Heterocyclic Building Blocks-piperidine

Paul, Raymond published the artcileDerivatives of 3-hydroxypiperidine, Recommanded Product: 1-Ethylpiperidin-3-ol, the publication is Compt. rend. (1945), 221(No. 15), 412-14, database is CAplus.

1,2-Epoxy-5-chloropentane (I) reacts with amines in most cases to form piperidine derivatives I and 1 mol. NHEt₂ at 100° form a colorless solid, apparently the 1-ethyl-3-hydroxypiperidine-EtCl (II). II warmed with concentrated KOH gives C₂H₄ and 1-ethyl-3-hydroxypiperidine (III), b₂₁ 97-98°, d₁₅²³ 0.966, n_D²³ 1.47427 (77% yield based on I). The intermediate 1-diethylamino-5-chloropentane is not isolated. N,N-Diethyltetrahydrofurfurylamine reacts with dry HBr to form a water-soluble product, which reacts with NH₃ to form the ethobromide (IV) of III. IV warmed with concentrated KOH gave C₂H₄ and 74% of III. I and EtNH₂ at 100° form a product which reacts in hot KOH solution to give 74% of III. BzCl and III form the HCl salt of the benzoate ester, colorless needles, m. 204° and possessing marked anesthetic properties. III and excess concentrated HCl at 150° or III and 1 mol. SOCl₂ at 100-120° give 1-ethyl-3-chloropiperidine (V), colorless liquid of moldy odor, b₂₀ 75°, d₁₅^19.5 0.996, n_D^19.5 1.46807. Picrate of V m. 156-7°; methiodide, m. about 210 °. Aniline and 1 mol. I give at 120° 1-phenyl-3-hydroxypiperidine, colorless liquid, b₁₆ 176°, d₁₆¹⁵ 1.099, n_D¹⁵ 1.57856, and not N-phenyltetrahydrofurfurylamine (VI), b₁₀ 155-6°, d₁₆¹¹ 1.075, n_D¹¹ 1.56456, which was obtained by the action of aniline and tetrahydrofurfuryl chloride (VII) at 150°. The piperidine ring is not always formed, as shown by the action of PhNHEt on I for 12 h. at 125°. N-Tetrahydrofurfuryl-N-ethylaniline (VIII), b₂₀ 176-7°, d₁₆²² 1.052, n_D²² 1.55962, was formed. VIII was also obtained by direct action of PhNHEt on VII.

Compt. rend. published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, Recommanded Product: 1-Ethylpiperidin-3-ol.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Mitchell, Robin E. published the artcileSynthesis of amino acid conjugates to 2-imino-3-methylene-5-carboxypyrrolidine and 2-imino-3-methylene-6-carboxypiperidine, Recommanded Product: (R)-6-Oxopiperidine-2-carboxylic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2010), 20(6), 1910-1912, database is CAplus and MEDLINE.

The four stereomers of 2-imino-3-methylene-5-(carboxy-L-valyl)pyrrolidine, a bacterial metabolite that is inhibitory to the fire blight bacterium Erwinia amylovora, were synthesized and compared for antibacterial activity. Several alternative amino acid conjugates with L,L-stereochem. were also prepared, and the synthesis was extended to 3-methylenepiperidine-6-L-carboxylic acid and a selection of 2-imino-3-methylenepiperidine-6-L-carboxy-L-amino acid conjugates. All synthetic amino acid conjugates (L,L-stereomers) were inhibitory to the growth of E. amylovora. The likely participation of the conjugated iminomethylene moiety as a Michael acceptor is implicated.

Bioorganic & Medicinal Chemistry Letters published new progress about 72002-30-3. 72002-30-3 belongs to piperidines, auxiliary class Piperidine,Chiral,Carboxylic acid,Amide, name is (R)-6-Oxopiperidine-2-carboxylic acid, and the molecular formula is C6H9NO3, Recommanded Product: (R)-6-Oxopiperidine-2-carboxylic acid.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Manap, Sevda published the artcileSynthesis and in vitro antioxidant and antimicrobial activities of novel 3-alkyl(aryl)-4-[3-methoxy-4-(2-furylcarbonyloxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones, and their N-acetyl, N-Mannich base derivatives, COA of Formula: C6H12N2O, the publication is Journal of the Iranian Chemical Society (2022), 19(4), 1347-1368, database is CAplus.

The reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones I (R = Me, Ph, Bn, etc.) with 3-methoxy-4-(2-furylcarbonyloxy)-benzaldehyde formed 3-alkyl(aryl)-4-[3-methoxy-4-(2-furylcarbonyloxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones II (R¹ = H). Moreover, their five N-acetyl derivatives II (R¹ = acetyl) were synthesized. Besides, compounds II (R¹ = morpholin-4-yl-methyl)/II (R¹ = N-methylpiperazinyl)/II (R¹ = (4-carbamoylpiperidin-1-yl)methyl)/III were obtained by Mannich reaction between compounds II (R¹ = H) and morpholine/N-methylpiperazine/piperidine-4-carboxyamide/piperazine in the presence of formaldehyde. Also, these compounds were evaluated for their in vitro antioxidant activity. Furthermore, in vitro antibacterial activity of the compounds was screened against six bacteria.

Journal of the Iranian Chemical Society published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, COA of Formula: C6H12N2O.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Deguchi, Yoshio published the artcilePiperidine derivatives, Computed Properties of 14613-37-7, the publication is Iyaku Shigen Kenkyusho Nempo (1956), 17-22, database is CAplus.

Dialkylureido-N-methylpiperidines and dialkylureidomethyl-N-methylpiperidines were prepared Pyridine-3-carboxylic acid amide (10 g.) is refluxed with 17.5 g. MeI and 30 cc. MeOH for 5 hrs., evaporated, the residue is dissolved in 30 cc. H₂O, warmed with freshly prepared AgCl (prepared from 20 g. AgNO₃ and 7 g. NaCl) for 3 hrs., and filtered. The filtrate is decolorized with active C and then catalytically reduced with 0.1 g. PtO₂ to give 85% N-methylpiperidine-3-carboxamide (I); hydrochloride m. 232° (alc.). Similarly was prepared N-methylpiperidine-4-carboxamide; hydrochloride, hygroscopic. A mixture of 7 g. I and 7 g. P₂O₅ is heated at 160-180° for 3 hrs., cooled, dissolved in 50 cc. H₂O with warming, neutralized with K₂CO₃, salted out, and the separated oil extracted with AcOEt to give 80% 3-cyano-N-methylpiperidine (II), b₂₀ 95-6°. Similarly was prepared 4-cyano-N-methylpiperidine, b₂₁ 97°. Into a cooled mixture of 1.3 g. LiAlH₄ and 150 cc. Et₂O is dropped a solution of 5.0 g. II in 50 cc. Et₂O during 90 min., the mixture stirred 1 hr., refluxed 30 min., 15 cc. H₂O added to decompose excess LiAlH₄, and filtered. The filtrate is dried with KOH, evaporated, and distilled in vacuo to give 90% 3-aminomethyl-N-methylpiperidine (III), b₂₀ 81-2°; dipicrate m. 231° (decomposition). Similarly was prepared 4-aminomethyl-N-methylpiperidine (IV), b₂₀ 80-1°; dipicrate m. 236° (decomposition). To a mixture of 32 g. KOH, 6.4 g. Br, and 400 cc. H₂O is dropped an aqueous solution of 5.7 g. I under ice cooling, then warmed at 70° for 1 hr., alkalized with KOH, distilled with steam, and the distilled solution treated with diluted HCl, concentrated in vacuo, alkalized with KOH, extracted with Et₂O, and the extract evaporated and distilled in vacuo to give 65% 3-amino-N-methylpiperidine (V), b₄₃ 74-5°; dipicrate m. 227° (decomposition). Similarly was prepared 4-amino-N-methyl-piperidine (VI), b₃₅ 70-1°; dipicrate m. 263° (decomposition). A mixture of 0.6 mole Me₂NH and 200 cc. PhMe is dropped into 50% phosgene-PhMe, refluxed 1 hr., and distilled in vacuo to give 40% dimethylcarbamoyl chloride (VII), b_55-60 85-8°. Similarly was prepared diethylcarbamoyl chloride (VIII), b_17-20 80°. A mixture of 2 moles III and 1 mole VII in Et₂O is kept at room temperature 1.5 hrs., refluxed 10 min., cooled, and filtered. The filtrate is evaporated and chromatographed using alumina to give 3-dimethylureidomethyl-N-methyl-piperidine, needles (petr.-ether), m. 66-9° (hygroscopic). Similarly were prepared following IX (starting materials, position of substituent, n, R, appearance, and m.p. given): III and VIII, 3, 1, Et, sirupy, -; IV and VII, 4, 1, Me, needles (hygroscopic), 40-4° (hydrochloride m. 230°); IV and VIII, 4, 1, Et, columns, 66-8°; V and VIII, 3, 0, Me, needles, 110-12°; V and VIII, 3, 1, Et, sirupy, (picrolonate m. 195-7°); VI and VII, 4, 0, Me, flakes, 138-9°; VI and VIII, 4, 0, Et, needles, 89-90°.

Iyaku Shigen Kenkyusho Nempo published new progress about 14613-37-7. 14613-37-7 belongs to piperidines, auxiliary class Piperidine,Amine, name is (1-Methylpiperidin-3-yl)methanamine, and the molecular formula is C7H16N2, Computed Properties of 14613-37-7.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Correale, Jorge published the artcileBruton’s tyrosine kinase inhibitors as potential therapies for multiple sclerosis, Computed Properties of 1971920-73-6, the publication is Lancet Neurology (2021), 20(9), 689-691, database is CAplus and MEDLINE.

A review. Over the past 30 years increasing numbers of mols. have been developed for treatment of multiple sclerosis. Bruton’s tyrosine kinase is a cytoplasmic tyrosine kinase expressed by B cells and myeloid cells. Both B cells and myeloid cells (particularly microglia) are important drivers of multiple sclerosis, suggesting that inhibitors of Bruton’s tyrosine kinase, such as the irreversible inhibitors evobrutinib, tolebrutininb, and orelabrutinib, and the reversible inhibitors fenebrutinib and BIIB091, might provide therapeutic benefits for patients. Bruton’s tyrosine kinase inhibitors could provide attractive therapeutic benefits for patients with multiple sclerosis, with potential advantages over monoclonal antibodies because they might be less likely to trigger antibody responses, allergic reactions,or neutralisation of their therapeutic actions. Addnl., these inhibitors, as small mols., might be able to access the CNS and inhibit microglial activation. However, whether Bruton’s tyrosine kinase inhibitors will be more efficacious than monoclonal antibodies remains to be established.

Lancet Neurology published new progress about 1971920-73-6. 1971920-73-6 belongs to piperidines, auxiliary class Other Aliphatic Heterocyclic,Piperidine,Alkenyl,Amine,Benzene,Ether,Inhibitor,Inhibitor, name is (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, and the molecular formula is C26H25N5O3, Computed Properties of 1971920-73-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Campbell, A. F. published the artcileThe separation of m-and p-cresols from coal-tar crude carbolic acid, Safety of 1-(Phenylsulfinyl)piperidine, the publication is Journal of Industrial and Engineering Chemistry (Washington, D. C.) (1922), 732-7, database is CAplus.

The fractions obtained by the distillation of the crude product consist principally of (1) PHOH, (2) o-cresol, (3) m- and p-cresols and (4) xylenols and other complex phenols. Fractionation of (3) gives a PhOH-free product containing 59-60% m-cresol. The sulfonation of this with 96%, H₂SO₄ at 40 for 6 hrs., and subsequent treatment with H₂O gives an extract (A) of non-sulfonated cresols and an aqueous solution (B) of monosulfonates containing 78-80% of the m-compound B is converted into the NH₄ salts through the Ba salts and on fractional crystallization yields a product containing 98-100% m-cresol. The further sulfonation of A with 96% H₂SO₄ gives a non-sulfonated product (C) containing about 80% p-cresol and a sulfonated product (D) containing about 58% m-cresol, which is further sulfonated for obtaining the m-compound C may be treated so that a product containing 89% p-cresol is obtained.

Journal of Industrial and Engineering Chemistry (Washington, D. C.) published new progress about 4972-31-0. 4972-31-0 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-(Phenylsulfinyl)piperidine, and the molecular formula is C11H15NOS, Safety of 1-(Phenylsulfinyl)piperidine.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Bobbitt, James M. published the artcileOxoammonium Salts. 6. 4-Acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium perchlorate: A stable and convenient reagent for the oxidation of alcohols. Silica gel catalysis, Computed Properties of 219543-09-6, the publication is Journal of Organic Chemistry (1998), 63(25), 9367-9374, database is CAplus.

The title piperidine-1-oxoammonium perchlorate I is a stable, nonhygroscopic oxoammonium salt that is easily prepared and can be used for the oxidation of alcs. to ketones or aldehydes in near quant. yields. The reaction is colorimetric, does not require anhydrous conditions, does not involve heavy metals, and can be carried out conveniently. Furthermore, the oxidant can be easily regenerated. The oxidation is somewhat specific in that the relative reactivities of an allyl alc. (geraniol), benzaldehyde, and 1-decanol are about 1001:0.1. The reaction is catalyzed by silica gel.

Journal of Organic Chemistry published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C11H21BF4N2O2, Computed Properties of 219543-09-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Akiyama, Yoshikatsu published the artcileSynthesis of Temperature-Responsive Polymers Containing Piperidine Carboxamide and N,N-diethylcarbamoly Piperidine Moiety via RAFT Polymerization, Product Details of C6H12N2O, the publication is Macromolecular Rapid Communications (2021), 42(15), 2100208, database is CAplus and MEDLINE.

In this study, poly(N-acryloylnipecotamide) (PNANAm), poly(N-acryloylisonipecotamide) (PNAiNAm), and poly(N-acryloyl-N,N-diethylnipecotamide) (PNADNAm) are synthesized as temperature-responsive polymers using reversible addition-fragmentation chain-transfer polymerization Aqueous solutions of the three polymers are examined via temperature-dependent optical transmittance measurements. The PNANAm sample with a hydrophilic terminal group shows an upper critical solution temperature (UCST) in phosphate-buffered saline (PBS) when its mol. weight (M_n) is �7600, whereas PNANAm (M_n < 7600) is soluble The UCST is influenced by mol. weight and polymer concentration In contrast, PNANAm sample with nonionic terminal group shows UCST, when M_n is < 7600, suggesting that the terminal nonionic group possibly increases UCST of PNANAm. The urea addition experiment suggests that the driving force for expression of UCST of PNANAm is the formation of inter- and intramol. hydrogen bonds among the polymer chains. PNAiNAm is soluble in PBS but exhibits an UCST in an appropriate concentration of ammonium sulfate. In contrast, PNADNAm exhibits a lower critical solution temperature Comparing the chem. structure of these polymers and their phase transition behaviors suggests that the carboxamide group position in the piperidine ring could determine the UCST expression. The results could help design temperature-responsive polymers with a desired cloud point temperature

Macromolecular Rapid Communications published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Product Details of C6H12N2O.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Abood, L. G. published the artcilePossible role of brain mitochondria in psychopharmacology, Application In Synthesis of 13444-24-1, the publication is Journal of Neuropsychiatry (1959), 92-5, database is CAplus.

cf. CA 53, 22487b. Experiments were performed on rat-brain mitochondria to determine the presence of cholinergic receptor sites. It was observed that the distribution of tritiated N-ethyl-3-piperidyl benzilate (JB-318) (I) was similar to that of acetylcholine in the cellular fractions of rat brain. The largest concentration was found in the mitochondria. It was concluded that the cholinergic receptor sites were in this fraction or granules associated with this fraction. The inhibition of a number of drugs upon the binding of I to mitochondria was chlorpromazine 80, 3-piperidyl benzilate (JB-305) and N,N’-piperazinodiethyl dibenzilate 50, hydroxyzine 44, and dinitrophenol 20%. It was suggested that if the receptor sites are confined to cytoplasmic particles, then the phenothiazine types of tranquilizers and the psycho-mimetic agents act at the mitochondrial level of the cell.

Journal of Neuropsychiatry published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, Application In Synthesis of 13444-24-1.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Fuson, Reynold C. published the artcileRing enlargement by rearrangement of the 1,2-aminochloroalkyl group; rearrangement of 1-ethyl-2-(chloromethyl)pyrrolidine to 1-ethyl-3-chloropiperidine, HPLC of Formula: 13444-24-1, the publication is Journal of the American Chemical Society (1948), 2760-2, database is CAplus.

Reduction of 1,2-dicarbethoxypyrrole over Raney Ni in dry MeOH at 70°/1500 lb. gives 95% 1,2-dicarbethoxypyrrolidine; further reduction over Cu chromite in EtOH at 250°/100 atm. gives 31% 1-ethyl-2-hydroxypyrrolidine (I); the HCl salt and benzoate-HCl are oils; benzoate picrate, m. 170.5-1.5°. Diethyl(tetrahydrofurfuryl)amine yields 43% 1-ethyl-3-hydroxypiperidine, which forms a HCl salt (II), m. 157-8°, and a benzoate picrate, yellow, m. 181.5-2.5°. I (4 g.) in 25 ml. CHCl₃ at 0°, treated with HCl to form the HCl salt and then with 4.8 g. SOCl₂ in CHCl₃, and the mixture stirred 30 min. at room temperature and refluxed 1 hr., gives 56% 1-ethyl-2-(chloromethyl)pyrrolidine-HCl (III), m. 165-70° (heated 20°/min.), solidifies, and m. 153.5-4°; slowly heated, III contracts at 165° and m. 193.5-4°; picrate, m. 128.5-9.5°. The Me₂CO used to wash the crude III yields 1.4 g. 1-methyl-2-(chloromethyl)pyrrolidine picrate (?) (IV), m. 163.5-4.5°; it is possible that I contained some 1-ethyl-2-(hydroxymethyl)pyrrolidine. II (5 g.) and 3.7 g. SOCl₂ in 50 ml. PhMe, refluxed 3 hrs., give 87% 1-ethyl-3-chloropiperidine (V) as the HCl salt (VI), m. 193.5-4°; a mixture of III and VI also m. 193.5-4°. The base from III appears to undergo rearrangement to V as rapidly as it is liberated, an ethylenimonium ion probably being an intermediate. The base (V) from VI does not undergo rearrangement on liberation. The attempt to prepare 1-methyl-3-chloropiperidine from IV was inconclusive.

Journal of the American Chemical Society published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, HPLC of Formula: 13444-24-1.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem