bluuebunny/crossref_metadata_2025 huggingface dataset:
The Amination of Heterocyclic Bases by Alkali Amides*The Chichibabin Reactions.
Authors: Leffler Marlin T.
Published: March 2011

Heterocyclic bases such as pyridine and quinoline and their derivatives react with metal amides to yield amino derivatives. For example, pyridine is converted to 2‐aminopyridine by the action of sodium amide; an intermediate metal derivative is formed, and this is hydrolyzed to the free amine. It has been suggested that the initial step in the reaction is the addition of the metal amide to the CHNgroup; the resulting product is then transformed to the metal derivative of the amine, either through intramolecular rearrangement or through decomposition to the amino compound and sodium hydride to give the metal derivative.
ThePerkin Reaction and Related Reactions
Authors: Johnson John R.
Published: March 2011

In 1868, W. H. Perkin described a synthesis of coumarin by heating the sodium salt of salicyaldehyde with acetic acid. Further study led to a new discovery for preparing cinnamic acid and its analogs by means of a synthesis of very general application, which became know as the Perkin reaction. In the course of study of unsaturated acids, Fittig made several important contributions to the mechanism of the Perkin reaction. Many studies have been made regarding this reaction and are described. The Perkin reaction may be regarded essential as the condensation of a carbonyl component A and an acid and dihydride‐salt combination B. The discussion here is a survey of the types of carbonyl components and acid anhydride salt combinations that can be used and of the yields obtained under favorable conditions.
The
F
ries Reaction
Authors: Blatt A. H.
Published: March 2011

The Fries reaction consists in the conversion of an ester of a phenol to an ortho‐ or para‐hydroxyketone, or a mixture of both, by treatment with aluminum chloride. Three different mechanisms for the fries rearrangement have received serious consideration.: the ester is assumed to react with aluminum chloride to give an acid chloride and a phenoxyaluminum chloride which combine to form a derivative of the hydroxyketone; one molecule of the phenyl ester is acylated by another molecule; the Fries reaction is considered ti be a true intramolecular rearrangement in which the acyl group shifts directly from the oxygen atom to the carbon atom of the ring.
TheClaisen Rearrangement
Authors: Tarbell D. Stanley
Published: March 2011

Allyl ethers of enols and phenols undergo rearrangement to C‐allyl derivatives when heated to sufficiently high temperatures. The reaction, named after its discoverer (Claisen, 1912) was first observed when ethylO‐allylacetonacetate was subjected to distillation at atmospheric pressure in the presence of ammonium chloride. The allyl ethers of phenols rearrange smoothly at temperatures of about 200°C in the absence of catalysts, Allyl ethers ofortho‐disubstituted phenols rearrange to the correspondingp‐allyphenols. The only known example of para rearrangement accompanied by inversion is the reaction of alpha‐ethylallyl 2‐carbomethoxy‐6‐methylphenyl ether. These rearrangements are discussed in detail.
The Preparation of Aliphatic Fluorine Compounds
Authors: Henne Albert L.
Published: March 2011

Reactions of four types have been used for introducing fluorine atoms in to aliphatic molecules. These are listed below in the order of their practical importance at the present time.

Interaction of organic halides or polyhalides with inorganic fluorides

Addition of hydrogen fluoride to olefins and acetylene

Direct fluorination of saturated compounds or additions of fluorine to unsaturated compounds

Replacement of the hydroxyl group of alcohols.

These reactions are discussed in this chapter.
TheCannizzaro Reaction
Authors: Geissman T. A.
Published: March 2011

The reaction in which two aldehyde groups are transformed into the corresponding hydroxyl and carbonyl functions, existing separately or in combination as an ester, has been termed the Cannizzaro reaction. Here the discussion is restricted to the dismutation of two similar aldehyde groups into the corresponding alcohol and carboxylic salt function by means of aqueous or alcoholic and alkali. The conversion of benzaldehyde into a mixture of benzyl alcohol and sodium benzoate is an example.
Reduction with Aluminum Alkoxides
Authors: Wilds A. L.
Published: March 2011

Verley and Meerwein and Schmidt discovered independently that an aldehyde can be reduced to the primary alcohol by treatment with aluminum ethoxide in the presence of ethanol. The reduction of the aldehyde occurs at the expense of an equivalent amount of ethanol which is oxdized to acetaldehyde. The reaction is reversible, but the equilibrium can be shifted to the point of complete reduction by removal of the acetaldehyde with a stream of hydrogen or nitrogen. This has the additional advantage of preventing side reactions such as aldol condensation between the original aldehdye and acetaldehyde. This method of reduction with aluminum chloride was found applicable to several aldehydes, but to only a few ketones of special types. This mild and specific method of reducing carbonyl compounds became know as the Meerwein‐Ponndorf‐Verley reduction Lund later studied the scope and limitations of the reaction.
The Willgerodt Reaction
Authors: Carmack Marvin , Spielman M. A.
Published: March 2011

The name of Conrad Willgerodt is associated with a group of closely related reactions which have a common feature the conversion of a carbonyl compound into an amide with the same number of carbon atoms. The original process involved the reaction of an appropriately substituted alkyl aryl ketone with an aqueous solution of yellow ammonium polysulfide at an elevated temperature to form an aryl‐substituted aliphatic acid amide, together with a smaller amount of the corresponding ammonium salt of the carboxylic acid. The Kindler variation promises to be more useful. It consists of heating a ketone with approximately equimolecular amounts of sulfur and dry amine.
Azlactones
Authors: Carter H. E.
Published: March 2011

Azlactones may be considered the anhydrides of alpha‐acylamino acids. It is convenient to classify them into two groups, saturated and unsaturated, since the two types show characteristic differences in properties, Azlactones have been of interest mainly as intermediates in the synthesis of other compounds. Saturated azlactones are obtained most often from the corresponding amino acids used in preparing derivatives of those amino acids. Unsaturated azlactones, on the other hand, usually are prepared by condensing an aldehyde with an acylglycine and are used in the synthesis of the corresponding amino and keto acids. Four methods by which azlactones are prepared are discussed in this chapter.
Substitution and Addition Reactions of Thiocyanogen*Present address, School of Biological Sciences, The Medical School, University of Tennessee, Memphis, Tenn.
Authors: Wood John L.
Published: March 2011

The direct replacement of a hydrogen atom by a thiocyano group through the use of thiocyanogen is termed thiocyanation. This replacement reaction is limited practically to aromatic amines and phenols. Thiocyanogen reacts with olefinic and acetylenic linkage, the reagent adding to the unsaturated linkage. Thicyanogen reacts with compounds of other types. Thiocyanogen reacts with aromatic compounds that are highly susceptible to substitution with the introduction of a thiocyano groups. Thiocyanation of aromatic amines, phenols is discussed. Addition of thiocyanogen to olefins and acetylenes, and miscellaneous syntheses are also discussed.
The Preparation of Amines by Reductive Alkylation
Authors: Emerson William S.
Published: March 2011

Reductive alkylation is the term applied to the process of introducing alkyl groups into ammonia or primary or secondary amine by means of an aldehdye or ketone in the presence of a reducing agent. This chapter is limited to those reductive alkylations in which the reducing agent is hydrogen and a catalysts or nascent hydrogen, usually from a metal‐acid combination; most of these reductive alkylations have been carried out with hydrogen and a catalyst.
The Acyloins
Authors: McElvain S. M.
Published: March 2011

Acyloins arre alpha‐hydroxy ketones of the general formula, RCHOHCOR, in which R represents an aliphatic analog of benzoins. The term acyloin is commonly used as a class name for the symmetrical keto alcohols and the name of the individual compound is derived by adding the suffix “oin” to the stem name of the acid to which the acyloin corresponds, e.g., acetoin, butyoin, etc. The commonest method of preparation of those acyloins in which the alkyl groups are identical is the reaction of sodium with esters of aliphatic acids in inert solvents. Salts of enediols are produced in this reaction. Other methods of preparation are discussed.
The Synthesis of Acetylenes
Authors: Jacobs Thomas L.
Published: March 2011

Many advances have been made in recent years in the methods for the synthesis of acetylenes and many compounds are now rather readily available in the pure state. Acetylene was first prepared by Davy, who treated acetylide with water. Propyne, the first substituted acetylene was obtained in 1861. At the present time alkynes are usually synthesized by the alkylation of sodium acetylide or substituted metallic acetylides, often in liquid ammonia and 1‐Alkynes are also obtained by dehydrohalogenation of suitable halides with sodium amide or in certain cases by ethanolic alkali. The present discussion will be limited to methods for the creation of a carbon‐carbon triple bond and to the alkylation of metallic acetylides.
The
D
iels‐
A
lder Reaction Quinones and Other Cyclenones*Present address, Chemistry Branch, Office of Naval Research.
Authors: Butz Lewis W. , Rytina Anton W.
Published: March 2011

Quinones and other cyclenones react by 1,4‐addition with conjugated dienes. A typical example is the reaction of butadiene with
p
‐benzoquinone yielding the diketohexahydronaphthalene. The direct synthesis of quinones with other cyclenones may be extended to provide a route to the preparation of fused‐ring aromatic systems. It is also possible to prepare fused‐ring ketones containing angular substituents. Diene syntheses described in this chapter may lead to the synthesis of compounds of steroidal structure. The stereochemcial configurations of Diels‐Alder addition products have been discussed elsewhere in this series, This problem is exceedingly complex with products described in this chapter and is impossible to predict stereochemical configurations of the adducts with any certainty.
The Leuckart Reaction
Authors: Moore Maurice L.
Published: March 2011

The Leuckart reaction is a process for reductive alkylation of ammonia or primary or secondary amines by certain aldehdyes and ketones, It is distinguished by the fact that the reduction is accomplished by formic acid or a derivative of formic acid and should be compared with reductive alkylation discussed elsewhere in this series. The reaction is carried out by heating a mixture of the carbonyl compound and the formic acid salt or formyl derivative of ammonia or the amine. Primary and secondary amines produced in the reaction often are obtained as the formyl derivatives and must be recovered by hydrolysis; tertiary amines are obtained as formate. Modifications of this reaction are discussed.
TheDarzens Glycidic Ester Condensation
Authors: Newman Melvin S. , Magerlein Barney J.
Published: March 2011

The Darzens glycidic ester condensation involves the condensation of an aldehdye and a ketone with an alpha‐halo ester to produce an alpha,beta‐epoxy ester (glycidic ester). The most frequently used condensing agents are sodium ethoxide and sodium amide. The glycidic esters are of interest primarily because they can be converted into aldehydes and ketones having a higher carbon content than the original aldehydes or ketones. This transformation occurs after hydrolysis to and decarboxylation of the epoxy acid and is accompanied by rearrangement when an aldehyde if formed. Darzens described another procedure which involves the reaction of aldehdyes and ketones with ethyl dichloracetate and dilute magnesium amalgam. Mechanisms of these reactions are discussed.
The Synthesis of Phosphonic and Phosphinic Acids
Authors: Kosolapoff Gennady M.
Published: March 2011

The phosphonic acids and the phosphinic acids may be regarded as derivatives of phosphoric acid in which one or two hydroxyls are replaced by organic radicals. Although individual phosphonic and phosphinic acids have been known for several decades, the syntheses of these two classes of compounds have not been well developed. This chapter is concerned only with the introduction of phosphorus‐containing functions, i.e, the synthesis of acids or their functional derivatives, which can be isolated and hydrolyzed to the acids.
The Preparation of Thiophenes and Tetrahydrothiophenes
Authors: Wolf Donald E. , Folkers Karl
Published: March 2011

Thiophenes and tetrahydrothiophenes are discussed as separate major divisions in this chapter because there are significant differences in the general methods by which these two similar types of compounds are prepared. The general reactions that lead to the formation of thiophenes may be segregated in the following five general classifications (1) Reaction of the 1,4‐difunctional compounds with sulfides; (2) reaction of unsaturated compounds with sulfides; (3) reaction of 1,2‐difunctional compounds with thiodiacetic acid and esters; (4) reaction of aryl methyl ketones with sulfides; (5) miscellaneous cyclization reactions. Similarly the reactions that form tetrahydrothiophenes may be grouped into four general classifications: (1) Reaction of 1,4‐difunctional compounds with sulfides; (2) Dieckmann cyclization; (3) Catalytic method; (4) miscellaneous methods. All of the above are discussed in this chapter.
Carbon‐Carbon Alkylations with Amines and Ammonium Salts
Authors: Brewster James H. , Eliel Ernest L.
Published: March 2011

This chapter is a review of those reactions of compounds containing labile amino groups in which a carbon‐carbon bond is formed by amine replacement as, for example, in the alkylation of diethyl malonate by 1‐dimethylamino‐3‐butanone. Attention has been given primarily to reactions of amines prepared by the Mannich reaction (Mannich bases), but for comparison, analogous reactions of simpler quaternary ammonium salts have been included.
ThevonBraun Cyanogen Bromide Reaction
Authors: Hageman Howard A.
Published: March 2011

The reaction of a tertiary amine with cyanogen bromide was first described in 1900 by Julius von Braun who elaborated the reaction to such an extent that it bears his name. Generally, a tertiary amine reacts with cyanogen bromide to yield an alkyl bromide and a disubstituted cyanamide. The direct conversion of secondary amines to disubstituted cyanamides with cyanogen bromide proceeds in low yield because some of the amine is converted to its hydrobromide. The material in this chapter is limited to a discussion of the reaction of tertiary amines with cyanogen bromide.
The Nitrosation of Aliphatic Carbon Atoms
Authors: Touster Oscar
Published: March 2011

The nitrosation reaction consists in the replacement of a hydrogen atom by the nitroso group with the formation of a nitroso or oximo derivative. With a few exceptions, the replacement of hydrogen on an aliphatic carbon atom requires the presence of an electron‐attracting groups adjacent to the carbon to be nitrosated. Acyl, aroyl, carbonyl, carboxy, carbalkoxyl, nitrogen, cyano, imino, and aryl groups may serve as activators. Monoketones are readily converted into alpha‐oximino ketones, whereas monoesters containing no other activating groups do not undergo the reaction. Victor Meyer discovered the reaction in 1873–1874.
The Synthesis of Ketones from Acid Halides and Organometallic Compounds of Magnesium, Zinc, and Cadmium
Authors: Shirley David A.
Published: March 2011

The synthesis of ketones from acid halides and organometallic compounds may be represented by the following equation:imageFreund fist observed the formation of ketones from simple acid chlorides and dimethyl‐ and diethyl‐zinc. Organometallic compounds of sodium, copper, magnesium, cadmium, mercury, aluminum, tin, and lead have also been found to give this reaction. Only organozinc, organocadmium, and organomagnesium reagents have been found to be generally useful for such syntheses, however. These reactions are reviewed in this chapter.
β‐Lactones
Authors: Zaugg Harold E.
Published: March 2011

β‐lactones contain a strained four membered heterocyclic ring. Consequently, they differ from the gamma and delta‐lactones both in the general methods available for their preparation and their chemical reactivity. Because of their high order of reactivity, only those β‐lactones with favorable physical properties can be isolated readily in pure form. The highly reactive β‐lactones are customarily prepared in order to transform them into other products. This chapter will consider, first the preparation of β‐lactones, and second, their reactions of synthesis value.
The Reaction of Diazomethane and its Derivatives with Aldehydes and Ketones
Authors: Gutsche C. David
Published: March 2011

Diazomethane and its derivatives react with aldehdyes and ketones usually under very mild conditions to yield a variety of interesting and often useful products. The reaction is most often carried out by either allowing the carbonyl compound to react with an ethereal solution of the diazomethane derivative with or without the addition of a catalyst, or by treating a methanol solution of the carbonyl compound with a nitrosoalkylurethane in the presence of a base, Only the reactions of diazomethane and its alkyl and aryl derivatives are discussed in detail.
TheGattermann Synthesis of Aldehydes
Authors: Truce WIlliam E.
Published: March 2011

Gatterman developed two methods for introducing the aldehdye group into aromatic compounds. The first of these known as the Gatterman Koch reaction uses a mixture of carbon monoxide and hydrogen chloride in the presence of a mixture of anhydrous aluminum chloride and cuprous chloride. It is not adaptable to the preparation of aldehydes from phenols or phenolic ethers, however. The second method employs a mixture of hydrogen cyanide and hydrogen chloride with or without a catalyst and permits the introduction of an aldehdye group into phenols, naphthols, and their ethers under special conditions into aromatic hydrocarbons and related compounds. This chapter is concerned with the second method. The mechanism of the reaction appears to be complex and has not been fully elucidated. Details on the scope, limitations and alternative methods, as well as experimental tests, are detailed.
TheBaeyer‐VilligerOxidation of Aldehydes and Ketones
Authors: Hassall C. H.
Published: March 2011

In 1899, Bayer and Vlliger showed that the oxidation of alicyclic ketones, menthone, tetrahydrocarvone, and camphor with permono‐sulfuric acid led to the formation of lactones. Further studies using a variety of ketones or aldehydes and hydrogen peroxide or peracids in various media have established that the oxidation is of wide applicability. The oxidation, the Baeyer‐Villiger reaction, is the subject of this review. As the oxidation normally employs mild conditions, gives reasonable yields, and shows a high degree of selectivity, it has proved useful in a variety of both synthetic and degradative studies. Recent investigations have led to a better definition of favorable experimental conditions and have extended the scope of the reaction.
The Reaction of Halogens with Silver Salts of Carboxylic Acids
Authors: Wilson C.V.
Published: March 2011

The action of halogens with dry metallic salts, particularly silver salts of carboxylic acids has merited earlier reviews. It has been pointed out that the halogen used, the ratio of silver salt to halogen, and the presence or absence of other active materials, such as olefins, acetylenes, or readily substituted aromatic rings plays a determining the course of the reactions. Thus it is possible to produce an organic halide containing one less carbon atom than the original acid; esters derived from two molecules of the acid by the loss of one molecule of carbon dioxide; esters of 1,2‐diols or halohydrins; halogenated aromatic compounds; and halogenated acetylenes. These reactions are the subject of this chapter.
ThePschorr Synthesis and Related Diazonium Ring Closure Reactions
Authors: DeTar DeLos F.
Published: March 2011

In the middle 1890s, three groups of chemists independently discovered a new cyclization reaction of certain appropriately constituted diazonium salts. Fischer and Schmidt reported that an aqueous solution of 2‐benzylbenzenediazonium chloride furnished fluorene on heating. Graebe and Ullman reported that 2‐benzoylbenzenediazonium chloride yielded fluorenone and Staedel reported a somewhat similar result from the action of nitrous acid on 2,2'‐diaminbenozpehnone, a reaction that produced a little 1‐hydroxyfluorenone. Two years later, Robert Pschorr applied the ring closure reaction to the diazonium salt derived from trans‐2‐amino‐alpha‐phenylcinnamic acid to obtain phenanthrene‐9‐carboxylic acid. The principal utility of these cyclizations reactions has been the synthesis of substituted ring structures in which the positions of the substituents are known.
The Coupling of Diazonium Salts with Aliphatic Carbon Atoms
Authors: Parmerter Stanley M.
Published: March 2011

A diazonium salt will couple with an aliphatic compound containing an activated carbon‐hydrogen bond. This discussion is limited to those reactions in which both the nitrogen atoms of the diazonium salts are retained in the resulting molecule. The discussion is further limited by the exclusion of coupling reactions, which occur with the elimination of a group from an activated methinyl compound, the Japp‐Klingemann reaction. These reactions are discussed in Chapter 2. Much of the early work with coupling was prompted by the desire to determine whether the products were of the azo or hydrazonestructure. It is difficult to establish the structures in such cases where the tautomeric forms are possible. It is generally considered that the hydrazone is the stable form.
The Japp‐Klingemann Reaction
Authors: Phillips Robert R
Published: March 2011

In an attempt to prepare an azo ester by coupling benzendiazonium chloride with ethyl‐2‐methylacetoacetate, Japp and Klingemann obtained a product, which was soon recognized as the phenylhydrazone of ethyl pyruvate. It thus appears that the acetyl group is displaced, actually the coupling product was unstable under the conditions of its formation, undergoing hydrolytic scission of the acetyl group and rearrangement of the azo structure. It was later discovered that, if the substituted acetoacetic ester was saponified and the cocoupling carried out on the sodium salt, the carboxylic function rather than the acetyl group, was lost and the product isolated was the phenylhydrazone of biacetyl. This reaction was extended to other systems containing methinyl groups.
TheMichael Reaction*This cooperative study was begun when the three authors were working at the Weizmann Institute of Science, Rehovoth.
Authors: Bergmann Ernst D. , Ginsburg David , Pappo Raphael
Published: March 2011

The Michael condensation in its original scope is the addition of an addend or donor containing an alpha‐hydrogen atom in the system OCCH to a carbon‐carbon double bond that forms part of a conjugated system of the general formula CCCO in an acceptor. The condensation takes place under the influence of alkaline reagents, typically alkali metal alkoxides. The range of addends is very broad. Typical acceptors are alpha, beta‐unsaturated aldehydes, keotnes, and acid derivatives. As an extension of the original scope, the Michael condensation has come to be understood to include addends and acceptors activated by groups other than carbonyl and carboxalkoxy. The wider scope is encompassed in this survey.
TheFavorskiĭ Rearrangement of Haloketones
Authors: Kende Andrew S.
Published: March 2011

The Favorskii rearrangement is the skeletal rearrangement of a alpha‐halogenated ketones in the presence of certain nucleophilic bases, such as hydroxides, alkoxides, or amines to give carboxylic acid salts, esters or amides, respectively. Monohaloketones undergo the reaction to yield derivatives of saturated acids having the same number of carbon atoms. In a similar manner, suitable dihaloketiones produce unsaturated carboxylic acids. Analogous rearrangements of trihaloketones can give rise to unsaturated halo acids. The Favorskii reaction has found application for the preparation of highly branched acyclic carboxylic acids. It is a preferred route to various 1‐cycloalkanecarboxylic acids and provides a direct method for ring contraction in simple alicyclic systems and in steroids.
Cyclobutane Derivatives from Thermal Cycloaddition Reactions*Contribution No. 2488 from the Gates and Crellin Laboratories of Chemistry. Supported in part by the National Science Foundation.
Authors: Roberts John D. , Sharts Clay M.
Published: March 2011

Preparation of substituted cyclobutanes and cyclobutenes by cyclo‐addition reactions of alkene and alkyne has become an important synthetic reaction and where applicable is the method of choice for four‐membered carbon ring compounds. Such cycloadditons may be achieved thermally under autogeneous pressure in the presence of free‐radical inhibitors or photochemically by irradiation with visible or ultraviolet light. The establishment of cyclobutane structure proved an example of waxing and waning in the interpretation of organic reactions. Many studies were done and they are discussed. A breakthrough came with the discovery by DuPont that octafluorocyclobutane can be formed readily by thermal dimerization of tetrafluoroethylene. Several developments followed. The cycloaddition illustrates two important points. First, fluorinated alkenes may add to non‐fluorinated unsaturated compounds much more readily than they dimerize. Second, when fluorinated alkenes are given a choice between four‐ and six‐membered rings, as is possible with a conjugated diene, the formation of the four‐membered ring is favored. This chapter gives information on the various studies done on this reaction, The scope, limitations, and comparison of added reactivities are detailed.
The Synthesis of Aliphatic and Alicyclic Nitro Compounds
Authors: Kornblum Nathan
Published: March 2011

This chapter is concerned with the synthesis of nitro compounds in which the nitro group is on a saturated carbon atom. The most important methods available are as follows: 1. Treatment of alkyl halides with silver nitrite; 2. Reaction of allyl bromides and iodides with sodium nitrite; 3. Oxidation of amines; 4. Oxidation of oximes; 5. Nitration of active methylene compounds; 6, Nitration of active methylene compounds with nitric acid. These reactions are discussed and also noted are miscellaneous reactions of limited utility. Comparison of methods is given.
Synthesis of Peptides with Mixed Anhydrides
Authors: Albertson Noel F.
Published: March 2011

A mixed acid anhydride, or mixed anhydride, is a dehydration product of two polyoxy acids. For a mixed anhydride to be of interest for peptide synthesis, one of the components must, in general, be an alpha‐acylamino acid. The nature of the second component acid may vary widely. In this chapter the term mixed anhydride will be used in a more general sense. In addition to conventional mixed anhydrides, from polyoxyacids, reference will be made to “mixed anhydrides” otherwise recognizable as acyl halides, ethers, esters, thiol esters, O‐acylisoureas and isoimides. This chapter is limited to a review of chemistry of the acyclic alpha‐amino acid mixed anhydrides, which the well‐know alpha‐acylamino acid chlorides and azides, which have been the subject of an excellent review. In general, discussion of the application of alpha‐acyllamino acid mixed anhydrides will be limited to non‐polymeric peptide bond formation and will not be concerned with acylations other than those that lead to a peptide bonds.
Desulfurization withRaney Nickel*The authors are indebted to Dr. Brian Green and Dr. John C. Knight for checking the final draft of this chapter.
Authors: Pettit George R. , van Tamelen Eugene E.
Published: March 2011

The conversion of an amine to an olefin by elimination of the nitrogen atom and an adjoining hydrogen atom is a useful procedure for degradation and synthesis. The Hofmann exhaustive methylation method has been used most often to bring about change, but other methods as the thermal decomposition of amine oxides and the pyrolysis of amine phosphates or acetyl or benzoyl derivative have often been employed to advantage. This chapter reviews the Hofmann elimination because of its extensive history. Alternative methods are considered.
Hydration of Olefins, Dienes, and Acetylenes
via
Hydroboration
Authors: Zweifel George , Brown Herbert C.
Published: March 2011

The hydroboration of olefins, dienes, and acetylenes involves the addition of a boron‐hydrogen bond to the carbon‐carbon multiple bond. This reaction provides a new, convenient route to the corresponding organoboranes and makes them readily available as intermediates in organic synthesis. One of the important reactions that the organoboranes undero is the rapid and essentially quantitative oxidation with alkaline hydrogen peroxide. The hydroboration of olefins involves a cis addition of the boron hydrogen bond, the boron atom becoming attached to the less substituted of the two olefinic carbon atoms of the double bond.

This chapter surveys the available information on the hydration of olefins, dienes, acetylenes, and their derivatives by the hydroboration‐oxidation procedure.
Formation of Carbon‐Hetero Atom Bonds by Free Radical Chain Additions to Carbon‐Carbon Multiple Bonds
Authors: Stacey F. W. , Harris J. F.
Published: March 2011

Free‐radical chain addition to carbon‐carbon multiple bonds to form carbon‐hetero atom bonds is an important synthetic method of wide scope. Carbon‐halogen, carbon‐sulfur, carbon‐silicon, carbon‐germanium, carbon‐phosphorus, and carbon‐nitrogen bonds have been formed by this method, In this chapter, the mechanism, scope, limitations, and experimental conditions are treated for the addition reactions that lead to the formation of the six types of carbon‐hetero atom bonds mentioned above. Since the direction of addition of free radicals to carbon‐carbon multiple bonds is common to all classes reviewed here, it is briefly explained.
TheDieckmann Condensation (Including theThorpe‐Ziegler Condensation)
Authors: Schaefer John P. , Bloomfield Jordan J.
Published: March 2011

The Dieckman condensation is an acetoacetic ester condensation in which a dicarboxylic ester is cyclized to a beta‐ketonic ester through the action of a base. The dicarboxylic ester must have at least one alpha‐hydrogen atom and the carbalkoxy groups must be situated that cyclization will result in a 4‐membered ring or larger ring. Discovery and development of the reaction are generally credited to Dieckmann, who found that heating an adipic or a pimelic ester with sodium and a trace alcohol led to cyclization with formation of a cyclopentanone or a cyclohexanone. The Dieckmann condensation has proved useful for the preparation of a variety of carbocyclic and heterocyclic ketones and has been extended to the synthesis of 7 and 8‐membered rings.
The Aldol Condensation
Authors: Nielsen Arnold T. , Houlihan William J.
Published: March 2011

The aldol condensation takes its name from aldol (3‐hydroxybutanal) a name introduced by Wurtz who first prepared the beta‐hydroxy aldehyde from acetaldehdye in 1872. The aldol condensation includes reactions producing beta‐hydroxy aldehydes or beta‐hydroxy ketones by self condensations or mixed condensations of aldehydes and ketones as well as reactions leading to alpha, beta‐unsaturated aldehydes or alpha,beta‐unsaturated ketones formed by dehydration of intermediate beta‐aldols or beta‐ketals. The Claisen‐Schmidt condensation is most often taken to be the condensation of an aromatic aldehyde or ketone usually in the presence of a basic catalyst. The term aldol condensation has also been applied to many other condensations involving the reaction of an aldehyde or ketone. These condenations are discussed. The present review includes examples that are solely condensation reactions of aldehydes and ketones.
The Synthesis of Substituted Ferrocenes and other π‐Cyclopentadienyl‐Transition Metal Compounds
Authors: Bublitz Donald E. , Rinehart Kenneth L.
Published: March 2011

The discovery of dicyclopentadienyliron (ferrocene) in 1951 led to the development of an entirely new area of organometallic chemistry that of the pi‐metallohydrocarbons. Representative compounds are the pi‐metalloarenes such as dibenzenechromium, the pi‐methallopseudoarenes such as ferrocene, and the pi‐metalloolefin complexes such as butadiene iron tricarbonyl Since there is a great amount of literature available at this time, the treatment here is limited to three dimensions: to include only compounds containing cyclopentadienyl rings, of these to include only those which have shown to undergo aromatic substitution,reactions and within this group only synthetic aspects of their chemistry. This nearly restricts the discussion to syntheses of substituted ferrocenes.
The γ‐Alkylation and γ‐Arylation of Dianions of β‐Dicarbonyl Compounds
Authors: Harris Thomas M. , Harris Constance M.
Published: March 2011

It is well known that beta‐diketones can undergo condensations at the alpha‐methylene group with alkyl halides and certain other reagents though the intermediate formation of monoanions. For example, acetylacetone on treatment with an alkali metal or an alkali metal alkoxide or carbonate forms a mono‐anion which can be alkylated with alkyl halides. In 1958, Hauser and Harris reported that, if benzoylacetone or acetylacetone is first converted to the dipotassium salt. The salt undergoes alkylation and other carbon‐carbon condensations at the terminal methyl group rather than at the methylene group. Rapid alkylation was observed when the salts were treated with benzyl chloride and after acidification, the terminal monobenzylation derivatives were obtained in good yield. Dibenzylation was not observed. In this chapter alkylations of these and other beta‐ketones via dianions are surveyed. Other alkylations are also discussed. Arylations are included because alkylation and arylation are methods for directly converting beta‐homologs without increasing their functionality.
TheRitter Reaction
Authors: Krimen L. I. , Cota Donald J.
Published: March 2011

The formation of N‐substituted amides by the addition of nitriles to alkenes in the presence of concentrated sulfuric acid was first described by Ritter in 1948. The reaction has been extended to the addition of nitriles to a wide variety of compounds capable of forming a carbonium ion, and it constitutes the only really useful procedure for the preparation of amides of tertiary carbinamines. In its most general form, the Ritter reaction involves the nucleophilic addition of a nitrile to a carbonium ion in the presence of sulfuric acid. Attention has been given to reactions in which the carbonium ion is generated in sulfuric acid, or less commonly in sulfonic acids, phosphoric acids, or boron trifluoride. For comparison, analogous reactions, which are initiated by a nitrilium ion, formed from a nitrile and a Friedel‐Crafts catalyst, have been included in this chapter.
Formation of Carbon‐Carbon Bondsviaπ‐Allylnickel Compounds
Authors: Semmelhack Martin F.
Published: March 2011

Transition metal complexes containing a planar three‐carbon ligand, the pi‐allyl group was first described in 1958 with the discovery of (pi‐1‐methylallyl)cobalt tricarbonyl. After this discovery, many other syntheses followed. This chapter deals with synthetic organic applications of pi‐allylnickel complexes. At this time, the study of this subject is in its infancy. The unifying aspect of pi‐allylnickel chemistry is the ability of the allyl ligand to form new carbon‐carbon bonds.
Oxidative Decarboxylation of Acids by Lead Tetraacetate
Authors: Sheldon Roger A. , Kochi Jay K.
Published: March 2011

Lead tetracetate, one of the most versatile oxidizing agents know in organic chemistry, is capable of reacting with a variety of common functional groups; its use in organic chemistry has been reviewed. The purpose of this chapter is to review the oxidative process involving the decarboxylation of acids, whereby carboxylic acids are converted to a variety of compounds depending on experimental conditions, e.g, solvent, structure of substrates, and presence of additives. The primary objective here is to evaluate critically the usefulness of this reaction in organic synthesis. Decarboxylation of alpha‐hydroxy and alpha‐amino acids by lead tetraacetate has been known for many years. Khararaschn and co‐workers reported exhaustive products studies of the decomposition of lead tetraacetate in acetic acid. Sodium acetate accelerates the reduction of lead tetraacetate but no carbon dioxides liberated. Mosher and Kahr also examined the thermal decomposition of various organic acids by lead tetraacetate. Since then many studies on the mechanism and synthetic utility of these reaction and its modifications have been reported.
Sensitized Photooxygenation of Olefins
Authors: Denny R. W. , Nickon A.
Published: March 2011

Sensitized photooxygenations of olefins have been extensively studied; they represent convenient methods for the introduction of oxygen at specific sites. When an aerated solution containing a monolefin, diene, or polyene, and a sensitizer is irradiated with light that can be absorbed by the sensitizer, oxygenated products are formed whose nature depends upon the structure of the substrate and the lability of the initial photoproducts under the reaction conditions. The ready reducibility of hydroperoxides to alcohols enhances the synthetic usefulness of these photoxygenations In this chapter, coverage is restricted to molecules with one or more carbon‐carbon double bonds.
The Synthesis of 5‐Hydroxyindoles by the
N
enitzescu Reaction
Authors: Allen George R.
Published: March 2011

The preparation of 5‐hydroxyindole derivatives by the reaction of benzoquinones with certain enamines was suggested by the work of Nenitzescu who reported that the parent quinone,
p
‐benzoquinone, reacts with ethyl 3‐aminocrotonate in boiling acetone to yield ethyl 5‐hydroxy‐2‐methylindole‐3‐carboxylate. The procedure was largely ignored until the 1950s when interest in melanin‐related substances and cognition of serotonin as a 5‐hydroxyindole derivative stimulated an exploration of this reaction.
TheClaisen andCope Rearrangements
Authors: Rhoads Sara Jane , Rebecca Raulins N.
Published: March 2011

Since the first observation of a thermal rearrangement vinyl allyl ether to the corresponding homoallylcyclic carbonyl compound by Claisen in 1912, rearrangements of vinyl and aryl allylic ethers have been extensively studied and exploited for their synthetic value. The corresponding rearrangement of substituted 1,5‐hexadiene was first recognized by Cope in 1940 as the carbon analog of the Claisen rearrangement. Today it is recognized that such transformations fall within the general category of a [3,3] sigamtropic reaction and that considerable variation may be accommodated in the basic requirement of a system of six atoms with terminal unsaturated linkage. This chapter attempts to survey the vas t accumulation of Claisen and Cope rearrangements recorded since the first coverage in 1944.
Substitution Reactions Using Organocopper Reagents
Authors: Posner Gary H.
Published: March 2011

Carbon‐carbon sigma‐bond formation one of the most fundamental operations in organic chemistry, is often accomplished by interaction of an organometallic reagent with an organic substrate having a suitable leaving group. Selective substitution of halogens and of alcohol derivatives by various hydrocarbon groups in many different types of organic substrates has been achieved most successfully using organocopper reagents. The wide scope and effectiveness of these reagents in coupling with halides and alcohol derivatives have made formation of the unsymmetrical coupling product R‐R' a useful reaction in organic synthesis, allowing efficient and specific substitution of X by alkyl, alkenyl, alkynyl, or aryl groups. Because selective coupling between organic substrate and organocopper reagent is usually achieved more effectively by stoichiometric than by catalytic organocopper reagents, and more effectively still by organocuprates(I) than by mono‐copper or by complexed organocopper reagents, the emphasis in this chapter is on organocuprates (I). Consideration is given to possible mechanisms of substitution reactions using organocopper reagents, to scope, limitations, and synthetic utility of these reactions, and to optimal experimental considerations for their application.
The
R
eformatsky Reaction
Authors: Rathke Michael W.
Published: March 2011

The Reformatsky reaction is the reaction of a carbonyl compound, usually an aldehyde or a ketone, with an alpha‐haloester in the presence of zinc metal to furnish, after hydrolysis, a β‐hydoxyester. Subsequent dehydration of the hydroxyester is commonly carried out to form an alpha, β‐unsaturated ester. This chapter summarizes some of the more important advances in the understanding and use of the Reformatsky reaction since the original chapter was published in volume 1 of this series.
Reduction and Related Reactions of α,β‐Unsaturated Carbonyl Compounds with Metals in Liquid Ammonia
Authors: Caine Drury
Published: March 2011

This chapter is concerned with the reduction and related reactions of alpha,beta‐unsaturated ketones by alkali and alkaline earth metals in liquid ammonia. Upon treatment with a metal in liquid ammonia (usually containing an ether co‐solvent) a simple alpha, beta‐unsaturated ketone is converted into the metal enolate corresponding to the saturated ketone. Research during the first half of the 20
th
Century revealed that a variety of organic compounds undergo reduction with metals in liquid ammonia but preparative metal‐ammonia reductions of alpha,beta‐unsaturated carbonyl compounds were apparently not described until 1951. In addition to affording a remarkable degree of stereoselectivity, many metal‐ammonia reductions of unsaturated carbonyl systems can be preformed in a variety of functional and protective groupings and the reaction is generally free of the rearrangements sometimes observed when chemical reduction methods are used. The unique features of metal‐ammonia reductions and related reaction have led to their wide application in total synthesis and transformations.
Homogeneous Hydrogenation Catalysts in Organic Synthesis
Authors: Birch A. J. , Williamson D. H.
Published: March 2011

During recent years, studies of the activation of hydrogen by soluble catalysts have been intensely pursued. The scope of this chapter has been limited to those catalysts utilizing hydrogen gas in the reduction of organic substrates. The first hydrogenation of an organic molecule using a soluble catalyst rather than classical divided metal catalysts was reported in 1938. Other catalyst studies followed. Homogeneous and heterogenous catalysts employ a similar range of metals, but soluble complex catalysts are uniform and therefore show more clearly defined activity and selectivity. Variations of ligands in a soluble catalyst, resulting in arrange of properties, may be likened to poisoning of metal surfaces; but use of different ligands in theory makes possible precise control of a range of properties in soluble catalysts. Many developments are to come and with them the increasing utility of soluble catalyst in general organic synthesis.
Selenium Dioxide Oxidation
Authors: Rabjohn Norman
Published: March 2011

Selenium dioxide has developed considerable stature since it was first reviewed in this series. Search for examples of oxidation by selenium dioxide or selenious acid is difficult because the terms are seldom indexed. Frequently it is difficult to decide whether selenium dioxide or selenious acid was the oxidizing agent employed in a reaction because it is impossible to determine if water was present. The determination is complex because the free acid or anhydride may react reversibly or irreversibly with various solvents such as alcohols or acids. To give selenium‐containing compounds of unknown structure which might be the real oxidizing gents. In this chapter, the practical aspects of oxidation with selenium dioxide are summarized. Mechanisms are treated in detail.
Echocardiography in Mice
Authors: Gao Shumin , Ho David , Vatner Dorothy E. , Vatner Stephen F.
Published: March 2011

Murine models have been utilized with increasing frequency mainly due to availability of genetically engineered models. With advancement in high spatial and temporal resolution, echocardiography is used extensively for the evaluation of cardiovascular function in murine models of cardiovascular disease. This review summarizes the general applications and methods involved in echocardiography used to study mouse models for cardiovascular research, based on 20 years of experience in the authors' laboratory. The goal of this article is to provide a practical guide to the use of echo techniques in mice to evaluate cardiac systolic and diastolic function. Curr. Protoc. Mouse Biol. 1:71‐83. © 2011 by John Wiley & Sons, Inc.
Operating Modes of Sandwiched Light‐Emitting Electrochemical Cells
Authors: Lenes Martijn , Garcia‐Belmonte Germà , Tordera Daniel , Pertegás Antonio , Bisquert Juan , Bolink Henk J.
Published: March 2011

Light‐emitting electrochemical cells (LECs) are promising lighting devices in which the redistribution of ionic charges allows for double electronic carrier injection from air‐stable electrodes. Uncertainties about the mode of operation are limiting the progress of these devices. Using fast (with respect to the current growth time) but resolutive electrical measurement techniques, the electronic transport mechanism in state‐of‐the‐art sandwiched devices can be monitored as a function of the operation time. The results indicate the formation of doped transport layers adjacent to the electrodes that reduces the extent of the central neutral light‐emitting layer where electronic transport is limited by space‐charge. Prolonged growth of the doped regions beyond that required for efficient injection should be prevented, as this decreases the efficiency and leads to low luminance devices.
Patterns of monoclonal immunoglobulins and serum free light chains are significantly different in black compared to white monoclonal gammopathy of undetermined significance (MGUS) patients
Authors: Weiss Brendan M. , Minter Alex , Abadie Jude , Howard Robin , Ascencao Joao , Schechter Geraldine P. , Kuehl Michael , Landgren Ola
Published: March 2011

Monoclonal gammopathy of undetermined significance (MGUS), the precursor to multiple myeloma, is more common in blacks than whites. The serum free light chain (sFLC) assay is an important prognostic test in MGUS, but no study has evaluated sFLC levels and ratios in black MGUS patients. One‐hundred and twenty‐five black MGUS patients at two urban centers were compared to the white population of the Mayo Clinic. The median age for blacks was 73 years [41–94] and 75% were male. The M‐protein isotype in blacks was 81% IgG, 13% IgA, 2% IgM, and 4% biclonal compared to 70%, 12%, 16%, and 2%, respectively, in whites, (P < 0.0005). The median M‐protein concentration for blacks was 0.44 gm/dL (trace‐2.33) compared to 1.2 gm/dl in whites. An abnormal sFLC ratio was present in 45% of black compared to 33% of white (P = 0.01) patients. Using the Mayo Clinic risk model, black patients had a significantly lower proportion of higher risk MGUS compared to whites: low 43%, low‐intermediate 45%, high‐intermediate 10%, and high 2% (P = 0.014). Black patients with MGUS have significantly different laboratory findings compared to whites. The biologic basis for these disparities and their effect on prognostic assessment is unknown. Prognostic models based on these biomarkers should be used cautiously in nonwhite populations. Am. J. Hematol. 2011. © 2011 Wiley‐Liss, Inc.