Reactions and Synthesis

Ring Synthesis and Destruction.—One method of preparing thiophens is by inserting a sulphur atom into an acyclic precursor. The sulphur-transfer reagent may be a simple inorganic compound, as illustrated by the formation of (11) from ethyl phenyl ketone (10) on treatment with pyridine and thionyl chloride. The simplest sulphur-transfer reagent is elemental sulphur, as in the production of the thiophen (13 X = S) from l,4-diphenyl-2,3-dibenzylbutadiene (12). The reaction of (12) with selenium dioxide affords the corresponding selenophen (13 X = Se).  

(Amsterdam), 1979, 3 (New Trends Heterocycl. Chem.), 250. 

Litvinov, in Topics in Organic Sulphur Chemistry , ed. M. Tisler, University Press, Ljubljana, 1978, p. 157 

Hydrogen sulphide reacts reversibly with many unsaturated or aromatic hydrocarbons, in the presence of mixed oxide catalysts, to produce thiophens these may be polycyclic, according to the complexity of the starting hydrocarbon. This reaction, which is believed to be the source of many of the sulphur compounds found in crude oil, has been studied in particular by Klemm and his co-workers, who have now published their detailed results. A typical example is the formation of the isomeric benzonaphthothiophens (15) and (16) from the reaction of 2-phenylnaphthalene (14) with hydrogen sulphide over a sulphided cobaltous oxide-molybdic oxide-alumina catalyst at 450—630 in a flow system. 

Thiophens may also be obtained from aldehydes in like manner. The kinetics and mechanism of these sulphurization reactions, and especially of the industrially important reverse reactions (hydrodesulphurization), have been examined in some detail thiols may be intermediates. 

Synthesis and Reactions.—Carotenoids. Several reviews survey recent progress in the synthesis and chemistry of carotenoids and related polyenes. Two other 

The preparation of -carotene [j8,/3-carotene (63)] in 50% yield by reductive coupling of retinaldehyde (67) with TiCl4-LiAlH4 has been described. Similarly )3-ionone (68) gives the symmetrical olefin (69). The enolic /3-diketone caro- 

The intermediate 8,8 -diapo-20-acetoxycarotene-8,8 -dial (81) has been used to synthesize the cross-conjugated carotenoid aldehydes , y-caroten-20-al (82), (2/ ,2 J )-2,2 -bis-(3-methylbutyl)-3,4,3, 4 -tetrahydro-t/ , /f-caroten-20-al (83), 

The model compounds (2/ ,65,2 / ,6 5)-2,2 -dimethyl--y,7-carotene (87) and (2/ ,2 7 ,6 S)-2,2 -dimethyl-/S,-y-carotene (88) have been prepared by standard methods from natural ( + )-(2S,61 )-ds-y-irone (86). Similarly, optically active 

Treatment of diadinoxanthin (62) bistrimethylsilyl ether with lithium aluminium hydride affords the bistrimethylsilyl ether of diatoxanthin (94), although similar 

A later rep t has demonstrated that the initial product urorosein (144) is uiKtable and decomposes in solution into a of products. After extenave chromatog- 

Recently, (he protected dimethoxy derivative 152 has been isolated in 70% yield from the Boc-protection of a nonseparable product mixture of the corresponding 2,8-dimethoxyindoIo[3,2-h]carbazole 153 and the isomeric indolo[2,3-c]carbazole derivative (cf. Section VI) obtained by a double Fischer cyclization using PPSE (00MI2). 

The dimerization reactions of 2-vinyh ndoles and their alcohol precursms have also been exjdored, giving rise to the formation of several dimeric structures, such as the 6,12-dihydroindolo[3,2-h]catbazole derivative 160, which was obtained on dimerization of 2-(a-hydroxyethyl)indole under acidic conditions (71JCXD17S9). 

In a related study, 161 was reported from a dimerization of a 3-vinylindole precursor (61JOC4254). I iously, a compound with the structure 162 had been suggested as a product originating from a dimerization of an alcohol precursor under acidic conditions (63G238). It has recently been demonstrated that the alcohol 163, when treated with aluminum trichloride in the presence of acetic anhydride, produced the indolocarbazole 160, which could be isolated in 41% yield as an 83 17 mixture of cis and trans isomers (98JCX32909). 

The spiro compound 164 has been claimed as a product from the dimerization of the 2-substituted indole 165 after treatment with hydrogen bromide in acetic acid (69GEP1901637). A recent reinvestigaticm of this reaction, however, indicates that the cycloheptadiindole 166 is in feet produced (98MI1), which is not unexpected, as similar dimerizations have previously been observed (89TSS49). 

The application of double Fischer indolization has been demonstrated to provide larger amounts of the indolocarbazole 4 from the treatment of the hisphenylhydra-zone 151 with aqueous sulfuric acid (63JCS2504). A considerably more efficient protocol has been devised by Robinson, who obtained 4 in 35% yield on treatment of 1,4-cyclohexanedione bisphenylhydrazone (151) in a mixture of acetic acid and sulfuric acid (63JCS3097). In spite of many recent developments, this is still the method of choice for the preparation of the parent system 4 as the starting materials are cheap and readily available. Cyclization of 151 in ethanol-water containing 

The different courses of the reactions of o-phenylenediamines and 1,8-diami-nonaphthalenes with quinones cannot be assigned to different terms for thermodynamic control. The spirocyclic isomers are most probably energy-preferable forms for both Type 10 and 11 compounds. The cyclization step is definitely kinetically 

The structure of the latter compound has been determined by X-ray diffraction study.11 Bromination of la with an equivalent amount of A-bromosuccinimide 

On prolonged passing of air through ethanol or acetonitrile solutions of 1 (R = H) in a quartz photoreactor with an immersed mercury lamp, 2, 3 -dihydro-2 -spiro-4-(2,6-di- ert-butylcyclohexadien-2,5-one)perimidin-4 -one 14 was isolated as the main product of the photooxidation reaction. With the A W -dimethyl derivative of 1, photooxidation results in the formation of the perimidinedione 15.12 

The first representative of a new group of photo- and thermochromic compounds in which the naphthalene fragment in spiroperimidine (1) is changed to a quinoline moiety has been obtained by coupling 2.6-di-fert-butyl-l, 4-bcnzo- 

An interesting rearrangement took place13 when la,4/ -di-iodo-2cr-acetoxy-tropan-3-one (14 R = I) and lcr-iodo-2cr-acetoxytropan-3-one (14 R = H) [products of the oxidation of tropan-3cr-ol by lead(iv) acetate in the presence of iodine] were subject to reduction to give (15). 

Substituted (e.g. /7-methyl, p-t-butyl, p-chloro, and p-amino)benzoate esters of nortropine were synthesized14 by A-demethylation of the corresponding tropanyl esters with 2,2,2-trichloroethyl chloroformate. 

The Katritzky synthesis15 of trop-3-en-2-ones was applied16 to acrylonitrile and the A-methyl and A-phenyl 3-hydroxypyridinium betaines, leading to the 6- and 1-exo- and -ent/o-cyano-derivatives (16). 

A total synthesis of diastereoisomers of anisodamine, an alkaloid from Anisodus tanguticus, has been claimed17 by Chinese authors. ( )-Acetyltropoylation of ( )-/ -acetoxy-3cr-hydroxytropane, followed by partial deacetylation, led to a diastereoisomeric mixture of 6/ -hydroxy-atropines. (—)-(S)-6/l-Hydroxyhyoscy-amine, a natural tropane, had earlier been obtained by total synthesis.18 In view of this and of the non-identity of the i.r. spectra of synthetic mixture and natural anisodamine , it remains uncertain whether the latter is identical with natural (—)-(5 )-6/ff-hydroxyhyoscyamine.18 

The 80 MHz H n.m.r spectrum of 7V-(cylcopropylmethyl)scopolaminium bromide in D20 has been analysed and the conclusions have been compared with those from X-ray crystal-structure studies.19 They were consistent with the equatorial position of the cyclopropylmethyl group, as shown in (17). All protons in symmetrical positions (1 and 5, 6 and 7, 2 and 4) of the tropane ring were found to be magnetically non-equivalent, as in scopolamine hydrobromide and in atropine. This was attributed to the different shielding effects that arise from the aromatic substituent which is attached to the asymmetric centre of the tropic acid moiety. The carboxyl group of the tropate residue was found to be opposite to H-3. 

Eight- to sixteen-step syntheses of isoiridomyrmecin and verbenalol,763 iridomyr-mecin764 allodolicholactone (first synthesis), iridomyrmecin and its iso-epimer785 and sarracenin766 have been reported. 

Secologanin on enzymic cleavage, acid treatment, and oxidation gave elenolide (248), and the sequence established the chirality as shown at the point of attachment of the side-chain.775 [10-13C]Secologanin was synthesized in a seven-step process from ethylene acetal.776 Hop ether (249), the irioid most simply related to geraniol, was synthesized in six steps from the protected lactol form of 3-formyl-2-methoxy-carbonylcyclopentan ol.7 7 7 

A full report has appeared on the direct lithiation of NN-di-isopropylformamide by t-butyl-lithium and the use of the acyl carbanion thus obtained in the synthesis of a-keto-amides. The lithium enolate of NN-dimethylacetamide has been isolated for the first time, as a white solid, and has been shown to react well with a usual range of electrophiles. A Canadian group have also discussed the synthesis and reactions of such enolates, in particular their behaviour with ketones from which 70% yields of jS-hydroxyamides can routinely be obtained. These enolates when generated as in the above methods, using lithium di-isopropylamide, also afford good yields of a-(methylthio)-amides when treated with dimethyl disulphide, in contrast to when sodium in liquid ammonia is used as base, which results in polysulphenylation of the amide.  

Synthesis and Reaction.—No less than three different groups have described various extensions to the general method for the homolagation of a-amino-acids by the reactions of electrophiles with enolates derived from Schiff s bases of a-amino-esters, originally reported by Stork s group last year. A full report has appeared on the electro-reductive coupling of Schiff s bases of a-amino-esters with alkyl halides yields of a-alkylated amino-acids are between 36 and 86% 

Anodic oxidation of /Sf-acylaminomalonic acid monoesters in acetic acid leads generally to excellent yields of a-acetoxy-a-amino-esters (169).  

Substituted glycines (171) have been prepared by Michael addition of Grignard reagents to 2-isocyanoacrylate esters (170), and the a-metallated isocyanide species (172) is found to react with simple Schiff s bases to give 2-imidazolines which on 

Shioiri, and S. Yamada, Chem. and Pharm. Bull. (Japan), 1977, 25, 2287. 

Phenylalanine esters can be prepared in a single step from a-nitrocinnamates by hydrogenation over 10% palladium on carbon, under acidic conditions. 

Convenient syntheses of a-amino-o)-(uracil- and thymin-)l-yl-n-alkanoic acids have been described. Alanine and phenylalanine have been prepared by alkylation of the trianion from hippuric acid with methyl iodide and benzyl bromide respectively, followed by hydrolysis.  

Horikawa, T. Iwasaki, K. Matsumoto, and M. Miyoshi, Tetrahedron Letters, 1976, 191. H. Poisel and U. Schmidt, Angew. Chem. Internat. Edn., 1976, 15, 294. 

Yoshimura, Ball. Chem. Soc. Japan., 1976, 49, 1909. 

Optically active a-amino acids have also been prepared, in 52—86% optical yield, by hydrogenation of the corresponding ajS-unsaturated compounds catalysed 

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In general, the methods of synthesis and reactions of oxiranes and thiiranes fused to ordinary or large rings are not particularly affected by the ring fusion. The reader is referred to Chapters 5.05 and 5.06, and reviews cited there, many of which include fused-ring examples. 

Synthesis and reactions of NADH and NADPH model compounds with interconversion of central and axial chirality 97YGK132. 

Synthesis and reactions of isoflavone analogs, 3-hetarylchromones 99KGS3. 

Recent progress in the synthesis and reactions of isothiochromans 980PP243. 

Synthesis and reactions of benzopentathiepine, 1,2,5-benzotrithiepine, 1,2,5-benzodithiaselenepine, and 1,2,5-benzoselenadithiepine derivatives 99PAC489. 

Synthesis and Reactions of Unsaturated Sugars 6-Deoxyhex-5-enose and 5-Deoxypent-4-enose Derivatives... 

Erik J. Sorensen was bom in 1966 in Oneida, New York. He graduated from Syracuse University with a B. A. in chemistry. He received his Ph. D. degree in chemistry from the University of California, San Diego in 1995 working under the guidance of Professor K. C. Nicolaou. His research interests are in the areas of total synthesis and reaction engineering. 

Figure 3.19 Synthesis and reactions of palladium(I) bis(diphenylphosphino)methane complexes.

C. Eabom and R. W. Bott, Synthesis and reactions of the silicon-carbon bond, Organo-metallic Compounds of the Croup IV Elements, ed. A. G. MacDiarmid, Vol. 1, Part 1. Marcel Dekker, New York (1968). 

Synthesis and reactions of aluminium hydride derivatives. S. Cucinella, A. Mazzei and W. Marconi, Inorg. Chim. Acta, Rev., 1970, 4, 51-71 (183). 

Synthesis and reaction chemistry of stable two-coordinate phosphorus cations (phosphenium ions). A. H. Cowley and R. A. Kemp, Chem. Rev., 1985,85, 367 (100). 

Comprehensive Organic Chemistry , Pergamon, Elmsford, NY, 1979, is a six-volume treatise on the synthesis and reactions of organic compounds. The first three volumes cover the various functional groups, vol. 4, heterocyclic compounds, and vol. 5, biological compounds such as proteins, carbohydrates, and lipids. Probably the most useful volume is vol. 6, which contains formula, subject, and author indexes, as well as indexes of reactions and... 

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