3969-84-4

Basic information

• Product Name: 3,4-O-ISOPROPYLIDENE-D-MANNITOL
• Synonyms: 3,4-ISOPROPYLIDENE-D-MANNITOL;3,4-O-ISOPROPYLIDENE-D-MANNITOL;3,4-Isopropylidene-D-mannitol,98%;3,4-O-Isopropylidene-D-mannitol ,98%;3,4-O-Isopropylidene-D-maitol;D-Mannitol, 3,4-O-(1-Methylethylidene)-;3,4-O-Isopropylidene-D-mannitol;(1R,1'R)
• CAS NO: 3969-84-4
• Molecular Formula: C₉H₁₈O₆
• Molecular Weight: 222.24
• Product Categories: Biochemistry;Dioxanes & Dioxolanes;Dioxolanes;O-Substituted Sugars;Sugar Alcohols;Sugars;Naphthyridine,Quinoline;Carbohydrate Synthesis;Monosaccharides;Specialty Synthesis
• Mol File: 3969-84-4.mol
• Article Data: 28

Chemical Properties

• Melting Point: 85-88 °C(lit.)
• Boiling Point: 283.41°C (rough estimate)
• Flash Point: 219.2 °C
• Appearance: White crystalline powder
• Density: 1,52g/cm
• Vapor Pressure: 1.53E-09mmHg at 25°C
• Refractive Index: 29 ° (C=3, H2O)
• Storage Temp.: Store at 0°C
• BRN: 82182
• CAS DataBase Reference: 3,4-O-ISOPROPYLIDENE-D-MANNITOL(CAS DataBase Reference)
• NIST Chemistry Reference: 3,4-O-ISOPROPYLIDENE-D-MANNITOL(3969-84-4)
• EPA Substance Registry System: 3,4-O-ISOPROPYLIDENE-D-MANNITOL(3969-84-4)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-36/37/38
• Safety Statements: 22-24/25-36-26
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 3969-84-4(Hazardous Substances Data)

Usage

Chemical Properties

White crystalline powder

InChI:InChI=1/C9H18O6/c1-9(2)14-7(5(12)3-10)8(15-9)6(13)4-11/h5-8,10-13H,3-4H2,1-2H3/t5-,6-,7-,8-/m1/s1

Synthetic route

(+)-1,2,3,4,5,6-tris-O-isopropylidene-D-mannitol (3969-59-3, 4239-88-7, 81704-51-0) → 3,4-di-O-isopropylidene-D-mannitol (3969-84-4)

mannitol triacetonide (3969-59-3) → 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) + 1,2:3,4-di-O-isopropylidene-D-mannitol (38145-93-6)

Conditions	Yield
With H-Beta zeolite; water In methanol at 20℃; for 6h; Product distribution; Further Variations:; Reagents; reaction time; molar ratio;	A 36% B 48%
With hydrogenchloride In ethanol at 45℃; for 1h;	A 36 % Chromat. B 42 % Chromat.
With hydrogenchloride In ethanol at 45℃; for 1h; Product distribution; time;	A 36 % Chromat. B 42 % Chromat.

mannitol (69-65-8) + acetone (67-64-1) → 3,4-di-O-isopropylidene-D-mannitol (3969-84-4)

Conditions	Yield
Stage #1: mannitol; acetone With sulfuric acid at 20℃; for 48h; Stage #2: With acetic acid In water for 2h; Further stages.;	38%
With sulfuric acid; acetic acid 1.) HOAc, 25 deg C, 20 h, 2.) 40 deg C, 1.75 h; Yield given. Multistep reaction;
With sulfuric acid; acetic acid 1.) 23 deg C, 24 h, 2.) 40 deg C, 2 h; Multistep reaction;
Stage #1: mannitol; acetone With sulfuric acid cyclocondensation; Stage #2: In water; acetic acid Hydrolysis; Further stages.;
Stage #1: mannitol; acetone With sulfuric acid cyclocondensation; Stage #2: With acetic acid at 40℃; for 2.5h; Hydrolysis; Further stages.;

acetic acid (64-19-7) + mannitol triacetonide (3969-59-3) → 3,4-di-O-isopropylidene-D-mannitol (3969-84-4)

3.4-isopropylidene-1.6-dibenzoyl-d-mannitol → 3,4-di-O-isopropylidene-D-mannitol (3969-84-4)

Conditions	Yield
With ammonia at 20℃;

water (7732-18-5) + 1,2;5,6-dianhydro-3,4-O-isopropylidene-D-mannitol (63700-05-0) → 3,4-di-O-isopropylidene-D-mannitol (3969-84-4)

mannitol (69-65-8) → 3,4-di-O-isopropylidene-D-mannitol (3969-84-4)

Conditions	Yield
With sodium carbonate; sulfuric acid In acetone
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / acetone / 24 h / Reflux 2: hydrogenchloride / water; methanol / 20 °C View Scheme
Multi-step reaction with 2 steps 1: indium(III) triflate / 3 h / 65 °C 2: methanol / 2 h / 40 °C / Acidic conditions View Scheme
Multi-step reaction with 2 steps 1: sulfuric acid / acetone 2: acetic acid / water / 1 h / 40 °C View Scheme

tert-butyldimethylsilyl chloride (18162-48-6) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,6-bis(tert-butyldimethylsilyloxy)-3,4-di-O-isopropylidene-D-mannitol (172995-87-8)

Conditions	Yield
With 1H-imidazole In dichloromethane at 0℃; for 2h;	100%
With triethylamine In N,N-dimethyl-formamide at 20℃; for 0.5h;	100%
With dmap; triethylamine In dichloromethane at 20℃; for 8h;	94%
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 1.25h;

1-bromomethyl-4-bromobenzene (589-15-1) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,2,5,6-tetra-O-(4-bromobenzyl)-3,4-O-isopropylidene-D-mannitol

Conditions	Yield
Stage #1: 3,4-di-O-isopropylidene-D-mannitol With 1H-imidazole; sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 0.5h; Inert atmosphere; Stage #2: 1-bromomethyl-4-bromobenzene In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 24h; Inert atmosphere;	100%

benzyl bromide (100-39-0) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,2,5,6-tetra-O-benzyl-3,4-O-isopropylidene-D-mannitol (20258-50-8)

Conditions	Yield
Stage #1: 3,4-di-O-isopropylidene-D-mannitol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Stage #2: benzyl bromide In N,N-dimethyl-formamide at 20℃;	98%
Stage #1: 3,4-di-O-isopropylidene-D-mannitol With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 0.75h; Inert atmosphere; Stage #2: benzyl bromide With tetra-(n-butyl)ammonium iodide In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil at 20℃; Inert atmosphere;	93%
With sodium hydride In N,N-dimethyl-formamide
With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 60℃;

trityl chloride (76-83-5) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → O3,O4-isopropylidene-O1,O6-ditrityl-D-mannitol (81841-56-7)

Conditions	Yield
With dmap In pyridine at 22℃; for 48h;	97%
With pyridine for 48h; Ambient temperature;	74%
With pyridine at 20℃; for 48h;

pivaloyl chloride (3282-30-2) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,6-dipivaloyl-3,4-isopropylidene-D-mannitol

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 24h;	95%

propargyl bromide (106-96-7) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → C21H26O6

Conditions	Yield
Stage #1: 3,4-di-O-isopropylidene-D-mannitol With sodium hydride In N,N-dimethyl-formamide for 0.25h; Stage #2: propargyl bromide In N,N-dimethyl-formamide; toluene at 20℃; for 25h;	94%

1-triphenylphosphoranylidene-2-propanone (1439-36-7) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → (5R,6R)-5,6-dihydroxy-5,6-O-isopropylidene-deca-3,7-diene-2,9-dione (1119511-32-8)

Conditions	Yield
With sodium periodate; silica gel In dichloromethane at 20℃; for 20h; Wittig reaction;	92%

benzoyl chloride (98-88-4) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,6-di-O-benzoyl-3,4-di-O-isopropylidene-D-mannitol (51432-64-5)

Conditions	Yield
With pyridine In dichloromethane at -80℃; for 4h;	90%
With pyridine In chloroform at 0℃;	80%
With pyridine In dichloromethane	72%

2,2-dimethoxy-propane (77-76-9) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → mannitol triacetonide (3969-59-3)

Conditions	Yield
In 1,2-dimethoxyethane for 48h; Heating;	89%

p-toluenesulfonyl chloride (98-59-9) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,6-di-O-(p-toluenesulfonyl)-3,4-O-isopropylidene-D-mannitol (53754-41-9)

Conditions	Yield
With pyridine Tosylation;	86%
In pyridine at 0℃; for 3.75h;	84%
With pyridine

benzyl bromide (100-39-0) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,6-di-O-benzyl-3,4-O-methylethylidene-D-mannitol (142285-64-1)

Conditions	Yield
Stage #1: 3,4-di-O-isopropylidene-D-mannitol With di(n-butyl)tin oxide In toluene for 15h; Substitution; Heating; Stage #2: benzyl bromide With tetra-(n-butyl)ammonium iodide In toluene at 70℃; for 15h; Substitution;	86%
Stage #1: 3,4-di-O-isopropylidene-D-mannitol With di(n-butyl)tin oxide In toluene Heating; Stage #2: benzyl bromide With cesium fluoride	82%
With di(n-butyl)tin oxide; cesium fluoride In hexane; N,N-dimethyl-formamide; toluene	65%
With di(n-butyl)tin oxide; cesium fluoride 1.) toluene; Yield given. Multistep reaction;

benzyl bromide (100-39-0) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,2,5,6-tetra-O-benzyl-D-mannitol (20196-69-4)

Conditions	Yield
With hydrogenchloride; acetyl chloride In methanol; hexane; N,N-dimethyl-formamide	81%
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil; N,N-dimethyl-formamide / 0.75 h / 0 - 20 °C / Inert atmosphere 1.2: 20 °C / Inert atmosphere 2.1: acetic acid / water / 100 °C View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C 1.2: 20 °C 2.1: hydrogenchloride / methanol; water / 4 h / Reflux View Scheme

benzyl chloride (100-44-7) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,2,5,6-tetra-O-benzyl-3,4-O-isopropylidene-D-mannitol (20258-50-8)

Conditions	Yield
With sodium hydroxide; potassium carbonate; tert-Amyl alcohol; tetra(n-butyl)ammonium hydrogensulfate In dimethyl sulfoxide; benzene for 12h; Ambient temperature;	80%

p-toluenesulfonyl chloride (98-59-9) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → C37H42O14S4

Conditions	Yield
With pyridine; triethylamine at 0 - 20℃; for 48h;	79%

phenyl isocyanate (103-71-9) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,6-di-O-(phenylcarbmoyl)-3,4-O-isopropylidene-D-mannitol (110101-27-4)

Conditions	Yield
With Zn naphthenate; triethylamine In N,N-dimethyl-formamide for 1h; Ambient temperature;	77%

1-Bromotetradecane (112-71-0) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → (4R,5R)-4,5-Bis-((R)-1,2-bis-tetradecyloxy-ethyl)-2,2-dimethyl-[1,3]dioxolane (128229-34-5)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 25℃; for 48h;	76%

4-Fluorobenzyl bromide (459-46-1) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,2,5,6-tetra-O-(4-fluorobenzyl)-D-mannitol

Conditions	Yield
	73%

4-trifluoromethylbenzyl chloride (939-99-1) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,2,5,6-tetra-O-(4-trifluoromethylbenzyl)-D-mannitol

Conditions	Yield
	72%

3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,2;5,6-dianhydro-3,4-O-isopropylidene-D-mannitol (63700-05-0)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate at 120℃; under 0.1 Torr; for 3h;	68%
Yield given. Multistep reaction;
Multi-step reaction with 2 steps 1: pyridine / CH2Cl2 / 4 h / 0 °C 2: K2CO3 / methanol / 2.5 h / 25 °C View Scheme

ethyl (triphenylphosphoranylidene)acetate (1099-45-2) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → (E)-3-[(4R,5R)-5-((E)-2-Ethoxycarbonyl-vinyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-acrylic acid ethyl ester (166239-53-8)

Conditions	Yield
With sodium periodate; silica gel In dichloromethane at 20℃; for 20h; Wittig reaction;	67%

4-Methylbenzyl bromide (104-81-4) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,2,5,6-tetra-O-(4-methylbenzyl)-D-mannitol

Conditions	Yield
	65%

4-cyanobenzyl bromide (17201-43-3) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 1,2,5,6-tetra-O-(4-cyanobenzyl)-D-mannitol

Conditions	Yield
	65%

trityl chloride (76-83-5) + 3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → 3,4-O-isopropylidene-1-O-trityl-D-mannitol (84608-23-1)

Conditions	Yield
With pyridine Ambient temperature;	63%

3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → (2R,3R,4R,5R)-3,4-O-(1-methylethylidene)-2,3,4,5-hexanetetraol (74044-75-0)

Conditions	Yield
Stage #1: 3,4-di-O-isopropylidene-D-mannitol With pyridine; p-toluenesulfonyl chloride In dichloromethane at 0℃; for 4h; Stage #2: With lithium aluminium tetrahydride In tetrahydrofuran for 3h; Further stages.;	61%
Multi-step reaction with 2 steps 1: pyridine / 0 °C 2: LiAlH4 / tetrahydrofuran View Scheme
Multi-step reaction with 3 steps 1: pyridine 2: K2CO3 / methanol 3: 85 percent / LiEt3BH / tetrahydrofuran / 2 h / 20 °C View Scheme

3,4-di-O-isopropylidene-D-mannitol (3969-84-4) + methyl iodide (74-88-4) → 3,4-O-isopropylidene-1,2,5,6-tetra-O-methyl-D-mannitol (77049-48-0)

Conditions	Yield
With sodium methylsulfinylmethanide In dimethyl sulfoxide 1.) 0 degC, 2.) 0 degC to r.t.;	60%

3,4-di-O-isopropylidene-D-mannitol (3969-84-4) → C18H30O12P2

Conditions	Yield
With Hexamethylphosphorous triamide In acetonitrile for 2h;	50%

Upstream product

• 69-65-8 mannitol 
• 67-64-1 acetone 
• 3969-59-3 1,2;3,4:5,6-tri-O-isopropylidene-D-glucitol 
• 51432-64-5 1,6-di-O-benzoyl-3,4-di-O-isopropylidene-D-mannitol 
• 7732-18-5 water 
• 63700-05-0 1,2;5,6-dianhydro-3,4-O-isopropylidene-D-mannitol 
• 3969-59-3 mannitol triacetonide 
• 3969-59-3 (+)-1,2,3,4,5,6-tris-O-isopropylidene-D-mannitol 
• 64-19-7 acetic acid 

Downstream Products

• 51432-64-5 O¹,O⁶-dibenzoyl-O³,O⁴-isopropylidene-mannitol 
• 1187-00-4 1,6-Bis-methansulfonyl-D-mannit 
• 52868-81-2 O²,O⁵-diacetyl-O³,O⁴-isopropylidene-O¹,O⁶-bis-(toluene-4-sulfonyl)-D-mannitol 
• 73346-74-4 (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol 
• 20196-69-4 1,2,5,6-tetra-O-benzyl-D-mannitol 
• 20196-70-7 (+)-(R)-2,3-bis(benzyloxy)propanal 
• 142285-64-1 1,6-di-O-benzyl-3,4-O-methylethylidene-D-mannitol 
• 171524-74-6 1,6-dideoxy-D-mannitol 2,5-di-p-toluenesulfonate 
• 74044-76-1 1,6-dideoxy-3,4-O-isopropylidene-D-mannitol 2,5-di-p-toluenesulfonate 
• 81841-57-8 3,4-disoprpylidene-1,6-di-O-triphenylmethyl-D-mannitol diacetate 
• 109074-99-9 (2S,3R,4R,5S) 1,2:5,6-N-benzyldiimino-3,4-O-isopropylidenehexanediol 
• 109107-29-1 (2S,3R,4R,5S) 1,2:5,6-N-benzyldiimino-3,4-O-isopropylidenehexanediol 
• 109075-06-1 (S)-2-((4R,5R)-2,2-dimethyl-5-((S)-1-tosylaziridin-2-yl)-1,3-dioxolan-4-yl)-1-tosyl-aziridine 
• 109075-07-2 (2S,3R,4R,5S) 1,2:5,6-N-tosyldiimino-3,4-O-isopropylidenehexanediol 

Relevant articles and documents

A latent reactive handle for functionalising heparin-like and LMWH deca- and dodecasaccharides

d-Glucosamine derivatives bearing latent O4 functionality provide modified H/HS-type disaccharide donors for a final stage capping approach enabling introduction of conjugation-suitable, non-reducing terminal functionality to biologically important glycosaminoglycan oligosaccharides. Application to the synthesis of the first O4-terminus modified synthetic LMWH decasaccharide and an HS-like dodecasaccharide is reported.

A NOVEL PROCESS FOR MAKING ALISKIREN, ITS NOVEL INTERMEDIATES AND CERTAIN NOVEL COMPOUNDS

A novel process for making Renin inhibitors like Aliskiren is disclosed. Its novel intermediate compounds and method of making them are also disclosed.

An efficient, one-pot synthesis of fosfomycin dialkyl esters from (R)-2-tosyloxypropanal

(R)-2-Tosyloxypropanal (4) was prepared from D-mannitol in a 7-step sequence (51% overall yield). Addition of dialkyl phosphonates to 4 in the presence of titanium isopropoxide and the subsequent treatment with DBU stereoselectively afforded, in one-pot, fosfomycin dimethyl (5a) and dibenzyl (5b) esters both in 58% isolated yield.