bluuebunny/crossref_metadata_2025 huggingface dataset:
Dehydration of 4‐oximinocarboxylic acids with dicyclohexylcarbodiimide
Authors: Masaki M. , Matsukubo H. , Masuzawa K. , Chigira Y. , Ohta M.
Published: March 2009

Treatment of 4‐oximino‐4‐phenylbutyric acid with dicyclohexylcarbodiimide gave 6H‐3‐phenyl‐4, 5‐dihydro‐6‐oxo‐1, 2‐oxazine (IId), which was characterized by its infrared spectrum and some reactions. Ring cleavage of IId was easily accomplished by acid or base such as hydrochloric acid, alcohol or amines. The treatment of 4‐oximino‐valeric acid with dicyclohexylcarbodiimide was also studied.
Studies of heteroaromatic systems by nuclear magnetic resonance spectroscopy. 4‐pyrimidones and 4‐pyrimidthiones
Authors: Bauer Ludwig , Wright George E. , Mikrut Bernard A. , Bell Charles L.
Published: March 2009

Proton magnetic resonance spectral parameters of 4‐pyrimidone, 1‐ and 3‐alkyl‐4‐pyrimidones as well as some of their thione analogs are presented and are compared to those of 4‐substituted pyrimidines. It was found that the ortho, meta and para coupling constants in each series were constant for 4‐substituted pyrimidines, the 1‐alkyl‐ and the 3‐alkyl‐4‐pyrimidones. A particularly large meta (J2, 6) coupling constant was an outstanding feature found in 1‐methyl‐, 1‐ethyl‐ and 1‐benzyl‐4‐pyrimidones and also in 1‐methyl‐4‐pyrimidthione but was virtually zero for the corresponding 3‐alkyl‐4‐pyrimidones. These findings are interpreted in terms of the aromatic character of these 4‐pyrimidones and thiones. During the synthetic aspects of this work, an interesting carbon‐sulfur cleavage was discovered when it was observed that 2‐benzylmercapto‐4‐pyrimidones were readily hydrolyzed by hot concentrated hydrochloric acid to the corresponding 2‐thiouracils.
Fused‐ring systems containing 1,2,4‐benzo thiadiazines. II. Reactions of o‐amino‐n‐hydroxybenzenesulfonamides
Authors: Wei Peter H. L. , Bell Stanley C. , Childress Scott J.
Published: March 2009

o‐Amino‐N‐hydroxybenzenesulfonamides have been treated with aldehydes to prepare 2‐hydroxy‐1,2,4‐benzothiadiazine 1,1‐dioxides. These products have permitted the fusion of an additional ring to the “b” face of the benzothiadiazine. Analogs of the tricyclic compounds have been made in other ways.
Pyrimidines. XVII. I‐(Tetrahydro‐2‐pyranyl)cytosine, ‐uracil, ‐thymine and related compounds
Authors: Noell C. Wayne , Cheng C. C.
Published: March 2009

In view of the reported biological activities of antibiotics Amicetin and Blasticidin S, 1‐(tetrahydro‐2‐pyranyl)cytosine, ‐uracil, ‐thymine and related compounds were synthesized. These compounds were prepared by the Hilbert‐Johnson method from 2‐chloro‐tetrahydropyran and corresponding 2,4‐dimethoxypyrimidines.
Preparation and some reactions of 3,9‐dichloro‐2,4,8,10‐tetraoxa‐3,9‐diphosphaspiro[5.5] undecane‐3,9‐disulfide
Authors: Rätz Rudi , Bliss Arthur D.
Published: March 2009

3, 9‐Dichloro‐2, 4, 8, 10‐tetraoxa‐3, 9‐diphosphaspiro[5. 5]undecane‐3,9‐disulfide (I), has been synthesized by treating a dimethylacetamide solution of 2, 4, 8, 10‐tetraoxa‐3,9‐diphosphaspiro[5. 5]undecane‐3, 9‐disulfide (III) with carbon tetrachloride. A number of other known methods for converting dialkyl phosphorothioites to thiophosphorochloridates were also applied to III, but all failed to produce I. Chlorination of either I or III gave an acyclic product, 4, 4‐bis(chloromethyl)‐1, 1, 7, 7‐tetrachloro‐2, 6‐dioxa‐1, 7‐di‐phosphaheptane‐1, 7‐dioxide (IV), in nearly quantitative yield. The same compound was also obtained by the previously known method of chlorinating 3, 9‐dichloro‐2,4,8,10‐tetraoxa‐3, 9‐diphosphaspiro[5.5]undecane (II). The treatment of pentaerythritol with phosphorus pentachloride gave IV in minor amount along with a 25% yield of 4,4‐bis‐(chloromethyl)‐1‐chloro‐2, 6‐dioxa‐1‐phosphacyclohexane‐1‐oxide (VII). The hydrolysis of I in heated aqueous sodium carbonate gave, after acidification, 3,9‐dihydroxy‐2,4,8,10‐tetraoxa‐3, 9‐diphosphaspiro[5. 5]undecane‐3, 9‐disulfide (VIII). A number of derivatives were prepared by reaction of I with phenoxides and amines. The corresponding thio‐phosphorofluoridate XI was prepared by treatment of I with potassium fluoride in dioxane.
Physical and chemical properties of hydroxyflavones. IV. Infrared absorption spectra of dihydroxyflavones containing the 5‐hydroxyl group
Authors: Looker J. H. , Hanneman W. W. , Kagal S. A. , Dappen J. I. , Edman J. R.
Published: March 2009

Solid state infrared curves (O‐H and C‐H stretching region) are given for 5, n‐dihydroxyflavones, where n is 2′, 3′, 4′, 6, 7 and 8. In chloroform solution spectra of 3,5‐dihydroxyflavone and 3‐hydroxy‐5‐methoxyflavone, the 3‐OH stretching band appears at 3400 and 3334 cm−1, respectively, indicative of a stronger hydrogen bond in the latter substance. Solid state and solution carbonyl bands are presented for twenty‐six flavone derivatives which contain a hydroxyl, methoxyl or acetoxyl group at the 5‐position. The solution spectra (dioxane or carbon tetrachloride) of fourteen flavone derivatives containing a free 5‐hydroxyl group show carbonyl bands at 1655±2 cm−1. Eleven flavones in which the 5‐hydroxyl is blocked (carbon tetrachloride solution) give spectra with flavone carbonyl bands at 1653±3 cm−1. The high resolution chloroform solution spectrum of 3, 5‐dihydroxyflavone possesses a multi‐peaked carbonyl band with midpoint at 1641 cm−1. The chloroform solution spectrum of 3‐hydroxy‐5‐methoxyflavone has a very strong band at 1616 cm−1, with shoulder at 1646 cm−1. Spectral data of this and a previous paper support the postulate that in 4′‐hydroxyflavone the flavone carbonyl oxygen is the donor atom in an intermolecular hydrogen bond. Certain details of synthesis, and analytical data, are given for 3, 5‐dihydroxyflavone.
Reaction of indolylmagnesium bromide and chloromethylpyridines. Synthesis of skatylpyridines and piperidines
Authors: Degraw Joseph I. , Kennedy Jill G. , Skinner W. A.
Published: March 2009

The reaction of indolylmagnesium bromide with the 2‐, 3‐, and 4‐chloromethyl‐pyridines is reported. Methods are described for the preparation of 2‐, 3‐ and 4‐skatylpyridine and 2‐, 3‐ and 4‐skatylpiperidine.
The synthesis and characterization of some 2,1,6‐triaryl and alkylsulfonylhydrazido‐s‐triazines
Authors: Herweh J. E.
Published: March 2009

2,4,6‐Trialkyl‐ and triarylsulfonylhydrazido‐s‐triazines (I) have been synthesized by the reaction of cyanuric chloride with a variety of sulfonylhydrazides in a hydrocarbon solvent. The subject compounds (I) were characterized by elemental analysis, molecular weight and spectroscopy.
Novel methylation. III. Methylation of tertiary amines such as pyridine and isoquinoline with alkyl carboxylates
Authors: Kametani Tetsuji , Kigasawa Kazuo , Hayasaka Tetsutaro , Hiiragi Mineharu , Ishimaru Haruhide , Asagi Setsu
Published: March 2009

The alkylation of tertiary amines, namely, 2‐dimethylaminoethanol, triethylamine, pyridine and isoquinoline with various alkyl carboxylates was investigated. This reaction afforded the corresponding quarternary ammonium salts, e.g., methylation of 2‐dimethyl‐aminoethanol with methyl salicylate.
Phenyl substituted dipyrazoles: 1,3‐Dipole addition reactions of sydnones and nitrilimines
Authors: Stille J. K. , Harris F. W. , Bedford M. A.
Published: March 2009

A series of phenyl substituted phenylene dipyrazoles has been synthesized by the 1,3‐dipole addition reactions of phenylenedisydnone and phenylenedinitrilimines on phenyl acetylene as well as the reactions of phenylsydnone and phenylnitrilimine on diethynyl‐benzenes. A preliminary study of solvents for the sydnone reaction has been made.
Syntheses and interconversions of some s‐triazolo[3,4‐a]isoquinolines
Authors: Sidhu G. S. , Naqui S. , Iyengar D. S.
Published: March 2009

s‐Triazolo[3,4‐a]isoquinoline (II) and its 3‐methyl analogue (III) have been synthesized from 1‐isoquinolylhydrazine (I) by cyclisation with formic and acetic acid. The 3‐hydroxy derivative (IV) has been shown to exist in the lactam form. Methylation with methyl iodide gave the N‐methyl derivative (V). Dimethyl sulphate and diazomethane also led exclusively to the same product. The O‐methyl derivative (IX) could be obtained only through the 3‐chloro compound (VIII). The chlorine atom in VIII undergoes nucleophilic replacement easily. The 3,6‐dichloro derivative (X) has also been prepared. Several interconversions in the series are described. Aryl hydrazones (XVIII) prepared from (I) have been oxidatively cyclised to give 3‐aryl‐s‐triazolo[3,4‐a]isoquinolines (XIX). U.V., I.R. and P.M.R. spectra have been recorded and used for assignment of structures in some cases.
The reduction products of 2‐phenyl‐1,3‐di(4‐pyridyl)‐2‐propanol
Authors: Derieg M. E. , Brust B. , Fryer R. Ian
Published: March 2009

A number of chemical modifications of 2‐phenyl‐1,3‐di(4‐pyridyl) ‐ 2 ‐ propanol are described. Dehydration, alkylation and hydrogenation, concomitant and independent, gave a variety of novel compounds. Independent syntheses produced the related compounds X and XVI which were subjected to some of the same reactions. Structural assignments (spectral) were corroborated by the synthesis of common reaction products.
Synthesis of vitamin b6derivatives. II. 3‐Hydroxy‐4‐hydroxymethyl‐2‐methyl‐5‐pyridine acetic acid and related substances
Authors: Tomita Isao , Brooks Houston G. , Metzler David E.
Published: March 2009

The syntheses of 3‐hydroxy‐4‐hydroxymethyl‐2‐methyl‐5‐pyridineacetic and ‐5‐pyridine‐propionic acids and several related compounds are described. Although acid hydrolysis of α4,3‐O‐isopropylidene‐5‐pyridoxic acid gives 5‐pyridoxic acid lactone (α‐pyracin), its higher homolog α4,3‐O‐isopropylidene‐pyridoxylformic acid gave a corresponding free alcohol whose carboxylic acid proton was shown to be exchanged rapidly with the 3‐phenolic and ‐4‐alcoholic ‐ protons in nuclear magnetic resonance studies. Inter‐molecular hydrogen bonding between the side chain carboxylic acid and pyridine nitrogen atoms is suggested in the solid state.
5‐Ethoxy‐3‐(trichloromethyl)‐1,2,4‐oxadiazole
Authors: Narayanan V. L. , Bernstein Jack
Published: March 2009

5‐Ethoxy‐3‐(trichloromethyl)‐1, 2, 4‐oxadiazole (V) was synthesized to elucidate the chemistry involved in the preparation of the hitherto unreported alkoxy‐1, 2, 4‐oxadiazoles and to determine the effect of the isosteric replacement of sulfur by oxygen on antifungal activity. Heating the “amino‐oxime” tautomer II of trichloroacetamidoxime with ethyl chloroformate furnished exclusively the O‐acylated product III. The trans configuration of III accounts for its resistance to cyclize under a variety of conditions, in contrast to the general behaviour of acylated amidoximes. Pyrolysis of III at 160° yielded IV which exists in the keto form. Refluxing IV with ethyl iodide in the presence of silver oxide gave an isomeric mixture which was separated by v.p.c. to give V and VI. Compound V retained 60% of the overall activity of the corresponding sulfur analog.
Studies on the benzo[1,2]cyclohepta[3,4,5‐d,e]isoquinoline ring system
Authors: Humber L. G. , Davis M. A. , Thomas R. A. , Otson R. , Watson J. R.
Published: March 2009

The syntheses of various oxidation states of the novel benzo[1, 2]cyclohepta[3, 4, 5‐d, e]‐isoquinoline ring system is described. The ring system was obtained by the Schmidt rearrangement, with exclusive alkyl migration, of 1, 6, 7, 11b‐tetrahydro ‐ 2H ‐ dibenz‐[cd,h]azulen‐2‐one and by a Bischler‐Napieralski reaction of suitable derivatives of 10, 11‐dihydro‐5H‐dibenzo[a, d]cycloheptene ‐ 5 ‐ methylamine. 4, 5, 10, 11 ‐ Tetramethoxy derivatives of the new ring system were best prepared by a Pictet‐Spengler reaction of the appropriate amine.
The synthesis of 2‐aryl‐3‐oxa‐1‐azaspiro [4.4]non‐1‐enes
Authors: Collins Paul W. , Andrako John
Published: March 2009

A series of 2‐aryl‐3‐oxa‐1‐azaspiro[4.4]non‐1‐enes was prepared by cyclization of the corresponding β‐acylamino alcohols (V) with thionyl chloride. Structure proofs for the β‐acylamino alcohols and the spiro compounds are given. Infrared and p.m.r. data are reported.
The chemistry of pyrazine and its derivatives. XI. The participation of tetramethylpyrazine in alkylation and aldol‐type reactions
Authors: Chakrabartty Sujit K. , Levine Robert
Published: March 2009

Using sodium amide and phenyllithium as the condensing agents, tetramethylpyrazine has been alkylated with several alkyl halides to give mixtures of alkyltrimethylpyrazines and what are believed to be 2,5‐dialkyl‐3,6‐dimethylpyrazines. Evidence in support of the structures of the dialkylated compounds is presented for the case where the alkylating agent is n‐butyl bromide. A number of carbinols have been prepared by the reaction of tetramethylpyrazine with aldehydes and ketones using phenyllithium as the condensing agent. One of these, 1‐(trimethylpyrazyl)‐2,4‐dimethyl‐2‐pentanol has been dehydrated to 1‐(trimethylpyrazyl)‐2, 4‐dimethyl‐1‐pentene.
The acylation of lepidine
Authors: Baum Burton M. , Levine Robert
Published: March 2009

A number of ketones have been prepared in good to high yields by acylating the methyl group of lepidine (III) with a variety of esters using sodium diisopropylamide (II) as the condensing agent. Two ketones, ethyl and isopropyl lepidyl ketone, have been shown to exist in two forms, the keto form and the intermolecular, hydrogen bonded, enolic form.
1,2,3‐benzotriazines. I. The synthesis of some benzimidazo [1,2‐c][1,2,3]‐benzotriazines and naphth[1′,2,(2′,1′):4,5]imidazo[1,2‐c][1,2,3]benzotriazine
Authors: Zaika Laura L. , Joullié Madeleine M.
Published: March 2009

A number of substituted benzimidazo[1, 2‐c][1,2,3]benzotriazines were prepared by the diazotization of the appropriate 2‐(o‐aminophenyl)benzimidazoles. Diazotization of 2‐(o‐aminophenyl)naphth[1,2‐d]imidazole yielded a new heterocyclic ring system. Various methods of preparation of 2 ‐ (o‐aminophenyl)benzimidazoles were investigated. The condensation of o‐phenylenediamines with anthranilic acids, in the presence of polyphosphoric acid, provided a convenient route to 2‐(o‐aminophenyl)benzimidazoles but in several cases the products were contaminated with considerable amounts of 6‐(o‐aminophenyl)benzimidazo[1,2 ‐c]quinazolines. 2 ‐ (o‐Aminophenyl)benzimidazoles were also obtained by the catalytic hydrogenation of 2‐(o‐nitrophenyl)benzimidazoles which resulted from the condensation of an o‐phenylenediamine with an o‐nitrobenzaldehyde in ethanol, nitrobenzene or acetic acid. When the condensation was carried out in nitrobenzene, small amounts of 2‐(o‐aminophenyl)benzimidazoles were also formed. The Weidenhagen synthesis, which involves the reaction of an aromatic diamine with an aldehyde in the presence of copper acetate and subsequent decomposition of the cuprous salt of the benzimidazole, yielded 2‐(o‐aminophenyl)benzimidazoles instead of the expected 2‐(o‐nitrophenyl)benzimidazoles when the decomposition was carried out in ethanol. When the cuprous salt was treated with hydrogen sulfide in dilute hydrochloric acid, a mixture of amino‐ and nitrobenzimidazoles resulted. The ultraviolet and infrared spectra of all the compounds prepared were examined.
Synthesis of 6‐substituted pyrimidines by the wittig reaction. I. Via 2‐amino‐4‐hydroxy‐5‐phenylbutylpyrimidine‐6‐carboxaldehyde
Authors: Baker B. R. , Jordaan Johannes H.
Published: March 2009

Condensation of isopropyl 6‐phenylhexanoate with ethyl diethoxyacetate followed by guanidine afforded 2 ‐ amino‐6‐diethoxymethyl‐5‐phenylbutyl‐4‐pyrimidinol (VII). Acid hydrolysis of VII gave an excellent yield of 2‐amino‐4‐hydroxy‐5‐phenylbutylpyrimidine‐6‐carboxaldehyde (IV); the latter could be condensed with stabilized Wittig reagents such as carbethoxymethylene triphenyl phosphorane and cinnamylidene triphenyl phosphorane, but not unstabilized Wittig reagents such as carbethoxypropylene or cyano‐propylene triphenyl phosphorane. Reduction of the Wittig products afforded pyrimidines with functionalized side‐chains in the 6‐position such as the 6‐phenylbutyl (XVIII) and 6‐carboxyethyl (XV) derivatives of 2‐amino‐5‐phenylbutyl‐4‐pyrimidinol.
Cyclic imides IV. The reaction of some N‐substituted nitrophthalimides with sodium methoxide
Authors: Caswell Lyman R. , Kao Teresa Ling‐Chun
Published: March 2009

Treatment of methyl 4‐nitrophthalimidoacetate (I) with sodium methoxide in refluxing methanol results in a Gabriel‐Colman rearrangement to give 7 ‐ nitro‐4‐hydroxy‐3‐carbomethoxy‐1(2H) ‐ isoquinolone (II). Under the same conditions, N‐substituted 3‐nitrophthalimides (IV) yield N‐substituted 3‐methoxyphthalimides (V).
Analogs of tetrahydrofolic acid. XXXIX . selective bromoacylation of polyfunctional molecules for synthesis of active‐site‐directed irreversible enzyme inhibitors
Authors: Baker B. R. , Santi Daniel V. , Coward James K. , Shapiro Howard S. , Jordaan Johannes H.
Published: March 2009

A number of methods for selective bromoacylation of side‐chain amino groups on 2‐amino‐4‐pyrimidinols or 2,4,6‐triaminopyrimidines have been developed for these extremely sensitive products. The choice of method depends upon whether (a) the aminopyrimidine is a stronger base than the amine to be bromoacylated, (b) as weak a base as the amine to be bromoacylated but the amine is more reactive, (c) the amine group to be bromoacylated is a strong aliphatic amine. In case (a) the aminopyrimidine can be protonated to protect it from acylation with an anhydride; in case (b), the reaction with an anhydride is controlled by temperature, stoichiometry, and time of reaction; in case (c), the reaction is selectively controlled by use of the less reactive p‐nitrophenyl esters. Other difficulties were solved such as (a) proper characterization of the products when combustion analyses were unsatisfactory due to polymerization; in these cases a combination of thin layer chromatography, color reactions, and derivatization were employed; and (b) insolubility leading to overreaction on the aminopyrimidine which was solved with partial aqueous systems.
1,2,3‐benzotriazines. II. Reactions of benzimidazo[1,2‐c][1,2,3]benzotriazines and naphth[1′,2′(2′,1′):4,5]imidazo[1,2‐c][1,2,3]benzotriazine
Authors: Zaika Laura L. , Joullié Madeleine M.
Published: March 2009

A number of methyl‐ and halogeno‐substituted benzimidazo[1,2‐c][1,2,3]benzotriazines were subjected to a series of hydrolytic cleavages in acid media. The reactions of these compounds with dilute sulfuric acid yielded 2‐(o‐hydroxyphenyl)benzimidazoles. Concentrated hydrochloric acid produced a mixture of 2‐(o‐chlorophenyl)‐ and 2‐(o‐hydroxyphenyl)benzimidazoles. Hydrogen chloride in ethanol caused the formation of 2‐ phenylbenzimidazoles contaminated with small amounts of 2 ‐ (o‐chlorophenyl)benzimidazoles. The benzimidazo[1,2‐c][1,2,3]benzotriazines underwent the Sandmeyer reaction to form 2‐(o‐chlorophenyl)‐ and 2‐(o‐bromophenyl)benzimidazoles in excellent yields. These reactions illustrated the behavior of these 1,2,3‐triazines as internal diazonium compounds. Naphth[1′,2′(2′,1′):4,5]imidazo[1,2‐c][1,2,3]benzotriazine behaved similarly. Bromination of some benzimidazo[1, 2 ‐ c][1,2,3]benzotriazines in aqueous medium yielded bromine‐substituted [1,2‐c][1,2,3]benzotriazines.
Synthesis of a series of isomers of coumestrol
Authors: Spencer R. R. , Knuckles B. E. , Bickoff E. M.
Published: March 2009

Three position isomers of the coumestan (2) coumestrol have been synthesized from appropriately substituted flavylium salts. The dimethyl ethers and diacetates of the isomers and several possible monomethyl ethers and their acetates have been prepared.
Thiaindanones III. beckmann rearrangement of oximes
Authors: Aparajithan K. , Thompson A. C. , Sam Joseph
Published: March 2009

The Beckmann rearrangement of 5‐methylthiaindan‐4‐one oximes (I) and thiaindan‐6‐one oximes (IV) proceeds with the migration of the alkyl group to yield dihydrothieno‐pyridones (II and V, respectively). In two instances, the corresponding lactones (VIIa and VIIb) also were isolated. None of the isomeric lactams (X and XI) were isolated from the Beckmann rearrangement reactions. Supporting evidence for the proposed structures is provided.
Thermal fragmentation of 3,5‐diaryl‐1,2,4‐oxadiazoles
Authors: Ainsworth C.
Published: March 2009

3,5‐Diaryl‐1,2,4‐oxadiazoles have been shown to undergo thermal fragmentation, and the pathway for the transformation is discussed.
Stereochemistry of cis‐ and trans‐1‐hydroxy‐1‐phenylquinolizidines
Authors: England James Don , Sam Joseph
Published: March 2009

cis and trans‐1‐Hydroxy‐1‐phenylquinolizidines were prepared from 1‐ketoquinolizidine and isolated by column chromatography. Infrared and nuclear magnetic spectral data were utilized for the elucidation of the structures.
Organosilicon compounds I. A novel synthesis of organosilicon substituted furfurals
Authors: Thames Shelby F. , Odom Homer C.
Published: March 2009

The use of the diethylacetal moiety of 2‐furfuraldiethylacetal as a carbonyl blocking agent during n‐butyllithium metalations is described. The synthesis of 5‐silicon substituted furfurals is accomplished for the first time with NMR data being employed as a means of structure proof. Furthermore, the isolation of the uniquely stable organo‐lithium salt, 5‐lithio‐2‐furfuraldiethylacetal, is reported.
The synthesis of 6,7‐dihydro‐5H‐pyrrolo[3,4‐d]pyrimidines. II. 4‐Hydroxy, 4‐mercapto, 2‐amino‐4‐hydroxy and 2,4‐dihydroxy derivatives
Authors: Sheradsky Tuvia , Southwick Philip L.
Published: March 2009

Several new types of compounds in the 6,7‐dihydro‐5H‐pyrrolo[3,4‐d]pyrimidine series have been prepared. Included are a 6‐acyl derivative unsubstituted in the pyrimidine ring, as well as 4‐hydroxy, 4‐mercapto, 2‐amino‐4‐hydroxy and 2,4‐dihydroxy derivatives. These products were derived directly or indirectly from 4‐cyano‐ or 4‐carbethoxy‐1‐acyl‐3‐amino‐3‐pyrroline intermediates. 3‐Hydroxy, 3‐amino, and 3‐thioformylamino‐1‐acyl‐3‐pyrroline‐4‐thiocarboxamides have been obtained and the 3‐thioformylamino derivatives shown to undergo base‐catalyzed cyclization to close a 4‐mercaptopyrimidine ring.
Irreversible enzyme inhibitors. LXXXIII. Candidate active‐site‐directed irreversible inhibitors of dihydrofolic reductase. VIII. Derivatives of 2,4‐diaminopyrimidine. II
Authors: Baker B. R. , Jordaan Johannes H.
Published: March 2009

2,4‐Diamino‐6‐(p‐aminophenethyl)pyrimidines with a 5‐phenylbutyl (XIX) and 5‐(p‐chlorophenyl) (VIII) substituent were synthesized by condensation of the corresponding pyrimidine‐6‐carboxaldehydes (XVI, X) with the Wittig reagent derived from p‐nitro‐benzyl bromide, followed by catalytic hydrogenation. Selective bromoacetylation of VIII and XIX afforded the candidate active‐site‐directed irreversible inhibitors of dihydrofolic reductase, namely, 6‐(p‐bromoacetamidophenethyl)‐2,4‐diaminopyrimidine with a 5‐(p‐chlorophenyl)‐ (IV) and 5‐phenylbutyl‐ (III) substituents. Although III and IV were excellent reversible inhibitors of dihydrofolic reductase, neither showed any inactivation of the enzyme; in contrast, the corresponding 2‐amino‐6‐(p‐bromoacetamidophenethyl)‐5‐phenylbutyl‐4‐pyrimidinol (II) ‐ which differs from III only in the 4‐substituent (NH2 vs. OH) ‐ was an excellent active‐site‐directed irreversible inhibitor of dihydrofolic reductase, but II was a poor reversible inhibitor. Thus the conformations of II and III are most probably different when complexed to dihydrofolic reductase.
Irreversible enzyme inhibitors. LXXXV. On the mode of pyrimidine binding of 5‐alkyl and 5‐arylpyrimidines to dihydrofolic reductase
Authors: Baker B. R. , Lourens Gerhardus J. , Jordaan Johannes H.
Published: March 2009

A series of 5‐isoamyl‐ and 5‐(p‐chlorophenyl)pyrimidines substituted with amino, alkylamino, mercapto, benzyloxy, hydroxy, or hydrogen at the 2‐ and 4‐positions and with amino or methyl at the 6‐position have been synthesized for evaluation of the mode of pyrimidine binding to dihydrofolic reductase. The studies were performed in order to determine where a bulky group could be placed on the pyrimidine ring that would still allow good binding; such studies are essential to find a suitable position for placement of a covalent forming group for design of active‐site‐directed irreversible inhibitors. Two classes of candidate compounds have emerged for further study as irreversible inhibitors, namely, 2‐amino‐4‐mercapto‐6‐(p‐bromoacetamidophenylalkyl)‐pyrimidines and 2,4‐diamino‐6‐(p‐bromoacetamidophenylalkyl)aminopyrimidines having a group such as phenyl, phenylbutyl or isoamyl at the 5‐position that can give strong hydrophobic bonding to the enzyme.
Synthesis and properties of 5‐isoxazolethiols
Authors: Adembri G. , Nesi R.
Published: March 2009

The synthesis of a new class of compounds, the 5‐isoxazolethiols, from 5‐chloro‐isoxazoles is described.

The chemical properties and tautomeric behaviour in solution and in solid state are deduced from UV and IR spectra. 5‐Ethylthioisoxazoles and 2‐methylisoxazoline‐5‐thiones were also synthesized to support our interpretation.
NMR analysis and synthesis of 6‐ and 8‐C‐methylisoflavones
Authors: Markham K. R. , Mabry T. J. , Rahman W. , Jehan Sardar
Published: March 2009

NMR data for eighteen 6‐ and 8‐C‐methylisoflavones provide conclusive evidence that in isoflavones, the C‐8 proton and C‐8 methyl signals occur downfield from the C‐6 proton and C‐6 methyl signals. Other useful NMR correlations and the synthesis of five new C‐methylisoflavones are described.
New aromatic systems having a fused thiazolium ring
Authors: Bradsher C. K. , Lohr D. F.
Published: March 2009

The method developed for the synthesis of thiazolo[3,2‐a]pyridinium salts has been extended to the first synthesis of simple thiazolo[3,2‐a]pyrimidinium, thiazolo[3,2‐a]‐pyrazinium and thiazolo[2, 3‐b]benzo[d]thiazolium salts. No method could be found for the cyclization of 4′‐bromo‐2‐(2‐benzoxazolylthio)acetophenone to the thiazolo[2,3‐b]‐benzoxazolium system.
Preparation of some 2,3,5,6,7,8,8a‐heptahydrothiazolo[3,2‐a]‐s‐triazine‐5,7‐diones
Authors: Penner H. P. , Conklin Alfred R.
Published: March 2009

A number of 2‐substituted‐2‐thiazolines have been found to react readily with two moles of isocyanic acid in ethereal solution to give 2, 3, 5, 6, 7, 8, 8a‐heptahydrothiazolo‐[3,2‐a]‐s‐triazine‐5, 7‐diones (IIa‐e). Preliminary reports indicate some activity of these compounds against Walker's carcinosarcoma 256 in rats.
1,2,5‐Selenadiazoles. Synthesis and properties
Authors: Shealy Y. Fulmer , Clayton Joe D.
Published: March 2009

4‐Amino‐1, 2, 5‐selenadiazole‐3‐carboxylic acid and 4‐amino‐1, 2, 5‐selenadiazole‐3‐carboxamides have been prepared by ring‐cleavage of [1, 2, 5]selenadiazolo[3, 4‐d]pyrimidin‐7(6H)‐one by basic reagents. The primary amide (III), as well as an N‐alkyl amide, may be produced by the action of a primary amine. Hydrazine reductively cleaves the selenadiazole ring. The preparation of similar 4‐ureido derivatives by ring‐cleavage of [1,2,5]selenadiazolo[3, 4‐d]pyrimidine‐5, 7(4 H, 6H)‐dione has been demonstrated with two examples.

N‐Butyl‐4‐ureido‐1, 2, 5‐selenadiazole‐3‐carboxamide is easily hydrolyzed in aqueous base to the corresponding acid, and it has been shown that this reaction proceeds by way of [1, 2, 5]selenadiazolo[3,4‐d]pyrimidine‐5, 7 (4H, 6H)‐dione.

The 4‐amino‐1, 2, 5‐selenadiazole‐3‐carboxylic acid derivatives have marked cytotoxic, antibacterial, and antifungal activity.
Reactions of 14‐hydroxy‐14‐azadispiro[5.1.5.2]pentadec‐9‐ene‐7,15‐dione and related compounds. II
Authors: Nightingale Dorothy V. , Johnson James E.
Published: March 2009

3 When 11‐diethyl‐ and 3, 11‐di‐n‐propyl‐14‐hydroxy‐14‐azadispiro[5.1. 5.2]pentadec‐9‐ene‐7, 15‐dione (E‐IV and n‐Pr‐IV) are heated with polyphosphoric acid at 55–65°, the 14‐hydroxyl group cyclizes at the 11‐carbon to form E‐VI and n‐Pr‐VI, the structures of which have been established. Compounds P‐IV, i‐Pr‐IV and t‐B‐IV do not cyclize under these conditions.

The Beckmann rearrangement of 12‐hydroxy‐12‐azadispiro[4.1.4.2]tridec‐8‐ene‐6, 13‐dione‐6‐oxime (P‐I) with polyphosphoric acid at 40–50° formed only the normal product, P‐II, which could not be cyclized.

Compound P‐IV was the only ketone of this series which would add hydrogen cyanide to form a cyanohydrin.
Oxazolidines versus schiff bases
Authors: Srivastava R. M. , Weissman Katherine , Clapp Leallyn B.
Published: March 2009

The formation of oxazolidines from propionaldehyde and aliphatic β‐aminoalcohols is complicated by the appearance of appreciable amounts of unsaturated Schiff bases. The simple Schiff base, often the dominant species when aromatic aldehydes react with amines, could not be detected in the present aliphatic systems. We conclude that in aliphatic systems the order of stability is magnified image and magnified image. The gem‐dimethyl group α to nitrogen stablizes the heterocyclic ring remarkably.
Irreversible enzyme inhibitors. LXXXIX. candidate active‐site‐directed irreversible inhibitors of dihydrofolic reductase. X. derivatives of 2‐amino‐5‐benzamidopropyl‐4‐pyrimidinol
Authors: Baker B. R. , Coward James K.
Published: March 2009

Since 2‐amino‐5‐benzamidopropyl‐6‐methyl‐4‐pyrimidinol (VII) was a reasonably good reversible inhibitor of dihydrofolic reductase, the benzamido group was substituted with p‐bromomethyl (XVIIa), m‐bromomethyl (XVIIIa), and p‐bromoacetyl (XIXa) groups; these compounds, and the corresponding 6‐phenylpyrimidines, were synthesized from the proper 2‐amino‐5‐aminopropyl‐4‐pyrimidinol (V) by devising methods that were compatible with the high reactivity of the halogen. Compounds XVII‐XIX showed in‐activation of dihydrofolic reductase; the fact that p‐nitrobenzyl bromide inactivated the enzyme as rapidly as XVII and XVIII and phenacyl bromide inactivated the enzyme as rapidly as XIX indicated that these inactivations proceeded by a random bimolecular mechanism and not the desired active‐site‐directed mechanism.
Synthesis of possible metabolites of chlorpromazine. I. 7‐hydroxy derivatives of chlorpromazine, nor1‐chlorpromazine and nor2‐chlorpromazine
Authors: Nodiff Edward A. , Ina Shuichiro , Oda Noriichi , Hayazaki Takanori , Nishibe Sansei , Kohno Tetsuya , Hausman Martin , Manian Albert A.
Published: March 2009

The title compounds and various derivatives have been prepared as analytical standards for the identification of chlorpromazine metabolites in biological materials. Additional evidence is presented for the existence of a halogen‐induced Smiles rearrangement in the phenothiazine series.
Purine nucleosides XVII. The synthesis and conformation of 6‐amino‐9‐β‐D‐ribopyranosylpurine and related derivatives prepared via the fusion procedure
Authors: Pan Yung Hsin , Robins Roland K. , Townsend Leroy B.
Published: March 2009

The preparation of 2, 6‐dichloro‐9‐(2′,3′,4′‐tri‐O‐acetyl‐β‐D‐ribopyranosyl)purine (I) has been accomplished utilizing the acid catalyzed fusion procedure. The displacement of the 6‐chloro group, or the 2‐ and 6‐chloro group has been studied. Several new 6‐substituted‐9‐(β‐D‐ribopyranosyl)purines have been prepared by catalytic dehalogenation of the corresponding 2‐chloropurine nucleosides. The conformation and configuration of these D‐ribopyranosylpurines has been assigned with the assistance of proton magnetic resonance studies.
5,6‐dihydro‐4H‐1,3,4‐thiadiazines. II. synthesis and use of 1‐(1‐methylhydrazino)‐2‐propanethiol for the preparation of various thiadiazines and a 2‐thiazolidinethione
Authors: Trepanier D. L. , Krieger P. E.
Published: March 2009

This paper reports the synthesis of 1‐(1‐methylhydrazino)‐2‐propanethiol and the results of a study of its reactions with benzaldehyde, benzonitrile, benzoyl chloride, triethyl orthoformate, succinonitrile, cyanogen bromide, and cyclopropylcyanide to give a thiadiazine directly or a product which can be converted to a thiadiazine. It also reports the condensation of 1‐(1‐methylhydrazino)‐2‐propanethiol with carbon disulfide to yield a 2‐thiazolidinethione.
The synthesis of some 1‐(β‐diethylaminoethyl)‐2‐(p‐ethoxybenzyl)‐5‐substituted benzimidazoles
Authors: Carroll F. I. , Handy R. W. , Kepler J. A. , Gratz Joan A.
Published: March 2009

The syntheses of several 5‐substituted benzimidazoles structurally related to the highly active analgesic 1‐(β‐diethylaminoethyl)‐2‐(p‐ethoxybenzyl)‐5‐nitrobenzimidazole are presented.
Structural modification studies of 3‐piperonylsydnone I. synthesis of piperonyl‐substituted pyrazoles, isoxazoles, triazoles, oxadiazoles and thiadiazoles
Authors: Boots Sharon G. , Cheng C. C.
Published: March 2009

As a structural modification study of the antimalarial compound 3‐piperonylsydnone, a number of pyrazoles, isoxazoles, 1,2,4‐triazoles, ψ‐1,2,4‐triazoles, 1,3,4‐oxadiazoles, 1,3,4‐thiadiazoles and their intermediates all of which contain the piperonyl moiety have been synthesized. The antimalarial activity of these compounds was found to be less than that of the original sydnone. With the exception of 2,4‐diamino‐5‐piperonylpyrimidine, among the compounds tested, those which showed survival time of eleven days or over all possess a N‐N linkage.
The synthesis of tetrahydroisoquinolines from 1,4‐dihydro‐3 (2H)‐isoquinolones
Authors: Finkelstein Jacob , Brossi Arnold
Published: March 2009

Experimental procedures are given for the facile synthesis of various types of 1,4‐dihydroisoquinolones and their reduction to the corresponding 1,2,3,4‐tetrahydroisoquinolines.
Pyrazolo‐N‐hydroxyuracils from the modified lossen rearrangement of vicinal pyrazoledicarbohydroxamates
Authors: Bauer Ludwig , Mahajanshetti C. S.
Published: March 2009

The reaction of 1‐phenyl‐3,4‐ and 4,5‐pyrazoledicarbohydroxamates, II and VIII, with benzene‐ and methanesulfonyl chlorides is reported. Each hydroxamate yielded two isomeric N‐phenyl‐N‐hydroxypyrimidinediones whose structures were established. The NMR spectra of a number of isomeric pyrazole derivatives are discussed.
Novel heterocyclic derivatives of quinuclidine
Authors: Renters William A. , Gibs Gabriel J. , Weiss Martin J.
Published: March 2009

Treatment of ethyl 3‐quinuclidinone‐2‐carboxyIate (III) with appropriate reagents gave 2,3‐fused heterocycles including pyrazolol, aminopyrimidinone, and aminopyridazinone types. The thiourea derivative of III could not be cyclized. Triazoline, pyrazoline, and isoxazoline derivatives were prepared by 1,3‐dipolar cycloadditions to the 2‐ and 3‐positions of methyl 2,3‐dehydroquinuclidine‐3‐carboxylate (XIIIa). Such facile formation of cycloaddition products was not possible with 2,3‐dehydroquinuclidine, which reacted only with phenylazide (in poor yield). Structural assignments for the products of cycloaddition were made by analogy, but alternative structures could not be ruled out by the nmr or mass spectra.
4‐thiazohne‐2‐thiones. III. The thermodynamic stability of intermediate, tautomeric thiazolidines and dithiocarbamates
Authors: Lamon R. W. , Humphlett W. J. , Blum W. P.
Published: March 2009

The intermediate products isolated from preparations of 3‐substituted 4‐thiazoline‐2‐thiones by the reaction of primary amines, carbon disulfide, and α‐haloketones may be either 4‐hydroxy‐thiazolidine‐2‐thiones or dithiocarbamates. Tautomeric equilibrium of the two types of intermediates in solution is demonstrated, and the more thermodynamically stable form is determined. Steric and electronic effects of substitution on stability are described.
The reaction of methyl propiolate with 2‐aminopyridines
Authors: Wilson J. G. , Bottomley W.
Published: March 2009

The structure (III) reported by Lappin (2) for the diadducts formed by the reaction of methyl propiolate with 2‐aminopyridines has been found to be incorrect. The correct structure (IV) has been proven by spectral studies and cyclisation to compound VII. In two cases new compounds having structures of the type (III) have been isolated. N.M.R. data are reported for all products.
New synthesis routes to 2‐halopyridines. I. 2‐chloropyridine
Authors: Boudakian Max M. , Frulla F. F. , Gavin David F. , Zaslowsky Joel A.
Published: March 2009

In contrast to the wide variety of products previously reported from the non‐photolytic liquid or vapor phase chlorination of pyridine (I), it has been demonstrated that the corresponding photochemical chlorination of I in carbon tetrachloride under reflux conditions gave 2‐chloropyridine (IV) in 62–78 percent yield.
Benzo[b]thiophene derivatives I. 6‐methoxybenzo[b]thiophene analogs of plant growth regulators
Authors: Schuetz Robert D. , Titus Richard L.
Published: March 2009

The acid catalyzed ring closure of an appropriately substituted phenyl ketoester sulfide served as the initial reaction in the synthesis of several 3,4‐ and 3,6‐disubstituted benzo[b]thiophenes. One of these compounds, 4‐methoxybenzo[b]thienyl‐3‐acetic acid, showed marked plant growth enhancement.
1‐(2‐pyridyl)‐3,4‐dihydro‐6,7‐dimethoxyisoquinoline and some of its hydrogenated and N‐substituted derivatives
Authors: Wenner Wilhelm , Stefaniw Mychajlo
Published: March 2009

The preparation of 1‐(2‐pyridyl)‐ and 1‐(2‐piperidyl)‐substituted, partly hydrogenated derivatives of 6,7‐dimethoxyisoquinoline is described.
1,4‐disubstituted pyridazino[4,5‐d] pyridazines
Authors: Dorman Linneaus C.
Published: March 2009

1,4‐Bis(methyIthio)pyridazino[4,5‐d]pyridazine (IV) was synthesized from 4,5‐pyridazinedi‐carboxylic acid in three steps. By employing IV as an intermediate, various 1,4‐disubstituted pyridazino[4,5‐d]pyridazine derivatives of classes 1,4‐N,S; 1,4‐N,O; 1,4‐O,S; and 1,4‐O,O were prepared by one‐step or two‐step nucleophilic substitution reactions. Steric, polar and resonance effects were observed in some of these reactions and are discussed.
The crystal molecular structure of cis‐13,13‐dimethyl‐13‐azoniabicyclo [10.1.0] tridecane iodide
Authors: Trefonas L. M. , Towns R. , Majeste R.
Published: March 2009

The crystal and molecular structure of cis‐13,13‐dimethyl‐13‐azoniabicyclo[10.1.0]tridecane iodide has been determined by a three‐dimensional, single‐crystal, x‐ray diffraction study. The compound crystallizes in the orthorhombic space group Pnam with cell dimensions aQ = 21.36 ± .01, bO = 9.07, cO = 8.29 Å. The aziridine ring is fused to the cyclododecane ring with fusion angles of 123.5°. The molecule is bisected by a mirror plane with the cyclododecane portion distorted from its anticipated square conformation. Transannular hydrogen interactions are estimated on the basis of geometric considerations. A final value of R = 0.112 was obtained for the 557 non‐equivalent reflections which were observed.
3‐H‐isoxazolin‐5‐ones
Authors: De Sarlo Francesco , Dini Giuliano
Published: March 2009

4‐Alkyl and 4‐phenyl isoxazolin‐5‐ones were prepared. The 4‐alkyl compounds were found to isomerize easily to α‐cyano carboxylic acids. The acidity and the tautomeric composition of the compounds prepared arc surveyed and compared to the results of the previous literature.
Synthesis and properties of fluorine‐containing heterocyclic compounds. V. Trifluoromethyl‐1,8‐ and 1,10‐phenanthrolines
Authors: Nyquist Edwin B. , Joullié Madeleine M.
Published: March 2009

The condensation of ethyl trifluoroacetoacetate with various heterocyclic amines yielded 2‐(trifluoromethyl)phenanthrolin‐4‐ones. The structures of these compounds were established from a study of their infrared and ultraviolet spectra. Substituted phenanthrolines were prepared by nucleophilic attack on a chlorophenanthroline. The oxidation of 5‐methoxy‐2‐trifluoromethyl‐1,10‐phenanthroline yielded an o‐quinone which was treated with typical quinone reagents. A molecular orbital calculation was carried out in an attempt to explain the ease of reduction of the 1,10‐phenanthroline system and the colors of the reduced compounds.
Naphthyridine chemistry. VIII. The mass spectra of the 1,X‐naphthyridines and some of their methyl derivatives
Authors: Paudler William W. , Kress Thomas J.
Published: March 2009

The mass spectra of the four parent 1,X‐naphthyridines, the 2,3 and 4‐monomethyl‐1,5‐,1,6‐. and 1,8‐ naphthyridincs, seven dimethyl‐1,8‐naphthyridines, and one trimethyl‐1,8‐naphthyridine are reported. Evidence for an azatropylium ion intermediate in the fragmentation of the methyl compounds is presented. The fragmentation modes of the naphthyridines are similar to those for the quinolines in addition to several new processes
as‐Triazine chemistry. V.The oxidative ring‐opening of 5,6‐diphenyl‐as‐triazine‐3(2H)‐ones with Organic Peracids
Authors: Sasaki Tadashi , Minamoto Katsumaro
Published: March 2009

The structures of the oxidation products of 5,6‐diphenyl‐as‐triazine‐3(2H)‐ones (Ia‐b) with organic peracids were chemically and spectroscopically reinvestigated and it was concluded that the products were 1,4‐dibenzoyl semicarbazide (IIa) and the 2‐methyl analogue (IIb).
A new synthesis of thiazolo[3,2‐a] pyrimidinones
Authors: Andrew H. F. , Bradsher C. K.
Published: March 2009

5H‐Thiazolo[3,2‐a]pyrimidin‐5‐ones (V) have been prepared by S‐alkylation of 6‐methyl‐2‐thiouracil (Ib) with bromoacetone or bromoacetophenone followed by cyclization in sulfuric acid. By the same series of reactions, 2‐thiouracil (Ia) gave rise to 7H‐thiazolo[3,2‐a]pyrimidin‐7‐ones (VI). The properties and structures of the intermediates and products are discussed.
PMR spectra and conformation of some four‐membered rings containing one nitrogen atom. 2‐Azetidinones, 2‐azetidinethiones and 1‐azetines
Authors: Vigevani Aristide , Gallo Gian Gualberto
Published: March 2009

By PMR studies at different temperatures a planar conformation is proposed for the 2‐azetidinone, 2‐azetidinethione and 1‐azetine rings. The chemical shifts and the vicinal and geminal coupling constants of the ring methylene protons are reported and discussed. The application of the relationship between the Jgem value and the angle between the methylene group and the adjacent 7r‐bond is considered.
Synthesis and reactions of 3,9‐diisocyanates and diisothiocyanates in the 2,4,8,10‐tetraoxa‐3,9‐diphosphaspiro[5.5] undecane series
Authors: Pivawer Philip M. , Bliss Arthur D. , Ratz Rudi
Published: March 2009

The synthesis of several novel phosphorus‐containing isocyanates and isothiocyanates is reported. These compounds are spiranes with two six‐membered dioxaphosphorinane rings in their respective molecule. The phosphorus‐bonded isocyanato and isothiocyanato groups are capable of undergoing addition reactions with active hydrogen atom‐containing compounds.
1‐Azetines
Authors: Pifferi Giorgio , Consonni Pietro , Pelizza Giuseppina , Testa Emilio
Published: March 2009

The synthesis, characteristics and chemical behaviour of some 3,3‐disubstituted‐2‐ethoxy‐ and 2‐ethy lthio‐1‐azetines, the first examples of a new class of heterocyclic compounds, are described.
NMR spectra of 2‐pyrone and 2‐pyrone derivatives
Authors: Pirkle W. H. , Dines Martin
Published: March 2009

An analysis of the complex NMR spectrum of 2‐pyrone is presented and the spectra of a series of variously substituted 2‐pyrones and 5,6‐dihydro‐2‐pyrones are discussed. It is demonstrated that NMR spectroscopy affords a convenient and reliable method of assigning the position of substituents on the 2‐pyrone nucleus.
Preparation of 4‐pyrimidinetliiones from acyl lsothiocyanate‐enamine adducts
Authors: Lamon Robert W.
Published: March 2009

Adducts formed from benzoyl isothiocyanate and l‐morpholinocyclopentene or β‐(N,N‐diethylamino)styrene and that prepared from acetyl isothiocyanate and l‐pyrrolidinoeyclopen‐tene gave 4‐pyrimidinethiones when treated with primary amines or ammonia. In some cases intermediates, the products of amine exchange, were isolated. These intermediates were readily cyclized to 4‐pyrimidinethiones with dilute alkali.
Studies on the syntheses of heterocyclic compounds. part CCLXXIX . Synthesis of O‐isobutylcularidine
Authors: Kametani T. , Iida H. , Kibayashi C.
Published: March 2009

Although various methods of oxepine formation from phenoxybenzene dicarboxylic acids was attempted, only 11‐hydroxy‐4‐isobutoxy‐7,8‐dimethoxydibenz[b,f]oxepin‐l‐ylaeetic acid lactone (XXX) was synthesized successfully. Compound XXX gave O‐isobutylcularidine (XXXVlIb) in a few steps. Our synthetic O‐isobutylcularidine was identical with that prepared from natural cularidine proving the structure for cularidine proposed by Manske. However, dealkylation of synthetic O‐isobutylcularidine was unsuccessful.
Synthesis of substituted dihydroisocarbostyrils from 5‐hydroxyamides obtained from dilithio‐N‐substituted o‐toluamides
Authors: Mao Chung‐Ling , Burnish I. T. , Hauser Charles R.
Published: March 2009

δ‐Hydroxyamides, prepared by condensation of ketones or aldehydes at the 2‐methyl group of Nsubstituted o‐toluamides by means of n‐butyllithium, were cyclodehydrated with sulfuric acid to form 2,3‐disubstituted and 2,3,3‐trisubstituted 3,4‐dihydroisocarbostyriIs. Also, δ‐hydroxyamides obtained from condensation of ketones at the 2‐benzyl group of N‐methyl‐o‐benzylbenzamide, were cyclodehydrated to give 2,3,3,4‐tetrasubstituted 3,4‐dihydroisocarbo‐styrils. All of the products appeared to be new. This new method, which involves an unusual acid catalyzed cyclodehydration, is convenient and apparently quite general.
Benzothiazoline derivatives. II. Preparation of N‐substituted derivatives of 2‐benzothiazolinethione by thiation of the 2‐oxo analogs
Authors: Sohar Paul , Denny George H. , Babson Robert D.
Published: March 2009

Thuiation of the benzoate and acetate esters of 3‐(2‐hydroxyethyl)‐2‐benzothiazolinone (Ig) gave the corresponding thiones. The benzoate was then deblocked to yield 3‐(2‐hydroxyethyl)‐2‐benzothiazolinethione (Ik), a compound not accessible by direct addition or substitution. Attempts to introduce a chlorine (or bromine) atom in place of the hydroxy 1 group in the latter compound or its S‐isomer, 2‐(2‐hydroxyethylthio)benzothiazole (11a), gave 2,3‐dihydrothiazolo‐[2,3‐b ] benzothiazolium chloride (or bromide) (IIIa or b). The latter compound undergoes dihydrothiazolo ring opening when treated with sodium hydroxide or sodium sulfide to give bis[2‐(2‐benzolhiazolinon‐,3‐yl)ethyl]disulfide (IVc) or bis[2‐(2‐benzothiazolinethion‐3‐yl)ethyl] disulfide (lVb),respectively. 2‐Benzothiazolinethione reacted with ethylenimine and with N‐phenylethylenimine to give S‐substituted derivatives. Addition to vinyl n‐butyl ether gave the expected N‐substituted derivative, which was found to undergo removal of the butyoxyethyl group when subjected to conventional conditions for ether cleavage.
Alkylidenebis‐1‐methyl‐2‐alkylidenehydrazines as intermediates in the reaction of methylhydrazine with aliphatic aldehydes
Authors: Rabjohn Norman , Sloan K. B.
Published: March 2009

It has been shown that heptylidenebis‐1‐methyl‐2‐heptylidenehydrazine (Va) is an intermediate in the reaction of methylhydrazine with heptanal. The bis‐compound (Va) reacts with methylhydrazine to give heptanal methylhydrazone (IIa), or with heptanal, in the presence of acid, to afford 5‐hexyl‐1‐methyl‐4‐pentyl‐2‐pyrazoline (Ia). The latter also results from the treatment of IIa with acid.
Pyrrolopyrimidine nucleosides. IV. The synthesis of certain 4,5‐disubstituted‐7‐(β‐d‐ribofuranosyl)pyrrolo[2,3‐d]pyrimidines related to the pyrrolo[2,3‐d]pyrimidine nucleoside antibiotics
Authors: Hinshaw Barbara C. , Gerster John F. , Robins Roland K. , Townsend Leroy B.
Published: March 2009

The treatment of 4‐chloro‐7‐(2′,3′,5′‐tri‐O‐acetyl‐β‐D‐ribofuranosyl)pyrrolo[2,3‐d]pyrimidine (4) with N‐bromoacetamide in methylene chloride has furnished the 5‐bromo derivative of 4 which on subsequent deacetylation provided a good yield of 5‐bromo‐4‐chloro‐7‐(β‐D‐ribo‐furanosyl)pyrrolo[2,3‐d] pyrimidine (6). Assignment of the halogen substituent to position 5 was made on the basis of pmr studies. Treatment of 6 with methanolic ammonia afforded 4‐amino‐5‐bromo‐7‐(β‐D‐ribofuranosyl)pyrrolo[2,3‐d ]pyrimidine (8, 5‐bromotubercidin) and a subsequent study has revealed that the 4‐chloro group of 6 was replaced preferentially in a series of nucleophilic displacement reactions. The analogous synthesis of 4,5‐dichloro‐7‐(β‐D‐ribo‐furanosyl)pyrrolo[2,3‐d]pyrimidine (13b) and 4‐chloro‐5‐iodo‐7‐(β‐D‐ribofuranosyl)pyrrolo[2,3‐d]pyrimidine (13a) from 4 furnished 5‐chlorotubercidin (15) and 5‐iodotubercidin (14), respectively, on treatment of 13b and 13a with methanolic ammonia. The possible biochemical significance of these tubercidin derivatives is discussed.