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Chemical Structure| 485-47-2 Chemical Structure| 485-47-2
Chemical Structure| 485-47-2

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Product Details of Ninhydrin

CAS No. :485-47-2
Formula : C9H6O4
M.W : 178.14
SMILES Code : O=C1C(O)(O)C(C2=C1C=CC=C2)=O
MDL No. :MFCD00003791
InChI Key :FEMOMIGRRWSMCU-UHFFFAOYSA-N
Pubchem ID :10236

Safety of Ninhydrin

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P264-P270-P280-P301+P312+P330-P302+P352-P305+P351+P338-P332+P313-P337+P313-P362+P364-P501

Application In Synthesis of Ninhydrin

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 485-47-2 ]

[ 485-47-2 ] Synthesis Path-Downstream   1~24

  • 1
  • [ 485-47-2 ]
  • [ 6099-90-7 ]
  • (trihydroxy-2,4,6 phenyl)-2 hydroxy-2 indanedione-1,3 monohydrate [ No CAS ]
  • 2
  • [ 485-47-2 ]
  • [ 14401-72-0 ]
  • 2-[2-(3,5-Dichloro-phenyl)-2-oxo-ethyl]-2-hydroxy-indan-1,3-dione [ No CAS ]
  • 3
  • [ 485-47-2 ]
  • [ 2338-18-3 ]
  • [ 67-63-0 ]
  • 5-bromo-2-aminoindane hydrobromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; H2; sodium hydroxide; sulfuric acid; bromine; hydroxylamine sulfate; acetic acid;palladium-carbon; In 5,5-dimethyl-1,3-cyclohexadiene; pentan-1-ol; water; (b) Alternately, (R)-(5-aminoindan-2-yl)-carbamic acid methyl ester is prepared as follows: A mixture of ninhydrin (33 g, 0.185 mol) and acetic acid (554 g) is stirred at room temperature (rt) under N2 until complete dissolution of ninhydrin. Sulfuric acid is then added (54.42 g, 0.555 mol) followed by hydroxylamine sulfate (31.63 g, 0.193 mol). The mixture is heated to 55 C. for 30 minutes and is then allowed to cool to room temperature. 10% Pd/C (2.64 g, 8% w/w) is added to the resulting yellow suspension and the mixture is hydrogenated at a pressure of H2 of 20 psi. After stirring for 1 hour at rt, the H2 pressure is increased to 40 psi and the temperature increased to 35 C. After stirring for 8 hours, the reaction is allowed to cool before filtration on a pad of Celite (20 g). The Celite cake is washed with acetic acid (70 g). The filtrate is concentrated, xylene (250 g) is added to the resulting slurry and the mixture concentrated again. Xylene (170 g) is added followed by slow addition of 20% NaOH (367 g) until a basic pH and a clear separation of the organic and aqueous layers is obtained. The xylene layer is then separated and filtered. The HCl salt is then precipitated out by slow addition of a 4 N HCl solution in 1-pentanol (51 g). The suspension is cooled to 0 C. and filtered. The cake is rinsed with heptane (100 g) and dried under vacuum to yield 2-amninoindane hydrochloride as a white powder. A solution of 118.8 g of <strong>[2338-18-3]2-aminoindane hydrochloride</strong> in 594 mL of water is heated to a temperature of 58-60 C. and 120.0 g of bromine is added over a period of 50 minutes while maintaining an internal temperature at 58 to 62 C. The mixture is stirred at 60-62 C for 1 hour and 107 mL of hydrobromic (48%) is added over a period of 5 minutes while maintaining the internal temperature of 60-62 C. The mixture is stirred for an additional 10 minutes. The reaction mixture is cooled to an internal temperature of 20-23 C. over a period of 1 hour. The resulting solid is collected by filtration, washed with 3*133 mL of 2-propanol and dried at 58-60 C. under vacuum (10-30 torr) to obtain crude (+-)-5-bromo-2-aminoindan hydrobromide.
  • 4
  • [ 485-47-2 ]
  • [ 2338-18-3 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; H2; sodium hydroxide; sulfuric acid; hydroxylamine sulfate; acetic acid;palladium-carbon; In 5,5-dimethyl-1,3-cyclohexadiene; pentan-1-ol; EXAMPLE 17 (R)-(5-Aminoindan-2-yl)-carbamic acid methyl ester A mixture of ninhydrin (33 g, 0.185 mol) and acetic acid (554 g) is stirrred at rt under N2 until complete dissolution of ninhydrin. Sulfuric acid is then added (54.42 g, 0.555 mol) followed by hydroxylamine sulfate (31.63 g, 0.193 mol). The mixture is heated to 55 C. for 30 minutes and is then allowed to cool to room temperature. 10% Pd/C (2.64 g, 8% w/w) is added to the resulting yellow suspension and the mixture is hydrogenated at a pressure of H2 of 20 psi. After stirring for 1 hour at rt, the H2 pressure is increased to 40 psi and the temperature increased to 35 C. After stirring for 8 hours, the reaction is allowed to cool before filtration on a pad of Celite (20 g). The Celite cake is washed with acetic acid (70 g). The filtrate is concentrated, xylene (250 g) is added to the resulting slurry and the mixture concentrated again. Xylene (170 g) is added followed by slow addition of 20% NaOH (367 g) until a basic pH and a clear separation of the organic and aqueous layers is obtained. The xylene layer is then separated and filtered. The HCl salt is then precipitated out by slow addition of a 4 N HCl solution in 1-pentanol (51 g). The suspension is cooled to 0 C. and filtered. The cake is rinsed with heptane (100 g) and dried under vacuum to yield 2-aminoindane hydrochloride as a white powder.
  • 5
  • [ 2243-82-5 ]
  • [ 485-47-2 ]
  • [ 1140529-24-3 ]
  • 6
  • [ 485-47-2 ]
  • [ 4506-66-5 ]
  • [ 1156494-18-6 ]
  • [ 1156494-19-7 ]
YieldReaction ConditionsOperation in experiment
With sodium acetate; In ethanol; at 20℃;Reflux; Example 3 [Synthesis of a compound shown by the formulas (B-1) and (B-3)]; Synthesis was performed by the following synthesis scheme. [Show Image] [Show Image] (1) Synthesis of a mixture of (Intermediate Ba) and (Intermediate Bb); To the mixture of 2.8 g of ninhydrin, 0.86 g of sodium acetate and 100 ml of ethanol with the mixture being stirred at room temperature, a solution of 1.5 g of 1,2,4,5-benzenetetramine tetrahydrochloride and 20 ml of ethanol was added dropwise. After the dropwise addition, stirring under reflux was performed for 2 hours. After cooling to room temperature, a deposited yellow solid was filtered off, washed with water and ethanol, and dried, whereby 1.8 g of a compound was obtained. As a result of mass spectroscopy of the resulting compound, a peak was observed at M/Z=386. As a result of the 1H-NMR measurement, a spectrum derived from the heteroaromatic ring was observed at 7.6 to 8.4 ppm. However, the mixture ratio of the compound (B-1) and the compound (B-3) could not be determined.
  • 7
  • [ 485-47-2 ]
  • [ 4506-66-5 ]
  • [ 109-77-3 ]
  • [ 1156494-20-0 ]
  • [ 1156494-21-1 ]
YieldReaction ConditionsOperation in experiment
Example 3 [Synthesis of a compound shown by the formulas (B-1) and (B-3)]; Synthesis was performed by the following synthesis scheme. [Show Image] [Show Image] (1) Synthesis of a mixture of (Intermediate Ba) and (Intermediate Bb); To the mixture of 2.8 g of ninhydrin, 0.86 g of sodium acetate and 100 ml of ethanol with the mixture being stirred at room temperature, a solution of 1.5 g of 1,2,4,5-benzenetetramine tetrahydrochloride and 20 ml of ethanol was added dropwise. After the dropwise addition, stirring under reflux was performed for 2 hours. After cooling to room temperature, a deposited yellow solid was filtered off, washed with water and ethanol, and dried, whereby 1.8 g of a compound was obtained. As a result of mass spectroscopy of the resulting compound, a peak was observed at M/Z=386. As a result of the 1H-NMR measurement, a spectrum derived from the heteroaromatic ring was observed at 7.6 to 8.4 ppm. However, the mixture ratio of the compound (B-1) and the compound (B-3) could not be determined.; (1) Synthesis of a mixture of (B-1) and (B-3); 0.3 g of malononitrile and 100 ml of pyridine was added to 1.7 g of the mixture of the (intermediate Ba) and the (intermediate Bb) which had been synthesized above, and the resultant was stirred under reflux for 12 hours. After cooling to room temperature, an orange crystal was filtered off, washed with hydrochloric acid, water and acetonitrile. The solid was purified through sublimation, whereby 1.5 g of a compound was obtained. The IR of this compound was measured. The results showed that the absorption derived from a carbonyl group disappeared and the absorption of a cyano group was newly observed at 2290 cm-1. As a result of mass spectroscopy, a peak was observed at M/Z=482. Elementary analysis: C30H10N8, calculated value: C, 74.69; H, 2.09; N, 23.23, actually measured value: C, 74.75; H, 2.25; N 23.39. The reduction potential of this compound was measured by the cyclic voltammetry as in Example 1. The reduction potential of the mixture of (B-1) and (B-3) was -0.9 V(vsFc+/Fc).
  • 8
  • [ 485-47-2 ]
  • [ 145091-87-8 ]
  • [ 1437802-73-7 ]
YieldReaction ConditionsOperation in experiment
Ca. 94% With acetic acid; at 20℃; for 0.166667h; The substrate <strong>[145091-87-8]5-methyl-2H-pyrazole-3-ol</strong> (1.00 g, 10.2 mmol) was added to a solution of ninhydrin (1.82 g, 10.2 mmol) in acetic acid (10 mL). The reaction mixture was stirred at room temperature for 10 min. Yellowish white solid product 4 was filtered out and washed thoroughly with cold water. The product was crystallized from acetone-hexane mixture (1.36g, yield ~ 94%). Yellowish white solid, mp 252-254 ºC; IR (KBr): (cm-1) 3371, 1710; 1HNMR (300 MHz, d6-DMSO) δ: 10.79 (bs, 2H), 7.88-7.85 (m, 4H), 6.32(s, 1H), 2.3 (s, 3H); 13C NMR (75 MHz, d6-DMSO) δ: 198.9,157.8, 140.5, 140.1, 136.3, 123.4, 117.8, 97.6, 75.6, 11.6.
  • 9
  • [ 485-47-2 ]
  • [ 54523-47-6 ]
  • 1,3-di(4-bromphenyl)indeno[a]cyclopenta-2,8-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
81.5% With potassium hydroxide; In methanol; ethanol; at 75℃; for 3h; The ninhydrin (2 · 86g, 14. 65mmol) and 1,3-bis (4-bromophenyl) -2-propanone (4. 996g, 13. 65mmol) was dissolved in hot ethanol 20ml, was slowly added dropwise plus 3. 5ml 10% KOH / MeOH solution, after completion of the dropwise addition under stirring for 3h at 75, until the solution stops the reaction from yellow to dark brown, the reaction was filtered and the resulting solid, recrystallized from ethanol, to give brown crystals 5 · 45g yield 81.5%
  • 10
  • [ 485-47-2 ]
  • [ 40461-93-6 ]
  • [ 15028-16-7 ]
  • [ 2338-18-3 ]
  • 11
  • [ 485-47-2 ]
  • [ 2338-18-3 ]
  • [ 83-33-0 ]
  • 12
  • [ 2934-05-6 ]
  • [ 485-47-2 ]
  • [ 1416231-31-6 ]
YieldReaction ConditionsOperation in experiment
70% With acetic acid; for 12h;Reflux; To a solution of ninhydrin (0.30 g, 1.68 mmol) in acetic acid (10 ml) was added <strong>[2934-05-6]2,4-diisopropylphenol</strong> (0.27 g, 1.51 mmol) which was then heated for 12 hrs under reflux. After vacuum concentration, recrystallization in methylene chloride afforded the title compound (0.40 g, 70%). [0616] mp: 205-206 C., [0617] 1H-NMR (300 MHz, CDCl3) delta 1.14-1.24 (m, 12H), 2.81 (q, J=7.2 Hz, 1H), 3.07 (q, J=7.2 Hz, 1H), 3.65 (s, 1H), 4.55 (s, 1H), 7.00 (d, J=1.7 Hz, 1H), 7.17 (s, 1H), 7.54 (d, J=8.4 Hz, 1H), 7.76-7.81 (m, 2H), 8.00 (d, J=7.6 Hz, 1H).
70% With acetic acid; for 12h;Reflux; To a solution of ninhydrin (0.30 g, 1.68 mmol) in acetic acid (10 ml) was added <strong>[2934-05-6]2,4-diisopropylphenol</strong> (0.27 g, 1.51 mmol) which was then heated for 12 hrs under reflux. After vacuum concentration, recrystallization in methylene chloride afforded the title compound (0.40 g, 70%). mp : 205-206C, 1H-NMR (300MHz, CDCl3) delta 1.14-1.24 (m, 12H), 2.81 (q, J = 7.2Hz, 1H), 3.07 (q, J = 7.2Hz, 1H), 3.65 (s, 1H), 4.55 (s, 1H), 7.00 (d, J = 1.7Hz, 1H), 7.17 (s, 1H), 7.54 (d, J = 8.4Hz, 1H), 7.76-7.81 (m, 2H), 8.00 (d, J = 7.6Hz, 1H).
  • 13
  • [ 485-47-2 ]
  • [ 4506-66-5 ]
  • [ 1156494-19-7 ]
YieldReaction ConditionsOperation in experiment
13% at 20℃; for 0.5h;Milling; Ninhydrin 5 (18 mg, 0.10 mmol) and 1,2,4,5-benzenetetramine tetrahydrochloride 15c (15 mg, 0.05 mmol) were ball-milled for 30 min at RT at 3600 rpm. Product was purified by radial chomatography (petrol/ethyl acetate) followed by recystallization from toluene. 8c. Yellow solid, 3 mg, yield 13percent, mp > 350°C; 1H NMR (400 MHz, CDCl3): H 7.71 (1H, t, J 7.6Hz), 7.87 (1H, t, J 7.6 Hz), 8.02 (1H, d, J 7.9 Hz), 8.26 (1H, d, J 7.9 Hz), 8.83 (1H, s), 9.19 (1H, s);13C NMR (100 MHz, CDCl3): C 120.1, 122.3, 124.5, 127.9, 129.2, 130.2, 132.4, 133.7, 137.1,138.2, 144.6, 151.1, 183.3; HRMS (m/z): calcd. for C24H10N4O2: 386.0804 found: 386.0811
  • 14
  • [ 485-47-2 ]
  • [ 4506-66-5 ]
  • spiro[dimethyl-3,10-dimethoxy-1α,12α,13β,14α,17α,18β-16,19-dioxahexacyclo[10,6,1.114,1702,1104,9013,18]-dodeca-2,4,6,8,10-pentaene-14,17-dicarboxylate-15,11'-9'H-indeno-9'-one-[1',2'-b]:1',4'-diaza-11'H-fluoreno[2',3'-g]quinoxalin] [ No CAS ]
  • 15
  • [ 580-15-4 ]
  • [ 485-47-2 ]
  • isochromeno[3′,4′:4,5]pyrrolo[3,2-f]quinolin-12(7H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With formic acid; at 100℃;Microwave irradiation; 2,2-Dihydroxyindene-1,3-dione (1; 0.178 g, 1.0 mmol) was introducedinto a 10 mL Initiator reaction vial. Naphthalen-2-amine (2a;0.143 g, 1.0 mmol) and HCO2H (1.0 mL) were subsequently addedto the reaction system. The reaction vial was capped and the mixturewas stirred for 10 min. The mixture was irradiated (time: 20 min,temperature: 100 C; absorption level: high; fixed hold time) untilTLC (PE-acetone, 3:1) revealed that conversion of the starting material1 was complete. The mixture was cooled to r.t. A diluted basicsolution was poured into the mixture until the HCO2H was neutralized,and then cold H2O (30 mL) was added into the mixture. Thesolid product was collected by Büchner filtration and washed withH2O and EtOH (95%), and subsequently dried and recrystallizedfrom EtOH (95%) to give the pure product 3a.Yield: 0.242 g (85%)
  • 16
  • [ 6972-82-3 ]
  • [ 485-47-2 ]
  • 1-methyl-2H-indeno[2,1-g]pteridine-2,4,6-(1H,3H)-trione [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With acetic acid;Reflux; General procedure: A mixture of 5,6-diamino-1-substituted uracils (3) (1.00 mmol) andninhydrin (1.00 mmol) in acetic acid (5 mL) was heated under refluxfor 10?15 min. The resulting precipitate was filtered hot, washed withethanol and crystallised from DMF/ethanol (1:3).
  • 17
  • [ 485-47-2 ]
  • [ 538-28-3 ]
  • 2-(benzylthio)-3a,8a-dihydroxy-3a,8a-dihydroindeno[1,2-d]imidazol-8(3H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
In ethanol; water; at 20℃; for 0.75h; General procedure: Alkyl halide (1 mmol) and thiourea (0.076 g, 1.0 mmol) were heated at reflux in EtOH (5 mL) for 2 h. The reaction mixture was cooled to room temperature, then ninhydrin (0.178 g, 1 mmol) in water (5 mL) was added and the mixture stirred for an additional 45 min. Compounds 4 were obtained in almost quantitative yields by filtration of the reaction mixture as white or light-cream solids. The filtrates could be washed with cold ethyl acetate or dichloromethane, if necessary.
  • 18
  • [ 107-97-1 ]
  • [ 485-47-2 ]
  • [ 13380-67-1 ]
  • 5'-(4-bromophenyl)-2'-methyl-2',3',3a',6a'-tetrahydro-4'H-spiro[indene-2,1'-pyrrolo[3,4-c]pyrrole]-1,3,4',6'(5'H)-tetraone [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% In methanol; at 100℃; under 750.075 Torr;Microwave irradiation; General procedure: A mixture of respective 3-(4- 1-(aryl/alkyl)-1H-pyrrole-2,5-dione (1 mmol), ninhydrin (1 mmol) and sarcosine in methanol was placed in a microwave synthesizer. The vial was subjected to microwave irradiation programmed at 100 C, 120W and 1 bar pressure. After completion of the reaction (TLC), the solvent was removed and the product was purified by column chromatography using petroleum ether-ethyl acetate mixture (4:1 v/v) as eluent to obtain pure cycloadduct 4.
  • 19
  • [ 2142-06-5 ]
  • [ 107-97-1 ]
  • [ 485-47-2 ]
  • 5'-benzyl-2'-methyl-2',3',3a',6a'-tetrahydro-4'H-spiro[indene-2,1'-pyrrolo[3,4-c]pyrrole]-1,3,4',6'(5'H)-tetraone [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% In methanol; at 100℃; under 750.075 Torr;Microwave irradiation; General procedure: A mixture of respective 3-(4- 1-(aryl/alkyl)-1H-pyrrole-2,5-dione (1 mmol), ninhydrin (1 mmol) and sarcosine in methanol was placed in a microwave synthesizer. The vial was subjected to microwave irradiation programmed at 100 C, 120W and 1 bar pressure. After completion of the reaction (TLC), the solvent was removed and the product was purified by column chromatography using petroleum ether-ethyl acetate mixture (4:1 v/v) as eluent to obtain pure cycloadduct 4.
  • 20
  • [ 20026-96-4 ]
  • [ 485-47-2 ]
  • [ 609-36-9 ]
  • ethyl 12-(4-chlorophenyl)-6,11-dioxo-1,2,3,4,6,11-hexahydro-4,11a-ethenopyrido[1,2-b]isoquinoline-13-carboxylate [ No CAS ]
  • 21
  • [ 485-47-2 ]
  • [ 498-63-5 ]
  • 3,3-bis(2-(hydroxymethyl)pyrrolidin-1-yl)isochroman-1,4-dione [ No CAS ]
  • 22
  • [ 769-42-6 ]
  • [ 107-97-1 ]
  • [ 485-47-2 ]
  • [ 4903-09-7 ]
  • 5'-(3-chloro-4-methoxyphenyl)-1',1'',3''-trimethyl-2''H-dispiro[indene-2,2'-pyrrolidine-4',5''-pyrimidine]-1,2'',3,4'',6''(1''H,3''H)-pentaone [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With magnesium silicate; In ethanol; at 120℃; under 1500.15 Torr; for 1h;Microwave irradiation; General procedure: To a solution of biphenyl carboxaldehyde 1d (0.1 g, 0.54 mmol) in ethanol (1.5 mL) was added N, N-dimethyl barbituric acid, 4 (0.1 g, 0.64 mmol), ninhydrin, 2 (0.1 g, 1.0 mmol), sarcosine, 3 (57 mg, 0.64 mmol) and magnesium silicate catalyst (10 mol%) at room temperature. The reaction mass was irradiated by microwave irradiations in a Microwave Vials 0.2-0.5mL of Biotage Initiator at 120 C, 300 W, 2 bar reactionpressure for 90 min and until the completion of starting material. The title compound was precipitated as yellow solid on standing the reaction mass. Then it was filtered and washed with cold methanol to remove polar impurities. The compound was further recrystallized using dichloromethane:methanol: tetrahydrofuran (3:1:1) to get 88% yield as colorless prisms.
  • 23
  • [ 485-47-2 ]
  • [ 521-73-3 ]
YieldReaction ConditionsOperation in experiment
90% With hydroxylamine hydrochloride; water; Thiamine hydrochloride; In 1,4-dioxane; at 90℃; for 0.833333h; General procedure: A mixture of ketone 1 (2 mM), hydroxylamine hydrochloride (3 mM) and thiamine hydrochloride (0.4 mM) was taken in 10mL dioxane:H2O (9:1) in a round-bottom flask and heated at 90 C for specific time (30-90 min). The progress of the reaction was monitored using thin layer chromatography (tlc). After completion of the reaction, the reaction flask was cooled to room temperature. The residue was taken in ethyl acetate (30 ml), washed with water (2x15 ml), brine (1x15 ml) and the organic layer was dried (anhyd. Na2SO4). The resulting ethyl acetate solution was concentrated and the desired amides 2 (75-95% yield) are obtained by recrystallization from ethanol.
  • 24
  • [ 63-91-2 ]
  • [ 485-47-2 ]
  • [ 399-25-7 ]
  • [ 95-54-5 ]
  • 5′-benzyl-3′-(2-fluorophenyl)-4′-nitrospiro[indeno[1,2-b]quinoxaline-11,2′-pyrrolidine] [ No CAS ]
YieldReaction ConditionsOperation in experiment
at 100℃; for 1h;Ionic liquid; General procedure: A mixture of β-nitrostyrene (1 mmol), ninhydrin (1 mmol), o-phenylenediamine (1 mmol) and L-Phenylalanine (1 mmol) were heated with stirring in [bmim]Br medium (3 mL) for 1 h at 100 C. After completion of reaction (TLC), ethyl acetate (2 × 5 mL) was added into reaction mixture and stirred for 10 min. The ethyl acetate phase was separated and removed under vaccum affording the pure products 6 inexcellent yields.
 

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