbocations have also been prepared and studied140,141. Because of the relatively large fluorine chemical shifts, anisotropy and ring current effect play a relatively much smaller role than they do in the case of proton shifts. Therefore, a better correlation of charge distribution with chemical shifts can be obtained. The trifluorocyclopropenium ion 81 was also reported142.  

A series of chloromethyl cations were observed, including phenyldichloromethyl cations120 122,143, and perchlorotriphenylmethyl ion 2144.  

West has characterized the perchloroallyl cation 83. A series of chloro-, as well as 

Three and five-membered ring halonium ions were obtained in our work with Bollinger148 and studied with Peterson149. Illustrative is the propylenebro-monium ion whose PMR spectrum is shown in Fig. 11. 

The X-ray characterization of the Sbly, salt of cation 250 by Laube et al.516 corroborates the above findings. The short C+-C1 distance (1.668 A versus 1.734 A for C ,2-CI) indicates significant chlorine back-donation resulting in partial double bond character in agreement with experimental findings and theoretical calculations. 

Trifluoromethyl-substituted517 and perfluorophenyl-substitutedcarbocations518,519 have also been prepared and studied. Because of the relatively large fluorine chemical shifts, anisotropy and ring current effects play a relatively much smaller role than they 

A series of chloromethyl cations were observed, including phenylchloromethyl cations382-384,525 526 and perchlorotriphenylmethyl ion 256.527 West and Kwito-wski528 have characterized the perchloroallyl cation 257. A series of chloro- as well as bromo- and iodomethyl cations have been observed (258-260) and the general stabilizing effect of halogen attached to carbocation center has been demonstrated.529 

Halpern, and co-workers530,531 were able to study these effects in detail using 13C NMR spectroscopy. 

Olah et al.532,533 studied trihalomethyl cations (CX3+, X = Cl, Br, I) under stable ion conditions. 13C NMR chemical shift values correlate well with the decreasing order of back-donation (Cl Br I). Similar correlation was also found for dimethylhalo-carbenium ions 258. The CF3+ fluoro analog, however, could not be observed under any conditions. This can be attributed to a combination of unfavorable thermodynamics (generation of CF3+ from CF4 is endothermic by about 20l calmol ) and the lack of stable alternate starting materials and a suitably strong Lewis acid.534 

---

Tables 3-11 are organized according to the a-heteroatom. Where there are two different hetero-substituted groups present in the carbanions, the listing in the tables is in accord with the priority sequence N, P, O, S, Se and halogen (as heteroatoms), COjR, CN, and metalloids. This takes no regard of the stabilizing effectiveness of the hetero-substituted groups present. Table 12 lists lithioformamides and -thioformamides.

Heteroboranes are those in which one or more non-boron atoms replace a BH vertex, together with groups that may be attached to these heteroatoms. Boranes that contain CH vertices constitute the vast family of carbaboranes. The possibility for carbon to participate in electron-deficient frameworks contradicted the former prejudice of the always electron-precise carbon as the well-behaved brother of naughty boron. So far, most elements have been introduced as heteroatoms into borane frameworks, with the exception of the halogens and the noble gases. 

Addition to carbon bearing the halogen 1 heteroatom such as N, S, or O, or double bond, or aryl group at a- or >position Increase alkylating activity by facilitating the departure of halogen and/or provide additional electrophilic functional group... 

The second ones are structural analogues with different masses or even the same mass. In the latter case, chromatographic separation between the analyte and its internal standard must be achieved when distinctive MRM (multiple reaction monitoring) transitions could not be found. It is preferable that the key structure and functionalities (e.g., -COOH, -S02, -NH2, halogens, and heteroatoms) of an internal standard are the same as those of the analyte and differ only by C-H moieties (length and/or position). Modifications in functionalities would result in significant differences in ionization efficiency and extraction recovery [8],... 

This procedure can be extended to compounds that contain heteroatoms such as oxygen, nitrogen, and halogen, as illustrated in Sample Problem 10.2. 

Trichlorosilanes are readily transformed to the pentafluorosilicate compounds (100) and (101) by reaction with excess potassium fluoride. The C—Si bond of the hexavalent organosilicon species is converted into a C—X (X = halogen or heteroatom like hydroxy and alkoxy) or a C—C bond. Thus, through the hydrosilylation reaction net transformations of alkenes and alkynes to halides, ethers and alcohols, as well as the construction of carbon frameworks, is easily achieved (Scheme 18). ... 

Organic sulfur compounds in which sulfur is bonded to a heteroatom other than oxygen have not been widely studied by photoelectron spectroscopy. Those studies which have been reported mostly involve either nitrogen or a halogen as the heteroatom. 

Active carbons are almost invariably associated with appreciable amounts of oxygen and hydrogen. In addition, they may be associated with atoms of sulfur, nitrogen, and halogens. These heteroatoms are derived from the starting material and become a part of the chemical structure as a result of imperfect carbonization, or they become chemically bonded to the surface during activation or during subsequent treatments. There is also evidence that the carbon can adsorb certain molecular species such as amines, nitrobenzene, phenols, and several other cationic species. 

Finally, addition of Pd-heteroatom bonds to 7r-compounds is extensively discussed in Part V. With halogens, O, and N as heteroatoms, anti addition is often observed. However, syn addition is also possible and has, in fact, been observed. Those Pd-heteroatom addition reactions that are not discussed in earlier sections are discussed in Sect vn.6. 

The above-described ATRP mechanism is identical either if polymerization occurs in bulk or if started from a surface (i.e., surface-initiated). Many commercially available initiators (e.g., alkyl halides) can be used, as long as they present a weak halogen-heteroatom bond. The initiator will provide the polymer a surface with simple halogen as end groups, which is easily converted into useful functionalities. The transition metal complexes used (Ru, Cu, Fe, Ni, among others) are responsible for the conversion into useful functionalities, removing the halides from the polymer surface. The surface is then ready for polymerization [131]. 

Some of the newer compounds may contain both saturated and unsaturated rings, heteroatoms such as oxygen, nitrogen, or sulfur, and halogen substituents. Others, such as synthetic pyrethroids, may have one or more chiral centers, often needing stereospecific methods of synthesis or resolution of isomers (42). Table 4 Hsts examples of some more complex compounds. Stmctures are shown ia Eigure 1 (25). 

The mode of attack of electrophilic reagents (E ) at ring carbon atoms is jS to the heteroatoms as shown, for example, in (11) and (12) the intermediates usually revert to type by proton loss. Halogenation takes place more readily than it does in benzene (Section 4.02.1.4.5). Nitration and sulfonation also occur however, in the strongly acidic environment required the compounds are present mainly as less reactive hydroxyazolium ions, e.g. (13). 

In azole chemistry the total effect of the several heteroatoms in one ring approximates the superposition of their separate effects. It is found that pyrazole, imidazole and isoxazole undergo nitration and sulfonation about as readily as nitrobenzene thiazole and isothiazole react less readily ica. equal to m-dinitrobenzene), and oxadiazoles, thiadiazoles, triazoles, etc. with great difficulty. In each case, halogenation is easier than the corresponding nitration or sulfonation. Strong electron-donor substituents help the reaction. 

Metalloid azoles frequently show expected properties, especially if not too many heteroatoms are present. Thus Grignard reagents prepared from halogen-azoles (see Section 4.02.3.9.3) show normal reactions, as in Scheme 60. 2-Lithioimidazoles react normally, e.g. with acetaldehyde (Scheme 61) (70AHC(12)103) 5-lithioisothiazoles (see Scheme 62) (72AHC(14)1) and 2-lithiothiazoles undergo many of the expected reactions. 

The incorporation of heteroatoms can result in stereoelectronic effects that have a pronounced effect on conformation and, ultimately, on reactivity. It is known from numerous examples in carbohydrate chemistry that pyranose sugars substituted with an electron-withdrawing group such as halogen or alkoxy at C-1 are often more stable when the substituent has an axial, rather than an equatorial, orientation. This tendency is not limited to carbohydrates but carries over to simpler ring systems such as 2-substituted tetrahydropyrans. The phenomenon is known as the anomeric ect, because it involves a substituent at the anomeric position in carbohydrate pyranose rings. Scheme 3.1 lists... 

The tendency of the halogens to form chain-like polyanions that are stabilized by delocalization of the negative charge [15,34] is a basic chemical principle. Donor-acceptor interactions between Lewis-acidic Br2 and halide anions, but also with polyhalides acting as Lewis bases, give rise to the formation of a variety of homo and heteroatomic adducts. The maximum number of atoms in these chains increases with the atomic weights... 

---