Nomen clature of hetero-Hantzsch–Widman nomenclature - Wikipedia

December , Cite as. As a single system of chemical nomenclature is used worldwide, it is the universal language of chemistry and thus a critical component to effectively communicate with others in the field. Polycyclic fused-ring arenes and heterocycles are classes of organic compounds that are finding growing importance in polymer chemistry, materials science, and pharmaceutical chemistry, yet the nomenclature of these compounds is rarely covered even in graduate texts and students are thus not taught how to apply this nomenclature as needed. As such, the current report aims to present the basic rules and application of fused-ring nomenclature such that one can apply it to most common cases. When introducing the subject of chemistry to new students, it is often acknowledged that the study of the subject has many similarities to learning a new language.

These possibilities will be illustrated above by clicking on the diagram. Oesper RE The birth of modern chemical nomenclature. Lastly, if the various rules above still allow multiple orientations, choose the one that gives the highest priority heteroatom the lowest position number [ 14171827 ]. An eBook reader can be a software hetrro for use on a computer such as Microsoft's free Reader application, or a book-sized computer that is used solely as a Nomen clature of hetero device such as Nuvomedia's Rocket eBook. In the case of example 1, cyclization to an oxirane competes with thietane formation, but the Stripping rustoleum paint nucleophilicity of sulfur dominates, especially if a weak base is used.

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Thiazoles and isothiazoles contain a sulfur and a nitrogen atom in the ring. The former participates in a cycloaddition reaction; however, the pyrrole simply undergoes electrophilic substitution at C In the thietane reaction hetegothe sulfur Nomen clature of hetero electrophilic chlorination to form a chlorosulfonium intermediate followed by a ring-opening Nomen clature of hetero ion substitution. The relatively rigid configuration of the substrate in example 3, favors oxetane formation and prevents an oxirane cyclization from occurring. Heterocycles with three atoms in the ring are higher in energy and more reactive because of ring strain. This is a controlling factor in the clatuee facile nitration at C The example shown in reaction 9 is a stable in the absence of oxygendistillable green liquid. A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring s. Other examples show similar addition reactions to thiiranes and aziridines. Oxygen and sulfur analogs are necessarily positively charged, as in the case of 2,4,6-triphenylpyrylium Panty teen movies.

A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring s.

  • Heterocyclic Chemistry.
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  • A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring s.

December , Cite as. As a single system of chemical nomenclature is used worldwide, it is the universal language of chemistry and thus a critical component to effectively communicate with others in the field. Polycyclic fused-ring arenes and heterocycles are classes of organic compounds that are finding growing importance in polymer chemistry, materials science, and pharmaceutical chemistry, yet the nomenclature of these compounds is rarely covered even in graduate texts and students are thus not taught how to apply this nomenclature as needed.

As such, the current report aims to present the basic rules and application of fused-ring nomenclature such that one can apply it to most common cases. When introducing the subject of chemistry to new students, it is often acknowledged that the study of the subject has many similarities to learning a new language.

Not only must one become fluent in the symbolic language of the subject symbols, chemical formulas, equations, etc. As a single system of chemical nomenclature is used worldwide, it is thus a critical component to effectively communicate with others in the field [ 1 ]. It is one such subset of modern chemical nomenclature, that of polycyclic fused-ring arenes and heterocycles, which is the focus of the current publication.

Chemical nomenclature can be traced back to the beginning of the modern period of chemistry at the end of the eighteenth century. Although Torbern Bergman — published a limited nomenclature in , most associate the formal beginnings of systemic chemical nomenclature with the efforts led by Guyton de Morveau — beginning in that same year [ 1 , 2 , 3 , 4 ]. These efforts resulted in the May publication of a page book titled Methode de Nomenclature Chimique Method of Chemical Nomenclature , which was coauthored by de Morveau, Antoine Lavoisier — , Claude Berthollet — , and Antoine de Fourcroy — [ 1 , 2 , 3 ].

This publication established a rational system that allowed one to know the composition of a chemical species directly from its name and is the system still in use today for the naming of simple inorganic compounds. Patterson began working on the numbering and nomenclature of cyclic systems as early as [ 13 ] and proposed to the editorial committee of the Journal of the American Chemical Society the publication of a catalog detailing the formula of cyclic organic systems, along with their names and numberings [ 10 ].

As such, an American commission was formed, of which Patterson was a member, which established a final set of numbering rules to be submitted to IUPAC [ 7 , 10 ]. As Patterson died in February of [ 11 , 12 ], he unfortunately did not live to see this occur. This now established nomenclature of fused-ring systems has continued to be modified and revised with the most current rules published in [ 18 ]. Although the importance of chemical nomenclature is generally recognized, particularly as part of the chemistry curriculum, the subject does not generally receive much interest among practicing chemists beyond its most basic application [ 19 ].

The practicing chemist typically regards formal chemical nomenclature as a necessary evil during the publication process, something imposed by more critical referees and journal editors to keep at least some structure and uniformity in the primary literature, as well as to facilitate communication or the retrieval of information [ 19 ].

In fact, it is now common for many authors to bypass the complication of correct formal nomenclature by reporting new species solely by structure and compound numbers without even an attempt to include any associated chemical names. A growing number of chemists also tend to rely on software programs to provide systematic names from structural formulas and while such programs perform reasonably well for simple systems, they often have more difficulty with fused-ring systems and cannot be relied upon to give the desired name without errors.

Of course, although everyone learns the basic chemical nomenclature used to name simple inorganic species and common organic compounds, more complex forms of nomenclature are typically only used by chemists in specific fields and are not taught as part of the general undergraduate curriculum.

This is especially true for the nomenclature of fused-ring arenes and heterocycles, which is not even mentioned in undergraduate texts and can only be found in a very limited number of graduate texts [ 20 , 21 , 22 , 23 , 24 ].

Even for those texts that do include this nomenclature, the coverage is extremely brief and not adequate for one to develop the ability to adequately apply this nomenclature with any competence or mastery. As a consequence, incorrect application of fusion nomenclature is somewhat commonplace in the scientific literature.

Because of this reality and the growing importance of fused-ring organic species in polymer chemistry, materials science, and pharmaceutical chemistry, it was felt that an educational guide to the application of this nomenclature is long overdue.

The aim of the following presentation is thus to present the basic rules of fused-ring nomenclature, along with their application via examples such that one can competently apply this nomenclature to most commonly encountered cases. The scope of this discussion, however, will be limited to conventional fused-ring systems without covering the more complicated bridged fused-ring analogs. It should also be pointed out that although the fused-ring nomenclature outlined by IUPAC and that of Chemical Abstracts Service CAS are very similar, there are some minor differences that date back to the initial development of this nomenclature in [ 16 ].

Whenever possible, such differences will be highlighted in the current discussion. To correctly apply the systematic numbering of fused-ring systems, the compound is first oriented such that the greatest number of rings lies in a horizontal row. The structure is then flipped such that the greater number of rings is positioned above and to the right of this horizontal row.

If multiple orientations give similar numbers of rings to the upper right, the one that has as few rings as possible to the lower left is chosen. Numbering then begins at the most counterclockwise position not involved in fusion of the top ring furthest to the right and proceeds clockwise around the exterior of the fused-ring compound. Thus, the two bridgehead positions of pentalene would be 3a and 6a. Rank of 1 is the highest priority parent, Refs. Other heteroatoms use the unsaturated suffix and saturation is expressed by hydro prefixes.

Finally, numbering of the ring begins with the most senior heteroatom and proceeds around the heterocycle to provide the lowest position numbers to the remaining heteroatoms. If multiple options exist, preference is given to assigning the lowest position numbers to the highest priority heteroatoms.

The numerical locants listed in front of the replacement prefixes are also given in decreasing order of heteroatom priority [ 20 , 27 , 29 ]. Examples of various common heterocycles having Hantzsch—Widman names are given in Fig. For systems with multiple heterocycles, a number of additional rules are used to determine priority, beginning with ranking nitrogen-containing systems over other heterocycles [ 15 , 27 , 28 ].

If none of the heterocycles contain nitrogen, then priority is given to the ring with the most senior heteroatom. The heteroatom ranking used here is the same as described above in the discussion of Hantzsch—Widman nomenclature. If priority still cannot be determined via these first two principles, then the following additional criteria are used in descending order: 1 the parent with the greatest number of rings; 2 the parent with the largest ring; 3 the parent with the most heteroatoms; 4 the parent with the greater variety of heteroatoms; 5 the parent with the greatest number of more senior heteroatoms [ 17 , 18 , 27 , 28 ].

Finally, the positions of the complete fused-ring heterocyclic structure are renumbered, ignoring the original numbering of either the parent or components.

This is accomplished in the same way as with the previously discussed polycyclic arenes, although with additional considerations for heteroatom position numbers. As before, the structure is oriented such that the greatest number of rings lies along the horizontal and to the upper right [ 14 , 17 , 18 , 21 ]. However, if multiple orientations are still possible, choose the one that would give the heteroatoms the lowest possible position numbers.

Lastly, if the various rules above still allow multiple orientations, choose the one that gives the highest priority heteroatom the lowest position number [ 14 , 17 , 18 , 27 ]. As with polycyclic arenes, numbering begins at the most counterclockwise position not involved in fusion of the top ring furthest to the right and proceeds clockwise around the exterior of the fused-ring compound.

Fused-ring heterocycles differ from arenes, however, in that any heteroatoms located at bridgehead positions are given position numbers see Fig. The remaining sections below will apply these basic rules of fused-ring heterocyclic nomenclature to commonly encountered situations.

As heterocycles always have higher priority than arenes, the parent of these examples is always the heterocycle. In addition, as there is no ambiguity in the fusion of the benzene, the fusion descriptor consists of only the italicized face letter of the parent heterocycle. Thus, as illustrated by the examples given in Fig. In addition to the fusion nomenclature discussed above, an alternate nomenclature system can be used specifically for fused-ring compounds consisting only of benzene fused to a single heterocyclic ring.

The resulting composite name is then prefixed by numerical locants giving the positions of the heteroatoms in the final system Fig.

These benzoheterocycle names i. Examples of fused-ring tricyclic heterocycles consisting of only two components. The first example given in Fig. As a nitrogen-based heterocycle, pyrrole has priority and is thus the parent here.

As with previous cases, the bracketed fusion descriptor is then inserted between the substituents and parent. The difference here is that the fusion descriptor must now detail two separate fusions, rather than just a single fusion. Both sets of fusion locants are included in the same set of brackets, although separated by a colon with the fusion containing the lowest locant letter given first [ 18 ]. To differentiate between the two identical substituents, unprimed numbers are used to describe the first substituent and primed numbers are used to describe the second.

Not only does this simplify the nomenclature, but also highlights the central heterocycle of interest in these compounds. However, as none of the heterocycles contain nitrogen, the parent is then determined by heteroatom priority and sulfur has higher priority than either phosphorus or arsenic.

As such, while structurally identical, the thiophene is the parent in both of these analogs and thus the correct names are not analogous to the pyrrole compound. As the parent occurs twice in these examples, the numerical prefix is still added, but is now applied to the parent.

In cases such as the thiazole examples given in Fig. In such cases where the application of the standard type 1 numerical prefix i. For such examples that contain two identical parents and a shared substituent, the fusion descriptor must again detail both separate ring fusions.

However, the difference here is that the use of primes is now applied to the parent locant letters as the two letters refer to two different parents. In contrast, all of the substituent numbers now refer to the single substituent and thus all numbers are unprimed. As with all fusion descriptors, the fused atoms of the attached substituent are described using the lowest possible position numbers of the substituent component and are always cited in the same direction as the letter locants [ 18 ].

However, in cases in which two identical parents share a substituent, the numbering used in the first fusion descriptor sets the overall numbering of the substituent and the position numbers for the second fusion descriptor are thus determined by the first fusion descriptor.

In cases were both locant letters are the same, the fusion with the lowest substituent numbers is listed first with the corresponding locant letter unprimed. The final two examples illustrate compounds in which the parent is a terminal ring with one substituent directly fused to the parent and a secondary substituent fused to the primary substituent.

Unlike the first two examples discussed above, the substituents here are not cited alphabetically, but are given in the order of fusion. Thus, the secondary substituent is cited first, followed by the primary substituent and then the parent. The two fusions are then described by two separate fusion descriptors. The primary fusion descriptor is described in exactly the same way as for all of the other examples already discussed above and this descriptor then sets the numbering of the first substituent.

The procedure for describing the fusion between the primary and secondary substituent is then similar, but consists of two sets of numerical locants separated by a colon rather than numbers and a letter locant separated by a hyphen [ 17 , 18 , 26 ]. The first two numbers describe the fusion positions of the secondary substituent and are given as primed numbers. The second two numbers describe the fusion positions of the primary substituent to the secondary [ 17 ], with the position numbers already determined by the fusion descriptor describing the fusion of the primary substituent to the parent.

In conclusion, as fused-ring organic species are continuing to grow in importance for applications in polymer chemistry, materials science, and pharmaceutical chemistry, basic knowledge of the nomenclature of these compounds is necessary to be able to effectively communicate with other scientists working in these fields. In fact, the proliferation of incorrect names in the chemical literature is due to the current lack of basic training in this nomenclature and contributes to unnecessary confusion in reports of these compounds.

As with all dialects of nomenclature, mastery requires learning a number of rules, as well as suitable practice in the application of these rules. However, if one can become proficient in the basic tasks of determining the correct parent ring system and then constructing the corresponding fusion descriptor, the process becomes fairly straightforward with most commonly encountered cases.

It is hoped that the overall discussion presented here should adequately prepare those that wish to learn the fundamentals of this system of nomenclature. Skip to main content Skip to sections. Advertisement Hide. Download PDF. ChemTexts December , Cite as.

The nomenclature of fused-ring arenes and heterocycles: a guide to an increasingly important dialect of organic chemistry. Lecture Text First Online: 17 September Introduction When introducing the subject of chemistry to new students, it is often acknowledged that the study of the subject has many similarities to learning a new language. As the study of organic chemistry did not really become a focus until the beginning of the nineteenth century, systemic organic nomenclature had to wait until efforts in , beginning with focused discussions at the International Congress of Chemistry held in Paris.

Although no rules of nomenclature were determined at the conference, it did establish a continuing International Commission of Chemical Nomenclature and these efforts ultimately led to the Geneva Nomenclature of , which became the initial basis of modern organic nomenclature [ 1 , 4 , 5 , 6 , 7 ].

Heterocycles with three atoms in the ring are higher in energy and more reactive because of ring strain. For other uses of "ring structure", see Ring structure. Embeds 0 No embeds. The benzoin condensation is limited to aromatic aldehydes, but the use of thiazolium catalysts has proven broadly effective for aliphatic and aromatic aldehydes. Other Reactions of Pyridine Thanks to the nitrogen in the ring, pyridine compounds undergo nucleophilic substitution reactions more easily than equivalent benzene derivatives.

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Example 1 in the following diagram shows one such transformation, which is interesting due to subsequent conversion of the addition intermediate into the corresponding thiirane.

The initial ring opening is stereoelectronically directed in a trans-diaxial fashion, the intermediate relaxing to the diequatorial conformer before cyclizing to a 1,3-oxathiolane intermediate. Other examples show similar addition reactions to thiiranes and aziridines. The acid-catalyzed additions in examples 2 and 3, illustrate the influence of substituents on the regioselectivity of addition.

Example 2 reflects the S N 2 character of nucleophile chloride anion attack on the protonated aziridine the less substituted carbon is the site of addition. The phenyl substituent in example 3 serves to stabilize the developing carbocation to such a degree that S N 1 selectivity is realized. The reduction of thiiranes to alkenes by reaction with phosphite esters example 6 is highly stereospecific, and is believed to take place by an initial bonding of phosphorous to sulfur.

By clicking on the above diagram , four additional example of three-membered heterocycle reactivity or intermediacy will be displayed. Examples 7 and 8 are thermal reactions in which both the heteroatom and the strained ring are important factors. Note that two inversions of configuration at C-2 result in overall retention. Many examples of intramolecular interactions , such as example 10, have been documented. As illustrated below, acid and base-catalyzed reactions normally proceed by 5-exo-substitution reaction 1 , yielding a tetrahydrofuran product.

However, if the oxirane has an unsaturated substituent vinyl or phenyl , the acid-catalyzed opening occurs at the allylic or benzylic carbon reaction 2 in a 6-endo fashion. Preparation Several methods of preparing four-membered heterocyclic compounds are shown in the following diagram. The simple procedure of treating a 3-halo alcohol, thiol or amine with base is generally effective, but the yields are often mediocre.

Dimerization and elimination are common side reactions, and other functions may compete in the reaction. In the case of example 1, cyclization to an oxirane competes with thietane formation, but the greater nucleophilicity of sulfur dominates, especially if a weak base is used.

In example 2 both aziridine and azetidine formation are possible, but only the former is observed. This is a good example of the kinetic advantage of three-membered ring formation. Example 4 demonstrates that this approach to azetidine formation works well in the absence of competition.

Indeed, the exceptional yield of this product is attributed to the gem-dimethyl substitution, the Thorpe-Ingold effect , which is believed to favor coiled chain conformations.

The relatively rigid configuration of the substrate in example 3, favors oxetane formation and prevents an oxirane cyclization from occurring. Finally, the Paterno-Buchi photocyclizations in examples 5 and 6 are particularly suited to oxetane formation. Reactions Reactions of four-membered heterocycles also show the influence of ring strain.

Some examples are given in the following diagram. In the thietane reaction 2 , the sulfur undergoes electrophilic chlorination to form a chlorosulfonium intermediate followed by a ring-opening chloride ion substitution. Strong nucleophiles will also open the strained ether, as shown by reaction 3b. Example 5 is an interesting case of intramolecular rearrangement to an ortho-ester.

Such electron pair delocalization is diminished in the penicillins, leaving the nitrogen with a pyramidal configuration and the carbonyl function more reactive toward nucleophiles. Preparation Commercial preparation of furan proceeds by way of the aldehyde, furfural, which in turn is generated from pentose containing raw materials like corncobs, as shown in the uppermost equation below. Similar preparations of pyrrole and thiophene are depicted in the second row equations.

Equation 1 in the third row illustrates a general preparation of substituted furans, pyrroles and thiophenes from 1,4-dicarbonyl compounds, known as the Paal-Knorr synthesis.

Many other procedures leading to substituted heterocycles of this kind have been devised. Two of these are shown in reactions 2 and 3. Furan is reduced to tetrahydrofuran by palladium-catalyzed hydrogenation. This cyclic ether is not only a valuable solvent, but it is readily converted to 1,4-dihalobutanes or 4-haloalkylsulfonates, which may be used to prepare pyrrolidine and thiolane.

Dipolar cycloaddition reactions often lead to more complex five-membered heterocycles. Indole is probably the most important fused ring heterocycle in this class. By clicking on the above diagram three examples of indole synthesis will be displayed.

The first proceeds by an electrophilic substitution of a nitrogen-activated benzene ring. The second presumably takes place by formation of a dianionic species in which the ArCH 2 — unit bonds to the deactivated carbonyl group.

Finally, the Fischer indole synthesis is a remarkable sequence of tautomerism, sigmatropic rearrangement , nucleophilic addition, and elimination reactions occurring subsequent to phenylhydrazone formation.

This interesting transformation involves the oxidation of two carbon atoms and the reduction of one carbon and both nitrogen atoms. These units are commonly used as protective groups for aldehydes and ketones, and may be hydrolyzed by the action of aqueous acid. It is the "aromatic" unsaturated compounds, furan, thiophene and pyrrole that require our attention.

This is illustrated by the resonance description at the top of the following diagram. The heteroatom Y becomes sp 2 -hybridized and acquires a positive charge as its electron pair is delocalized around the ring. An easily observed consequence of this delocalization is a change in dipole moment compared with the analogous saturated heterocycles, which all have strong dipoles with the heteroatom at the negative end.

As expected, the aromatic heterocycles have much smaller dipole moments, or in the case of pyrrole a large dipole in the opposite direction. An important characteristic of aromaticity is enhanced thermodynamic stability , and this is usually demonstrated by relative heats of hydrogenation or heats of combustion measurements.

By this standard, the three aromatic heterocycles under examination are stabilized, but to a lesser degree than benzene. Additional evidence for the aromatic character of pyrrole is found in its exceptionally weak basicity pK a ca. The corresponding values for the saturated amine pyrrolidine are: basicity Another characteristic of aromatic systems, of particular importance to chemists, is their pattern of reactivity with electrophilic reagents.

Whereas simple cycloalkenes generally give addition reactions, aromatic compounds tend to react by substitution. As noted for benzene and its derivatives, these substitutions take place by an initial electrophile addition, followed by a proton loss from the "onium" intermediate to regenerate the aromatic ring. The reaction conditions show clearly the greater reactivity of furan compared with thiophene. All these aromatic heterocycles react vigorously with chlorine and bromine, often forming polyhalogenated products together with polymers.

The exceptional reactivity of pyrrole is evidenced by its reaction with iodine bottom left equation , and formation of 2-acetylpyrrole by simply warming it with acetic anhydride no catalyst. Reactions of pyrrole require careful evaluation, since N-protonation destroys its aromatic character. For example, pyrrole reacts with acetic anhydride or acetyl chloride and triethyl amine to give N-acetylpyrrole.

Consequently, the regioselectivity of pyrrole substitution is variable, as noted by the bottom right equation. The intermediate formed by electrophile attack at C-2 is stabilized by charge delocalization to a greater degree than the intermediate from C-3 attack.

From the Hammond postulate we may then infer that the activation energy for substitution at the former position is less than the latter substitution. Functional substituents influence the substitution reactions of these heterocycles in much the same fashion as they do for benzene.

Indeed, once one understands the ortho-para and meta-directing character of these substituents, their directing influence on heterocyclic ring substitution is not difficult to predict. The following diagram shows seven such reactions. The third reaction has two substituents of different types in the 2 and 5-positions.

Finally, examples 4 through 7 illustrate reactions of 1,2- and 1,3-oxazole, thiazole and diazole. Note that the basicity of the sp 2 -hybridized nitrogen in the diazoles is over a million times greater than that of the apparent sp 3 -hybridized nitrogen, the electron pair of which is part of the aromatic electron sextet. Other possible reactions are suggested by the structural features of these heterocycles. For example, furan could be considered an enol ether and pyrrole an enamine.

Such functions are known to undergo acid-catalyzed hydrolysis to carbonyl compounds and alcohols or amines. Since these compounds are also heteroatom substituted dienes, we might anticipate Diels-Alder cycloaddition reactions with appropriate dienophiles. These possibilities will be illustrated above by clicking on the diagram. As noted in the upper example, furans may indeed be hydrolyzed to 1,4-dicarbonyl compounds, but pyrroles and thiophenes behave differently.

The second two examples, shown in the middle, demonstrate typical reactions of furan and pyrrole with the strong dienophile maleic anhydride. The former participates in a cycloaddition reaction; however, the pyrrole simply undergoes electrophilic substitution at C Thiophene does not easily react with this dienophile.

The pyrrole compound on the left is essentially unreactive, as expected for an amide, but additional nitrogens markedly increase the rate of hydrolysis.

This effect has been put to practical use in applications of the acylation reagent 1,1'-carbonyldiimidazole Staab's reagent. Another facet of heterocyclic chemistry was disclosed in the course of investigations concerning the action of thiamine following diagram. As its pyrophosphate derivative, thiamine is a coenzyme for several biochemical reactions, notably decarboxylations of pyruvic acid to acetaldehyde and acetoin.

Early workers speculated that an "active aldehyde" or acyl carbanion species was an intermediate in these reactions. Many proposals were made, some involving the aminopyrimidine moiety, and others, ring-opened hydrolysis derivatives of the thiazole ring, but none were satisfactory. This puzzle was solved when R.

Breslow Columbia found that the C-2 hydrogen of thiazolium salts was unexpectedly acidic pK a ca. As shown, this rationalizes the facile decarboxylation of thiazoliumcarboxylic acids and deuterium exchange at C-2 in neutral heavy water.

Appropriate thiazolium salts catalyze the conversion of aldehydes to acyloins in much the same way that cyanide ion catalyzes the formation of benzoin from benzaldehyde, the benzoin condensation.

By clicking on the diagram , a new display will show mechanisms for these two reactions. Note that in both cases an acyl anion equivalent is formed and then adds to a carbonyl function in the expected manner. The benzoin condensation is limited to aromatic aldehydes, but the use of thiazolium catalysts has proven broadly effective for aliphatic and aromatic aldehydes.

This approach to acyloins employs milder conditions than the reduction of esters to enediol intermediates by the action of metallic sodium.

The most important condensed ring system related to these heterocycles is indole. Some electrophilic substitution reactions of indole are shown in the following diagram.

Whether the indole nitrogen is substituted or not, the favored site of attack is C-3 of the heterocyclic ring. Bonding of the electrophile at that position permits stabilization of the onium-intermediate by the nitrogen without disruption of the benzene aromaticity.

These units are commonly used as protective groups for aldehydes and ketones, as well as synthetic intermediates, and may be hydrolyzed by the action of aqueous acid. The reactivity of partially unsaturated compounds depends on the relationship of the double bond and the heteroatom e.

Fully unsaturated six-membered nitrogen heterocycles, such as pyridine, pyrazine, pyrimidine and pyridazine, have stable aromatic rings. Oxygen and sulfur analogs are necessarily positively charged, as in the case of 2,4,6-triphenylpyrylium tetrafluoroborate. The resonance description drawn at the top of the following diagram includes charge separated structures not normally considered for benzene. The greater electronegativity of nitrogen relative to carbon suggests that such canonical forms may contribute to a significant degree.

WordPress Shortcode. Published in: Education. Full Name Comment goes here. Are you sure you want to Yes No. Siddharth Jain , School of pharmacy davv indore. Show More. No Downloads. Views Total views. Actions Shares. Embeds 0 No embeds. No notes for slide. Heterocyclic compounds bascis of nomenclature 1. Quin and John A. Tyrell 4. Ring size is designated by stems that follow the prefix: 3- atoms,-ir-; 4-atoms, -et-; 5-atoms, -ol-; 6-atoms, -in-; 7- atoms, -ep-;8-atoms, -oc-; 9-atoms, -on-; and so on.

If fully unsaturated, the name is concluded with a suffix for ringsize: 3-atoms, -ene except -ine- for N ; 4-, 5-, and 6- atoms, -e;7-, 8-, and 9- atoms, -ine. If fully saturated, the suffix is -ane for all ring sizes, except forN, which uses -idine for rings of 3-, 4-, or 5-atoms, and for 6-atoms, a prefix of hexahydro- is used. Also, the name oxane, notoxinane, is used for the 6-membered ring with O present. Corresponding to the no.

Each heteroatom is then given a number as found in the ring, with that of highest priority given position 1. After the name is established, the ring atoms are given new numbers for the entire bicycle. Heterocyclic compounds Benzo-fused rings These need not be in numerical order.

Nomenclature of heterocyclic (secound year)

Heterocyclic Chemistry. Compounds classified as heterocyclic probably constitute the largest and most varied family of organic compounds. After all, every carbocyclic compound, regardless of structure and functionality, may in principle be converted into a collection of heterocyclic analogs by replacing one or more of the ring carbon atoms with a different element. Even if we restrict our consideration to oxygen, nitrogen and sulfur the most common heterocyclic elements , the permutations and combinations of such a replacement are numerous.

Devising a systematic nomenclature system for heterocyclic compounds presented a formidable challenge, which has not been uniformly concluded. Many heterocycles, especially amines, were identified early on, and received trivial names which are still preferred. Some monocyclic compounds of this kind are shown in the following chart, with the common trivial name in bold and a systematic name based on the Hantzsch-Widman system given beneath it in blue.

The rules for using this system will be given later. For most students, learning these common names will provide an adequate nomenclature background. An easy to remember, but limited, nomenclature system makes use of an elemental prefix for the heteroatom followed by the appropriate carbocyclic name.

A short list of some common prefixes is given in the following table, priority order increasing from right to left. The Hantzsch-Widman system provides a more systematic method of naming heterocyclic compounds that is not dependent on prior carbocyclic names. It makes use of the same hetero atom prefix defined above dropping the final "a" , followed by a suffix designating ring size and saturation.

As outlined in the following table, each suffix consists of a ring size root blue and an ending intended to designate the degree of unsaturation in the ring. In this respect, it is important to recognize that the saturated suffix applies only to completely saturated ring systems , and the unsaturated suffix applies to rings incorporating the maximum number of non-cumulated double bonds. Systems having a lesser degree of unsaturation require an appropriate prefix, such as "dihydro"or "tetrahydro".

Despite the general systematic structure of the Hantzsch-Widman system, several exceptions and modifications have been incorporated to accommodate conflicts with prior usage. Examples of these nomenclature rules are written in blue, both in the previous diagram and that shown below.

Note that when a maximally unsaturated ring includes a saturated atom, its location may be designated by a " H " prefix to avoid ambiguity, as in pyran and pyrrole above and several examples below. When numbering a ring with more than one heteroatom, the highest priority atom is 1 and continues in the direction that gives the next priority atom the lowest number. All the previous examples have been monocyclic compounds.

Polycyclic compounds incorporating one or more heterocyclic rings are well known. A few of these are shown in the following diagram. As before, common names are in black and systematic names in blue. The two quinolines illustrate another nuance of heterocyclic nomenclature. Thus, the location of a fused ring may be indicated by a lowercase letter which designates the edge of the heterocyclic ring involved in the fusion, as shown by the pyridine ring in the green shaded box.

Heterocyclic rings are found in many naturally occurring compounds. Most notably, they compose the core structures of mono and polysaccharides , and the four DNA bases that establish the genetic code.

By clicking on the above diagram some other examples of heterocyclic natural products will be displayed. Oxiranes epoxides are the most commonly encountered three-membered heterocycles. Epoxides are easily prepared by reaction of alkenes with peracids, usually with good stereospecificity. Because of the high angle strain of the three-membered ring, epoxides are more reactive that unstrained ethers. Addition reactions proceeding by electrophilic or nucleophilic opening of the ring constitute the most general reaction class.

Example 1 in the following diagram shows one such transformation, which is interesting due to subsequent conversion of the addition intermediate into the corresponding thiirane. The initial ring opening is stereoelectronically directed in a trans-diaxial fashion, the intermediate relaxing to the diequatorial conformer before cyclizing to a 1,3-oxathiolane intermediate. Other examples show similar addition reactions to thiiranes and aziridines.

The acid-catalyzed additions in examples 2 and 3, illustrate the influence of substituents on the regioselectivity of addition. Example 2 reflects the S N 2 character of nucleophile chloride anion attack on the protonated aziridine the less substituted carbon is the site of addition.

The phenyl substituent in example 3 serves to stabilize the developing carbocation to such a degree that S N 1 selectivity is realized. The reduction of thiiranes to alkenes by reaction with phosphite esters example 6 is highly stereospecific, and is believed to take place by an initial bonding of phosphorous to sulfur.

By clicking on the above diagram , four additional example of three-membered heterocycle reactivity or intermediacy will be displayed. Examples 7 and 8 are thermal reactions in which both the heteroatom and the strained ring are important factors. Note that two inversions of configuration at C-2 result in overall retention. Many examples of intramolecular interactions , such as example 10, have been documented.

As illustrated below, acid and base-catalyzed reactions normally proceed by 5-exo-substitution reaction 1 , yielding a tetrahydrofuran product. However, if the oxirane has an unsaturated substituent vinyl or phenyl , the acid-catalyzed opening occurs at the allylic or benzylic carbon reaction 2 in a 6-endo fashion.

Preparation Several methods of preparing four-membered heterocyclic compounds are shown in the following diagram. The simple procedure of treating a 3-halo alcohol, thiol or amine with base is generally effective, but the yields are often mediocre.

Dimerization and elimination are common side reactions, and other functions may compete in the reaction. In the case of example 1, cyclization to an oxirane competes with thietane formation, but the greater nucleophilicity of sulfur dominates, especially if a weak base is used. In example 2 both aziridine and azetidine formation are possible, but only the former is observed.

This is a good example of the kinetic advantage of three-membered ring formation. Example 4 demonstrates that this approach to azetidine formation works well in the absence of competition. Indeed, the exceptional yield of this product is attributed to the gem-dimethyl substitution, the Thorpe-Ingold effect , which is believed to favor coiled chain conformations. The relatively rigid configuration of the substrate in example 3, favors oxetane formation and prevents an oxirane cyclization from occurring.

Finally, the Paterno-Buchi photocyclizations in examples 5 and 6 are particularly suited to oxetane formation. Reactions Reactions of four-membered heterocycles also show the influence of ring strain. Some examples are given in the following diagram. In the thietane reaction 2 , the sulfur undergoes electrophilic chlorination to form a chlorosulfonium intermediate followed by a ring-opening chloride ion substitution.

Strong nucleophiles will also open the strained ether, as shown by reaction 3b. Example 5 is an interesting case of intramolecular rearrangement to an ortho-ester. Such electron pair delocalization is diminished in the penicillins, leaving the nitrogen with a pyramidal configuration and the carbonyl function more reactive toward nucleophiles.

Preparation Commercial preparation of furan proceeds by way of the aldehyde, furfural, which in turn is generated from pentose containing raw materials like corncobs, as shown in the uppermost equation below. Similar preparations of pyrrole and thiophene are depicted in the second row equations. Equation 1 in the third row illustrates a general preparation of substituted furans, pyrroles and thiophenes from 1,4-dicarbonyl compounds, known as the Paal-Knorr synthesis. Many other procedures leading to substituted heterocycles of this kind have been devised.

Two of these are shown in reactions 2 and 3. Furan is reduced to tetrahydrofuran by palladium-catalyzed hydrogenation. This cyclic ether is not only a valuable solvent, but it is readily converted to 1,4-dihalobutanes or 4-haloalkylsulfonates, which may be used to prepare pyrrolidine and thiolane. Dipolar cycloaddition reactions often lead to more complex five-membered heterocycles. Indole is probably the most important fused ring heterocycle in this class.

By clicking on the above diagram three examples of indole synthesis will be displayed. The first proceeds by an electrophilic substitution of a nitrogen-activated benzene ring.

The second presumably takes place by formation of a dianionic species in which the ArCH 2 — unit bonds to the deactivated carbonyl group. Finally, the Fischer indole synthesis is a remarkable sequence of tautomerism, sigmatropic rearrangement , nucleophilic addition, and elimination reactions occurring subsequent to phenylhydrazone formation. This interesting transformation involves the oxidation of two carbon atoms and the reduction of one carbon and both nitrogen atoms.

These units are commonly used as protective groups for aldehydes and ketones, and may be hydrolyzed by the action of aqueous acid. It is the "aromatic" unsaturated compounds, furan, thiophene and pyrrole that require our attention. This is illustrated by the resonance description at the top of the following diagram. The heteroatom Y becomes sp 2 -hybridized and acquires a positive charge as its electron pair is delocalized around the ring. An easily observed consequence of this delocalization is a change in dipole moment compared with the analogous saturated heterocycles, which all have strong dipoles with the heteroatom at the negative end.

As expected, the aromatic heterocycles have much smaller dipole moments, or in the case of pyrrole a large dipole in the opposite direction.

An important characteristic of aromaticity is enhanced thermodynamic stability , and this is usually demonstrated by relative heats of hydrogenation or heats of combustion measurements. By this standard, the three aromatic heterocycles under examination are stabilized, but to a lesser degree than benzene.

Additional evidence for the aromatic character of pyrrole is found in its exceptionally weak basicity pK a ca. The corresponding values for the saturated amine pyrrolidine are: basicity Another characteristic of aromatic systems, of particular importance to chemists, is their pattern of reactivity with electrophilic reagents.

Whereas simple cycloalkenes generally give addition reactions, aromatic compounds tend to react by substitution. As noted for benzene and its derivatives, these substitutions take place by an initial electrophile addition, followed by a proton loss from the "onium" intermediate to regenerate the aromatic ring. The reaction conditions show clearly the greater reactivity of furan compared with thiophene. All these aromatic heterocycles react vigorously with chlorine and bromine, often forming polyhalogenated products together with polymers.

The exceptional reactivity of pyrrole is evidenced by its reaction with iodine bottom left equation , and formation of 2-acetylpyrrole by simply warming it with acetic anhydride no catalyst. Reactions of pyrrole require careful evaluation, since N-protonation destroys its aromatic character.

For example, pyrrole reacts with acetic anhydride or acetyl chloride and triethyl amine to give N-acetylpyrrole. Consequently, the regioselectivity of pyrrole substitution is variable, as noted by the bottom right equation. The intermediate formed by electrophile attack at C-2 is stabilized by charge delocalization to a greater degree than the intermediate from C-3 attack.

From the Hammond postulate we may then infer that the activation energy for substitution at the former position is less than the latter substitution. Functional substituents influence the substitution reactions of these heterocycles in much the same fashion as they do for benzene. Indeed, once one understands the ortho-para and meta-directing character of these substituents, their directing influence on heterocyclic ring substitution is not difficult to predict.