SN2 Type Research Articles

Studies on the terpenoids and related alicyclic compounds. XXXIII. Acid-catalyzed allylic rearrangement of 1-hydroxy-2-en- and 3-hydroxy-1-en-5.ALPHA.-cholestanes.

The reaction mechanism and the stereochemistry of an acid-catalyzed allylic rearrangement of four allylic alcohols of 5α-cholestane, the 3-hydroxy-1-enes (5 and 6) and the 1-hydroxy-2-enes (7 and 8), were investigated. The allylic alcohols were heated in dioxane containing a small amount of 1N H2SO4. After the equilibration of the reaction, the products ratio of the four allylic alcohols, 5 : 6 : 7 : 8, was found to be 25 : 20 : 52 : 3, regardless of the stereochemistry of the starting materials. The mechanism of the allylic rearrangement is of SN1 type. The products ratio could be explained in terms of the relative stabilities of the C-1 and C-3 carbocations in the intermediates and the thermodynamic stability of each allylic alcohol.

Sulphoxide substituted pyridines as phase-transfer catalysts for nucleophilic displacements and alkylations

2-Methylsulphinyl-, 2-methylsulphinylmethyl-, 2,6-bis(methylsulphinyl)-, 2,6-bis(methylsulphinylmethyl)-pyridines, bis(2-pyridylmethyl) sulphoxide, and 2-methylsulphinylpyridine N-oxide have been prepared. These sulphoxides served as good phase-transfer catalysts which accelerate SN2 type displacements of octyl bromide with various nucleophiles (thiolate, cyanide, thiocyanate, and phenoxide) in solid–liquid two-phase systems. Alkylations of phenylacetonitrile and benzyl methyl ketone with alkyl halides were also carried out in liquid–liquid two-phase systems in the presence of the above sulphoxides to afford the corresponding monoalkylated products in high yields. Pyridine derivatives bearing polysulphinyl groups were found to be even more effective catalysts for these two-phase alkylations. Neither 2-methylthio- nor 2-methylsulphonyl-pyridine catalysed SN2 type displacement reactions effectively.

ChemInform Abstract: NUCLEOPHILIC SUBSTITUTION WITH PHOSPHIDE ANIONS PREPARED BY AN ACTION OF SODIUM DIHYDRIDOBIS(2‐METHOXYETHANOLATO)ALUMINATE ON PHOSPHORUS COMPOUNDS

AbstractBei Umsetzung des Phosphinoxids (I) mit Alkylhalogeniden (II) entstehen gemäß der Titelreaktion die Derivate (III) mit einer neu gebildeten P‐C‐Bindung.

Nucleophilic Substitution with Phosphide Anions Prepared by an Action of Sodium Dihydridobis(2-methoxyethanolato)aluminate on Phosphorus Compounds

Abstract Phosphide anions, prepared by an action of sodium dihydridobis(2-methoxyethanolato)aluminate on derivatives of phosphine, phosphine oxide, or phosphorus esters, react with primary and secondary alkyl halides to produce phosphine derivatives having a newly formed phosphorus-carbon bond. The reactivity increases in the order of chloride<bromide<iodide and of secondary<primary in alkyl halide. Reaction of phosphide anion is also feasible with p-toluenesulfonate. Reaction of an anion of diphenylphosphine oxide seems to proceed mainly as an SN2 type process.

Kinetics and mechanisms of nucleophilic displacements with heterocycles as leaving groups. Part 11. ρ* plots for the solvolysis of 1-s-alkyl-5,6-dihydro-2,4-diphenylbenzo[h]quinolinium cations

The ρ* values for (1c–h) for (i) solvolysis in trifluoroacetic acid (–5.7), (ii) for solvolysis in pentanol (–1.2), and (iii) for unimolecular reaction with piperidine in chlorobenzene (–3.1) are discussed with respect to (a) the hypothesis that ρ* is a measure of the cation character of the transition state and (b) the SN2 (intermediate) mechanism. The results are explained for (i) in terms of determining ion-molecule pair dissociation, for (ii) as rate determining SN2 type solvent attack, and for (iii) as rate-determining ion-molecule pair formation.

Synthèse stéréospecifique de nucléosides pyrimidiques par la méthode de Hilbert–Johnson

Condensation of 2,4-dimethoxy pyrimidine with bromoglucosides derived from methyl 4-deoxypentopyranosides 2–7 and from 3,5,6-tri-O-benzoyl glucofuranose, 20, leads in a stereospecific manner to the nucleosides 8–13 and 22 with the trans 1′,2′ configuration. The stereochemistry of this reaction is not influenced by the structure of the starting sugar but rather is directed by the presence of the C-2 hydroxyl group. The synthesis of epoxide 18, obtained by the action of NaH on the bromohydrine 17, derived from 7, supports the intervention of a reaction assisted by an epoxide-like intermediate derived from the trans-bromohydrine. On the other hand, the cis-bromohydrine undergoes direct substitution of anomeric halogen by base. The possibility of the formation of a carbocation-like intermediate is discounted since SN1 type glycosylation reactions of 19 by MeOH or t-BuOH lead preferentially to products with the cis-configuration. [Journal translation]

Mechanism of phosphorylation catalyzed by chloroplast coupling factor 1. Stereochemistry.

The reaction mechanism and substrate specificity of soluble chloroplast coupling factor 1 (CF1) from spinach were determined by using the purified isomers of chromium-nucleotide complexes either as substrates for the enzyme or as inhibitors of the Ca2+-dependent ATPase activity. The isolation of CrADP( [32P]Pi) formed upon the addition of the enzyme to [32P]Pi and lambda-bidentate CrADP and the observation that the lambda-bidentate CrADP epimer was 20-fold more effective in inhibiting the Ca2+-dependent ATPase activity than was the delta epimer suggest that the substrate of phosphorylation catalyzed by CF1 is the lambda-bidentate metal ADP epimer. Tridentate CrATP was hydrolyzed by soluble CF1 to CrADP(Pi) at an initial rate of 3.2 mumol (mg of CF1)-1 min-1, indicating that the tridentate metal ATP is the substrate for ATP hydrolysis. From these results a mechanism for the phosphorylation of ADP catalyzed by coupling factor 1 is proposed whereby the bidentate metal ADP isomer associates with the enzyme, phosphate inserts into the coordination sphere of the metal, and the oxygen of the beta-phosphate of ADP attacks the inorganic phosphate by an SN2 type reaction. The resulting product is the tridentate ATP ligand.

Desorption chemical ionization mass spectrometry of epimeric 3‐hydroxysteroids and derivatives. Stereoselectivity and nucleophilic substitution with ammonia

AbstractThe desorption chemical ionization mass spectra, using ammonia as reagent gas, of several epimeric 3‐hydroxysteroids and their ether and carboxylic acid ester derivatives are reported. In the case of steroids possessing a Δ4‐ or Δ5‐3α‐benzoate moiety, stereospecific stabilization of the protonated molecular ion [M+H]+ is observed. This behavior is rationalized in terms of interaction of the double bond and the protonated benzoate group at C‐3. Nucleophilic substitution by NH3 is observed when a double bond is present in the vicinity of the substitution center. The nature and the stereochemistry of the leaving group influence this substitution reaction. Our results seem to indicate the operation of a two‐step mechanism (e.g. SN1 type reaction) rather than a SN2 type mechanism for the formation of the substitution ion [MOR+NH3]+.

Purification and properties of a new enzyme, DL-2-haloacid dehalogenase, from Pseudomonas sp.

A new enzyme, DL-2-haloacid dehalogenase, was isolated and purified to homogeneity from the cells of Pseudomonas sp. strain 113. This enzyme catalyzed non-stereospecific dehalogenation of both of the optical isomers of 2-chloropropionate through an SN2 type of reaction; L- and D-lactates were formed from D- and L-2-chloropropionates, respectively. The enzyme acted on 2-halogenated aliphatic carboxylic acids whose carbon chain lengths were less than five. It also dehalogenated trichloroacetate to form oxalate and showed maximum activity at pH 9.5. The Michaelis constants for substrates were as follows: 5.0 mM for monochloroacetate, 1.1 mM for L-2-chloropropionate, and 4.8 mM for D-2-chloropropionate. DL-2-Haloacid dehalogenase was inhibited by HgCl2, ZnSO4, and MnSO4, but was not affected by thiol reagents, such as p-chloromercuribenzoate and iodoacetamide. This enzyme had a molecular weight of about 68,000 and appeared to be composed of two subunits identical in molecular weight.

ChemInform Abstract: TETRAKIS(SULFOXIDES) AS PHASE TRANSFER CATALYSTS

AbstractAnhand der Umsetzungen von Octylbromid mit Kaliumrhodanid, Kaliumcyanid, Kaliumphenolat bzw. Kaliumthiophenolat wird untersucht, inwieweit die im Formelschema vorgestellten Verbindungen als Phasentransfer‐Katalysatoren dienen können.

Nucleophilic substitution at sulphonyl sulphur part 3. Hydrolysis of substituted thiophene‐2‐sulphonyl chlorides catalysed by silver nitrate and silver nitrite salts

AbstractHydrolysis reactions of substituted thiophene‐2‐sulphonyl chlorides (5‐methyl, 5‐H, 5‐chloro, 5‐nitro) catalysed by silver nitrate and silver nitrite salts have been studied in water at 25°. Salt effects by potassium nitrate, sodium perchlorate and mercuric bromide have also been investigated. For the catalysis effected with silver nitrate, the pseudo‐first order rate constants depend on the first power of silver ion concentration, while nitrate anion is not involved in the transition state. The corresponding curved Hammett plot suggests a transition state with a partially developed sulphonylium character. With silver nitrite, the rate dependence on both silver and nitrite ion concentrations would indicate that silver is involved in the transition state as well as nitrite. Also, in this case the curved Hammett plot obtained suggests a partial positive charge on the sulphur atom in the transition state. A comparison with uncatalysed hydrolysis reactions would support a previous interpretation that thiophene‐2‐sulphonyl chlorides hydrolyze by an SN2 type mechanism which can shift toward an SN1 or an SAN process depending on the ring substituent.

TETRAKIS-SULFOXIDES AS PHASE TRANSFER CATALYSTS

Abstract Tetrakis(alkyl-sulfinylmethyl)methanes serve as highly efficient phase transfer catalysts in SN2 type displacement reactions of n-octyl bromide with a few nucleophiles.

Nucleophilic substitution at sulphonyl sulphur. Part 2. Hydrolysis and alcoholysis of aromatic sulphonyl chlorides

Kinetics of hydrolysis, methanolysis and ethanolysis of furan-2- and -3-, thiophen-2- and -3-, and benzene-sulphonyl chlorides have been measured. Fair correlations with Taft σ* values for heterocycles are found; more satisfactory trends are observed by applying the two-parameter (polar and steric) Taft–Pavelich equation, particularly for the hydrolysis reaction including data for aliphatic sulphonyl chlorides. In this case the negative δ value, which is related to the steric parameter, is consistent with steric acceleration due to relief of strain in the transition state. Alcoholysis rates of substituted thiophen-2-sulphonyl chlorides (5-CH3, 5-Cl, 4-NO2, and 5-NO2) have been also measured in order to compare the substituent effects with those already observed for hydrolysis. The data are in accord with previous findings, that an SN2 type mechanism takes place which is shifted toward an SN1 process (looser transition state) or an SAN process (tighter transition state) in the hydrolysis and alcoholysis reactions, respectively.

Enhanced reactivities in substitution and elimination reactions in dimethyl sulphoximide

The dielectric constants of dimethyl sulphoximide (DMSOI), tetramethylene sulphoximide (TMSOI), and dimethyl N-methylsulphoximide (N-MeDMSOI) were measured. The sulphoximides were tested as solvents for typical nucleophilic substitutions (SN2) and base-catalysed E2 reactions. The rates for several SN2 reactions and the activation parameters of the typical SN2 reaction between butyl bromide and sodium azide in DMSOI revealed that it behaves almost like a polar aprotic solvent despite the presence of the protic NH group. In a mixed solvent of DMSOI and MeOH, the rates of a few SN2 reactions were enhanced more than those in dimethyl sulphoxide–MeOH or dimethylformamide–MeOH. The rate enhancements of SN2 reactions in various mixed solvents appeared to be related to their pKa values. While the rate of the E2 reaction of 1-methylheptyl bromide with sodium methoxide or potassium t-butoxide in DMSOI is substantially higher (240 times) than that in methanol or t-butyl alcohol, the orientation of olefin formation in elimination from 2-substituted octanes in sulphoximides is similar to that in MeO––MeOH. Solvolyses of some alkyl tosylates and halides in DMSOI afforded the corresponding dimethyl N-alkyl sulphoximides in moderate yields. These results indicate that the sulphoximides belong to a new type of solvent which is protic in origin but also behaves almost like a characteristic polar aprotic solvent.

Synthesis of (1‐14C)valine

AbstractThe method for the synthesis of DL‐(1‐14C)valine (reaction of ethyl N‐(1‐phthalimido)‐isobutyl‐1‐carbamate with K14CN in ethyl alcohol, followed by acidic hydrolysis of the labelled nitrile) reported by Egyed et al. (Acta Chim. Hung. 38: 123, 1963) was studied. The yield of valine could be increased to 75‐80 % by using dry isopropyl alcohol and extending the hydrolysis with hydrochloric acid‐acetic acid to 36 hours. This is better than or comparable to the yields obtained with the Strecker or Bucherer methods. Since the replacement of the phthalimido ring with cyanide proved to be of the SN1 type, a stereospecific synthesis of L‐ or D‐(1‐14C)valine was not possible.

Friedel-Crafts Reaction of Aromatics with Epoxides. Stereochemistry and Selectivities

Abstract The Friedel-Crafts reaction of toluene and anisole with 2-methyloxirane and 2,3-dimethyloxiranes was examined. The inter- and intramolecular selectivities of 2-methyloxirane were between those of conventional methylation and isopropylation. It was also found that all the positional isomers formed by the aluminum chloridecatalyzed reaction of toluene and anisole had almost completely inverted configurations of the epoxide carbons. These results are explained by a mechanism of the SN2 type. Diminished stereospecificities were observed in aluminum bromide-catalyzed reactions.

エポキシドの酸触媒加溶媒分解 機構と立体化学

Ring-opening of epoxide involves two major subjects of study, positional selectivity and stereochemistry. It appears that the reactions with nucleophiles under basic conditions proceed through SN2 type substitution and no serious problem on both mechanism and stereochemistry remains unsolved. In contrast, the results under acidic conditions are confusing. We have critically discussed the mechanisms proposed so far and shown our conclusion. On the basis of this conclusion together with a new concept of microscopic structure of solvation, the wide range changes of stereochemistry of acid catalyzed solvolysis of stilbene oxide from inversion to retention in binary solvents have been explained. This idea might be applicable to the other types of solvolysis.

Kinetics of the Reaction of α-Chloro Aliphatic Acids with Aqueous Ammonia

Abstract The kinetics of the reaction of α-chloro aliphatic acids (CAA’s) with aqueous ammonia to form the corresponding α-amino acids and α-hydroxy acids have been studied by measuring the produced chloride ion. The observed rate for CAA’s having COOH on a s-C (s-CAA’s) is expressed as: v=(k1+k2[NH3]ex)[CAA], while the rate for CAA having COOH on a t-C (t-CAA): v=k1[CAA], These results together with previous observations indicate that the mechanism changes with substrate, i.e., pure SN2 type for chloroacetic acid to pure SN1 type for α-chloroisobutyric acid. The exclusion of α-lactone mechanism and the effect of carboxylato group are discussed. The reactivity of ammonia toward α-chloro aliphatic acids is as twice as that of hydroxide ion.

ChemInform Abstract: THE REACTION OF ALKYL HALIDES WITH MERCURY(II) AND POTASSIUM THIOACETATES AND SELENOCYANATES

AbstractHg‐ bzw. K‐thioacetat (I) reagieren mit Alkylhalogeniden in Hexan bzw. DMF zu Alkylthioacetaten (II).

ChemInform Abstract: REACTIVITY AND ION PAIRING OF ALKALI β‐KETOENOLATES

AbstractLösungen von Alkalimetallund Tetrabutylammoniumsalzen von Dibenzoylmethan und Dipivaloylmethan in Dimethylsulfoxid und THF werden durch eine Reihe vonvMethoden zur Bestimmung des Grades der Assoziation und der Natur der assoziierten Spezies untersucht.