Showing papers on "Alkylation published in 1977"

Phase Transfer Catalysis in Organic Synthesis

Abstract: 1. Introduction and Principles.- 1.1 Introduction.- 1.2 Early Examples.- 1.3 The Coalescence of Ideas.- 1.4 The Principle of Phase Transfer Catalysis.- 1.5 Evidence for the Mechanism of Phase Transfer Catalysis.- 1.6 Charged Catalysts: Quaternary Ions.- 1.7 Uncharged Catalysts: The Amines.- 1.8 Uncharged Catalysts: The Crown Ethers.- 1.9 Uncharged Catalysts: The Cryptands.- 1.10 Catalyst Comparisons.- 1.11 Solvents.- 1.12 The Role of Water in Phase Transfer Catalysis.- 1.13 Summary.- References.- 2. The Reaction of Dichlorocarbene With Olefins.- 2.1 Introduction.- 2.2 The Mechanism of the Dichlorocyclopropanation Reaction.- 2.3 Catalytic Cyclopropanation.- 2.4 Dichlorocyclopropanation of Simple Olefins.- 2.5 Cyclopropanation of Enamines.- 2.6 Dichlorocyclopropanation Followed by Rearrangement.- 2.7 Carbene Addition to Indoles.- 2.8 Carbene Addition to Furans and Thiophenes.- 2.9 Carbene Addition to Polycyclic Aromatics.- 2.10 Carbene Addition to Conjugated Olefins.- 2.11 Michael Addition of the Trichloromethyl Anion.- 2.12 Dichlorocarbene Addition to Allylic Alcohols: A Cyclopentenone Synthon.- 2.13 Dichlorocarbene to Phenols: Reimer-Tiemann Reactions.- References.- 3. Reactions of Dichlorocarbene With Non-Olefinic Substrates.- 3.1 Introduction.- 3.2 C - H Insertion Reactions.- 3.3 Reaction With Alcohols: Synthesis of Chlorides.- 3.4 Carbene Addition to Imines.- 3.5 Addition to Primary Amines: Synthesis of Isonitriles...- 3.6 Reaction With Hydrazine, Secondary, and Tertiary Amines.- 3.7 Dehydration With Dichlorocarbene.- 3.8 Miscellaneous Reactions of Dichlorocarbene.- References.- 4. Dibromocarbene and Other Carbenes.- 4.1 Introduction.- 4.2 Dibromocarbene Addition to Simple Olefins.- 4.3 Dibromocarbene Addition to Strained Alkenes.- 4.4 Dibromocarbene Addition to Indoles.- 4.5 Dibromocarbene Addition to Michael Acceptors.- 4.6 Other Reactions of Dibromocarbene.- 4.7 Other Halocarbenes.- 4.8 Phenylthio- and Phenylthio(chloro)carbene.- 4.9 Unsaturated Carbenes.- References.- 5. Synthesis of Ethers.- 5.1 Introduction.- 5.2 Mixed Ethers: The Mechanism.- 5.3 Rate Enhancement in the Williamson Reaction.- 5.4 Methylation.- 5.5 Phenyl Ethers.- 5.6 Methoxymethyl Ethers of Phenol.- 5.7 Diethers From Dihalomethanes.- 5.8 The Koenigs-Knorr Reaction.- 5.9 Epoxides.- References.- 6. Synthesis of Esters.- 6.1 Introduction.- 6.2 Tertiary Amines and Quaternary Ammonium Salts.- 6.3 Noncatalytic Esterification in the Presence of Ammonium Salts.- 6.4 Polycarbonate Formation.- 6.5 Crown Catalyzed Esterification.- 6.6 Crown Catalyzed Phenacyl Ester Synthesis.- 6.7 Crown Catalyzed Esterification of BOC-Amino Acid to Chloromethylated Resins.- 6.8 Cryptate and Resin Catalyzed Esterifications.- 6.9 Synthesis of Sulfonate and Phosphate Esters by PTC.- References.- 7. Reactions of Cyanide Ion.- 7.1 Introduction.- 7.2 The Mechanism and General Features of the Cyanide Displacement Reaction.- 7.3 The Formation of Alkyl Cyanides.- 7.4 Formation of Acyl Nitriles.- 7.5 Synthesis of Cyanoformates.- 7.6 Cyanohydrin Formation.- 7.7 The Benzoin Condensation.- 7.8 Hydrocyanation, Cyanosilylation, and Other Reactions.- References.- 8. Reactions of Superoxide Ions.- 8.1 Introduction.- 8.2 Reactions at Saturated Carbon.- 8.3 Additions to Carbonyl Groups.- 8.4 Reactions With Aryl Halides.- References.- 9. Reactions of Other Nucleophiles.- 9.1 Introduction.- 9.2 Halide Ions.- 9.3 Azide Ions.- 9.4 Nucleophile Induced Elimination Reactions.- 9.5 Nitrite Ion.- 9.6 Hydrolysis Reactions.- 9.7 Anionic Polymerization Initiation.- 9.8 Organometallic Systems.- 9.9 Isotopic Exchange.- References.- 10. Alkylation Reactions.- 10.1 Introduction.- 10.2 The Substances Alkylated.- 10.3 Phase Transfer Alkylating Agents.- 10.4 Alkylation of Reissert's Compound.- References.- 11. Oxidation Reactions.- 11.1 Introduction.- 11.2 Permanganate Ion.- 11.3 Chromate Ion.- 11.4 Hypochlorite Ion.- 11.5 Catalytic Oxidation.- 11.6 Singlet Oxygen.- 11.7 Oxidation of Anions.- 11.8 Phosphorylation.- References.- 12. Reduction Techniques.- 12.1 Introduction.- 12.2 Borohydrides.- 12.3 Stoichiometric Reduction Systems.- 12.4 Other Catalytic Reductions.- 12.5 Altered Reactivity.- References.- 13. Preparation and Reactions of Sulfur Containing Substrates.- 13.1 Introduction.- 13.2 Preparation of Symmetrical Thioethers.- 13.3 Preparation of Mixed Sulfides.- 13.4 Preparation of Sulfides From Thiocyanates.- 13.5 Preparation of Alkylthiocyanates.- 13.6 Sulfides Resulting From Michael Additions.- 13.7 Synthesis of ?, ?-Unsaturated Sulfur Compounds.- 13.8 Other Phase Transfer Reactions of Sulfur Containing Substances.- References.- 14. Ylids.- 14.1 Introduction.- 14.2 Phase Transfer Wittig Reactions.- 14.3 The Wittig-Horner-Emmons Reaction.- 14.4 Sulfur Stabilized Ylids.- References.- 15. Altered Reactivity.- 15.1 Introduction.- 15.2 Cation Effects.- 15.3 Affected Anions.- 15.4 Ambident Nucleophiles.- References.- 16. Addendum: Recent Developments in Phase Transfer Catalysis.- Author Index.

Formation and metabolism of alkylated nucleosides: possible role in carcinogenesis by nitroso compounds and alkylating agents.

Abstract: Publisher Summary Alkylation of nucleic acids occurs both physiologically within living cells and after the administration of compounds that are either themselves direct chemical alkylating agents or are converted into alkylating agents by metabolic activation. Some of these compounds are highly potent carcinogens. Carcinogenicity of these agents is due to the alkylation of certain cellular components because no other degradation product nor is the compound itself oncogenic. This chapter deals with the formation and metabolism of alkylated purines in nucleic acids. It briefly discusses other alkylation reactions leading to the alkylphosphate triester production and alkylated pyrimidines. It also presents evidences favoring particular critical targets for the action of alkylating carcinogens. The attack on nucleic acids by carcinogenic alkylating agents is not entirely random and generally leads to the formation of alkylated nucleosides at many different sites distributed throughout the cellular nucleic acids. Carcinogenesis is not necessarily mediated through mutagenesis in somatic cells. However, it is observed that carcinogenic action could be mediated through a distinct action of the electrophilic reactant.

Alkylation, arylation, and vinylation of acyl chlorides by means of organotin compounds in the presence of catalytic amounts of tetrakis(triphenylphosphine)palladium(o)

Abstract: Alkylation, arylation, and vinylation of acyl chlorides by means of organotin compounds in the presence of catalytic amounts of tetrakis(triphenylphosphine)palladium(O) were demonstrated. The corresponding ketons were obtained in fairly good yields.

Reductive alkylation of amino groups.

Abstract: Publisher Summary Many simple aldehydes and ketones react rapidly and reversibly with amino groups of proteins. Neither the initial adduct or the Schiff base formed upon dehydration is very stable in dilute aqueous solution, but extensive modification of protein amino groups can be obtained by the reduction of the Schiff base to a stable secondary amine. Reductive alkylation of protein amino groups can, thus, be accomplished with many different aldehydes and ketones under very mild conditions by using sodium borohydride as the reductant. Under the conditions described in the chapter, both α- and ɛ-amino groups are readily modified, but other common protein groups are not affected. Because the modified groups experience only a small change in basicity and, at neutral pH, retain their normal cationic charges, the overall charge and the relative distribution of charged groups in most proteins are not greatly changed by reductive alkylation. By using a large variety of readily available aldehydes and ketones, the size, shape, and hydrophobicity of added substituents can be easily varied. Reductive alkylation procedure is applicable to most proteins, except those containing readily reducible components or prosthetic groups, such as pyridoxal phosphate and rhodopsin, or those which are not stable at the required alkaline pH values.

A General Route to Terminally Substituted Allylic Derivatives of Silicon and Tin. Preparation of Allylic Lithium Reagents.

Abstract: : It is obvious that this new route to allylic compounds of silicon and tin should be quite general in its scope of applicability. By appropriate variation of the phosphorus ylide and the carbonyl substrate in these reactions, allylic derivatives of silicon and tin of type Me3MCH2C(R)=CR'R'', where R, R' and R'' should be capable of wide variation, should be accessible. The allyltins thus prepared would provide starting materials for many new allylic lithium reagents. In many cases the direct lithiation procedure, the reaction of RLi/Lewis base or RLi/Me3OK with an appropriate unsaturated hydrocarbon, would provide the simplest route to the desired allylic lithium reagent. However, the additives which usually are required to effect such metalations may not always be compatible with other functionality in the carbonyl reactant or may interfere in other ways. Also, there will be instances when the appropriate unsaturated hydrocarbon is not available. Thus the versatility of our new procedure and its ease of application may prove very useful in organic and organometallic synthesis.

Sites in nucleic acids reacting with alkylating agents of differing carcinogenicity of mutagenicity.

Abstract: The site of alkylation of a nucleic acid, in vivo, is greatly dependent on the type of alkylating agent. Most alkylating agents of low mutagenicity or carcinogenicity (such as dimethylsulfate) react primarily with the ring nitrogens. The carcinogenic N-nitroso compounds have a great affinity for alkylating oxygens and react with all ring oxygens as well as the phosphodiesters and, in the case of RNA, with the 2'-O of ribose. Ethylating agents, though in absolute terms less reactive than the corresponding methylating agents, show even greater affinity toward oxygens. It appears that the ethyl nitroso compounds that are carcinogenic are also the most reactive with oxygens.

Alkylation of aromatic hydrocarbons

Abstract: Highly stable and active catalysts are provided for the alkylation of aromatic hydrocarbons with C2 -C4 olefins. The catalysts are extruded composites of an acidic, crystalline aluminosilicate zeolite, e.g. Y zeolite, and a porous mineral oxide binder. The basic novel feature of the invention resides in the shape and size of the catalyst extrudates. By shaping the extrudates so as to give a high ratio of external surface area to volume, resistance to deactivation is found to be much improved, as well as activity and selectivity.

Metabolic activation of chlorinated ethylenes: dependence of mutagenic effect on electrophilic reactivity of the metabolically formed epoxides.

Abstract: In chlorinated ethylenes, the chlorine substitution exerts, by its electron withdrawal effect, a stabilization of the molecule which increases with the number auf chlorine residues. All chlorinated ethylenes are metabolically transformed, in a first step reaction, to epoxides which may rearrange to aldehydes or acyl chlorides, respectively, undergo hydrolysis to diols, conjugate with glutathione, or react, by alkylation, with cellular macromolecules. The electrophilicity of the epoxides is high with those having an unsymmetric chlorine substitution, and comparatively low with the others bearing symmetric chlorine residues. According to in vitro mutagenicity testing in a modified Ames system, the following rule on structure/activity-relationship has been worked out: mutagenic potential is bound to unsymmetric substitution and high chemical reactivity (as with vinyl chloride, vinylidene chloride, and trichloroethylene), symmetric substitution results in lower chemical reactivity and non-mutagenicity. So far, the rule is substantiated by positive carcinogenic effects in animal experiments with vinyl chloride, vinylidene chloride and trichloroethylene.

Metabolism and mutagenicity of halogenated olefins--a comparison of structure and activity.

Abstract: Chlorinated ethylenes are metabolized in mammals, as a first step, to epoxides. The fate of these electrophilic intermediates may be reaction with nucleophiles (alkylation), hydrolysis, or intramolecular rearrangement. The latter reaction has been studied in the whole series of chlorinated epoxiethanes. The rearrangement products found were: acyl chlorides (tetrachloro-, trichloro-, and 1,1-dichloroethylenes), or chlorinated aldehydes (1,2-dichloroethylenes, cis- and trans-, vinyl chloride). The metabolities found in vivo are identical with, or further derivatives of these rearrangment products, with one important exception: trichloroethylene. With this compound, in vivo rearrangement yields chloral exclusively. The mechanism of the different rearrangement has been identified as a Lewis acid catalysis. All chlorinated ethylenes have been investigated in a tissue-mediated mutagenicity testing system. The prominent molecular feature of those with mutagenic effects (trichloro-, 1,1-dichloro-, and monochloroethylene) is unsymmetric chlorine substitution which renders the epoxides unstable, whereas symmetric substitution confers relative stability and nonmutagenic property.

Solid phosphoric acid-catalyzed alkylation of aromatic hydrocarbons.

Abstract: A process for the alkylation of aromatic hydrocarbons using a solid phosphoric acid catalyst in which liquid phosphoric acid is removed from the bottoms stream of the rectification column to which the alkylation zone effluent is charged. The acid is removed by passing the bottoms stream into a settling vessel operated at a lower pressure and temperature than the bottom of the rectification column.

A study of catalysis by metal phosphates. IV. The alkylation of phenol with methanol over metal phosphate catalysts.

Abstract: The catalytic methylation in the vapor phase over various metal phosphates has been investigated using a conventional flow reactor at temperatures ranging from 350 to 500 °C under atmospheric pressure The Ca3(PO4)2 catalyst was excellent in both its activity and its selectivity for ortho-methylation, giving predominantly o-cresol and 2,6-xylenol, whereas the BPO4 or CaHPO4 catalyst simultaneously promoted the formation of anisole The activity of Ca3(PO4)2 was significantly higher than that of the CaO or MgO catalyst The influences of the reaction temperature, the contact time, and the calcination temperature of the catalyst upon the conversion of phenol, and the yields of the products were investigated in detail over the Ca3(PO4)2 catalyst The activities and the selectivities of various catalysts were discussed in connection with their acid-base properties The mechanism of the participation of both the acidic and basic sites in the methylation was also discussed

Hydrogen bonding in organic synthesis. Part 6. C-Alkylation of β-dicarbonyl compounds using tetra-alkylammonium fluorides

Abstract: Mono-C-alkylation of a number of β-dicarbonyl compounds using alkyl iodides and tetra-alkylammonium fluorides is described. Yields are high with primary iodides and isopropyl iodide, but much lower with s-butyl and t-butyl iodides. The reactions occur under mild conditions with no apparent O-alkylation or other competing reactions.

A New Synthetic Route to (±)-Perhydrohistrionicotoxin

Abstract: Starting from ethyl 2-cyclohexen-1-carboxylate (3) the total synthesis of the perhydrohistrionicotoxin intermediate 23 was achieved in 25% overall-yield. The two key steps involve a positionally specific addition of HOBr to the oxime-olefin 7 and the alkylation of bromooxime 17 with 1-lithio-1-butyne. The latter represents a novel method for stereospecific and position-specific introduction of a nucleophilic butyl equivalent in α-position to a ketonic carbonyl group.

The stereochemistry of conjugate addition of lithium dialkyl cuprate reagents to some carbohydrate α-enones

Abstract: Conjugate addition-alkylation reactions of lithium dialkyl cuprates to hex-2-enopyrano-4-ulosides (1), hex-3-enopyrano-2-ulosides (2), and hex-1-enopyrano-3-uloses (3) have been investigated. Extensive studies with 1 show that the homogeneous system using the soluble tri-n-butylphosphine copper(I) complex is less satisfactory than the heterogeneous medium in which copper(I) iodide is used. The use of Grignard reagents versus alkyl lithiums has also been investigated, the latter being found preferable. 1,2-Addition was observed in some cases, but conditions were developed to avoid formation of these side products.With α-enones 1 and 2 alkylation is completely stereoselective, the newly introduced alkyl group being in axial orientation. With 3 a complex mixture is obtained from which equatorial and axial adducts can be isolated in approximately equal amounts.