Compounds heterocyclic

Compounds called azarenes containing one or more heterocyclic nitrogen atoms (e.g. pyridine, quinoline, acridine) have low-lying n — n transitions, which explains their relatively low fluorescence quantum yields in hydrocarbons. 

However, the fluorescence characteristics of these compounds are strongly solvent-dependent. In protic solvents such as alcohols, hydrogen bonds can be formed between the nitrogen atoms and the solvent molecules. This results in an inversion of the lowest-lying rt-n and n-n states. As the lowest-lying transition becomes of n — n character in these solvents, the fluorescence quantum yield is much higher than in hydrocarbon solvents. 

In some heterocyclic compounds such as acridine, the n-n absorption band is difficult to distinguish from the much more intense n-n absorption bands. 

There are many interesting derivatives of quinoline and acridine obtained by substitution. In particular, 8-hydroxyquinoline (oxine) is the second complexing agent in importance after EDTA. Sulfonation in position 5 leads to a compound which is soluble in water and that exhibits outstanding fluorogenic properties (i.e. fluorescence enhancement) on complexation with metal ions (e.g. aluminum). 

The properties of the related heterocydes containing oxygen and sulfur (e.g. dibenzofuran, dibenzothiophene) can be similarly interpreted. 

Heterocyclic coupling components have, in a similar manner as heterocyclic diazo components (sect. 2.1.4), recently become very important and are used in large scale industrial production of dyestuffs and chemicals. A recent review deals with the industrial um of pyrazolones 75, iminopyrazoles 76, pyridones 77, amino-pyrimidines 78, aminopyridines 79, hydrochinolines 80 and aminothiazoles 81 as coupling components. 

Recently the interaction of arenediazonium ions with some purine bases, nucleosides and nucleotides was investigated Adenine, adenosine and 5 -adenylic 

The fact that adenosine and its derivatives are azo coupling components is used for immobilizing nicotinamide-adenine nucleotide (NAD ) for affinity chromatography purposes. In 87a NAD is bonded to a matrix through an azo bond. 87a is used for the purilication of dehydrogenase enzymes Butler and coworkers have studied the reactions of arenediazonium ions with pyrroles Pyrroles are known to react readily with diazonium ions under 

Several papers have appeared rKently dealing with azo coupling reactions with various indole systems as coupling components 

The rates of azo coupling at the 3-position for a series of 2-, 2,4- and 2,4,6-substituted indoles 93 (41) with p-substituted arenediazonium ions in mixed aqueous and some aprotic solvents are reported The pH-dependence of these azo coupling reactions will be discussed in Section 4.1 and their kinetic hydrogen isotope effects in Section 4.3. 

Heterocyclic Compounds. - Some heterocyclic compounds have more reactive C=C double bonds than in benzenoid structures and most are readily reduced at the cathode. The majority of studies have been carried out using cathodes of high H2 overvoltage but occasional studies have been made on Pt. A combination of electrochemical and catalytic technique has been carried out in the hydrogenation of the pyrrole ring in which active Ni powder or platinized Pt was added to the electrolyte. The reduction was then found to proceed independently of the cathode material. 

The electroreduction of pyridine has been effected at a Ni cathode in the presence of Hg and Ag catalysts. However, in the absence of these catalysts the reduction was found to proceed slowly on Pt, Cu, and Fe cathodes but faster on a Ag cathode.  

The hydrogenation of pyridine to piperidine is difficult to perform both catalytically and electrochemically. However a study of the electrolytic reduction of pyridine at a Raney Ni cathode at atmospheric pressure resulted in near theoretical rates and good yields (90%),  

In another electrocatalytic study the effect of cathodic polarization on the catalytic hydrogenation of furfural and furfuryl alcohol at a Pd/Pt electrode catalyst was investigated. It was found that the rate of H2 absorption from the gas phase did not change when polarization currents of less than 

6mAcm were applied. At current densities above this it was found that H2 absorption decreased and only incomplete conversion was obtained. 

Heterocyclic compounds are those compounds that contain a ring made up of more than one kind of atom. The most common from a flavor chanistry point of view are  

Furan Thiphene Imidazole Oxazole Thiazole F yrazole 

The heterocyclic compounds containing O, N, or S, typically have very potent and often characteristic odors [22-24], They are essential to the flavor of some plants and are key volatiles in defining the flavor of many thermally processed foods. Examples of members of this class of aroma compounds have been presented in Chapter 5. 

Internal esterification resulting in the loss of one molecule of water from the y- and 5-hydroxyacids yields a class of cyclic compounds called lactones. The five-mem-bered ring system is readily formed and the resulting y-lactones are very stable. 

As a group, the lactones are powerful and distinctive flavorants, which are responsible for many of the characteristic notes of fruits, e.g., peaches and apricots. A comparison of the odors of 8- and y-lactones indicates that the increase in the size of the ring in the 5-compound results in an increased odor intensity but that the y-lactones have in addition some green nuances not present in the 8-lactones. Many lactones have a strong musk-hke odor that is very persistent. In the aromatic series, the best known lactone is coumarin, but this is no longer permitted for use in foods. The part played by lactones in foods has been reviewed by Maga [25] and Dufosse et al. [26]. 

In CCD, heterocyclic compounds are drawn with the heteroatom toward the bottom or bottom right and numbered counterclockwise. Many other information sources show the heteroatom at the top. 

Stereochemical configuration is shown with the use of solid wedge and hashed lines. There are some general rules used in CCD to avoid ambiguity  

Re-entrant bonds Similar ambiguity in stereochemical interpretation occurs when a stereobond is drawn inside the obtuse angle between two other bonds as opposed to the reflex angle. 

Examples often occur in large ring systems, but it is often possible to redraw the ring to avoid a reentrant bond. 

Using stereobonds to imply perspective One exception to the rule above occurs when the stereocentre is part of a bridged ring system. In this case the reentrant bonds are drawn using stereobonds since they are naturally pointing out of the plane of the paper, and the alternative results in ambiguous stereochemistry. 

The reactivity of heterocyclic compounds towards e-q can generally be deduced from the chemical behaviour of the aliphatic and aromatic systems discussed in the previous Sections. Thus one finds, for instance, that pyrrolidine (1) (tetraethyleneimine) (Szutkaetai., 1965) and proline 

The effect of the NH electron-donating group in a heterocyclic system on an electrophilic centre is demonstrated again in the case of indole (7), which is significantly less reactive than styrene (k= 7-8 x 10 and 1-1 x 1010 m-1 sec-1, respectively) (Hart et al., 1964b). Here the 

NH group deactivates both the ethylenic bond and the aromatic nucleus. As the reactivity of tryptophane (8) in alkaline solution (k = 1-8 x 108 M-1 sec-1) (Braams, 1966) is significantly lower than that reported for 

Imidazole (9) seems to be more reactive than pyrrole, its carbon 

The imidazolium ion is much more reactive (k = 4x 10 M-1 sec-1) (Braams, 1966) than the base. This may be explained by the strong inductive effect of the ammonium group on the C=N— reactive centre. Histidine shows good agreement with the behaviour of imidazole k = 3-9 x 10 M-1 sec-1 for the acid form and 1-2 x 107 m-1 sec-1 for the basic form (Braams, 1966). 

They are moderately toxic to mammals, the lDjq of all three compounds for rats ranging between 1400 and 2000 mg/kg. 

An example of the simultaneous anti-powdery mildew and acaricidal action is the biological effect of 6-methyl-2,3-quinoxalinedithiol cyclic carbonate (oxythio-quinox, 30) and of the related 2,3-quinoxalinediyl cyclic trithiocarbonate (thioquinox, 31), introduced originally as fungicides against powdery mildew and discussed already under the heading fungicides. These compounds were developed by research workers of the Bayer Co. in the course of their study of the acylated derivatives of 2,3-dimercaptoquinoxaline (Sasse et ai, 1958 19 Basse, 1960). 

They have scarcely any insecticidal effect and exert their action primarily against larvae and eggs of acaridae. 

The most important examples of compounds used specifically as acaricides but possessing a weak insecticidal action are S-(4-chlorophenylthiomethyl)-diethyl phosphorothiolothionate (carbophention, 32) and its 3,5-dichlorphenyl analogue (phenkapton, 33). These compounds are very similar to each other, but have been developed by two independent research groups (Fancher, 1954 Gatzi and Muller, 1955). 

They are prepared by treating the respective thiophenol with formaldehyde and hydrochloric acid, followed by reaction of the substituted chloromethyl phenyl 

Introduction of Fluorine.—Of the several methods available for the introduction of fluorine into a heterocyclic nucleus, that involving halogen exchange with the corresponding chloro-compound continues to be the most widely used recent patents indicate an emphasis on the use of hydrogen fluoride rather than a metallic fluoride as the reagent, especially when restricted replacement of chlorine is desired. 

Treatment of pentachloropyridine with hydrogen fluoride at 180 °C under pressure gives a mixture of trichloro-2,6-difluoro- and dichIoro-2,4,6-tri-fluoro-pyridine. Gas-phase fluorination of pentachloropyridine and of 2,4, 2,4,6-trichlorop3rrimidine with hydrogen fluoride over chromium oxide-fluoride and aluminium oxide-fluoride (or A1203) has also been achieved tetrachloropyrimidine gives 5-chloro-2,4,6-trifluoro- (61%), 5,6-dichloro-2,4-difluoro- (33 %), and 4,5,6-trichloro-2-fluoro-pyrimidine (6 %).  

Displacement of nitro-groups by fluoride ion has been reported 2-fluoro-pyridine, 4-fluoropyridine, and 2-fluorothiazoIe (244) were prepared in 60, 60, and 20 % yield, respectively, by treating the corresponding nitro-compound with potassium fluoride in -methyl-2-pyrrolidone or hexamethylphos-phoramide.  

The Balz-Schiemann reaction has been used for the preparation of the 4-iluoro-derivatives of pyridine and 2,5-, 2,6-, and 3,5-lutidine it has also been used to obtain 5-fluoronicotinic acid, required for conversion into the corresponding pyridylmethanol via LiAlH reduction of the ethyl ester. The introduction of F into fluoroaromatic compounds has been achieved via isotopic exchange in diazonium tetrafluoroborates. U.v. irradiation of aqueous solutions of the appropriate diazonium tetrafluoroborates has been used to procure the first ring-fluorinated imidazoks, e.g. photolysis of the diazonium solution obtained by adding sodium nitrite to 2-amino-imidazole in aqueous fluoroboric acid provides 2-fluoroimidazole contaminated with only a small amount of 2-azidoimidazole, the sole product of thermal decomposition of imidazole-2-diazonium tetrafluoroborate. 

Hedbom, E. Heigstrand, A. Misiomy, W. E. Stjemstrom, and G. Westin, Acta Pharm. Suecica, 1972, 9, 259. 

Heterocycies form the largest class of organic compounds. In fact, many natural products and most drugs contain heterocyclic rings. The colors of flowers and plants, antibiotics known to all as penicillins, compounds that transport the oxygen we breathe to our vital organs, and the components of DNA responsible for the genetic code are all heterocyclic compounds. 

From an organic chemist s viewpoint, heteroatoms are atoms other than carbon or hydrogen that may be present in organic compounds. The most common heteroatoms are oxygen, nitrogen, and sulfur. In heterocychc compounds, one or more of these heteroatoms replaces carbon in a ring. 

Heterocycies can be divided into two subgroups nonaromatic and aromatic. We have already encountered a few nonaromatic heterocycies—ethylene oxide and other cyclic ethers (Chapter 8), cyclic hemiacetals such as glucose (Chapter 9), cyclic esters called lactones (Chapter 10), and cyclic amines such as morphine (Chapter 11). In general, these nonaromatic heterocycies behave a great deal like their acyclic analogs and do not require special discussion. 

Aromatic heterocycies are extremely important, and that is where we will focus most of our attention. We begin with an important six-membered ring aromatic nitrogen heterocycle, pyridine. 

Online homew/ork for this chapter can be assigned in OWL, an online homework assessment tool. 

There is available a large amount of qualitative information about the nitration of heterocyclic compounds, but quantitative information is still not very extensive, being limited to nitrogen systems. 

For this series of compounds qualitative information is quite extensive. Application of the criteria discussed in 8.2, in particular comparison with the corresponding methyl quaternary salt, establishment of the rate profile for nitration in sulphuric acid, and consideration of the encounter rate and activation parameters, shows that 2,4,6-collidine is nitrated as its cation. The same is true for the 3-nitration of 2,4-  

The similarity of their rate profiles, and the similarity of their rate constants for nitration at a particular temperature and acidity show that 4-pyridone, i-methyl-4-pyridone, and 4-methoxypyridine are all nitrated as their cations down to about 85 % sulphuric acid. The same is true of 2-methoxy-3-methylpyridine. In contrast, 3- and 5-methyl-2-pyridone, i,5-dimethyl-2-pyridone and 3-nitro-4-pyridone all react 

The 2-nitration of 3-hydroxy- and 3-methoxy-pyridine in 85-96% sulphuric acid involves the conjugate acids, whilst the 3-nitration of 6-hydroxy and 6-methoxy-2-pyridone in 70-77 % sulphuric acid involves the free bases, which react at, or near to the encounter rate.  

The interest attaching to the nitration of pyridine i-oxide and its derivatives has already been mentioned ( 8.2.5). Some data for these reactions are given in tables 8.1, 8.2 and 8.4. The 4-nitration of pyridine I-oxide is shown to occur through the free base by comparison with the case of i-methoxypyridinium cation ( 8.2.2), by the nature of the rate profile ( 8.2.1), and by consideration of the encounter rate ( 8.2.3). - Some of these criteria have been used to show that the same is true for 

Atoms other than carbon and hydrogen that appear in organic compounds are called heteroatoms. Cyclic organic compounds that contain one or more heteroatoms are called heterocycles. Heterocyclic compounds are the largest class of organic compounds and can be either aromatic (such as pyridine, pyrrole, and furan) or nonaromatic (such as piperidine, pyrrolidine, and tetrahydrofuran). 

Polycyclic aromatic heterocycles that contain pyridine rings fused with benzene rings include quinoline and isoquinoline. Quinine, used to treat malaria, is an example of a naturally occurring quinoline. 

The diazines (pyridazine, pyrimidine, and pyrazine) are six-membered aromatic heterocycles that have two nitrogens in the ring. Cytosine, thymine, and uracil are derivatives of pyrimidine that are important bases in nucleic acids (DNA and RNA). Heterocyclic analogs of the aromatic hydrocarbon naphthalene include pteridines, which have four nitrogens in the rings. Naturally occurring pteridine derivatives include xanthopterin (a pigment) and folic acid (a vitamin). Methotrexate is a pteridine used in cancer chemotherapy. 

Pyrylium ions are six-membered heterocycles in which a positively charged sp2-hybridized oxygen replaces the nitrogen in pyridine. The pyrylium ring appears in many naturally occurring flower pigments. 

Pyrrole, furan, and thiophene are five-membered aromatic heterocycles with one heteroatom. In pyrrole, the nitrogen is sp2-hybridized and contributes two electrons to the 6n aromatic ring. Furan and thiophene are isoelectronic with pyrrole, the [—(N )=] unit being replaced by —( 0 )— and -( S )- units, respectively. Pyrrole, furan, and thiophene are electron-rich (there are six n electrons distributed over five atoms) and undergo electrophilic 

Not all cyclic compounds are hydrocarbons. Many substances include an atom other than carbon, called a heteroatom (Section 1.7), as part of a ring. A ring that contains at least one heteroatom is c ed a heterocycle, and a substance based on a heterocyclic ring is a heterocyclic compound. Each of the following heterocyclic ring systems will be encountered in this text  

The names cited are common names, which have been in widespread use for a long time and are acceptable in lUPAC nomenclature. We will introduce the systematic nomenclature of these ring systems as needed in later chapters. 

The shapes of heterocyclic rings are very much like those of their all-carbon analogs. Thus, six-membered heterocycles such as piperidine exist in a chair conformation analogous to cyclohexane. 

The hydrogen attached to nitrogen can be either axial or equatorial, and both chair conformations are approximately equal in stability. 

PROBLEM 3.14 Draw or build a molecular model of what you would expect to be the most stable conformation of the piperidine derivative in which the hydrogen bonded to nitrogen has been replaced by methyl. 

Sulfur-containing heterocycles are also common. Compounds in which sulfur is the heteroatom in three-, four-, five-, and six-membered rings, as well as larger rings, are all well known. Two interesting heterocyclic compounds that contain sulfur-sulfur bonds are lipoic acid and lenthionine. 

This limited methodology must be compared to a new approach for the synthesis of 2-amino 2-deoxycarbohydrates based on the cycloaddition of azodicarboxylates on glycals. This 4 + 2 cycloaddition is initiated by irradiation at 350 nm and seems highly stereoselective. After hydrolysis and reduction, compounds like 43 (Z = Ac) are obtained in good yields [45]. 

As mentioned earlier in this chapter, it is not possible in this book to deliver a comprehensive treatment of the fragmentations of organic ions. Nevertheless, a short reference to MS of heterocyclic compounds should be made here, while being aware that this topic could easily fill an entire textbook of its own [191]. 

As mentioned in the beginning of this chapter, there is by far no chance for a comprehensive treatment of the fragmentations of organic ions in this context. Nevertheless, we should not finish without having briefly addressed the mass spectrometry of heterocyclic compounds, an issue filling a book of its own. [215] 

The mechanistic rationale for the high stereoselectivity is provided by the intermediate production of the trans-iodonium species 279 and its collapse to the bridged oxonium species 280 prior to the introduction of the toxyloxy ligand. 

Similarly, intramolecular participation of nitrogen in the oxidation of carbamates 281 affords bridgehead heterocycle 282 in high yield. 

Hydrazones 285 are oxidatively cyclized by IBD to form 286. Similar cyclization is accessible by using lead tetra-acetate as an oxidant, but results are inferior to those with IBD [89JCS(P1)543]. 

Histidine was discovered in 1896 by Kossel amongst the decomposition products of sturine, the protamine obtained from the ripe testis of the sturgeon. In the same year Hedin isolated a base from the products of hydrolysis of various proteins, which he. regarded as identical with Kossel s histidine, and this was subsequently shown to be the case by Kossel and Kutscher. Kutscher also found it in antipeptone obtained by the pancreatic digestion of fibrin, and Schulze and Winterstein have shown that it occurs as a decomposition product of various vegetable proteins. 

This assumption of Pauly s was confirmed by Knoop and Windaus, who found that histidine is resistant to reduction by sodium and alcohol whereas the pyrimidine rii is very unstable towards this reagent. On reducing Frankel s oxydesaminohistidine, which is obtained from histidine by the action of nitrous acid, they obtained /8-imidazole-propionic acid. This compound was identical with the synthetical product prepared from glyoxylpropionic acid, ammonia and formaldehyde —  

In connection with histidine, the work of Windaus and Knoop on the formation of methylimidazole from glucose must be mentioned on account of the possible synthesis in the animal body of both histidine and purine bases. 

In the presence of ammonia and formaldehyde, also a product from the sugar, methylimidazole is formed as follows — 

This condensation with formaldehyde as well as with methyl glyoxal is confirmed by the formation of dimethylimidazole when ammonia acts upon glucose and acetaldehyde. 

The use of metallated thiazoles, thiazolines, oxazolines, and dihydrooxazines as anion-equivalents in organic syntheses has been advanced extensively [1-6]. Table 7 summarizes the conditions for preparative metallations of a numbers of substituted heterocycles. 

Altman LJ, RichheimerSL(1971) Tetrahedron Lett. 4709 compare Knaus G, Meyers AI (1974) J Org Chem 39 1192 

Meyers AI, Nabeya A, Adickes HW, Politzer IR, Malone GR, Kovelesky AC, Nolen RL, Portnoy RC (1973) J Org Chem 38 36 

Meyers AI, Mihelich ED (1976) Angew Chem 88 321 Angew Chem, Int ed 15 499 

Geosmin is a natural product that smells like dirt. It is produced by several microorganisms and can be obtained from beet extracts. Complete the following decalin ring skeleton, placing the substituents of geosmin in their proper orientations. 

Acetaldehyde ammonia trimer (hexahydro-2,4,6-trimethyl-l,3,5-triazine trihydrate) [76231-37-3] M 183.3, m 94-96°, 95-97°, 97°, b 110°(partly dec). It crystallises from Et0H/Et20. When prepared, it separates as the trihydrate which can be dried in a vacuum over CaCl2 at room temperature to give the anhydrous compound with the same melting point. The dihydrate melts at 25-28°, then resolidifies and melts again at 94-95°. IT IRIUTATES THE EYES AND MUCOUS MEMBRANES. [Nielson et al. J Org Chem 38 3288 1973, Beilstein 26 III/TV 25.] 

2-Acetamido-5-nitrothiazole (Acinitrazole) [140-40-9] M 187.2, m 264-265°. Recrystallise acinitrazole from EtOH or AcOH. [Hurd Wehrmeister JH/w Chem Soc 71 4007 1949, Beilstein 27III/IV 4676.] 

4-Acetamido-2,2,6,6-tetramethylpiperidine-l-oxyl (acetamidoTEMPO) [14691-89-5] M 213.3, m 144-146°, 146-147°. Dissolve the 1-oxyl in CH2CI2, wash it with saturated K2CO3, then saturated aqueous NaCl, dry (Na2S04), filter and evaporate. The red solid is reciystallised from aqueous MeOH, m 147.5°. [Ma Bobbitt J Org Chem 56 6110 1991, Rozantsev Kokhanov Bull Acad Sci USSR, Div Chem Sci 15 1422 1966, Beilstein 22/8 V 174.] 

Acetoacetylpiperidide [1128-87-6] M 169.2, b 88.9°/0.1mm, no 1.4983. Dissolve it in benzene, extract with 0.5M HCl to remove basic impurities, wash with water, dry, and distil it at 0.1mm [Wilson JOrg Chem 28 3U1963], [Beilstein ItllN nil] 

l R-4-Acetoxy-3-[l-(tert-butylmethylsilyloxy)ethyl]-2-azetinone. See in Miscellaneous As, B, P, Si, 

Microbiological detection with Staph, aureus ATCC 6538 P or Sarcina lutea ATCC 9341. 

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A white solid, m.p. 178 C. Primarily of interest as a brominaling agent which will replace activated hydrogen atoms in benzylic or allylic positions, and also those on a carbon atom a to a carbonyl group. Activating influences can produce nuclear substitution in a benzene ring and certain heterocyclic compounds also used in the oxidation of secondary alcohols to ketones. 

Decolorisation by Animal Charcoal. It sometimes hap pens (particularly with aromatic and heterocyclic compounds) that a crude product may contain a coloured impurity, which on recrystallisation dissolves in the boiling solvent, but is then partly occluded by crystals as they form and grow in the cooling solution. Sometimes a very tenacious occlusion may thus occur, and repeated and very wasteful recrystallisation may be necessary to eliminate the impurity. Moreover, the amount of the impurity present may be so small that the melting-point and analytical values of the compound are not sensibly affected, yet the appearance of the sample is ruined. Such impurities can usually be readily removed by boiling the substance in solution with a small quantity of finely powdered animal charcoal for a short time, and then filtering the solution while hot. The animal charcoal adsorbs the coloured impurity, and the filtrate is usually almost free from extraneous colour and deposits therefore pure crystals. This decolorisation by animal charcoal occurs most readily in aqueous solution, but can be performed in almost any organic solvent. Care should be taken not to use an excessive quantity... 

The physical properties of a number of aliphatic ethers are collected in Table 111,60. Some related heterocyclic compounds are included in the Table. 

This reagent affords compounds (1 1) with aromatic hydrocarbons and other classes of organic compounds (heterocyclic compounds, aromatic ethers, etc.). 

Division III. Heterocyclic compounds (Heterocyclic stem nuclei). The carbon atoms are joined in closed rings which include one or more other kinds of atoms as ring components. Anhydrides and imides of dibasic acids, as well as lactones, lactams, etc. are thus included in this division... 

Elderfield, Heterocyclic Compounds, Volumes I-IV, 1951-1954 (J. Wiley Chapman and Hall). 

This term denotes all compounds with substituents containing atoms other than carbon, and includes heterocyclic compounds. 

Retro-Synthetic Analysis (= Antithesis 193 3.1.5 Aromatic and Heterocyclic Compounds... 

Acheson, R. M. 1976 B, An Introduction to the Chemistry of Heterocyclic Compounds, Wiley New York London Sydney... 

Typical nucleophiles known to react with coordinated alkenes are water, alcohols, carboxylic acids, ammonia, amines, enamines, and active methylene compounds 11.12]. The intramolecular version is particularly useful for syntheses of various heterocyclic compounds[l 3,14]. CO and aromatics also react with alkenes. The oxidation reactions of alkenes can be classified further based on these attacking species. Under certain conditions, especially in the presence of bases, the rr-alkene complex 4 is converted into the 7r-allylic complex 5. Various stoichiometric reactions of alkenes via 7r-allylic complex 5 are treated in Section 4. 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Pd-cataly2ed reactions of butadiene are different from those catalyzed by other transition metal complexes. Unlike Ni(0) catalysts, neither the well known cyclodimerization nor cyclotrimerization to form COD or CDT[1,2] takes place with Pd(0) catalysts. Pd(0) complexes catalyze two important reactions of conjugated dienes[3,4]. The first type is linear dimerization. The most characteristic and useful reaction of butadiene catalyzed by Pd(0) is dimerization with incorporation of nucleophiles. The bis-rr-allylpalladium complex 3 is believed to be an intermediate of 1,3,7-octatriene (7j and telomers 5 and 6[5,6]. The complex 3 is the resonance form of 2,5-divinylpalladacyclopentane (1) and pallada-3,7-cyclononadiene (2) formed by the oxidative cyclization of butadiene. The second reaction characteristic of Pd is the co-cyclization of butadiene with C = 0 bonds of aldehydes[7-9] and CO jlO] and C = N bonds of Schiff bases[ll] and isocyanate[12] to form the six-membered heterocyclic compounds 9 with two vinyl groups. The cyclization is explained by the insertion of these unsaturated bonds into the complex 1 to generate 8 and its reductive elimination to give 9. 

There are a number of other sources of information available about the synthesis of indoles. The most comprehensive entree to the older literature is through Volume 25, Parts I-IIl, of The Chemistry of Heterocyclic Compounds, which were published between 1972 and 1979[23]. Work to the early 1980s is reviewed in Comprehensive Heterocyclic Chemistry[24 and a second edition is forthcoming[25]. Other reviews emphasizing recent developments are also availablc[26-28]. 

Piperazinothiazoies (2) were obtained by such a replacement reaction, Cu powder being used as catalyst (25. 26). 2-Piperidinothiazoles are obtained in a similar way (Scheme 2) (27). This catalytic reaction has been postulated in the case of benzene derivatives as a nucleophilic substitution on the copper-complexed halide in which the halogen possesses a positive character by coordination (29). For heterocyclic compounds the coordination probably occurs on the ring nitrogen. 

The chemistry of heterocyclic compounds is one of the most complex branches of organic chemistry. It is equally interesting for its theoretical implications, for the diversity of its synthetic procedures, and for the physiological and industrial significance of heterocyclic compounds. 

This IS the thin iourth volume in iht senes THE CHEMISTRY OF HETEROCYCLIC COMPOUNDS... 

Since then, the fundamental physicochemical aspects of the synthesis and properties of ev anines have been exhaustively reviewed by Heseltine and Stunner in the fourth edition of Mee s treatise (3) and by Sturmer in Weissberger s edition of the Chemistry of Heterocyclic Compounds (4). So the purpose of this section dealing especially with thiazolomethine dyes is to give, apart from a complete and recent list of dyes and references, a description of the particularities of their chemistry and chiefly of the reaction mechanisms involved in their synthesis that have remained unknown or have not been discussed until now. 

D. Stunner, Syntheses and Properties of Cyanine and Related Dyes. The Chemistry of Heterocyclic Compounds. Wiley. New York. 1977. 

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