N,N-DIMETHYLUREA (1,3-DIMETHYLUREA)

N,N-Dimethylurea, also known as 1,3-Dimethylurea, is an organic compound derived from urea where two methyl groups are attached to the nitrogen atoms. 
It belongs to the class of urea derivatives and is often used as an intermediate in organic synthesis, particularly in pharmaceutical and agrochemical industries.

CAS Number:  544-88-7

Synonyms:
1,3-Dimethylurea,N,N-Dimethylurea,Dimethylurea,1,3-Dimethylcarbamide, Ureidodimethane,N,N-Dimethylcarbamide

Introduction
1.1 Background and Importance
N,N-Dimethylurea (1,3-Dimethylurea) is a derivative of urea in which both nitrogen atoms are methylated. 
Urea itself has long been recognized as a fundamental molecule in organic chemistry and biochemistry. 
The introduction of methyl groups at the nitrogen positions modifies both the chemical and physical properties of the molecule, increasing its utility as a synthetic intermediate.

This compound is significant in organic synthesis, particularly in pharmaceuticals and agrochemicals, due to its ability to serve as a building block for heterocyclic compounds, herbicides, and other biologically active molecules. 
It is valued for its relatively low toxicity, high solubility, and reactivity under mild conditions.

Historical Development
The origin of substituted ureas traces back to the 19th century with the synthesis of urea by Friedrich Wöhler, which disproved the vitalism theory by showing organic molecules could be synthesized from inorganic precursors. 
Since then, numerous derivatives like N,N-Dimethylurea have been explored for their diverse chemical properties and applications.

Over time, N,N-Dimethylurea gained prominence as a reagent and intermediate in organic synthesis, providing more favorable physical properties than urea itself, such as improved solubility and reduced hydrogen bonding, facilitating its use in various chemical reactions.

Overview of Chemical Family
N,N-Dimethylurea belongs to the broad family of urea derivatives characterized by the presence of the urea functional group (-NH-CO-NH-) with various substitutions on the nitrogen atoms. 
These derivatives are widely used as intermediates for synthesizing pharmaceuticals, dyes, resins, and polymers.
The methylation of urea alters its reactivity, making N,N-Dimethylurea more suitable for certain applications.

Chemical and Physical Properties
Molecular Structure and Formula
N,N-Dimethylurea's molecular formula is C3H8N2O, with a molecular weight of 88.11 g/mol. 
The molecule features a central carbonyl group flanked by two nitrogen atoms, each substituted with a methyl group. 
This symmetric substitution reduces intermolecular hydrogen bonding relative to urea, which influences physical properties such as melting point and solubility.

Physical Properties
Appearance: White crystalline solid
Melting Point: Approximately 78–81 °C
Boiling Point: Decomposes before boiling, typically not distilled
Density: Around 1.05 g/cm³ at 20 °C
Solubility: Highly soluble in water, ethanol, methanol, and other polar solvents; practically insoluble in nonpolar solvents like hexane

Spectroscopic Characteristics
Infrared (IR) Spectroscopy: Shows characteristic absorption bands for the carbonyl (C=O) group around 1670 cm⁻¹. N-H stretching vibrations are absent or weak due to substitution, replaced by C-H stretching vibrations of the methyl groups around 2900 cm⁻¹.

Nuclear Magnetic Resonance (NMR):
¹H NMR: Presents singlet peaks for methyl groups attached to nitrogen, typically appearing around 2.8–3.2 ppm.
¹³C NMR: Shows signals for the carbonyl carbon around 160–165 ppm and methyl carbons around 30 ppm.
Mass Spectrometry (MS): Molecular ion peak (M⁺) at m/z = 88, confirming the molecular weight.

Synthesis and Production Methods
Industrial Synthesis Routes
N,N-Dimethylurea is primarily synthesized via the methylation of urea using methylating agents such as methyl iodide, dimethyl sulfate, or formaldehyde combined with formic acid (Eschweiler–Clarke type methylation). 
The process is typically conducted under controlled temperature and pressure to optimize yield and minimize byproducts.

Laboratory Synthesis Methods
In the lab, N,N-Dimethylurea can be prepared by reacting urea with formaldehyde and formic acid, a process analogous to the Eschweiler–Clarke reaction, which selectively methylates amines. 
Alternatively, direct methylation of urea using methyl iodide or dimethyl sulfate under basic conditions is performed.

Another synthetic route involves the condensation of methyl isocyanate with methylamine, but this is less common due to the toxicity of methyl isocyanate.

Reaction Mechanisms
The methylation proceeds via nucleophilic attack of the urea nitrogen on electrophilic methyl groups provided by the methylating agent. 
The presence of base ensures that the nitrogen remains nucleophilic by deprotonating intermediate species. 
The reaction can yield mono-, di-, or trimethylated urea species depending on conditions.

Yield and Purification
Typical yields range from 70% to 95%, depending on reaction conditions and purification steps. 
The product is purified by recrystallization from polar solvents such as water or methanol. 
Impurities include unmethylated urea and partially methylated derivatives, which can be removed by fractional crystallization or chromatography.

Chemical Reactivity and Applications
Reactivity Profile
N,N-Dimethylurea exhibits typical urea chemistry but with altered reactivity due to methyl substitutions. 
The carbonyl carbon remains electrophilic, allowing for reactions such as acylation and condensation with amines and alcohols.

The methyl groups reduce hydrogen bonding, enhancing solubility and sometimes altering reaction rates. 
It is relatively stable but reactive under acidic or basic catalysis.

Use as an Intermediate in Organic Synthesis
It serves as a precursor for heterocyclic compounds, such as imidazoles and triazines, which are important scaffolds in medicinal chemistry. 
It also participates in the synthesis of pesticides and herbicides.

Applications in Pharmaceuticals and Agrochemicals
Pharmaceutical applications include use as intermediates in the synthesis of drugs like sulfonylureas, which are antidiabetic agents. 
In agrochemicals, it is involved in the manufacture of herbicides and fungicides.

Role in Catalyst Systems
N,N-Dimethylurea can act as a ligand or stabilizer in catalyst formulations, enhancing catalyst activity or selectivity in organic reactions.

Analytical Methods
Chromatographic Techniques
Gas Chromatography (GC):
Due to its relatively low volatility and thermal stability, N,N-Dimethylurea is less frequently analyzed by GC directly. 
However, derivatization techniques can be employed to increase volatility and detect trace impurities or degradation products. 
GC coupled with mass spectrometry (GC-MS) is useful for structural confirmation of derivatives.

High-Performance Liquid Chromatography (HPLC):
HPLC is the preferred method for quantitative analysis of N,N-Dimethylurea in complex mixtures. Using reversed-phase columns and UV detection at wavelengths around 200–220 nm, N,N-Dimethylurea can be accurately separated and quantified. Gradient elution with aqueous buffers and organic solvents (e.g., acetonitrile) optimizes resolution.

Spectroscopic Techniques
Ultraviolet-Visible (UV-Vis) Spectroscopy:
Though N,N-Dimethylurea lacks extensive conjugation, its carbonyl group absorbs in the low UV range (~190–210 nm), allowing UV detection primarily for purity assessment or monitoring reaction progress.

Infrared (IR) Spectroscopy:
IR spectroscopy is valuable for identification by monitoring characteristic peaks such as carbonyl stretching at ~1670 cm⁻¹ and N–C stretching modes. Fourier-transform infrared (FTIR) instruments provide rapid qualitative analysis and can detect functional group modifications.

Nuclear Magnetic Resonance (NMR) Spectroscopy:
¹H and ¹³C NMR are indispensable tools for structural elucidation and purity evaluation. 
Chemical shifts of methyl protons (~2.9 ppm) and carbonyl carbons (~160 ppm) confirm substitution patterns. Two-dimensional NMR (COSY, HSQC) further aids in assignment.

Quantification and Purity Testing
Quantitative analysis combines chromatographic and spectroscopic data. Titrimetric methods are rarely used. 
Instead, a combination of HPLC for quantification and NMR or IR for structural confirmation ensures product consistency. 
Purity typically exceeds 98% for industrial and pharmaceutical standards.

Industrial Significance and Market
Production Scale and Economics
N,N-Dimethylurea is manufactured at multi-ton scales globally, primarily serving the pharmaceutical and agrochemical industries. 
Production facilities leverage continuous flow reactors to optimize yield and minimize waste.

Economic factors influencing production include the cost of raw materials such as urea and methylating agents, energy consumption, and environmental compliance costs. Advances in green chemistry aim to reduce hazardous byproducts and improve atom economy.

Market Demand and Trends
Market demand for N,N-Dimethylurea correlates closely with pharmaceutical and agrochemical growth. 
Its role as a synthetic intermediate for bioactive molecules ensures steady demand. 
Emerging markets in Asia-Pacific show increasing consumption due to expanding chemical manufacturing sectors.

Trends include the development of more sustainable synthetic routes and incorporation in novel drug candidates. 
The push for environmentally friendly processes may influence future market dynamics.

Regulatory Status
N,N-Dimethylurea is regulated under various chemical safety laws depending on jurisdiction, including REACH in the EU and TSCA in the USA. 
While not classified as a high-risk chemical, manufacturers must comply with occupational safety standards, waste management protocols, and transportation regulations.

Recent Research and Developments
New Synthesis Approaches
Recent studies explore catalytic methylation methods using less toxic methyl donors and greener solvents, aiming to replace traditional methyl iodide or dimethyl sulfate routes. 
Biocatalytic approaches and microwave-assisted synthesis have shown promise for higher efficiency and lower environmental impact.

Novel Applications
Emerging applications include:
Use as a component in polymer crosslinkers to modify material properties.
Precursor for novel heterocycles with potential antimicrobial or anticancer activity.
Role as a stabilizer in advanced catalyst formulations for asymmetric synthesis.

Research Challenges and Future Directions
Current challenges focus on enhancing selectivity of methylation to reduce side-products, improving sustainable production methods, and expanding the compound’s utility in materials science. Research also aims at developing N,N-Dimethylurea derivatives with tailored biological activities.

Conclusion
N,N-Dimethylurea is a versatile and valuable urea derivative with broad applications in organic synthesis, pharmaceuticals, and agrochemicals. 
Its unique chemical and physical properties arise from the methyl substitutions on the nitrogen atoms, influencing reactivity and solubility.

The compound’s established industrial production and analytical methods provide a solid foundation for its continued use and innovation. 
Ongoing research into greener synthesis routes and new applications promises to expand its importance in both industrial and academic chemistry.

SAFETY INFORMATION ABOUT N,N-DIMETHYLUREA

First aid measures:
Description of first aid measures:
General advice:
Consult a physician. 
Show this safety data sheet to the doctor in attendance.
Move out of dangerous area:
 
If inhaled:
If breathed in, move person into fresh air. 
If not breathing, give artificial respiration.
Consult a physician.
In case of skin contact:
Take off contaminated clothing and shoes immediately. 
Wash off with soap and plenty of water.
Consult a physician.
 
In case of eye contact:
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
Continue rinsing eyes during transport to hospital.
 
If swallowed:
Do NOT induce vomiting. 
Never give anything by mouth to an unconscious person. 
Rinse mouth with water. 
Consult a physician.
 
Firefighting measures:
Extinguishing media:
Suitable extinguishing media:
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, Nitrogen oxides (NOx), Hydrogen chloride gas
 
Advice for firefighters:
Wear self-contained breathing apparatus for firefighting if necessary.
Accidental release measures:
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. 
 
Avoid breathing vapours, mist or gas. 
Evacuate personnel to safe areas.
 
Environmental precautions:
Prevent further leakage or spillage if safe to do so.
Do not let product enter drains.
Discharge into the environment must be avoided.
 
Methods and materials for containment and cleaning up:
Soak up with inert absorbent material and dispose of as hazardous waste. 
Keep in suitable, closed containers for disposal.
 
Handling and storage:
Precautions for safe handling:
Avoid inhalation of vapour or mist.
 
Conditions for safe storage, including any incompatibilities:
Keep container tightly closed in a dry and well-ventilated place. 
Containers which are opened must be carefully resealed and kept upright to prevent leakage.
Storage class (TRGS 510): 8A: Combustible, corrosive hazardous materials
 
Exposure controls/personal protection:
Control parameters:
Components with workplace control parameters
Contains no substances with occupational exposure limit values.
Exposure controls:
Appropriate engineering controls:
Handle in accordance with good industrial hygiene and safety practice.
Wash hands before breaks and at the end of workday.
 
Personal protective equipment:
Eye/face protection:
Tightly fitting safety goggles. 
Faceshield (8-inch minimum). 
Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
 
Skin protection:
Handle with gloves. 
Gloves must be inspected prior to use. 
Use proper glove
removal technique (without touching glove's outer surface) to avoid skin contact with this product. 
Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. 
Wash and dry hands.
 
Full contact:
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm
Break through time: 480 min
Material tested:Dermatril (KCL 740 / Aldrich Z677272, Size M)
Splash contact
Material: Nitrile rubber
Minimum layer thickness: 0.11 mm
Break through time: 480 min
Material tested:Dermatril (KCL 740 / Aldrich Z677272, Size M)
It should not be construed as offering an approval for any specific use scenario.
 
Body Protection:
Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection:
Where risk assessment shows air-purifying respirators are appropriate use a fullface respirator with multi-purpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. 
 
If the respirator is the sole means of protection, use a full-face supplied air respirator. 
Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so. 
Do not let product enter drains.
Discharge into the environment must be avoided.
 
Stability and reactivity:
Chemical stability:
Stable under recommended storage conditions.
Incompatible materials:
Strong oxidizing agents:
Hazardous decomposition products:
Hazardous decomposition products formed under fire conditions. 
Carbon oxides, Nitrogen oxides (NOx), Hydrogen chloride gas.
 
Disposal considerations:
Waste treatment methods:
Product:
Offer surplus and non-recyclable solutions to a licensed disposal company. 
Contact a licensed professional waste disposal service to dispose of this material.
Contaminated packaging:
Dispose of as unused product