Experimental procedure syntheses

Experimental procedures have been described in which the desired reactions have been carried out either by whole microbial cells or by enzymes (1—3). These involve carbohydrates (qv) (4,5) steroids (qv), sterols, and bile acids (6—11) nonsteroid cycHc compounds (12) ahcycHc and alkane hydroxylations (13—16) alkaloids (7,17,18) various pharmaceuticals (qv) (19—21), including antibiotics (19—24) and miscellaneous natural products (25—27). Reviews of the microbial oxidation of aUphatic and aromatic hydrocarbons (qv) (28), monoterpenes (29,30), pesticides (qv) (31,32), lignin (qv) (33,34), flavors and fragrances (35), and other organic molecules (8,12,36,37) have been pubflshed (see Enzyp applications, industrial Enzyt s in organic synthesis Elavors AND spices). 

The synthetic procedure described is based on that reported earlier for the synthesis on a smaller scale of anthracene, benz[a]anthracene, chrysene, dibenz[a,c]anthracene, and phenanthrene in excellent yields from the corresponding quinones. Although reduction of quinones with HI and phosphorus was described in the older literature, relatively drastic conditions were employed and mixtures of polyhydrogenated derivatives were the principal products. The relatively milder experimental procedure employed herein appears generally applicable to the reduction of both ortho- and para-quinones directly to the fully aromatic polycyclic arenes. The method is apparently inapplicable to quinones having an olefinic bond, such as o-naphthoquinone, since an analogous reaction of the latter provides a product of undetermined structure (unpublished result). As shown previously, phenols and hydro-quinones, implicated as intermediates in the reduction of quinones by HI, can also be smoothly deoxygenated to fully aromatic polycyclic arenes under conditions similar to those described herein. 

SYNTHESIS AND DEGRADATION OF THE PREGNANE SIDE-CHAIN / 137 EXPERIMENTAL PROCEDURES... 

The following experimental procedures do not fall into any convenient categories, but all require reagents and techniques of general interest in organic synthesis. 

This series of reagents is characterized by the use of metals under the appropriate conditions. In this regard, a mixture of zinc dust and titanium tetrachloride in ether provided a useful synthesis of vinyl sulphides43, with the possibility of further substitution alpha to the sulphur atom, as outlined in equation (16). The reaction is easy to carry out and gave yields of 49 to 87%, although the authors do not provide much detail of their experimental procedure and of the purity (chemical or stereochemical) of their products. 

There is no rigid definition of what constitutes a suitable synthesis. The major criterion by which syntheses are judged is the potential value to the scientific community. An ideal synthesis is one which presents a new or revised experimental procedure applicable to a variety of related compounds, at least one of which is critically important in current research. However, syntheses of individual compounds that are of interest or importance are also acceptable. 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

Wang et al. reported two different reaction conditions for a solvent free Friedlander quinoline synthesis. Initially, they reported the reaction of 2-acetyl anilines 73 with a variety of P-diketoesters 74 using / -Ts()H as the catalyst under microwave conditions to form substituted quinolines 75 <060BC104>. They also reported the same reaction using BiCl3 as the catalyst under thermal conditions <06LOC289>. Both sets of conditions afford high yields and simpler experimental procedures. 

Miriyala and Williamson have described the synthesis of /i-kctocarboxam idcs from primary and secondary amines and 2,2-dimethyl-2H,4H-l,3-dioxin-4-ones as reactive a-oxoketene precursors (Scheme 6.158) [304], The experimental procedure involved heating a mixture of the dioxinone with 2-3 equivalents of the amine at ca. 180 °C for 1-3 min under solvent-free conditions in a sealed vessel by microwave irradiation. A small collection of 18 /3-ketocarboxamides was prepared in very high yields using this protocol. 

The 1,2,3-thiadiazole literature was extensively reviewed in CHEC(1984) <1984CHEC(6)447> and CHEC-II(1996) <1996CHEC-II(4)289>. It covered the literature up to 1996 and cited many excellent references to 1,2,3-thiadiazoles. A further review on the chemistry of 1,2,3-thiadiazoles, which gives a critical review of methods of synthesis and is accompanied by experimental procedures, appeared in Science of Synthesis <2004HOU(13)253>. Another review of 1,2,3-thiadiazoles also appeared in 2004 . An annual review of the chemistry of 1,2,3-thiadiazoles appears in Progress in Heterocyclic Chemistry (Chapter 5.5). This review covers the 1,2,3-thiadiazole literature up to 2006. 

A review on the chemistry of 1,2,4-thiadiazoles, which gives a critical discussion of methods of synthesis and is accompanied by experimental procedures, appeared in Science of Synthesis <2004HOU277>. An annual review of... 

Goodman, M., Felix, A., Moroder, M and Toniolo, C. (Eds.) (2002). Houben-Weyl Methods of Organic Chemistry, Vol E22, Synthesis of Peptides and peptidomimetics. Vol E22a, The synthesis of peptides, 901pp. Goerg Thieme Verlag Methods with experimental procedures. 

Organic Synthesis welcomes and encourages submission of experimental procedures which lead to compounds of wide interest or which illustrate important new developments in methodology. The Editorial Board will consider proposals in outline format as shown below, and will request full experimental details for those proposals which are of sufficient interest. Submissions which are longer than three steps from commercial sources or from existing Organic Syntheses procedures will be accepted only in unusual circumstances. 

In the latter case the experimental procedure depends on the synthesis method employed (see Section 1.5). 

The experimental proeedures in this text are intended for use only by persons skilled in organie synthesis, and are condueted at ones own risk. WILEY-VCH and the author diselaim any liability for any injuries or damages claimed to have resulted from the experimental procedures described herein. In many of the reactions presented benzene is used as solvent. The replacement of benzene by a less toxic solvent, such as, e.g., toluene, might in many instances lead to comparable results, and is strongly recommended. 

Zeolite membranes are generally synthesized as a thin, continuous film about 2-20 xm thick on either metallic or ceramic porous supports (e.g., alumina, zirco-nia, quartz, siHcon, stainless steel) to enhance their mechanical strength. Typical supported membrane synthesis follows one of two common growth methods (i) in situ crystallization or (ii) secondary growth. Figure 10.2 shows the general experimental procedure for both approaches. 

Figure 10.2 Schematic of the experimental procedures involved for two common zeolite synthesis methods including in situ crystallization and secondary (seeded) grow.

Considering that the described reaction is feasible for both aromatic and aliphatic aldehydes, that the experimental procedure is very easy, that the yields, in spite of moderate, are not far from the theoretical, the described method is certainly a useful contribution for the synthesis of symmetrical divinyl tellurides. 

Ready access to a-aminoketones [92IJC(B)349] via the HTIB-mediated approach has offered a superior alternative to the most widely used Marck-wald s synthesis (1892CB2354) of 2-mercaptoimidazoles 138 (Scheme 40). This synthesis can be accomplished by following two experimental procedures involving single or multisteps as outlined in Scheme 40. This method is applicable to the synthesis of 4-(2-thienyl)imidazoles (138, R = 2-thienyl), as well [94IJC(B)116). 

The ease of the synthesis maybe disclosed by the experimental procedure. An evacuated 100-mL flask was filled with N2O4/NO2 to a pressure of ca. 650 mbar (296 mg, 6.4 mmol NO2). The sampling flask was connected to an evacuated 1-L flask, which was then connected to an evacuated 10-mL flask that was cooled to 5 °C and contained the nitroxyl 4a or 4b, or the nitroxyl precursor to 7 (500 mg, 2.70 mmol). After 1 h, the cooling bath was removed and excess NO2 and NO were condensed in a cold trap at 77 K for further use. The yield was 665 mg (100%) of pure 6a, 6b, or 7 [19]. Similarly, 2-g quantities of tetra-methylpiperidine-AT-oxyl (TEMPO) or 0.2 g of the ferromagnetic 2-fluoro-phenyl-tetramethylnitronyl nitroxide stable radical [21] were reacted at -10 °C (initial pressure of NO2 0.03 bar) or 5 °C (0.3 bar NO2) in 12 h with a quantitative yield of pure 8 or 9, respectively [19]. 

The technically most important polysulfide is poly thiophenylene or poly(p-phe-nylene sulfide), PPS. It is obtained by reacting sodium sulfide and p-dichlo-robenzene in a polar solvent, for example, l-methyl-2-pyrrolidone at about 280 °C under pressure. The mechanism of the reaction is very complex and cannot be described by a simple aromatic substitution. This synthesis requires special autoclaves and is therefore not suitable for a laboratory course (for an experimental procedure see Table 2.3). 

The experimental procedure is exemplified here with the synthesis of a-6T in = 6) from o -4T (n = 4) (Kagan Arora, 1983). The reaction of two equivalents of q -2T n = 2) with one equivalent of LDA and then with one equivalent of CuCL yields o -4T in high yields. a-2T is obtained from thiophene in a similar way. Then, the reaction of two equivalents of o -4T with one equivalent of LDA followed by one equivalent of CuCF produces o -6T (n = 6). Stoichiometry is thus important. In more detail, a-6T is prepared in the following way. n-BuLi is added... 

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