Dialkyl Acetals Research Articles

1,2-Dihydroisoquinolines. XXII. Benzo[b]quinolizine derivatives

Some time ago it was reported that 4,6,11,11a-tetrahydro-1H-benzo[b]quinolizin-2(3H)-ones are produced when N-benzylaminoacetaldehyde dialkyl acetals react with methyl vinyl ketone in acid solution. These structures have now been confirmed, the scope of the reaction broadened and the conformations of the products investigated. Some of these ketones have been treated with phenyl- magnesium bromide, but no useful central nervous system activity has been found for any of the tertiary alcohols produced.

Acetals and thioacetals from thiodiglycolaldehyde: Some oxidation products

Thiodiglycolaldehyde (2,2′-thiobisacetaldehyde, 1a) reacted severally with methanol, ethanol, and 2-propanol to give mixtures variously of thiodiglycoaldehyde bis(dialkyl acetals) ( 3a,b), cis-2,6-dialkoxy-1,4-oxathianes ( 5b-d), and trans-2,6-dialkoxy-1,4-oxathianes ( 7a-c). Thiodiglycolaldehyde bis(di-isopropyl acetal) ( 3c) was not formed in the reaction of 1a and 2-propanol, but 3c was obtained after bromoacetaldehyde di-isopropyl acetal was treated with sodium sulfide. The stereoisomers corresponding to 2,6-dimethoxy-1,4-oxathiane ( 5b, 7a) were obtained from the acyclic dimethyl acetal 3a. The reaction between 1a and thiols in acid media have been studied. With ethanethiol, thiodiglycolaldehyde bis(diethyl dithioacetal) was the only product, but a mixture of thiodiglycolaldehyde bis(di- tert-butyl dithioacetal), cis-2,6-bis( tert-butylthio)-1,4-dithiane, and trans-2,6-bis( tert-butylthio)-1,4-dithiane was obtained from 2-methyl-2-propanethiol. On oxidation to sulfones of the stereoisomers of 2,6-dialkoxy-1,4-oxathiane and 2,6-bis(alkylthio)-1,4-dioxane with hydrogen peroxide, the configurations were retained, but the stereoisomers of 2,6-bis( tert-butylthio)-1,4-dithiane were transformed into the same oxidation product.

Synthesis and structures of some diglycolaldehyde thioacetals

Diglycolaldehyde (2,2′-oxybisacetaldehyde, 1a) reacts with thiols under conditions similar to those for monosaccharides. The nature of the reaction products depends on the degree of α-substitution of the thiol. The acyclic dithioacetal 2a was the only product isolated when methanethiol was used, but mixtures of acyclic dithioacetals, cis-2,6-bis(alkylthio)-1,4-dioxanes, and trans-2,6-bis(alkylthio)-1,4-dioxanes were obtained when ethanethiol, 1-propanethiol, and 2-propanethiol were used. From 1a and 2-methylpropane-2-thiol, the acyclic dithioacetal 2e and the cis (7) and trans (8) stereoisomers of 3,5-bis( tert-butylthio)-1,4-oxathiane were isolated. On the other hand, when diglycolaldehyde bis(dialkyl acetals) ( 9a–d) or 2,6-di-isopropoxy-1,4-dioxane ( 10) were treated with primary or secondary thiols in acid media, the acyclic dithioacetals were isolated as the only products. The acyclic dithioacetal 2e and the oxathiane derivatives 7 and 8 were obtained when 9a–d or 10 were treated with 2-methylpropane-2-thiol under the above conditions.

ChemInform Abstract: REACTION OF ACETALS WITH GRIGNARD REAGENTS

AbstractDie ogß‐ungesättigten Acetale (I) reagieren mit den Alkyl‐Grignard‐Reagenzien in Gegenwart von TiCl4 zu den Allylethern (II).

Reaction of Acetals with Grignard Reagents

Abstract The reaction of dialkyl acetals derived from α,β-unsaturated aldehydes with Grignard reagents using TiCl4in THF afforded the cross coupling products, allyl ethers, in high yields. The TiCl4-promoted reaction of alkyl 2,4-dichlorophenyl acetals, synthesized from 3,4-dihydro-2H-pyran or ethyl vinyl ether and 2,4-dichlorophenol, with Grignard reagents in THF at low temperature afforded the corresponding unsymmetrical ethers in high yields. When alkyl 2,4-dichlorophenyl acetals, synthesized from aromatic aldehyde or vinyl ethers and 2,4-dichlorophenol, were treated with Grignard reagents in benzene or toluene at room temperature in the absence of TiCl4, the cross coupling reaction took place and the corresponding ethers were isolated in good yields.

A novel synthesis of 5-fluorouracil derivatives having oxacycloalkane moieties

5-Fluorouracil derivatives having oxacycloalkane moieties were synthesized in good yields by the reaction of trimethylsilyloxyalkanal dialkyl acetals with 2,4-bis(trimethylsilyl)-5-fluorouracil in the presence of SnCl 4.

New functional allylic lithium reagents: gem-dialkoxyallyllithium reagents: a useful route to β-silyl- and β-stannylpropionate esters

The reaction of sec-butyllithium with acrolein dialkyl acetals in THF or in THF/Et 2O/pentane at -95°C results in formation of gem-dialkoxyallyllithium reagents, Li[CH 2CHC(OR) 2]. These react with organosilicon and organotin chlorides to give ketene acetals, R 3SiCH 2CHC(OR) 2 and R 3SnCH 2CHC(OR) 2. The acid hydrolysis of these products produces β-substituted propionic acid esters, R 3SiCH 2CH 2CO 2R and R 3SnCH 2CH 2CO 2R. Reactions of these lithium reagents with allyl bromide gave esters of 5-hexonoic acid, CH 2CH(CH 2) 3CO 2R (R = Me, Et).

A Precautionary Note Regarding Derivatization of Secondary Amines with Dialkylacetals of Formamide Other Than the Diethyl Derivative

Abstract In an earlier communication we reported GC-MS studies on the reaction products of secondary amino tricyclics and dimethylformamide.1 The diethyl acetal reaction products were identified as N-ethyl derivatives on the basis of mass spectroscopic analysis. In a follow-up study, we reported the same reaction products were formed from other DMF -dialkyl acetals, such as dimethyl and dipropyl acetals.2 In view of this unusual reaction we reinvestigated the structure of the reaction products utilizing alternative spectroscopic methods, viz. NMR and IR.

On-column gas chromatographic synthesis of 1,3-dialkyl (c = 1-10), benzyl, and cyclohexyl barbiturate derivatives.

Procedures are described for the on-column gas chromatographic synthesis of various N-alkyl-N-alkyl barbiturates where groups added to the nitrogens are benzyl, cyclohexyl, or straight chains with 1 to 10 carbons. The 1,3-dialkyl barbiturates having methyl, ethyl, n-propyl, n-butyl, cyclohexyl, isopropyl, or t-butyl groups can be prepared on-column by injecting an aliquot of a chloroform solution of the barbiturate with the appropriate N,N-dimethylformamide dialkyl acetal. The 1,3-dialkyl barbiturates where benzyl or butyl through decyl groups are added can be similarly prepared with N,N-dimethylformamide dineopentyl acetal and the appropriate alcohol to yield the desired compound. The 1-alkyl (I)-3-alkyl-(II) barbiturates where the alkyl groups differ are prepared by on-column reaction reaction of a barbiturate with aliquots of each of the respective reagents giving the desired groups.

Formylation of Secondary Amines with Dialkyl Acetals of Dimethylformamide

Abstract The product of the reaction of dialkyl acetals of N, N-dimethyl-formamide with desipramine has been found to be N-formyldesipramine, and not the N-ethyl derivative as reported earlier. Evidence for the structure was obtained from NMR, IR and mass spectra of the compound as well as comparison with N-formyl and N-ethyldesipramine prepared by alternate routes.

A Precautionary Note Regarding Derivatization of Secondary Amines with Dialkylacetals of Formamide Other Than the Diethyl Derivative

Abstract We have extended our earlier work on alkylation of secondary amino compounds with dimethylformamide diethyl acetal to other alkyl acetals, such as dimethyl and dipropyl acetal. All the alkylating DMT-dialkyl acetal reagents tested gave only N-ethyl derivatives of the secondary amines. The reagent purity was tested by preparing the esters of carboxylic acids, where the appropriate alkyl (methyl or propyl) ester is obtained. It is concluded that all dimethylformamide dialkyl acetals yield a single N-ethyl derivative of secondary amine. The reaction mechanism is not understood.

A dipole moment study of the structures of some ketene acetals

The dipole moments of several acyclic and cyclic ketene acetals have been determined in benzene solution at 293 K using the Halverstadt-Kumler method. For ketene dialkyl acetals (alkyl = Me, Et) the results point to a predominance of the s-cis,s-trans retamer, which disagrees with the conclusions drawn previously from 13C NMR chemical shift data, i.e. the s-cis,s-cis form is the more stable species. In the case of 2-methoxyfuran, the dipole moment measurements confirm the previous findings based on the 13C NMR spectra, viz the s-cis form is the predominating rotamer. The dipole moments and structures of some other ketene acetals are also discussed.

Reduction of Acetals with TiCl4–LiAlH4

Abstract The reduction of dialkyl acetals derived from aromatic aldehydes and ketones with TiCl4–LiAlH4 in THF or diethyl ether at room temperature afforded the coupling products, pinacol ethers or olefins, in high yields. On the other hand, when acetals derived from aliphatic aldehydes and ketones were treated with TiCl4–LiAlH4 in diethyl ether, the reductive dealkoxylation took place and the corresponding ethers were isolated in good yields. As to the reaction mechanism we propose that Ti(II) is the reactive species in reductive coupling reaction of acetals derived from aromatic aldehydes and ketones, and that Ti(0)–H2AlCl complex may be the reactive species in reductive dealkoxylation of acetals derived frcm aliphatic aldehydes and ketones.

13C NMR study of the structures of some acyclic and cyclic ketene acetals

A 13C NMR study of the spatial structures of some acyclic and cyclic ketene acetals (for example, ketene dimethyl acetal and 2-methylene-1,3-dioxolane) has been carried out. The conclusions obtained are based on observation of the effect of structural changes on the 13C NMR chemical shift of the β carbon on the ketene moity. Since the extent of p-π conjugation and hence the 13C chemical shift of this carbon depend on the spatial orientation of the alkoxy groups about the O-C(sp2) bonds, the shift concerned may be used as a measure of the planarity of the system. The most stable retamers of ketene dimethyl acetal are s-cis,s-cis (planar) and s-cis,gauche (slightly nonplanar), in the order of decreasing stability. For ketene dialkyl acetals, the relative stability of the planar s-cis,s-cis form decreases with increasing bulkiness of the alkyl groups, but at least for primary and secondary alkyl groups, the s-cis,s-cis rotamer appears to be the most favored species. The conformations of 5- to 8-membered cyclic ketene acetals are discussed and compared with those of the corresponding cyclic vinyl ethers and hydrocarbons.

Gas-liquid chromatography of resin acid esters

A number of alkyl esters of resin acids were prepared with dialkyl acetals of dimethylformamide, and their gas chromatographic characteristics evaluated with several packed columns. The cyanosilicone liquid phases allow for simultaneous determination of levopimaric and palustric acids, a determination previously unattainable by gas-liquid chromatography.

Simultaneous Determination of Cocaine and Benzoyl Ecgonine in Urine by Gas Chromatography with On-Column Alkylation

A gas chromatographic procedure has been developed for the simultaneous determination of cocaine and benzoyl ecgonine in urine specimens. The two drugs are extracted by isopropanol/chloroform from urine samples saturated with a bisalt buffer. The organic extract is evaporated to dryness, and an aliquot of the residue is injected onto the gas chromatograph to determine the presence of cocaine and the location of any extraneous peaks. Benzoyl ecgonine is then analyzed as its particular alkyl ester subject to the least interference from extraneous peaks as observed in an initial underivatized injection. The reconstituted residue is co-injected with the appropriate dimethylformamide dialkyl acetal for on-column alkylation. The use of two columns or more than one benzoyl ecgonine alkyl ester gives positive identification, and the use of isopropyl benzoyl ecgonine as an internal standard allows accurate quantification.

Die präparative Chemie derO- undN-funktionellen Orthokohlensäure-Derivate

The methods for the preparation of O- and N-functional orthocarbonic acid derivatives are reviewed, and a survey of the reactions of these compounds with electrophilic and nucleophilic reagents is given. 1. Synthesis of Orthocarbonic Acid Esters 1.1 Reaction of Substituted Trichloromethanes with Alcohols, Alkoxides, Phenols, or Phenoxides 1.2. Reaction of Substituted Dichloromethanes with Alcohols or Phenols 1.3. Reaction of Trialkoxycarbenium Salts with Alkoxides 1.4. Reaction of Cyanic Acid Esters with Alcohols 1.5. Thermolysis of Cyclic Carbonic Acid Derivatives 1.6. Reaction of Carbon Disulfide with Thallium(I) Alkoxides 1.7. Reaction of Carbon Disulfide with Organotin Compounds 1.8. Reaction of Zinc Xanthates with Alcohols 1.9. Transesterification of Orthocarbonic Acid Esters 2. Synthesis of Orthocarbamic Acid Esters 2.1. Reaction of Trihetero-substituted Carbenium Ions with Alkoxides 2.2. Alcoholysis of Tetramethylurea Diethyl Acetal 2.3. Transesterification of Orthocarbamic Acid Esters 2.4. Spirocyclic Orthocarbamic Acid Esters from Organotin Compounds 3. Synthesis of Bis[dialkylamino]-dialkoxymethanes (Tetraalkylurea Dialkyl Acetals) 3.1. Reaction of Bis[dialkylamino]-ethoxycarbenium Tetrafluoroborates with Alkoxides 3.2. Reaction of Tetraalkylurea Dichlorides (Chloroformamidinium Chlorides) with Alcohols or Alkoxides 3.3. Reaction of 2,2-Dichloro-1,3-benzodioxole with Amines 3.4. Spirocyclic Urea Acetals from Organotin Compounds 4. Synthesis of Alkoxytris[dialkylamino]methanes 5. Synthesis of Tetrakis[dialkylamino]methanes 6. Reactions of O- and N-Functional Orthocarbonic Acid Derivatives 6.1. Reactions with Electrophilic Agents 6.2. Reactions with Nucleophilic Agents 6.3. Miscellaneous Reactions of Orthocarbonic Acid Derivatives

Esterification of polymeric carboxylic acids

AbstractPolymers containing pendant carboxyl groups have been essentially completely esterified with little apparent change in molecular weight by the use of one of the following reagents: (1) trialkyl orthoesters, (2) dimethylformamide dialkyl acetals, (3) tertiary amines followed by alkyl halides, (4) quaternary ammonium hydroxide followed by alkyl halides. The use of some of these methods permits preparation of certain polymers that were previously not readily accessible.

Nucleophilic reactivity of organophosphorus compounds. Part 3. Kinetics and mechanism of the reaction of phosphorus acids with keten OO-acetals in aprotic medium

The kinetics of the reactions of OO-diethyl S-hydrogen phosphorodithioate and O-ethyl S-hydrogen methylphosphonodithioate with p-nitrophenylketen dialkyl acetals in di-n-butyl ether as solvent are reported and discussed in terms of a mechanism which involves a highly reversible protonation (probably to an ion-pair) followed by nucleophilic attack by the phosphorus anion on the intermediate carbonium ion of the ion-pair.

ChemInform Abstract: REACTIONS OF KETENE ACETALY PART 5, THE REACTION WITH P‐BENZOQUINONE DIHALIDES

Abstractp‐Benzochinondichlorid (Ia) reagiert mit Ketendimethylacetal (II) zu dem Benzofuran (III), den Naphthochinonen (IVa) und (IVb) und dem Ester (Va).