Examples of Synthesis

Simple cyclobutanes do not readily undergo such reactions, but cyclobutenes do. Ben-zocyclobutene derivatives tend to open to give extremely reactive dienes, namely ortho-c]uin(xlimethanes (examples of syntheses see on p. 280, 281, and 297). Benzocyclobutenes and related compounds are obtained by high-temperature elimination reactions of bicyclic benzene derivatives such as 3-isochromanone (C.W. Spangler, 1973, 1976, 1977), or more conveniently in the laboratory, by Diels-Alder reactions (R.P. Thummel, 1974) or by cycliza-tions of silylated acetylenes with 1,5-hexadiynes in the presence of (cyclopentadienyl)dicarbo-nylcobalt (W.G, Aalbersberg, 1975 R.P. Thummel, 1980). 

Syntheses in Solvent Systems. Very few examples of syntheses of metal carbonyls in aqueous solution are reported. An exception is the preparation of Co2(CO)g from CoSO (66% yield) or C0CI2 (56% yield) and CO at 9.6—11 MPa (95—110 atm) in aqueous ammonia at 120°C for 16—18 h (101). Triiron dodecacarbonyl is prepared almost exclusively in aqueous solution. Quantitative yields of Fe2(CO)22 have been obtained by oxidising alkaline solutions of carbonyl ferrates with manganese dioxide (102—104). 

Other examples of syntheses under physiological conditions will be found under arecaidine, lobelia, papaverine, cusparia bark alkaloids, harmala alkaloids, rutascarpine and yohimbine. 

Scheme 9.3 illustrates some examples of syntheses of allylic carbinols via allylic boranes and boronate esters. Entries 1 and 2 are among the early examples that... 

Imidazolides of aromatic sulfonic acids react much more slowly in alcoholysis reactions than the carboxylic acid imidazolides. Although the reaction with phenols is quantitative when a melt is heated to 100 °C for several hours, with alcohols under these conditions only very slight alcoholysis is observed. In the presence of 0.05 equivalents (catalytic amount) of sodium ethoxide, imidazole sodium, of NaNH2, however, imidazolides of sulfonic acids react with alcohols almost quantitatively and exothermically at room temperature in a very short time to form sulfonic acid esters (sulfonates). (If the ratio of sulfonic acid imidazolide to alcoholate is 1 2, ethers are formed see Chapter 17). The mechanism of catalysis by base corresponds to that operative in the synthesis of carboxylic esters by the imidazolide method. Because of the more pronounced nucleophilic character of alkoxide ions, sulfonates can also be prepared in good yield by alcoholysis of their imidazolides in the presence of hydroxide ions i.e., with alcoholic sodium hydroxide. 45 Examples of syntheses of sulfonates are presented below. 

The photocyclization of enamides has been widely employed in the construction of heterocyclic systems the N-acryloyl-2-aminopyridines 37, for example, are converted on irradiation to the lactams 38.36 Numerous benzylisoquinoline alkaloids have been prepared using this approach, and in particular, the syntheses of benzo[c]phenanthridine alkaloids have been reviewed.37 Thus, irradiation of the [Z]-l-ethylidene-2-benzoyltetra-hydroisoquinoline 39 affords the corresponding 8-oxoberberine 4038 competing photoisomerization to the E-isomer is observed but cyclization occurs only via the Z-isomer. Examples of syntheses of Amaryllidaceae and indole alkaloids have also been reported. In this way, the precursor 41 of ( )-lycoran has been obtained by oxidative cyclization of the enamide 42.39... 

In this section, selected examples of syntheses of insect defensive compounds will be presented. The impact of asymmetric synthesis and the increasing use of organometallic reagents, notably transition metal catalysts, will be highlighted. 

The majority of cyclic peptides synthesized on solid support are cyclized in the head-to-side-chain or side-chain-to-side-chain mode. For this purpose the amino acids involved in cyclization must be side-chain protected in a manner that allows for an additional level of orthogonal deprotection. Thus, upon assembly of the fully protected linear precursor on-resin, deprotection of the functionalities involved in the lactam ring formation is performed, followed by regio-selective cyclization by amide bond formation, and finally by the resin-cleavage/deprotection step as outlined in Scheme 16. In Table 8, examples of syntheses of such cyclic peptides are listed with the relevant information regarding protection scheme, resin anchor, and mode of cyclization. 

Additional examples of syntheses illustrate some of the more unusual tactics taken to produce pyrrolo[2,3- -pyrimidines. Recently a group of sulfdimines, 144, have been converted to products 145 under the influence of sunlight (Equation 53) <2005TL5551>. 

Isolated examples of syntheses of thieno[2,3-,7 pyrimidines commencing with either amino- or nitrothiophene possessing no other functionality have been described <2004CHE370, 1996J(P1)417, 1996J(P1)1403>. 

There are no further examples of syntheses in this class, and the reader is again referred to the very few examples that are reported in CHEC-II(1996) <1996CHEC-II(7)785>. 

Some further examples of syntheses at organic-water interface are ... 

In Table 3 some examples of syntheses of heterohelicenes are given. Similar to the synthesis of carbohelicenes heterohelicenes can be obtained by the photoreaction of 1,2-diheteroaryl ethylenes as well as from bis(heteroarylvinyl) aromatics (diolefins). 

Other examples of syntheses where a hydrazide is the probable intermediate appear in Section I,C,l,b. The hydrazide cyclization can be used to prepare tetrahydrotriazolopyridines (60), starting from cyclic iminoethers.84-87... 

Examples of syntheses in which the heterocyclic ring is generated by cyclization of an exocyclic amine to an electrophilic carbon atom include the preparation of triazolo[4,3-6]triazoles (137) by elimination of alkanethiol from guanidine derivatives 136137 (cf. 132 - 133), and many examples (mostly in patents) of pyrazolo[l,5-a]benzimidazoles prepared according to Eq. (18).138-142... 

Acidic cyclodehydration of 3-amino-2-formamidothiazolium mesylate to give 138143 and preparation of imidazo[l,2-a]imidazoles (140 X = NH)144 and imidazo[2,l-6]thiazoles (140 X = S)145 by dehydrative cyclization of the corresponding imidazoles (139 X = NH, S) are examples of syntheses by cyclization of exocyclic amines to carbonyl groups. 

There are not many examples of syntheses of fused 1,3,5-triazines from [5 +1] atom cyclizations. The basic synthetic strategy is similar to the syntheses of 1,3,5-triazines from biguanides, but in this case the five-atom component incorporates a heterocyclic substituent. The examples in equations (55)—(57) illustrate the approach (74JHC991,75HCA761,80JHC1121). 

Dioxins and 1,4-dithiins have often been prepared by elimination reactions of appropriately substituted saturated analogues. However, in the more recent literature a number of examples of syntheses of 1,4-dithiins are described which utilize reactions involving unsaturated precursors. Examples of 1,4-oxathiins are relatively scarce and no general preparative routes have been developed. 

The reaction principle of the Kolbe synthesis can be extended both to higher carboxylic acids (e.g. methyl suberate228)) and to the dimerization of two different carboxylic acids (cross Kolbe coupling). A few examples of syntheses studied on the laboratory scale are listed below. 

Additional examples of syntheses of polycyclic triazoles continue to be reported. 2-(2 -Hydroxyphenyl)benzotriazole (84) is prepared in >90% yield from azointermediate (83) by reaction with Raney nickel and DMSO, DMS or thiophene [95JAP07228577]. 2-Methylbenzo-triazole (85) is cyclized under acidic conditions and subsequently converted into the chloro analog (86) by treatment with POCl3 [95FES47],... 

Another interesting investigation was reported by J.A. Prieto et al. describing the microwave-assisted VO(acac)2-catalyzed epoxidation [179] of hindered homoallylic alcohols. From a synthetic point of view this is of particular interest as the literature abounds with examples of syntheses of 3,4-epoxy alcohols, owing to their potential in the generation of valuable intermedi-... 

Phenanthridines are obtained from 2,2 -disubstituted biphenyls in which the substituents react intramolecularly to form the heterocyclic ring. The oldest examples of syntheses of this type involve Hofmann65 and Curtius66- 67 reactions on biphenic acid, and have been explained... 

Examples of syntheses from three-membered heterocycles are the synthesis of the oxadiazolylpropylamine (122) from acylhydrazine ArCONHNH2 and 3,3-dimethyl-2-dimethylaminoazirine (78HCA2419), and the conversion of 3,3-dialkyldiaziridines into oxadiazolines (123) on heating above 150 °C with an anhydride (R3C0)20 (76MIP42300). 

This chapter deals with the use of micro emulsions as media for organic synthesis. The distinguishing characteristics of micro emulsion-based reactions, as well as typical examples of syntheses carried out in such media, will be discussed. Emphasis will be put on recent development in the area. 

In each subsection, any examples of syntheses that lead directly to pyrazines usually precede any that afford di-, tetra-, or hexahydropyrazines (piperazines) in that order. Examples of any pre-1978 syntheses in each broad category may be located from the cross-references (e.g., H 49) to appropriate subsections in Barlin s parent volume.1686 Less comprehensive reviews of primary syntheses in the pyrazine series have appeared in recent years.743,1287,1426,1677... 

Here is an example of synthesizing a signed relational operator. In this case, the operands for the relational operator are integer variables. 

Various examples of syntheses with triiTiethyl(perfluorophenyl)silane are given in Table 3. 

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