Markownikoff Rule Research Articles

Regioselective addition of sulfur dichloride and selenium tetrachloride to diallyldimethylsilane as the method of preparation of eight-membered heterocycles containing silicon and chalcogens

The electrophilic additiob of sulfur dichloride and selenium tetrachloride to diallyldimethylsilane proceeds strictly according Markownikoff rule and results in the formation of previously unknown saturated siliconcontaining heterocycles, 5,5-dimethyl-3,7-dichloro-1,5-thiasilacyclooctane and 5,5-dimethyl-1,1,3,7-tetrachloro-1,5-selena(IV)silacyclooctane. The structure of heterocycles obtained was confi rmed by 1H, 13C NMR spectra, in the case of selenium-containing heterocycle, by 77Se NMR spectrum, among them the 2D HMBC spectrum.

Monoterpenoids dithiophosphates. Synthesis and biological activity

O,O-Dialkyldithiophosphoric acids adds at the double bond of the racemic camphene and (+)- limonene in the presence of Lewis acids in accordance with the Markownikoff rule with the formation of Sterpenyl esters of dithiophosphoric acids. The reaction with camphene is accompanied by the rearrangement of camphane structure to that of bornane. Addition of dithiophosphoric acid to (+)-limonene proceeds with the participation of the exocyclic double bond. Toxic and genotoxic properties of the monoterpenoid dithiophosphates were studied.

New Method of Synthesis of β-Haloalkyl Alkynyl Sulfides: Reaction of Alkynesulfenamides with Olefins in the Presence of Phosphoryl Halides

Reactions of alkynelsufenamides with olefins (such as cyclohexene, norbornene, 1-hexene, 1-octene, allylbenzene, and styrene) in the presence of phosphoryl halides (POCl3, POBr3) afforded 70–95% of β-halo-substituted alkyl alkynyl sulfides. The reactions with cyclohexene and norbornene are characterized by trans stereoselectivity. Alkynylsulfenylation of terminal alkyl- and benzylacetylenes occurs in a regioselective fashion with predominant formation of the corresponding anti-Markownikoff adducts, while the addition to styrene yields halogen-containing sulfides according to the Markownikoff rule.

Functional Methacryloyloxy Acetals: V. Electrophilic Addition of Carboxylic Acids to 2-Vinyloxyethyl Methacrylate

Mono- and dicarboxylic acids (acetic, methacrylic, E-crotonic, and malonic) quantitatively add to 2-vinyloxyethyl methacrylate under mild conditions (1 wt % CF3COOH, 20–60°C, 1–4 h) according to the Markownikoff rule to give the corresponding mono- and bis-adducts with high regio- and chemoselectivity. The products may be regarded as a new family of functionalized methacrylates.

Mechanism of Catalytic Addition of Benzeneselenol to Alkynes

Addition of benzeneselenol to terminal alkynes HCIACR, catalyzed by Pd(0) complexes, leads to formation of mixtures of mono- and bis(phenylseleno)alkenes, depending on the nature of the R substituent. Electron-donor groups (R = Bu, CH2OH, CH2NMe2) give rise to addition according to the Markownikoff rule, whereas from alkynes with electron-acceptor groups (R = Ph, COOMe) mixtures of products are formed as a result of side reactions. A probable reaction mechanism includes oxidative addition of benzeneselenol to the metal, alkyne insertion into the PdASe bond, and reductive elimination.

Reaction of 2-Alkoxypropenals with 2-Mercaptoethanol *

The reaction between 2-alkoxypropenals and 2-mercaptoethanol was studied at 20 and 60°C by means of 1HNMR and GC-MS methods. Under kinetically controlled conditions (20°C, 7-30 days) with no catalyst the addition of 2-mercaptoethanol to 2-alkoxypropenals occurs along Markownikoff rule. The arising 2'-hydroxyethylthio-2-alkoxypropanal undergoes isomerization into the 2-hydroxy-3-alkoxy-3-methyl-1,4-oxathiane that at heating in the presence of catalytic amounts of acids is converted into 2-methyl-2-formyl-1,3-oxathiolane. The reaction of 2-alkoxypropenals with 2-mercaptoethanol at heating (60°C, 3 h) in the presence of acids affords 2-methyl-2,2'-bi(1,3-oxathiolane) even at 2-mercaptoethanol deficit. At the double excess of the latter the 2-methyl-2,2'-bi(1,3-oxathiolane) was obtained in quantitative yield. The presumable schemes of conversion of 2-hydroxy-3-alkoxy-3-methyl-1,4-oxathiane into 2-methyl-2-formyl-1,3-oxathiolane and 2-acetyl-1,3-oxathiolane are discussed.

Synthesis of β-haloacids by radiation

Hydrogen halides add to alkenes yielding the corresponding haloalkane. The addition of HX ordinally follows the course of Markownikoff's rule. In this paper we analyze the HBr addition reaction to unsaturated carboxylic acids. The course of the addition is anti-Markownikoff. This implies that the reaction goes through free radical mechanism and the haloacid formed is in the β-position. The acids under study are fumaric, itaconic, citraconic acids and the methyl ester of fumaric acid. The β-haloacids formed are easily purified from the bulk solutions.

Simple, though efficient procedures for the introduction of fluorine into a unsaturated hydrocarbons

When olefins are treated with a source of “positive halogen” (such as N-chloro-, N-bromo- or N-iodosuccinimide) in the presence of triethylamine-tris(hydrofluoride), 2-fluoroalkyl chlorides, bromides or iodides are formed with excellent yields. Reductive replacement of the heavier halogen leads to fluoroalkanes, its base-promoted elimination to 1-fluoroalkenes. ▪ Terminal olefines obey the MARKOWNIKOFF rule. On the other hand, branched olefms show different regioselective outcome depending on the N-halosuccimimide employed. ▪ 1-Bromo-2,2-fluoroalkanes are readily accessible by two consecutive additions of the elements of bromine and fluorine, a dehydrobromination step being interposed. They can be converted into α,α-difluoroalkanals either by bromine/acetate substitution followed by hydrolysis and SWERN oxidation or by bromine/thiopbenolate substitution followed by oxidation and PUMMERER isomerization. ▪ These methods can be applied to the synthesis of new compounds exhibiting well defined organoleptic, therapeutic or pesticidal activity. Typical examples will be presented.

Reactions of N-substituted allylacetic acid amides with selenium and tellurium tetrahalides

The addition of selenium tetrabromide to the olefinic bond of N-substituted allylacetic acid amides (reagent molar ratio 2∶1) proceeds counter to Markownikoff's rule with the formation of tetrahydrofuran derivatives. The addition of tellurium tetrahalides under the same conditions (reagent molar ratio 1∶1) proceeds in accordance with Markownikoff's rule with the formation of tetrahydropyran derivatives.

Synthesis of 2-substituted tetrahydrofurans

We have developed a three-stage scheme for the preparative synthesis of 2-substituted tetrahydrofurans from allyl halides and aldehydes to give the first stage — a Grignard reaction — mixed alkoxides, which on treatment with acetic anhydride are converted to 4-acetoxy-1-alkenes. Addition of hydrogen bromide to the latter contrary to Markownikoff's rule gives 4-acetoxy-1-bromoalkanes, which as a result of hydrolysis form 2-R-tetrahydrofurans.

Markownikoff's rule: What did he say and when did he say it?

Markownikoff's rule: What did he say and when did he say it?

Reactions of primary aliphatic and cycloaliphatic amines with 1-butyl acrylate

The addition reactions of primary aliphatic and cycloaliphatic amines with 1-butyl acrylate have been investigated by means of near IR spectroscopy. The additions proceed contrary to the Markownikoff rule and are consecutive competitive reactions which can be treated as isolated reactions with respect to the considerable difference between rate constants of the individual steps. The value of rate constants determined from the spectral data have been compared and discussed in terms of the steric hindrance of alkyl groups which co-determines the reactivity of amines in the reactions investigated.

ChemInform Abstract: 1,3‐Iodofunctionalization of Cyclopropanes by Means of the Mercury(II) Salt ‐ Iodine Combination.

AbstractPhenylcyclopropane (I) is regioselectively converted to the 3‐iodo‐1phenylpropane derivatives (IV) by reaction with the mercury(II) salts (II) and iodine (III), according to the Markownikoff rule.

Protonation and hydrolysis of ?-piperidinocrotonaldehyde

1. Treatment of α-piperidinocrotonaldehyde with hydrogen chloride or trifluoroacetic acid gave the corresponding enammonium salt. Reaction of the aldehyde with acetic acid caused dissociation and polymerization. 2. Hydration of the double bond of a-piperidinocrotonaldehyde in acid medium proceeded according to the Markownikoff rule to yield the piperidine salt and ethylglyoxal.

Hydrohalogenation of 1-vinylpyrazoles

1. In accordance with Markownikoff's rule, at 20–25°C 1-vinylpyrazole and 4-bromo-1-vinylpyrazole add predominantly hydrogen halides at the double bond of the vinyl group. Under these conditions, formation of the corresponding hydrohalides is characteristic of the more basic alkyl-substituted 1-vinylpyrazoles. 2. Addition of hydrogen halides to 1-vinylpyrazoles at 0–15°C occurs only at the N2 atom with formation of salts.

Electrophilic reactions of halides of group vi elements. 7. Reactions of allylbenzene and allyl phenyl ether with selenium tetrahalides

The reaction of selenium tetrachloride with allylbenzene and allyl phenyl ether proceeds in accordance with the Markownikoff rule to give 1:2 adducts. The use of selenium tetrabromide changes the course of the reaction and leads to the production of a mixture of adducts in accordance with and counter to the Markownikoff rule, as well as products of cyclization of the intermediate monoadducts to 2-bromomethyl-2,3-dihydrobenzo[b]selenophene or 2-bromomethyl-benzo-1,4-selenoxane derivatives.

Reactions of imidobis(sulfuryl fluoride) and N-chloroimidobis(sulfuryl fluoride) with olefins

Reactions of HN(SO 2F) 2 and ClN(SO 2F) 2 with cis -and trans -(CH 3)CHCH(CH 3), H 2CCF 2, and cis CHFCHF have been studied. The addition of ClN(SO 2F) 2 with cis -and trans -(CH 3)CHCH(CH 3) is stereospecific and trans while the addition to cis -CHFCHF is non-stereospecific. Addition of HN(SO 2F) 2 follows Markownikoff's rule and ClN(SO 2F) 2 addition always places the N(SO 2F) 2 group on the most positive carbon. 1H, 19F nmr and infrared spectroscopy and mass spectrometry have been used to characterize the adducts.

Quantum-chemical calculations of transition states and activation energies of molecular 1,2-elimination (1,2-addition) of HNO2

1. Quantum-chemical calculations of the reactants and the transition states in the reaction of 1,2-addition (1,2-elimination) of HNO2 to a double bond have been carried out. The orbital interactions of the reactants were analyzed, and it was shown that in the course of addition electron density is transferred from HNO2 to the olefin, i.e., HNO2 acts as a nucleophile. 2. The regioselectivity of the addition reaction of HNO2 is determined by the character of the lower vacant MO of the olefin. The addition to nitroethylene should proceed with a lower energy of activation than in the reaction with ethylene, and in opposition to the Markownikoff rule, while the addition to alkyl-substituted ethylene is according to the Markownikoff rule. 3. The introduction of an additional nitro group to the molecule of nitroethane and also replacement of the methyl group in nitroethane by an amino group lead to a considerable decrease in the activation energy of the reaction of the 1,2-elimination of HNO2. 4. The dipole moment of the transition state of the 1,2-elimination of HNO2 is much smaller than in the initial nitroethane, which is explained by mutual compensation of the component due to the polarization of the HNO2-ethylene system and the dipole moment of the HNO2 molecule itself.

Cob(I)alamin als Katalysator. 6. Mitteilung [1]. Bildung und Fragmentierung von Alkylcobalaminen, ein Gleichgewichtsprozess zwischen nukleophiler Addition und reduktiver Fragmentierung

Cob(I)alamin as Catalyst. 6. Communication [1]. Formation and Fragmentation of Alkylcobalamins: the Nucleophilic Addition – Reductive Fragmentation EquilibriumIsolated olefines can be saturated using catalytic amounts of cob(I)alamin in aqueous acetic acid; as electron source an excess of zinc dust is added to the solution containing the homogeneous catalyst. During this overall hydrogenation of isolated double bonds intermediate alkylcobalamins are formed (compare e.g. Schemes 2, 4, 5, 7 and 12). Clear evidence is presented that the nucleophilic attack on the isolated double bond is carried out by cob(I)alamin and not by cob(II)alamin also present in the system (see Scheme 3b and 3c). As this catalytic saturation of olefins depends on the pH of the solution, characterized by a slow reaction at pH = 7.0 compared to the same reduction in aqueous acetic acid (see Scheme 2, 2 → 4, and Scheme 3a), it is reasonable to accept the participation of an electrophilic attack by a proton during the generation of alkylcobalamins. – We use the term nucleophilic addition to describe the formation of alkylcobalamins from a proton, an olefin and cob(I)alamin (compare Schemes 4–7 and 12).A special sequence of experiments showed the nucleophilic addition to be regioselective. Preferentially the higher substituted alkylcobalamin revealed to be produced. Therefore, the nucleophilic addition of cob(I)alamin follows the Markownikoff rule (compare chap. 4: formation and fragmentation of β‐hydroxyalkylcobalamins).Under the reaction conditions applied the intermediate alkylcobalamins can be present in base‐on and base‐off forms. They are known to exist as octahedral complexes and might also be stable to some extent as tetragonal‐pyramidal species. In addition the base‐off forms can partially be protonated at the dimethylbenzimidazole moiety in aqueous acetic acid (compare Scheme 12). From this equilibrium of intermediate alkylcobalamins three modes of decay disclosed to be possible: (i) The reductive fragmentation leading to an olefin, a proton, and cob(I)alamin is the formal retro‐reaction of the nucleophilic addition (see Schemes 2, 4 and 6–12). This equilibrium of an associated alkylcobalamin and the corresponding dissociation products revealed to be a fast process compared to the reductive cleavage of the Co, C‐bond cited below (s. (iii)). (ii) As the second reaction pattern an oxidative fragmentation producing an olefin, a hydroxy anion (or water, respectively) and cob (III)alamin has been observed (see Schemes 7, 8, 10 and 12). (iii) The slow reductive cleavage of the Co, C‐bond, initiated by addition of electrons (see [1a] [24]), was the third reaction path observed (see Schemes 2, 4–8 and 10–12). – The stereochemistry of the three transformations originating from the intermediate alkylcobalamins is unknown up to now. The antiperiplanar pattern of the fragmentation reactions presented in the Schemes has been chosen arbitrarily (see e.g. Scheme 12).

Phase-transfer catalysis in reaction promoted by hydroalogenic acids

Recently we reported that lipophilic quaternary ammonium and phosphonium salts show a high catalytic activity in reactions promoted by hydroalogenic acids in aqueous-organic two phase systems, such as the conversion of alcohols to the corresponding halides [1] (eqn. l) and the cleavage of ethers [2] (eqns. 2 and 3). ▪ This catalytic system can also be advantageously utilized in other reactions, such as the facile addition of hydroalogenic acids to carbon-carbon double bonds according to Markownikoff's rule [3](eqn. 4), and the hydrolysis of ethers [4] (eqns. 5 and 6) and of other derivatives of carboxylic acids [4]. ▪ The factors which affect the reactions will be discussed.