3056-33-5

Basic information

• Product Name: N,9-Diacetylguanine
• Synonyms: 9-diacetylguanine;2-ACETYLAMINO-6-OXO-9-ACETYLPURINE;2,9-DAG;2,9-DIACETATEGUANINE;2,9-DIACETYLGUANINE;(9-acetyl-6,9-dihydro-6-oxo-1h-purin-2-yl)acetamide;DIACETYL GUANINE;N2,9-DIACETYLGUANINE
• CAS NO: 3056-33-5
• Molecular Formula: C₉H₉N₅O₃
• Molecular Weight: 235.2
• EINECS: 221-287-0
• Product Categories: Pyridines, Pyrimidines, Purines and Pteredines;Purine;Nucleotides and Nucleosides;Biochemistry;Nucleobases and their analogs;Nucleosides, Nucleotides & Related Reagents;Bases & Related Reagents;Nucleotides;Building Blocks;Heterocyclic Building Blocks;Purines
• Mol File: 3056-33-5.mol
• Article Data: 20

Chemical Properties

• Melting Point: 285 °C(lit.)
• Appearance: white or brownish crystalline powder
• Density: 1.67 g/cm³
• Refractive Index: 1.752
• Storage Temp.: -20°C Freezer
• Solubility: Aqueous Base (Slightly, Heated), DMSO (Slightly, Heated)
• PKA: 8.37±0.20(Predicted)
• CAS DataBase Reference: N,9-Diacetylguanine(CAS DataBase Reference)
• NIST Chemistry Reference: N,9-Diacetylguanine(3056-33-5)
• EPA Substance Registry System: N,9-Diacetylguanine(3056-33-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39-36
• WGK Germany: 3
• Hazardous Substances Data: 3056-33-5(Hazardous Substances Data)

Usage

Description

N,9-Diacetylguanine, also known as Acicclovir EP Impurity L, is a white or brownish crystalline powder with specific chemical properties. It is a significant compound in the field of pharmaceuticals, particularly for the synthesis of acyclic analogues of deoxyguanosine.

Uses

Used in Pharmaceutical Industry:
N,9-Diacetylguanine is used as a key intermediate for the synthesis of acyclic analogues of deoxyguanosine. These analogues are essential in the development of antiviral medications, particularly those targeting herpes simplex virus (HSV) and other related viral infections. N,9-Diacetylguanine plays a crucial role in the pharmaceutical industry by contributing to the creation of effective antiviral drugs.

InChI:InChI=1/C9H9N5O3/c1-4(15)11-9-12-7-6(8(17)13-9)10-3-14(7)5(2)16/h3H,1-2H3,(H2,11,12,13,15,17)

Synthetic route

2-amino-1,9-dihydro-6H-purin-6-one (73-40-5) + acetic anhydride (108-24-7) → 2,9-diacetylguanine (3056-33-5)

Conditions	Yield
In N,N-dimethyl acetamide at 160℃; for 18h;	97%
In N,N-dimethyl-formamide at 160℃; for 2h; Acetylation;	95%
for 16h; Heating;	95%

acetic anhydride (108-24-7) + G (118-00-3) → 2,9-diacetylguanine (3056-33-5) + 1,2,3,5-tetraacetylribose (13035-61-5)

Conditions	Yield
Stage #1: acetic anhydride; G at 136℃; for 1h; Stage #2: With trifluoroacetic acid at 60 - 100℃;	A 96% B 86%

guanine powder + acetic anhydride (108-24-7) → 2,9-diacetylguanine (3056-33-5)

Conditions	Yield
With acetic acid at 135℃; for 7.5h;	95%

2-amino-1,9-dihydro-6H-purin-6-one (73-40-5) + acetyl chloride (75-36-5) → 2,9-diacetylguanine (3056-33-5)

Conditions	Yield
With pyridine; dmap at -5 - 20℃;	91.7%

2-amino-1,9-dihydro-6H-purin-6-one (73-40-5) + acetic anhydride (108-24-7) → N,N'-diacetylguanine (137226-08-5) + 2,9-diacetylguanine (3056-33-5)

Conditions	Yield
In acetic acid at 140℃; for 18h; Yield given. Title compound not separated from byproducts;

2-amino-1,9-dihydro-6H-purin-6-one (73-40-5) → 2,9-diacetylguanine (3056-33-5)

Conditions	Yield
With acetic anhydride

2,9-diacetylguanine (3056-33-5) → N-(6-oxo-6,9-dihydro-1H-purin-2-yl)acetamide (19962-37-9)

Conditions	Yield
In ethanol; water for 2h; Reflux;	98%
With ethanol In water Reflux;
In ethanol; water at 80℃;	12 g

2-acetoxyethyl acetoxymethyl ether (59278-00-1) + 2,9-diacetylguanine (3056-33-5) → 2-acetylamino-9-(2-acetoxyethoxymethyl)purine-6-one (75128-73-3)

Conditions	Yield
at 105℃; for 80h;	95.1%
With toluene-4-sulfonic acid In toluene at 110℃; Temperature; Large scale;	94.3%

2,9-diacetylguanine (3056-33-5) → 2-amino-1,9-dihydro-6H-purin-6-one (73-40-5)

Conditions	Yield
With sodium hydroxide In water for 1h; Heating;	95%

diphenylcarbamic chloride (83-01-2) + 2,9-diacetylguanine (3056-33-5) → N2-acetyl-O6-(diphenylcarbamoyl)guanine (112233-74-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In pyridine for 1h; Ambient temperature;	92%
Stage #1: diphenylcarbamic chloride; 2,9-diacetylguanine With pyridine; N-ethyl-N,N-diisopropylamine for 4h; Stage #2: In ethanol; water at 70℃; for 3.5h;	91%
With ethanol; N-ethyl-N,N-diisopropylamine 1.) pyridine, room temp., 1 h, 2.) heating; Yield given. Multistep reaction;
Stage #1: diphenylcarbamic chloride; 2,9-diacetylguanine With pyridine; N-ethyl-N,N-diisopropylamine at 20℃; for 2h; Stage #2: With ethanol; water for 1.5h; Heating / reflux;

2-(acetoxymethoxy)-1,3-propanediyl diacetate (86357-13-3) + 2,9-diacetylguanine (3056-33-5) → 9-(1,3-diacetoxy-2-propoxymethyl)-N2-acetylguanine (86357-14-4)

Conditions	Yield
With boron trifluoride diethyl etherate In N,N-dimethyl-formamide at 100℃; for 10h; Solvent; Temperature; Microwave irradiation;	85.3%

2,9-diacetylguanine (3056-33-5) → 2-amino-6-chloropurine (10310-21-1)

Conditions	Yield
With trichlorophosphate In 1,2-dichloro-ethane at 80℃;	84%

2,9-diacetylguanine (3056-33-5) → 2-Amino-6-chloropurin (10310-21-1)

Conditions	Yield
With trichlorophosphate In 1,2-dichloro-ethane; PEG-2000 at 80℃; for 6.33333h;	84%

2-(4-nitrophenyl)ethanol (100-27-6) + 2,9-diacetylguanine (3056-33-5) → N2,N9-diacetyl-O6-2-(4-nitrophenyl)ethylguanine (917376-69-3)

Conditions	Yield
With ethyl azodicarboxylate; triphenylphosphine In 1,4-dioxane for 24h;	80%
With triphenylphosphine; diethylazodicarboxylate In 1,4-dioxane at 20℃; Condensation; Mitsunobu reaction;

2-acetoxyethyl acetoxymethyl ether (59278-00-1) + 2,9-diacetylguanine (3056-33-5) → 7-<(2-acetoxyethoxy)methyl>-N2-acetylguanine (91702-60-2)

Conditions	Yield
With titanium tetrachloride In acetic acid at 10 - 15℃; for 6h;	65.4%

2-(4-nitrophenyl)ethanol (100-27-6) + 2,9-diacetylguanine (3056-33-5) → N2-acetyl-O6-(2-(p-nitrophenyl)ethyl)guanine (218152-30-8)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate at 20℃;	64%

trans-2,3-Dichlorotetrahydrofuran (3511-19-1, 13129-90-3, 29120-50-1, 106445-14-1) + 2,9-diacetylguanine (3056-33-5) → trans-9-(3-chlorotetrahydrofuran-2-yl)guanine (106445-17-4)

Conditions	Yield
With Bis(p-nitrophenyl) phosphate In sulfolane at 100℃; for 16h;	59.7%

2,9-diacetylguanine (3056-33-5) + 1,3-dipivaloyloxy-2-((methylsulfinyl)methoxy)propane (100675-34-1) → 2,2-Dimethyl-propionic acid 2-(2-acetylamino-6-oxo-1,6-dihydro-purin-7-ylmethoxy)-3-(2,2-dimethyl-propionyloxy)-propyl ester (119824-58-7) + N2-acetyl-9-((1,3-pivaloyloxy-2-propoxy)methyl)guanine (100675-29-4)

Conditions	Yield
With toluene-4-sulfonic acid In dimethyl sulfoxide; N,N-dimethyl-formamide at 105℃; for 42h;	A 17% B 44.5%

1-benzyloxy-3-benzyloxy-2acetyloxymethoxypropane (84245-11-4) + 2,9-diacetylguanine (3056-33-5) → N2-acetyl-7-<<1,3-bis(benzyloxy)-2-propoxy>methyl>guanine (84222-48-0) + N2-acetyl-9-<<1,3-bis(benzyloxy)-2-propoxy>methyl>guanine (82410-30-8)

Conditions	Yield
With toluene-4-sulfonic acid In sulfolane at 95℃; for 72h; Yield given;	A n/a B 31%
With toluene-4-sulfonic acid In sulfolane at 95℃; for 72h; Yields of byproduct given;	A n/a B 31%
With toluene-4-sulfonic acid In sulfolane at 95℃; for 85h;	A n/a B 31%

2,9-diacetylguanine (3056-33-5) + Acetic acid 5-(diethoxy-phosphoryl)-pentyloxymethyl ester (174538-08-0) → [5-(2-Acetylamino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-pentyl]-phosphonic acid diethyl ester (174538-32-0)

Conditions	Yield
With toluene-4-sulfonic acid In acetonitrile for 96h; Heating;	31%

2,9-diacetylguanine (3056-33-5) + (+/-)-1-(acetoxymethoxy)-2,3-diacetoxypropane (96429-67-3) → (+/-)-N2-acetyl-7-<(2,3-diacetoxy-1-propoxy)methyl>guanine (96429-69-5) + (+/-)-N2-acetyl-9-<(2,3-diacetoxy-1-propoxy)methyl>guanine (96429-68-4)

Conditions	Yield
With ethanesulfonic acid at 155 - 160℃; for 1.25h;	A n/a B 29%

1,3-DIOXOLANE (646-06-0) + acetic anhydride (108-24-7) + 2,9-diacetylguanine (3056-33-5) → 2-acetylamino-9-(2-acetoxyethoxymethyl)purine-6-one (75128-73-3) + 7-<(2-acetoxyethoxy)methyl>-N2-acetylguanine (91702-60-2)

Conditions	Yield
With toluene-4-sulfonic acid; acetic acid In toluene at 120℃; for 2.5h;	A 29% B 29%

Acetic acid 2-(2-oxo-propoxy)-ethyl ester (102728-65-4) + 2,9-diacetylguanine (3056-33-5) → 2-acetylamino-9-(2-acetoxyethoxymethyl)purine-6-one (75128-73-3) + 7-<(2-acetoxyethoxy)methyl>-N2-acetylguanine (91702-60-2)

Conditions	Yield
With toluene-4-sulfonic acid 1.) 120-125 deg C, 2.) 150 deg C, 45 min;	A 27% B 22%

2,9-diacetylguanine (3056-33-5) + Acetic acid 2-acetoxymethoxy-3,3,3-trifluoro-propyl ester (181183-09-5) → Acetic acid 2-(2-acetylamino-6-oxo-1,6-dihydro-purin-7-ylmethoxy)-3,3,3-trifluoro-propyl ester + Acetic acid 2-(2-acetylamino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-3,3,3-trifluoro-propyl ester

Conditions	Yield
With toluene-4-sulfonic acid at 145℃; for 16h;	A 14% B 22%

1,3-DIOXOLANE (646-06-0) + 2,9-diacetylguanine (3056-33-5) → 2-acetylamino-9-(2-acetoxyethoxymethyl)purine-6-one (75128-73-3) + 7-<(2-acetoxyethoxy)methyl>-N2-acetylguanine (91702-60-2)

Conditions	Yield
With acetic anhydride; toluene-4-sulfonic acid In acetic acid for 1h; Heating;	A 18% B 2.3%

2,9-diacetylguanine (3056-33-5) + Acetic acid 6-(diethoxy-phosphoryl)-hexyloxymethyl ester (174538-09-1) → [6-(2-Acetylamino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-hexyl]-phosphonic acid diethyl ester (174538-33-1)

Conditions	Yield
With toluene-4-sulfonic acid In acetonitrile for 96h; Heating;	14%

2,9-diacetylguanine (3056-33-5) + diethyl <4-(acetoxymethoxy)butyl>phosphonate (174538-07-9) → diethyl <4-<(2-acetamido-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy>butyl>phosphonate (174538-31-9)

Conditions	Yield
With toluene-4-sulfonic acid In acetonitrile for 96h; Heating;	12%

trans-2,3-Dichlorotetrahydrofuran (3511-19-1, 13129-90-3, 29120-50-1, 106445-14-1) + 2,9-diacetylguanine (3056-33-5) → trans-N2-acetyl-9-(3-chlorotetrahydrofuran-2-yl)guanine (106445-16-3) + trans-N2-acetyl-7-(3-chlorotetrahydrofuran-2-yl)guanine (106445-15-2)

Conditions	Yield
With Bis(p-nitrophenyl) phosphate In N,N-dimethyl-formamide 1) 90 to 95 deg C, 1 h, 2) RT, 16 h;	A 11% B 10.9%

allyloxymethyl acetate (98485-52-0) + 2,9-diacetylguanine (3056-33-5) → 7-allyloxymethylguanine + 9-allyloxymethylguanine

Conditions	Yield
With ammonia; toluene-4-sulfonic acid 1.) DMSO, from 95 deg C to 100 deg C, 40 h, 2.) MeOH, RT, 24 h; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;
With ammonia; toluene-4-sulfonic acid 1.) DMSO, from 95 deg C to 100 deg C, 40 h, 2.) MeOH, RT, 24 h; Yield given. Multistep reaction. Yields of byproduct given;

allyloxymethyl acetate (98485-52-0) + 2,9-diacetylguanine (3056-33-5) → 7-allyloxymethyl-N-acetylguanine + 9-allyloxymethyl-N-acetylguanine

Conditions	Yield
With toluene-4-sulfonic acid In dimethyl sulfoxide at 95 - 100℃; for 40h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With toluene-4-sulfonic acid In dimethyl sulfoxide at 95 - 100℃; for 40h; Yield given. Yields of byproduct given;

2-methoxy-ethanol (109-86-4) + acetic anhydride (108-24-7) + 2,9-diacetylguanine (3056-33-5) → 2-acetylamino-9-(2-acetoxyethoxymethyl)purine-6-one (75128-73-3) + 7-<(2-acetoxyethoxy)methyl>-N2-acetylguanine (91702-60-2)

Conditions	Yield
With toluene-4-sulfonic acid 1.) AcOH, 2.) toluene, reflux, 16 h; Yield given. Multistep reaction. Yields of byproduct given;

Upstream product

• 73-40-5 2-amino-1,9-dihydro-6H-purin-6-one 
• 108-24-7 acetic anhydride 
• 75-36-5 acetyl chloride 
• 118-00-3 G 

Downstream Products

• 75128-73-3 2-acetylamino-9-(2-acetoxyethoxymethyl)purine-6-one 
• 91702-60-2 7-<(2-acetoxyethoxy)methyl>-N²-acetylguanine 
• 86357-14-4 9-(1,3-diacetoxy-2-propoxymethyl)-N²-acetylguanine 
• 19962-37-9 N-(6-oxo-6,9-dihydro-1H-purin-2-yl)acetamide 
• 10310-21-1 2-amino-6-chloropurine 
• 10310-21-1 2-Amino-6-chloropurin 
• 19916-73-5 2-Amino-6-benzyloxypurine 
• 144084-37-7 O⁶-(4-fluorobenzyl)guanine 
• 118-00-3 G 
• 112233-75-7 2-(acetylamino)-6-(diphenylcarbamoyloxy)-9-(β-D-tri-O-acetylribofuranosyl)-9H-purine 
• 106445-20-9 N²-(p-anisyldiphenylmethyl)-(β-(DL)-erythro-furanosyl)guanine 
• 106445-18-5 trans-N²-(p-anisyldiphenylmethyl)-9-(3-chlorotetrahydrofuran-2-yl)guanine 
• 106445-19-6 (RS)-N²-(p-anisyldiphenylmethyl)-9-(2,5-dihydrofuran-2-yl)guanine 
• 91702-61-3 7-(2-Hydroxyethoxymethyl)guanine 

Relevant articles and documents

Voltammetric study of the affinity of divalent heavy metals for guanine-functionalized iron oxide nanoparticles

In this study, a novel nanobiomaterial based on (3-aminopropyl)triethoxysilane (APTES)-coated iron oxide (Fe3O4) nanoparticles functionalized with newly synthesized guanine hydrazide (GH) was elaborated. A boron-doped diamond electrode coated with GH-APTES–Fe3O4 nanoparticles was used to assess the interaction of heavy metal ions with guanine hydrazide. The adsorption isotherms were electrochemically investigated and it was shown that the adsorption capacity of the nanoparticles towards heavy metals decreased in the following order: Cu2+ > Pb2+ > Cd2+. From the calibration curves, the sensitivities of detection were as follows: 171.6 μA/μM for Cu(II), 156 μA/μM for Pb(II), and 101.4 μA/μM for Cd(II). Graphic abstract: [Figure not available: see fulltext.].

Small Molecules in the Cone Snail Arsenal

Cone snails are renowned for producing peptide-based venom, containing conopeptides and conotoxins, to capture their prey. A novel small-molecule guanine derivative with unprecedented features, genuanine, was isolated from the venom of two cone snail species. Genuanine causes paralysis in mice, indicating that small molecules and not just polypeptides may contribute to the activity of cone snail venom.

Synthesis of some biologically active halogenopurines

A series of some biologically active halogenopurines were synthesized from commercially available guanine (1). The reaction of guanine with acetic anhydride yielded 2,9-diacetylguanine (2-1) by acetylation reaction. Further treatment of 2-1 with POCl3 by PEG-2000 phase transfer catalysis furnished the important compound 3a, then 2-amino-6-halogenopurines (3b-d) were obtained through chlorine-exchange halogenations between KX and 3a by TPPB phase transfer catalyst. Further, 2-halogenopurines (2-2a-d, 4-2a-d, 5a-d) were efficiently prepared from 2-amino-6-substituted purines (1, 3a, 4-1) via a diazotization catalyzed by their corresponding CuX, and some new compounds 2-2a, 2-2c, 2-2d, 4-2c, 4-2d, 5b, 5c and 5d have been discovered. The structures of synthesized compounds were mainly established on the basis of their elemental analysis, 1H NMR, as well as their mass spectral data. All the title compounds were screened for their antifungal activities, and some of the compounds showed promising activity.