Advances in Heterocyclic Chemistry

1. Auflage 2015
ISBN: 978-0-12-802337-2
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, Band Volume 115, 378 Seiten

Reihe: Advances in Heterocyclic Chemistry

Advances in Heterocyclic Chemistry is the definitive series in this area-one of great importance to organic chemists, polymer chemists, and many biological scientists. As the disciplines of biology and organic chemistry increasingly intersect, the nomenclature of organic chemistry is increasingly used in explanations across a variety of applications and areas of study. Users will find this comprehensive update of the subject matter to be a valuable addition to their library of reference materials. - Represents the definitive resource available on heterocyclic chemistry - Contains discussions of great importance to organic chemists, polymer chemists, and many biological scientists - Provides new discussion material for topics including diels-alder of furans for synthesis, metal carbenoids, electron rich heterocycles, synthesis of heterocyclic natural products, viridin, wortmanin, and dihydropyridine intermediates - Discusses how the nomenclature of the field is increasingly used in explanations across a variety of applications and areas of study

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3. Preparation, Structure, and Properties of Iodine Heterocycles

3.1. Cyclic Iodonium Salts and Ylides

Three-membered cyclic iodonium salts are common intermediates in the reactions of alkenes with electrophilic iodine species. Usually these compounds are highly unstable; however, the three-membered cyclic iodonium salts derived from sterically hindered alkenes have been isolated and even characterized by single-crystal X-ray diffraction (1994JA2448). In particular, X-ray diffraction data on cyclic iodonium salt 23 derived from adamantylideneadamantane indicate that the halonium ion portion of salt 23 is essentially symmetrical with the following averaged structural parameters: I–C, 2.48 Å; C–C, 1.45 Å; I–C–C angle, 72°; C–I–C angle, 36°. The 13C NMR spectra of ion 23 and the iodonium ion of bicyclo[3.3.l]nonylidenebicyclo[3.3.l]nonane 24 have been investigated in dichloromethane solution. The low-temperature 13C NMR spectra of 23 and 24 indicate that the iodonium ion has two perpendicular planes of symmetry (Figure 5).

The most important representatives of stable cyclic iodonium salts, dibenziodolium or diphenyleneiodonium (DPI) salts, have been prepared as the iodide 26, the hexafluorophosphate 28, the tetrafluoroborate 29, and the chloride 31, and can be obtained by three different procedures summarized in Scheme 1. DPI iodide 26 was originally prepared by Mascarelli and Benati in 1909 (1909GCI619) by diazotization of 2,2'-diaminodiphenyl 25 with sodium nitrite in a hydrochloric acid solution followed by addition of potassium iodide. A similar reaction starting from 2-amino-2'-iododiphenyl 27 affords DPI as hexafluorophosphate 28 or tetrafluoroborate 29 in excellent yields (1968T3717). The third method involves the peracetic acid oxidation of 2-iodobiphenyl 30 to an iodine(III) intermediate which cyclizes to DPI in the acidic solution and is finally isolated as the chloride salt 31 (1956JA3819). More recently, these methods were used for the preparation of the tritium-labeled DPI and its 4-nitro derivative (2000JLCR515).

Figure 5 Stable three-membered cyclic iodonium salts derived from sterically hindered alkenes.

The structure of dibenziodolium tetrafluoroborate 29 was established by single-crystal X-ray analysis (1972JOC879). In particular, the dibenziodolium ion is planar with deviations from the mean molecular plane of less than 0.03 Å. The C–I–C bond angle of 83° in structure 29 is smaller than the corresponding bond angle in a non-cyclic iodonium salt, for example, DPI chloride (93°) (1956DAN71). The C–I bond lengths of 2.08 Å are close to the typical C–I bond lengths in hypervalent iodine compounds. A relatively long distance of 3.65 Å between the iodine center and the nearest tetrafluoroborate anion is consistent with the ionic character of this compound. Dibenziodolium salts have a relatively high thermal stability. The tetrafluoroborate salt 31 has a melting point of 239–240 °C; however, the X-ray structural data do not support any aromatic character of the iodolium ring.

Scheme 1

DPI chloride 31 has found some applications in biological studies (2013MI2). In particular, DPI is a potent hypoglycemic agent at a dose as low as 4 mg/kg body weight (1973JBC6050). It is assumed that DPI binds covalently to a 23.5 kDa protein within Complex I resulting in irreversible inhibition of NADH oxidation (1973JBC6050, 1976BJ307). DPI inhibits gluconeogenesis in isolated rat hepatocytes (1975BST333), causes swelling of rat liver mitochondria (1972BC39), induces cardiomyopathy (1986BST1209), induces mitochondrial myopathy (1988JNS335, 1988BP687), inhibits the superoxide production of neutrophils (1991BBRC143, 1988BJ887, 1986BJ111, 1987BP489), as well as nitric oxide synthase (1991FASEB98, 2007JFSN74), and NADPH oxidase (1993BJ41, 1992EJB61, 1991FRBM25). In modern biochemical and pharmacological research, DPI is often used as an NADPH oxidase inhibitor (2012JPET873, 2012BBRC329, 2012BP422, 2012PLoSe33817, 2012JCP1347, 2011WASJ67, 2011MGM241, 2011HMR619, 2010FS2437, 2010PNAS3030, 2009BP493, 2009ABP995, 2009TOL180, 2008AJPG99, 2008JPET50, 2007PP890, 2007CR663, 2007NPLG348, 2007BC1159, 2007JN1205, 2007CS1610, 2001FASEB2539, 1994NL63).

The chemistry of several other cyclic iodonium salts has been summarized in a review by Grushin (2000CSR315). Examples of known cyclic iodonium salts include 4,5-phenanthryleneiodonium salts 32 (1969T4339), 10H-dibenz[b,e]iodinonium salt 33 (1965JOC1141), 10,11-dihydrodibenz[b,f]iodeponium salt 34 (1965JOC1141), phenoxiodonium salt 35 (1965JOC1141), 10-acetylphenaziodonium salt 36 (1965JOC1141), 10-oxidophenothiiodonium salt 37 (1965JOC1141), the bicyclic bisiodonium salt 38 (1969JOC456), benziodolium chloride 39 (1972JOC879), and iodolium salt 40 (1981JOC4069; Figure 6).

Several macrocyclic iodonium salts, rhomboids 43, a square 46, and a pentagon 48, have been prepared from the appropriate precursors 41, 42, 44, 45, and 47 (Scheme 2; 1993JA9808, 2003JOC9209, 1993JA11626). The structures of these iodonium-containing charged macrocycles were established using elemental analysis, multinuclear NMR, and mass spectrometry. These iodonium-containing macromolecules may find potential application in nanotechnology (2003JOC9209).

The unusually stable cyclic iodonium ylides 50 can be synthesized via the intramolecular transylidation of a preformed acyclic ylide 49 (Scheme 3; 1992CC1487). X-ray structural analysis for cyclic ylide 50 shows a distorted five-membered ring with an ylidic bond length of 2.1 Å and a C–I–C bond angle of 82°, which is smaller than the usual value (90°) for ylides (1992CC1487).

Figure 6 Examples of cyclic iodonium salts.

3.2. Trivalent Iodine Heterocycles

The most important and practically useful trivalent iodine heterocycles have a five-membered ring, although several examples of four-membered and six-membered heterocycles with iodine(III) atom in the ring are also known. The unsaturated heterocyclic systems with a hypervalent iodine atom in the ring generally do not possess any significant aromatic character because of the large iodine atom size precluding p-orbital overlap with the much smaller atoms of carbon, oxygen, or nitrogen, and also due to the electronic nature and the geometry of hypervalent bonding.

Typical examples of five-membered trivalent iodine heterocycles are represented by cyclic compounds 51–59, which incorporate iodine, oxygen, nitrogen, and some other elements, in the heterocyclic ring (Figure 7). Iodoxolones 51 represent the only known examples of iodine heterocycles in which the hypervalent iodine atom is not connected to an aromatic ring. The collective name “benziodoxoles” is commonly used for the heterocycles 52 with iodine and oxygen atoms in a five-membered ring and various substituents X attached to iodine (1992MI7). The first representatives of benziodoxoles, 1-hydroxy-1,2-benziodoxol-3-(1H)-one and 1-chloro-1,2-benziodoxol-3-(1H)-one, were first prepared over 100 years ago by oxidation or chlorination of 2-iodobenzoic acid (1892B2632). In the mid-1980s, 1-hydroxybenziodoxoles attracted a significant research interest due to their excellent catalytic activity in the cleavage of toxic phosphates and reactive esters (2002CR2497). More recently, various new benziodoxole derivatives have been synthesized and their usefulness as reagents for organic synthesis, and particularly for atom–transfer reactions (2011CC102), has been demonstrated. Compared to benziodoxoles 52, the analogous five-membered iodine–nitrogen heterocycles, benziodazoles 53, have received much less attention and, in some cases, their structural assignment was not reliable. The first readily available benziodazole derivative, acetoxybenziodazole (53, Y = OAc, Z = H), was synthesized in 1965 by the peracetic acid oxidation of 2-iodobenzamide (1965CC449).

Scheme 2

Scheme 3

Figure 7 Typical examples of iodine(III) five-membered heterocyclic systems.

Besides benziodoxoles and benziodazoles, the other known five-membered iodine(III) heterocyclic systems are represented by the less common compounds 54–59 (Figure 7), which...