- 1,3-Dialkyl-3-acyltriazenes: Products and Rates of Decomposition in Acidic and Neutral Solutions
-
The products and mechanism of hydrolytic decomposition of a series of 1,,3-dialkyl-3-acyltriazenes were studied in both acidic and neutral buffers.In the acidic region, the products are alkyl alcohols derived from the N(1) alkyl group and amides derived from the intact N(3) portion of the molecule.The solvent deuterium isotope effect (kH2O/kD2O)) is less than 1.0.The mechanism is specific acid catalyzed, involving rapid reversible protonation of the 3-acyl group followed by scision of the N(2)-N(3) bond to generate an amide and an alkyl diazonium ion.The (2-hydroxyethyl)diazonium ion gives ethylene glycol and acetaldehyde, while the (2-chloroethyl)diazonium ion yields 2-chloroethanol.In the neutral region, the products are similar to those found in acidic buffers, alkyl alcohols, and amides.At this pH the (2-chloroethyl)diazonium ion produces ethylene glycol and acetaldehyde in addition to 2-chloroethanol.The solvent deuterium isotope effect (kH2O/kD2O) is greater than 1.0.The mechanism involves unimolecular heterolylsis of the N(2)-N(3) bond to form an amide anion and an alkyldiazonium ion.The methyldiazonium ion leads to incorporation of deuterium in the methyl group of the products, indicating the existence of an equilibrium between the metastable methyldiazonium ion and diazomethane.
- Smith, Richard H.,Wladkowski, Brian D.,Herling, Julie A.,Pfalzgraff, Timothy D.,Pruski, Brunon,et al.
-
-
Read Online
- Base sequence selectivity in the alkylation of DNA by 1,3-dialkyl-3- acyltriazenes
-
The base sequence selectivity of DNA alkylation for a series of structurally related 1,3-dialkyl-3-acyltriazenes was examined with calf thymus DNA or polymers containing the sequences GGG, CGC, TGT, and AGA. The reaction products at the N7 and the O6 positions of guanine were identified, quantitated, and then correlated with the decomposition rates of the triazenes, 1-(2-chloroethyl)-3-methyl-3-carbethoxy- (CMC), 1-(2-chloroethyl)- 3-methyl-3-acetyl- (CMA), 1-(2-hydroxyethyl)-3-methyl-3-carbethoxy- (HMC), 1- (2-hydroxyethyl)-3-methyl-3-acetyl-(HMA), and 1,3-dimethyl-3-acetyl- (DMA). The results of these studies revealed that DNA sequences with runs of purines were more reactive toward alkylation by all of the triazenes tested, irrespective of whether the alkylation was measured by N7, O6, or total guanine adducts. Within this generalization, the (hydroxyethyl)triazenes showed a preference for the AGA sequence, while the (chloroethyl)triazenes favored the GGG sequence. The structure of the 3-acyl group of the triazene also played a role in the extent of alkylation of a particular sequence of DNA. Both the (chloroethyl)- and the (hydroxyethyl)triazenes produced higher alkylation product yields for the 3-carbethoxytriazenes as compared with the 3-acetyl derivatives for most of the sequences examined. These overall patterns correlated well with the order of decomposition of the triazenes at 37 °C: HMC > DMA > HMA > CMC > CMA. This study has demonstrated how varying the structure of 1,3-dialkyl-3-acyltriazenes can modulate DNA alkylation, a finding which may be important in the design of new triazene antitumor agents.
- Smith,Taneyhill,Michejda,Smith Jr.
-
-
Read Online
- A Class of N-O-Type Oxidants to Access High-Valent Palladium Species
-
This article presents a new class of mild reagents that is capable of oxidizing palladacycle(II) complexes to high-valent palladium species, promoting the formation of C-N bonds in stoichiometric and catalytic conditions. The weak N-O bond and the extremely electron-withdrawing benzenesulfonate group on the oxygen atom of the oxidant are crucial moieties to ensure the desired activity. The oxidation mechanism could involve outer-sphere single-electron transfer processes, opening the possibility for a complementary reactivity of Pd(IV) species.
- Nappi, Manuel,Gaunt, Matthew J.
-
p. 143 - 148
(2018/12/11)
-
- Capture-Collapse Heterocyclization: 1,3-Diazepanes by C-N Reductive Elimination from Rhodacyclopentanones
-
Rhodacyclopentanones derived from carbonylative C-C activation of cyclopropyl ureas can be "captured" by pendant nucleophiles prior to "collapse" to 1,3-diazepanes. The choice of N-substituent on the cyclopropane unit controls the oxidation level of the product, such that C4-C5 unsaturated or saturated systems can be accessed selectively.
- McCreanor, Niall G.,Stanton, Steven,Bower, John F.
-
supporting information
p. 11465 - 11468
(2016/10/06)
-
- COMPOSITIONS AND METHODS FOR THE TREATMENT OF RESTLESS LEG SYNDROME AND FIBROMYALGIA
-
The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of fibromyalgia, restless leg syndrome may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of motor neurone disease, diabetic neuropathy, postherpetic neuralgia, acute opioid withdrawal management, obsessive-compulsive disorder, premature ejaculation, PTSD, injury, post-operative pain, osteoarthritis, rheumatoid arthritis, multiple sclerosis, spinal cord injury, migraine, HIV related neuropathic pain, bipolar depression, depression, stress, cancer pain and lower back pain.
- -
-
Paragraph 0122; 0123
(2015/05/26)
-
- COMPOSITIONS AND METHODS FOR THE TREATMENT OF CHRONIC PAIN
-
The disclosures herein provide compounds of formula (I) or its pharmaceutical acceptable salts, as well as polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These salts may be formulated as pharmaceutical compositions. The pharmaceutical compositions may be formulated for peroral administration, transdermal administration, transmucosal, syrups, topical, extended release, sustained release, or injection. Such compositions may be used to treatment of neurological disorders or conditions such as pain or its associated complications.
- -
-
Paragraph 00176-00177
(2013/03/28)
-
- Dibutyltin oxide catalyzed aminolysis of oxalate to carbamate, oxamate and derivatives of imidazolidine trione
-
Catalytic aminolysis of oxalates by simple and substituted ureas has been shown to give carbamates, oxamates and derivatives of imidazolidine trione. Various substituted ureas and oxalates were screened to verify the applicability of the protocol. The rol
- Kunde, Lalita B.,Kalyani, Vishwanath S.,Gupte, Sunil P.
-
experimental part
p. 402 - 407
(2010/08/06)
-
- Process for the preparation of alkyl carbamates
-
The invention relates to an efficient process for the preparation of methyl methyl carbamate by reacting methyl amine or N,N'-dimethyl urea with carbon monoxide, an oxidizing agent and a monoalcohol in the presence of a catalyst system including (i) a precursor selected from the group consisting of platinum group metals and soluble compounds of platinum group metals, and (ii) a promoter comprising at least one halogen containing compound selected from the group consisting of alkali metal halides, alkaline earth metal halides, quaternary ammonium halides, oxo acids of halogen atoms and their salts, and complex compounds containing halogen ions, organic halides and halogen molecules.
- -
-
-
- Specificity of DNA alkylation by 1-(2-chloroethyl)-3-alkyl-3- acyltriazenes depends on the structure of the acyl group: Kinetic and product studies
-
The reactions of calf thymus DNA with ten 1-(2-chloroethyl)-3-alkyl-3- acyltriazenes of varying acyl side chain structure were studied alone, or in the presence of porcine liver esterase in pH 7.0 phosphate buffer. In several of the key triazenes, the acyl substituent contained a free carboxylic acid group. With esterase present in the reaction mixture, the resultant levels of DNA alkylation could be correlated with the kinetic rates of decomposition of the triazenes. Under these conditions, the predominant pathway of decomposition involved deacylation of the parent triazene and eventual production of an alkanediazonium ion. This intermediate subsequently alkylated DNA-guanine to give 7-alkylguanine as the principal reaction product. In the absence of esterase, the order of DNA alkylation for all of the acyltriazenes did not correlate with their respective rates of decomposition, leading to the conclusion that the triazenes did not decompose by the expected mode of uncatalyzed N(2)-N(3) heterolyic cleavage. The major DNA alkylation product from the N(3)-methyltriazenes was 7-methylguanine, instead of the expected 7-(chloroethyl)- and 7-(hydroxyethyl)guanine products, which suggested that the acyl group was being hydrolyzed. However, acyltriazenes with an N(3)-benzyl group rather than a methyl in this position produced very little 7-benzylguanine product, contrary to prediction. An alternative mechanism involving internally assisted hydrolysis of the side chain ester is proposed to explain these results. NMR product analysis and computational studies were carried out to lend support to the postulated mechanism.
- Smith,Schmidt,Czerwinski,Taneyhill,Snyder,Kline,Michejda,Smith Jr.
-
p. 466 - 475
(2007/10/03)
-
- DICHLORONITROACETIC ACID DERIVATIVES AS ACYLATING AGENTS FOR PRIMARY AMINES, AMMONIA, AND PHENYLHYDRAZINE
-
The corresponding carbamic acid derivatives were obtained (28-91percent) yields) as a result of the reaction of dichloronitroacetic acid derivatives, O2NCCl2COR, (1a-c, R=OEt, OCH2Ph, NH2) with ammonia, methylamine, benzylamine, glycine, phenylhydrazine, and aniline. The probable mechanism of the process and factors that affect the nature of the departing group were discussed. Keywords: dichloronitroacetic acid derivatives, aminolysis, intermediate states, mechanisms of reactions.
- Yurtanov, A. I.,Adkhamova, Z. M.,Baidildaeva, S. K.
-
p. 891 - 894
(2007/10/02)
-
- Process for the preparation of alkyl methylcarbamates
-
Alkyl carbamates are prepared by reacting a primary alkyl amine, secondary alkyl amine or dialkyl urea with carbon monoxide, an oxidizing agent and an aliphatic or alicyclic monoalcohol in the presence of a catalyst comprising (i) a platinum group metal and (ii) a halogen compound.
- -
-
-
- Chemical Ionization Mass Spectra of Urethanes
-
Chemical ionization mass spectra using methane as the reagent gas are reported for 33 urethanes of general structure RNHCO2C2H5 nH2n+1 (n=1-8), CH2CH=CH2, cyclo-C6H11, Ph, PhCH2, PhCH2CH2, and Ph(CH3)CH> and R2NCO2C2H5 nH2n+1 (n=1-4)>.Abundant MH+ ions are present in all the spectra, accompanied by satellite peaks corresponding to + and +.Four classes of fragment ions are of general importance in the spectra.Two of these, + and +, are associated with the CO2C2H5 group.The other two, corresponding to alkane and alkene elimination from MH+, arise from the RNH or R2N function.The mechanisms whereby these fragment ions are formed are discussed and their analytical utility is illustrated by reference to the spectra of the four isomeric C4H9NHCO2C2H5 and the eight isomeric C5H11NHCO2C2H5 compounds.The results of 2H-labelling studies are presented and a comparison is made between the methane and ammonia chemical ionisation spectra of selected urethanes.
- Wright, Andrew D.,Bowen, Richard D.,Jennings, Keith R.
-
p. 1521 - 1528
(2007/10/02)
-
- SYNTHESIS OF 5,5'-METHYLENEBISPYRIMIDINE DERIVATIVES AND 3,4-DITHIA(6.1)(1.5) PYRIMIDINOPHANE
-
Convenient syntheses of 3,6-dimethyl-1,3-oxazine-2,4(3H)-dione (3) and 5,5'-methylenebis(1-(2-hydroxyethyl)-3,6-dimethyl-2,4(1H,3H)-pyrimidinedione (5) are described.Compound 3 was prepared by the reaction of N-methylurethane with diketene, followed by alkali treatment, and 5 was obtained by treatment of 1-(2-hydroxyethyl)-3,6-dimethyl-2,4(1H,3H)-pyrimidinedione (4) with paraformaldehyde and hydrochloric acid in quantitative yield.Bromination of 5 was carried out with 47percent hydrobromic acid to give 5,5'-methylenebis(1-(2-bromoethyl)-3,6-dimethyl-2,4(1H,3H)-pyrimidinedione) (6).The reaction of 6 with thiourea afforded 7 and subsequent treatment of 7 with sodium hydroxide gave 5,5'-methylenebis(1-(2-mercaptoethyl)-3,6-dimethyl-2,4(1H,3H)-pyrimidinedione) (9).Compound 9 was oxidized to 8,11,15,18-tetramethyl-3,4-dithia(6.1)(1.5)-1,2,3,4-tetrahydro-2,4-dioxopyrimidinophane (10) with iodine under conditions of high dilution.Keywords: methylenebispyrimidine; dithiapyrimidinophane; 1,3-oxazine-2,4-dione; ring transformation; diketene; N-methylurethane; N-acetoacetyl-N-methylurethane.
- Kinoshita, Toshio,Tanaka, Hirokazu,Furukawa, Sunao
-
p. 1809 - 1813
(2007/10/02)
-
- The photochemical addition of N-haloamides to olefins: a comparison of cyclic and acyclic N-halo-N-alkylamides and N-halo-N-acylamides (N-haloimides)
-
Upon photochemical decomposition in the presence of cyclohexene and 1-octene, an N-halo-N-acylamide (N-haloimide) leads to better yields of addition than its N-halo-N-alkyl analogue, and cyclic N-halo-N-alkyl and N-halo-N-acylamides add more efficiently than their acyclic analogues.The yields of addition were higher with N-chlorosuccinimide which has been added also to 1-methylcyclohexene than with N-bromosuccinimide which did not add to 1-methylcyclohexene.
- Lessard, Jean,Couture, Yvon,Mondon, Martine,Touchard, Daniel
-
p. 105 - 112
(2007/10/02)
-
- THE ELECTROCHEMICAL REDUCTION OF N-FLUOROETHANS IN ACETONITRILE. THE GENERATION OF CARBETHOXYNITRENE
-
The electrochemical reduction of N-fluoro-N-methylurethan (1a) and N-fluorourethan (2a) in acetonitrile generates the amide anion and fluoride ion.Both the fluoride and the amide react with the starting N-fluoroamide either as bases or as nucleophiles.Many products are formed and the coulometric results are low (0.5 to 0.7 F/mol).In the case of NFU (2a), abstraction of the proton on nitrogen both by the urethan anion and the fluoride anion generates the conjugate base EtOCOF (7) which immediately undergoes α-elimination of the fluoride ion to give carbethoxynitrene (11).This nitrene was generated also by treating NFU (2a) with a base such as triethylamine of lithium hydride.The α-elimination of F1- from EtOCOF is much easier than α-elimination of Cl1- from EtOCOCl.
- Lessard, Jean,Berube, Denis
-
p. 768 - 777
(2007/10/02)
-
- Orthoamides, XXXVIII. - Contributions to the Chemistry of Orthocarbonic Acid Esters and α,α,α-Trialkoxyacetonitriles
-
The reactivity of the orthocarbonates 4 and the nitriles 1 has been investigated.Carboxylic acids are esterified by 4b. Orthocarbonates 4c-f and 9b are prepared by transesterification of 4b.Mixed substituted orthocarbonates 8c-f are obtained from the nitriles 1a,b.The nitriles 2a and 3a react with alkali alcoholate in alcohol to yield the orthocarbamic acid esters 13a,b. Spirocyclic orthocarbonates 17a-d are prepared from 4b and 1,2 or 1,3-dioles, respectively. The reaction of phenol with 1b affords the mixed substituted orthocarbonate 18a. Catechol is converted by 1a into the orthocarbonate 20a.Reactions of 4b with amines and ami ne derivatives are studied. In the course of these investigations guanidines 21, imidocarbonic acid esters 22a-c, 30, carbamic acid esters 25, ureas 26, the isourea derivative 29, as well as the 1,3,4-oxadiazole 31 are prepared. The mechanism of these reactions is discussed. Imidocarbonic acid esters 22d-f, 38, N-cyanocarbamates 39, and isoureas 37 can be prepared from 1b and amines or amine derivatives. 2a as well as 13b react with cyanamide to give the N-cyanoisourea 40. Ureas 26 are formed in the reaction of 1a,b with secondary amines at elevated temperatures.The guanidinium cyanide 41a can be obtained by reaction of pyrrolidine with 1b in ether, whereas under similiar conditions from 1a and pyrrolidine the amidine 42 is produced. o-Aminophenol, o-phenylenediamine and anthranilic acid are cyclized by 4b or 1b to afford the heterocyclic compounds 43-45. α- and β-amino acids are transformed by 4b or 1b into the N-(ethoxycarbonyl)amino acid esters 46 and 47, respectively.
- Kantlehner, Willi,Maier, Thomas,Loeffler, Wolfgang,Kapassakalidis, Joanis J.
-
p. 507 - 529
(2007/10/02)
-
- The photochemical addition of N-haloamides to olefins: the influence of various factors on the competition between 1,2-addition and hydrogen abstraction
-
In the photodecomposition of N-haloamides (ZCONRX) in the presence of olefins, the 1,2-addition chain competes with the hydrogen abstraction chain(s) leading to the parent amide (the quantum yields for these processes are greater than unity).The following factors were shown to have an influence on this competition as measured by the yield of 1,2-addition and the yield of parent amide in methylene chloride solutions: (i) the N-halogen (higher yields of addition with X=Cl than with X=Br); (ii) the electronegativity of Z (increase of the yield of addition as the electronegativity of Z increases); (iii) the temperature (higher yields of addition at lower temperatures, and at -70 degC, better yields of addition (>90percent, R=H) for X=Br than for X=Cl); and (iv) the size of R (dramatic decrease of the yield of 1,2-addition in going from R=H to R=CH3).Surprisingly, the presence of a scavenger for HX had no influence on the yield of 1,2-addition.Both the size and electronegativity of Z had an effect on the stereochemistry of 1,2-addition to cyclohexene.High yields of addition to a variety of olefins were obtained with N-chloroamides such as ClCH2CONHCl, C2H5OCONHCl, CF3CONHCl.Their addition to enol ethers at -70 degC led to the synthesis of α-amido acetals or ketals (aldehydes or ketones) and to an α-amido glycoside in good yields.
- Lessard, Jean,Mondon, Martine,Touchard, Daniel
-
p. 431 - 450
(2007/10/02)
-
- Nucleophilic Substitutions to Carbonic Acid Derivates. XII. Kinetics and Mechanism of the Reaction of N-Nitro-N-alkyl-urethanes with Primary Aliphatic Amines
-
The aminolysis of N-alkyl-N-nitrourethanes takes place, as the kinetical studies demonstrate, by means of several consecutive steps.The nucleophilic attack of the amine (first step; reaction B), as well as the proton-transfere (second step; reaction C), are quick pre-equilibres, followed by the slow, rate-determining elimination of the nitramino-group (reaction D).During the deprotonation, an intermediate with two to the nitramino-group antiperiplanar orbitals is formed, providing the necessary mesomeric assistance of the elimination.
- Bacaloglu, R.,Prodan-Deac, Y.,Csunderlik, C.,Csomos, P.
-
-